US20220401387A1 - Compositions and methods affecting exercise performance - Google Patents
Compositions and methods affecting exercise performance Download PDFInfo
- Publication number
- US20220401387A1 US20220401387A1 US17/577,505 US202217577505A US2022401387A1 US 20220401387 A1 US20220401387 A1 US 20220401387A1 US 202217577505 A US202217577505 A US 202217577505A US 2022401387 A1 US2022401387 A1 US 2022401387A1
- Authority
- US
- United States
- Prior art keywords
- composition
- subject
- compositions
- exercise
- oil
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 145
- 238000000034 method Methods 0.000 title claims description 38
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 19
- 235000013361 beverage Nutrition 0.000 claims description 18
- 239000003755 preservative agent Substances 0.000 claims description 16
- 239000000796 flavoring agent Substances 0.000 claims description 12
- 230000036314 physical performance Effects 0.000 claims description 12
- 230000002335 preservative effect Effects 0.000 claims description 11
- 235000003599 food sweetener Nutrition 0.000 claims description 10
- 239000003765 sweetening agent Substances 0.000 claims description 10
- 239000003086 colorant Substances 0.000 claims description 9
- 239000004034 viscosity adjusting agent Substances 0.000 claims description 9
- 239000003963 antioxidant agent Substances 0.000 claims description 8
- 235000013355 food flavoring agent Nutrition 0.000 claims description 8
- 244000223760 Cinnamomum zeylanicum Species 0.000 claims description 7
- 235000017803 cinnamon Nutrition 0.000 claims description 7
- 235000006886 Zingiber officinale Nutrition 0.000 claims description 6
- 235000008397 ginger Nutrition 0.000 claims description 6
- 230000007423 decrease Effects 0.000 claims description 4
- 239000003995 emulsifying agent Substances 0.000 claims description 4
- 239000003002 pH adjusting agent Substances 0.000 claims description 4
- 235000002566 Capsicum Nutrition 0.000 claims description 3
- 240000008574 Capsicum frutescens Species 0.000 claims description 3
- 230000003078 antioxidant effect Effects 0.000 claims description 3
- 239000001390 capsicum minimum Substances 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000007884 disintegrant Substances 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 239000004094 surface-active agent Substances 0.000 claims description 2
- 241000234314 Zingiber Species 0.000 claims 2
- 239000012190 activator Substances 0.000 abstract description 50
- 102000001671 Acid Sensing Ion Channels Human genes 0.000 abstract description 14
- 108010068806 Acid Sensing Ion Channels Proteins 0.000 abstract description 14
- 238000011084 recovery Methods 0.000 abstract description 13
- 102000042565 transient receptor (TC 1.A.4) family Human genes 0.000 abstract description 3
- 108091053409 transient receptor (TC 1.A.4) family Proteins 0.000 abstract description 3
- 108091006146 Channels Proteins 0.000 description 26
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 26
- 102000003566 TRPV1 Human genes 0.000 description 21
- 101150016206 Trpv1 gene Proteins 0.000 description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
- -1 L-aspartyl-L-phenyl-alanine ester Chemical class 0.000 description 17
- 235000020357 syrup Nutrition 0.000 description 17
- 239000006188 syrup Substances 0.000 description 17
- 238000011282 treatment Methods 0.000 description 16
- 238000012360 testing method Methods 0.000 description 14
- 108010036769 TRPA1 Cation Channel Proteins 0.000 description 12
- 102000012253 TRPA1 Cation Channel Human genes 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 229940068196 placebo Drugs 0.000 description 11
- 239000000902 placebo Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 9
- 235000002780 gingerol Nutrition 0.000 description 9
- 230000036651 mood Effects 0.000 description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 7
- 208000002193 Pain Diseases 0.000 description 7
- 239000006172 buffering agent Substances 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 239000003792 electrolyte Substances 0.000 description 7
- NLDDIKRKFXEWBK-AWEZNQCLSA-N gingerol Chemical compound CCCCC[C@H](O)CC(=O)CCC1=CC=C(O)C(OC)=C1 NLDDIKRKFXEWBK-AWEZNQCLSA-N 0.000 description 7
- JZLXEKNVCWMYHI-UHFFFAOYSA-N gingerol Natural products CCCCC(O)CC(=O)CCC1=CC=C(O)C(OC)=C1 JZLXEKNVCWMYHI-UHFFFAOYSA-N 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 7
- 235000002639 sodium chloride Nutrition 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 239000002562 thickening agent Substances 0.000 description 7
- 229940088594 vitamin Drugs 0.000 description 7
- 229930003231 vitamin Natural products 0.000 description 7
- 235000013343 vitamin Nutrition 0.000 description 7
- 239000011782 vitamin Substances 0.000 description 7
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 101000764872 Homo sapiens Transient receptor potential cation channel subfamily A member 1 Proteins 0.000 description 6
- 102100026186 Transient receptor potential cation channel subfamily A member 1 Human genes 0.000 description 6
- 235000006708 antioxidants Nutrition 0.000 description 6
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 6
- 229940117916 cinnamic aldehyde Drugs 0.000 description 6
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 description 6
- 235000010755 mineral Nutrition 0.000 description 6
- 239000011707 mineral Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 244000246386 Mentha pulegium Species 0.000 description 5
- 235000016257 Mentha pulegium Nutrition 0.000 description 5
- 235000004357 Mentha x piperita Nutrition 0.000 description 5
- 208000007101 Muscle Cramp Diseases 0.000 description 5
- 208000000112 Myalgia Diseases 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 5
- 235000012907 honey Nutrition 0.000 description 5
- 235000001050 hortel pimenta Nutrition 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 210000003205 muscle Anatomy 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 229960004793 sucrose Drugs 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 235000005747 Carum carvi Nutrition 0.000 description 4
- 240000000467 Carum carvi Species 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 229920000161 Locust bean gum Polymers 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical class [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 241001315609 Pittosporum crassifolium Species 0.000 description 4
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 244000078534 Vaccinium myrtillus Species 0.000 description 4
- 244000273928 Zingiber officinale Species 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 4
- 229960002504 capsaicin Drugs 0.000 description 4
- 235000017663 capsaicin Nutrition 0.000 description 4
- 230000001351 cycling effect Effects 0.000 description 4
- 239000008121 dextrose Substances 0.000 description 4
- CBOQJANXLMLOSS-UHFFFAOYSA-N ethyl vanillin Chemical compound CCOC1=CC(C=O)=CC=C1O CBOQJANXLMLOSS-UHFFFAOYSA-N 0.000 description 4
- RRAFCDWBNXTKKO-UHFFFAOYSA-N eugenol Chemical compound COC1=CC(CC=C)=CC=C1O RRAFCDWBNXTKKO-UHFFFAOYSA-N 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 235000010420 locust bean gum Nutrition 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 208000013465 muscle pain Diseases 0.000 description 4
- 235000013615 non-nutritive sweetener Nutrition 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 235000021580 ready-to-drink beverage Nutrition 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 235000010356 sorbitol Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- RUVINXPYWBROJD-ONEGZZNKSA-N trans-anethole Chemical compound COC1=CC=C(\C=C\C)C=C1 RUVINXPYWBROJD-ONEGZZNKSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 244000299461 Theobroma cacao Species 0.000 description 3
- 235000011941 Tilia x europaea Nutrition 0.000 description 3
- 235000009754 Vitis X bourquina Nutrition 0.000 description 3
- 235000012333 Vitis X labruscana Nutrition 0.000 description 3
- 240000006365 Vitis vinifera Species 0.000 description 3
- 235000014787 Vitis vinifera Nutrition 0.000 description 3
- 235000010443 alginic acid Nutrition 0.000 description 3
- 229920000615 alginic acid Polymers 0.000 description 3
- ZOJBYZNEUISWFT-UHFFFAOYSA-N allyl isothiocyanate Chemical compound C=CCN=C=S ZOJBYZNEUISWFT-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 229960001948 caffeine Drugs 0.000 description 3
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 3
- 239000010630 cinnamon oil Substances 0.000 description 3
- 239000010634 clove oil Substances 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- RBCYRZPENADQGZ-UHFFFAOYSA-N dihydrocapsaicin Natural products COC1=CC(COC(=O)CCCCCCC(C)C)=CC=C1O RBCYRZPENADQGZ-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 230000003340 mental effect Effects 0.000 description 3
- 229960001047 methyl salicylate Drugs 0.000 description 3
- RGOVYLWUIBMPGK-UHFFFAOYSA-N nonivamide Chemical compound CCCCCCCCC(=O)NCC1=CC=C(O)C(OC)=C1 RGOVYLWUIBMPGK-UHFFFAOYSA-N 0.000 description 3
- 230000036284 oxygen consumption Effects 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- AIUJHENHBJHHMY-UHFFFAOYSA-N 1-[2-(1-adamantyl)ethyl]-1-pentyl-3-(3-pyridin-4-ylpropyl)urea Chemical compound C1C(C2)CC(C3)CC2CC13CCN(CCCCC)C(=O)NCCCC1=CC=NC=C1 AIUJHENHBJHHMY-UHFFFAOYSA-N 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 2
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 2
- PCZMUTQYZKAXBW-KHPPLWFESA-N 2-(4-hydroxy-3-methoxyphenyl)-n-[(z)-octadec-9-enyl]acetamide Chemical compound CCCCCCCC\C=C/CCCCCCCCNC(=O)CC1=CC=C(O)C(OC)=C1 PCZMUTQYZKAXBW-KHPPLWFESA-N 0.000 description 2
- JVJFIQYAHPMBBX-UHFFFAOYSA-N 4-hydroxynonenal Chemical compound CCCCCC(O)C=CC=O JVJFIQYAHPMBBX-UHFFFAOYSA-N 0.000 description 2
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 235000019489 Almond oil Nutrition 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 244000099147 Ananas comosus Species 0.000 description 2
- 235000007119 Ananas comosus Nutrition 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- NPBVQXIMTZKSBA-UHFFFAOYSA-N Chavibetol Natural products COC1=CC=C(CC=C)C=C1O NPBVQXIMTZKSBA-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- UBJVUCKUDDKUJF-UHFFFAOYSA-N Diallyl sulfide Chemical compound C=CCSCC=C UBJVUCKUDDKUJF-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 240000002943 Elettaria cardamomum Species 0.000 description 2
- 241000207934 Eriodictyon Species 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- 235000000495 Erythronium japonicum Nutrition 0.000 description 2
- 240000000745 Erythronium japonicum Species 0.000 description 2
- 239000005770 Eugenol Substances 0.000 description 2
- 235000016623 Fragaria vesca Nutrition 0.000 description 2
- 240000009088 Fragaria x ananassa Species 0.000 description 2
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229920002148 Gellan gum Polymers 0.000 description 2
- 241000202807 Glycyrrhiza Species 0.000 description 2
- 229920002907 Guar gum Polymers 0.000 description 2
- AKDLSISGGARWFP-UHFFFAOYSA-N Homodihydrocapsaicin Chemical compound COC1=CC(CNC(=O)CCCCCCCC(C)C)=CC=C1O AKDLSISGGARWFP-UHFFFAOYSA-N 0.000 description 2
- 229920001144 Hydroxy alpha sanshool Polymers 0.000 description 2
- 102000004310 Ion Channels Human genes 0.000 description 2
- 108090000862 Ion Channels Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 235000013740 Juglans nigra Nutrition 0.000 description 2
- 244000184861 Juglans nigra Species 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 235000019501 Lemon oil Nutrition 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
- 235000014749 Mentha crispa Nutrition 0.000 description 2
- 244000078639 Mentha spicata Species 0.000 description 2
- 241000498779 Myristica Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- OPZKBPQVWDSATI-KHPPLWFESA-N N-Vanillyloleamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)NCC1=CC=C(O)C(OC)=C1 OPZKBPQVWDSATI-KHPPLWFESA-N 0.000 description 2
- VQEONGKQWIFHMN-UHFFFAOYSA-N Nordihydrocapsaicin Chemical compound COC1=CC(CNC(=O)CCCCCC(C)C)=CC=C1O VQEONGKQWIFHMN-UHFFFAOYSA-N 0.000 description 2
- BXBVPYSHEOQGHP-UHFFFAOYSA-N Nordihydrocapsiate Chemical compound COC1=CC(COC(=O)CCCCCC(C)C)=CC=C1O BXBVPYSHEOQGHP-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 206010033425 Pain in extremity Diseases 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 235000010401 Prunus avium Nutrition 0.000 description 2
- 240000008296 Prunus serotina Species 0.000 description 2
- 235000014441 Prunus serotina Nutrition 0.000 description 2
- UVMRYBDEERADNV-UHFFFAOYSA-N Pseudoeugenol Natural products COC1=CC(C(C)=C)=CC=C1O UVMRYBDEERADNV-UHFFFAOYSA-N 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- 235000008981 Smilax officinalis Nutrition 0.000 description 2
- 240000002493 Smilax officinalis Species 0.000 description 2
- 239000004283 Sodium sorbate Substances 0.000 description 2
- 244000228451 Stevia rebaudiana Species 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000004376 Sucralose Substances 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 235000009470 Theobroma cacao Nutrition 0.000 description 2
- 235000007423 Tolu balsam tree Nutrition 0.000 description 2
- 244000007731 Tolu balsam tree Species 0.000 description 2
- 235000003095 Vaccinium corymbosum Nutrition 0.000 description 2
- 235000017537 Vaccinium myrtillus Nutrition 0.000 description 2
- 235000009499 Vanilla fragrans Nutrition 0.000 description 2
- 244000263375 Vanilla tahitensis Species 0.000 description 2
- 235000012036 Vanilla tahitensis Nutrition 0.000 description 2
- 229930003268 Vitamin C Natural products 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- YGCFIWIQZPHFLU-UHFFFAOYSA-N acesulfame Chemical compound CC1=CC(=O)NS(=O)(=O)O1 YGCFIWIQZPHFLU-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 229940023476 agar Drugs 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 2
- 239000008168 almond oil Substances 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229940011037 anethole Drugs 0.000 description 2
- 239000010617 anise oil Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 235000013734 beta-carotene Nutrition 0.000 description 2
- 239000011648 beta-carotene Substances 0.000 description 2
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 2
- 229960002747 betacarotene Drugs 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 235000021014 blueberries Nutrition 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 239000004301 calcium benzoate Substances 0.000 description 2
- 235000010237 calcium benzoate Nutrition 0.000 description 2
- MCFVRESNTICQSJ-RJNTXXOISA-L calcium sorbate Chemical compound [Ca+2].C\C=C\C=C\C([O-])=O.C\C=C\C=C\C([O-])=O MCFVRESNTICQSJ-RJNTXXOISA-L 0.000 description 2
- 235000010244 calcium sorbate Nutrition 0.000 description 2
- 239000004303 calcium sorbate Substances 0.000 description 2
- HZQXCUSDXIKLGS-UHFFFAOYSA-L calcium;dibenzoate;trihydrate Chemical compound O.O.O.[Ca+2].[O-]C(=O)C1=CC=CC=C1.[O-]C(=O)C1=CC=CC=C1 HZQXCUSDXIKLGS-UHFFFAOYSA-L 0.000 description 2
- ZICNYIDDNJYKCP-SOFGYWHQSA-N capsiate Chemical compound COC1=CC(COC(=O)CCCC\C=C\C(C)C)=CC=C1O ZICNYIDDNJYKCP-SOFGYWHQSA-N 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 description 2
- 235000005300 cardamomo Nutrition 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000013626 chemical specie Substances 0.000 description 2
- 235000015120 cherry juice Nutrition 0.000 description 2
- 235000020426 cherry syrup Nutrition 0.000 description 2
- 235000015218 chewing gum Nutrition 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 239000010636 coriander oil Substances 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229940099112 cornstarch Drugs 0.000 description 2
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
- VEVZSMAEJFVWIL-UHFFFAOYSA-O cyanidin cation Chemical compound [O+]=1C2=CC(O)=CC(O)=C2C=C(O)C=1C1=CC=C(O)C(O)=C1 VEVZSMAEJFVWIL-UHFFFAOYSA-O 0.000 description 2
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical class OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 2
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- PFRGXCVKLLPLIP-UHFFFAOYSA-N diallyl disulfide Chemical compound C=CCSSCC=C PFRGXCVKLLPLIP-UHFFFAOYSA-N 0.000 description 2
- UBAXRAHSPKWNCX-UHFFFAOYSA-N diallyl trisulfide Chemical compound C=CCSSSCC=C UBAXRAHSPKWNCX-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 239000001567 elettaria cardamomum seed Substances 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 2
- 229940073505 ethyl vanillin Drugs 0.000 description 2
- 229960002217 eugenol Drugs 0.000 description 2
- 239000010643 fennel seed oil Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 235000010492 gellan gum Nutrition 0.000 description 2
- 239000000216 gellan gum Substances 0.000 description 2
- 235000001727 glucose Nutrition 0.000 description 2
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 2
- 235000010417 guar gum Nutrition 0.000 description 2
- 239000000665 guar gum Substances 0.000 description 2
- 229960002154 guar gum Drugs 0.000 description 2
- 235000019534 high fructose corn syrup Nutrition 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- LTINPJMVDKPJJI-UHFFFAOYSA-N iodinated glycerol Chemical compound CC(I)C1OCC(CO)O1 LTINPJMVDKPJJI-UHFFFAOYSA-N 0.000 description 2
- IYRMWMYZSQPJKC-UHFFFAOYSA-N kaempferol Chemical compound C1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 IYRMWMYZSQPJKC-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000171 lavandula angustifolia l. flower oil Substances 0.000 description 2
- 239000010501 lemon oil Substances 0.000 description 2
- 239000004571 lime Substances 0.000 description 2
- 239000000711 locust bean gum Substances 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- KZMACGJDUUWFCH-UHFFFAOYSA-O malvidin Chemical compound COC1=C(O)C(OC)=CC(C=2C(=CC=3C(O)=CC(O)=CC=3[O+]=2)O)=C1 KZMACGJDUUWFCH-UHFFFAOYSA-O 0.000 description 2
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 2
- 239000001683 mentha spicata herb oil Substances 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 230000007102 metabolic function Effects 0.000 description 2
- 239000001673 myroxylon balsanum l. absolute Substances 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- RUVINXPYWBROJD-UHFFFAOYSA-N para-methoxyphenyl Natural products COC1=CC=C(C=CC)C=C1 RUVINXPYWBROJD-UHFFFAOYSA-N 0.000 description 2
- 235000010987 pectin Nutrition 0.000 description 2
- 239000001814 pectin Substances 0.000 description 2
- 229920001277 pectin Polymers 0.000 description 2
- 235000019477 peppermint oil Nutrition 0.000 description 2
- 238000011056 performance test Methods 0.000 description 2
- 229940067107 phenylethyl alcohol Drugs 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 150000004804 polysaccharides Chemical class 0.000 description 2
- 239000004300 potassium benzoate Substances 0.000 description 2
- 235000010235 potassium benzoate Nutrition 0.000 description 2
- 229940103091 potassium benzoate Drugs 0.000 description 2
- 235000010241 potassium sorbate Nutrition 0.000 description 2
- 239000004302 potassium sorbate Substances 0.000 description 2
- 229940069338 potassium sorbate Drugs 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 235000013995 raspberry juice Nutrition 0.000 description 2
- 235000020440 raspberry syrup Nutrition 0.000 description 2
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 235000019719 rose oil Nutrition 0.000 description 2
- 239000010666 rose oil Substances 0.000 description 2
- 239000008132 rose water Substances 0.000 description 2
- 239000010668 rosemary oil Substances 0.000 description 2
- 229940058206 rosemary oil Drugs 0.000 description 2
- 235000019204 saccharin Nutrition 0.000 description 2
- 229940081974 saccharin Drugs 0.000 description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
- WUILNKCFCLNXOK-CFBAGHHKSA-N salirasib Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CSC1=CC=CC=C1C(O)=O WUILNKCFCLNXOK-CFBAGHHKSA-N 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- LROWVYNUWKVTCU-STWYSWDKSA-M sodium sorbate Chemical compound [Na+].C\C=C\C=C\C([O-])=O LROWVYNUWKVTCU-STWYSWDKSA-M 0.000 description 2
- 235000019250 sodium sorbate Nutrition 0.000 description 2
- 235000010199 sorbic acid Nutrition 0.000 description 2
- 239000004334 sorbic acid Substances 0.000 description 2
- 229940075582 sorbic acid Drugs 0.000 description 2
- 235000019721 spearmint oil Nutrition 0.000 description 2
- 239000000021 stimulant Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 235000019408 sucralose Nutrition 0.000 description 2
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 2
- 239000010678 thyme oil Substances 0.000 description 2
- 229940088660 tolu balsam Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 235000012141 vanillin Nutrition 0.000 description 2
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 2
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 2
- 235000019154 vitamin C Nutrition 0.000 description 2
- 239000011718 vitamin C Substances 0.000 description 2
- 239000008170 walnut oil Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 2
- OJYLAHXKWMRDGS-UHFFFAOYSA-N zingerone Chemical compound COC1=CC(CCC(C)=O)=CC=C1O OJYLAHXKWMRDGS-UHFFFAOYSA-N 0.000 description 2
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 2
- PFTAWBLQPZVEMU-ZFWWWQNUSA-N (+)-epicatechin Natural products C1([C@@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-ZFWWWQNUSA-N 0.000 description 1
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 description 1
- PFTAWBLQPZVEMU-UKRRQHHQSA-N (-)-epicatechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-UKRRQHHQSA-N 0.000 description 1
- 229930014124 (-)-epigallocatechin gallate Natural products 0.000 description 1
- ZMYMOKYVEYEAEH-RQLXMFKESA-N (2e)-2-[3-[(1r,2s,4as,8as)-5,5,8a-trimethylspiro[3,4,4a,6,7,8-hexahydro-1h-naphthalene-2,2'-oxirane]-1-yl]propylidene]butanedial Chemical compound C([C@]12[C@H](CC\C=C(/CC=O)C=O)[C@@]3(C)CCCC([C@@H]3CC2)(C)C)O1 ZMYMOKYVEYEAEH-RQLXMFKESA-N 0.000 description 1
- AVTQSDUNQOANPK-MCJWARNPSA-N (2e)-2-[3-[(1s,2s,4as,8ar)-2-formyl-5,5,8a-trimethyl-1,2,3,4,4a,6,7,8-octahydronaphthalen-1-yl]propylidene]butanedial Chemical compound O=CC\C(C=O)=C/CC[C@H]1[C@@H](C=O)CC[C@H]2C(C)(C)CCC[C@@]21C AVTQSDUNQOANPK-MCJWARNPSA-N 0.000 description 1
- WSWCOQWTEOXDQX-MQQKCMAXSA-M (E,E)-sorbate Chemical compound C\C=C\C=C\C([O-])=O WSWCOQWTEOXDQX-MQQKCMAXSA-M 0.000 description 1
- FTVWIRXFELQLPI-ZDUSSCGKSA-N (S)-naringenin Chemical compound C1=CC(O)=CC=C1[C@H]1OC2=CC(O)=CC(O)=C2C(=O)C1 FTVWIRXFELQLPI-ZDUSSCGKSA-N 0.000 description 1
- NBXZJPXDDBBXBL-KHPPLWFESA-N (Z)-N-[2-(4,5-dihydroxy-5-methylcyclohexa-1,3-dien-1-yl)ethyl]octadec-9-enamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)NCCC1=CC=C(O)C(C)(O)C1 NBXZJPXDDBBXBL-KHPPLWFESA-N 0.000 description 1
- BTKHXNIRAYKGMN-KHPPLWFESA-N (z)-n-[[4-(2-aminoethoxy)-3-methoxyphenyl]methyl]octadec-9-enamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)NCC1=CC=C(OCCN)C(OC)=C1 BTKHXNIRAYKGMN-KHPPLWFESA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- LZPKWQOLOCLSBO-UHFFFAOYSA-N 6-(trifluoromethyl)-1,3-dihydroindol-2-one Chemical compound FC(F)(F)C1=CC=C2CC(=O)NC2=C1 LZPKWQOLOCLSBO-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- ZAWCPGMKVKTLKI-FTOUISBVSA-N Aframodial Natural products O=C/C(=C\C[C@@H]1[C@@]2(C)[C@H](C(C)(C)CCC2)CC[C@@]21OC2)/CC=O ZAWCPGMKVKTLKI-FTOUISBVSA-N 0.000 description 1
- 240000004246 Agave americana Species 0.000 description 1
- JDLKFOPOAOFWQN-VIFPVBQESA-N Allicin Natural products C=CCS[S@](=O)CC=C JDLKFOPOAOFWQN-VIFPVBQESA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- MVVPIAAVGAWJNQ-DOFZRALJSA-N Arachidonoyl dopamine Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCC1=CC=C(O)C(O)=C1 MVVPIAAVGAWJNQ-DOFZRALJSA-N 0.000 description 1
- 244000201691 Arctic bramble Species 0.000 description 1
- 235000010646 Arctic bramble Nutrition 0.000 description 1
- 241001444063 Aronia Species 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 235000021537 Beetroot Nutrition 0.000 description 1
- 244000017106 Bixa orellana Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 244000178937 Brassica oleracea var. capitata Species 0.000 description 1
- SGHZXLIDFTYFHQ-UHFFFAOYSA-L Brilliant Blue Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 SGHZXLIDFTYFHQ-UHFFFAOYSA-L 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- KAWOEDMUUFFXAM-UHFFFAOYSA-N CC1(C)CCCC2(C)C(C)C(C=O)=CCC21 Polymers CC1(C)CCCC2(C)C(C)C(C=O)=CCC21 KAWOEDMUUFFXAM-UHFFFAOYSA-N 0.000 description 1
- CNKCFVAEACZBPL-UHFFFAOYSA-N CCCCCCCCC(=O)CCc1ccc(O)c(OC)c1 Chemical compound CCCCCCCCC(=O)CCc1ccc(O)c(OC)c1 CNKCFVAEACZBPL-UHFFFAOYSA-N 0.000 description 1
- UTKDXJYSROHIAZ-SOFGYWHQSA-N COc1cc(CCC(=O)CCCC/C=C/C(C)C)ccc1O Chemical compound COc1cc(CCC(=O)CCCC/C=C/C(C)C)ccc1O UTKDXJYSROHIAZ-SOFGYWHQSA-N 0.000 description 1
- BFEOGMIKWIXECL-VQHVLOKHSA-N COc1cc(CCC(=O)CCCCC/C=C/C(C)C)ccc1O Chemical compound COc1cc(CCC(=O)CCCCC/C=C/C(C)C)ccc1O BFEOGMIKWIXECL-VQHVLOKHSA-N 0.000 description 1
- QNFIJPVLXBFLBB-UHFFFAOYSA-N COc1cc(CCC(=O)CCCCCC(C)C)ccc1O Chemical compound COc1cc(CCC(=O)CCCCCC(C)C)ccc1O QNFIJPVLXBFLBB-UHFFFAOYSA-N 0.000 description 1
- IMOSRVGESJZTCF-UHFFFAOYSA-N COc1cc(CCC(=O)CCCCCCC(C)C)ccc1O Chemical compound COc1cc(CCC(=O)CCCCCCC(C)C)ccc1O IMOSRVGESJZTCF-UHFFFAOYSA-N 0.000 description 1
- BJPIHLJLSGTDCK-UHFFFAOYSA-N COc1cc(CCC(=O)CCCCCCCC(C)C)ccc1O Chemical compound COc1cc(CCC(=O)CCCCCCCC(C)C)ccc1O BJPIHLJLSGTDCK-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- ZEWSMOFWZCBFSU-UHFFFAOYSA-N Capsiconiate Natural products COC1=CC(C=CCOC(=O)CCCCC=CC(C)C)=CC=C1O ZEWSMOFWZCBFSU-UHFFFAOYSA-N 0.000 description 1
- 240000004160 Capsicum annuum Species 0.000 description 1
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 235000009467 Carica papaya Nutrition 0.000 description 1
- 240000006432 Carica papaya Species 0.000 description 1
- 244000241235 Citrullus lanatus Species 0.000 description 1
- 235000012828 Citrullus lanatus var citroides Nutrition 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010010305 Confusional state Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- 235000015655 Crocus sativus Nutrition 0.000 description 1
- 244000124209 Crocus sativus Species 0.000 description 1
- 235000003392 Curcuma domestica Nutrition 0.000 description 1
- 244000008991 Curcuma longa Species 0.000 description 1
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- GCPYCNBGGPHOBD-UHFFFAOYSA-N Delphinidin Natural products OC1=Cc2c(O)cc(O)cc2OC1=C3C=C(O)C(=O)C(=C3)O GCPYCNBGGPHOBD-UHFFFAOYSA-N 0.000 description 1
- UBSCDKPKWHYZNX-UHFFFAOYSA-N Demethoxycapillarisin Natural products C1=CC(O)=CC=C1OC1=CC(=O)C2=C(O)C=C(O)C=C2O1 UBSCDKPKWHYZNX-UHFFFAOYSA-N 0.000 description 1
- VYFYYTLLBUKUHU-UHFFFAOYSA-N Dopamine Natural products NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 1
- 239000001692 EU approved anti-caking agent Substances 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 229920000219 Ethylene vinyl alcohol Polymers 0.000 description 1
- IKYCZSUNGFRBJS-UHFFFAOYSA-N Euphorbia factor RL9 = U(1) = Resiniferatoxin Natural products COC1=CC(O)=CC(CC(=O)OCC=2CC3(O)C(=O)C(C)=CC3C34C(C)CC5(OC(O4)(CC=4C=CC=CC=4)OC5C3C=2)C(C)=C)=C1 IKYCZSUNGFRBJS-UHFFFAOYSA-N 0.000 description 1
- TXDUTHBFYKGSAH-SFHVURJKSA-N Evodiamine Chemical compound C1=CC=C2N(C)[C@@H]3C(NC=4C5=CC=CC=4)=C5CCN3C(=O)C2=C1 TXDUTHBFYKGSAH-SFHVURJKSA-N 0.000 description 1
- HMXRXBIGGYUEAX-SFHVURJKSA-N Evodiamine Natural products CN1[C@H]2N(CCc3[nH]c4ccccc4c23)C(=O)c5ccccc15 HMXRXBIGGYUEAX-SFHVURJKSA-N 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 235000005206 Hibiscus Nutrition 0.000 description 1
- 235000007185 Hibiscus lunariifolius Nutrition 0.000 description 1
- 244000284380 Hibiscus rosa sinensis Species 0.000 description 1
- 206010020400 Hostility Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- GQODBWLKUWYOFX-UHFFFAOYSA-N Isorhamnetin Natural products C1=C(O)C(C)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 GQODBWLKUWYOFX-UHFFFAOYSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 235000010804 Maranta arundinacea Nutrition 0.000 description 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- VOEKGBXENFNRQW-UHFFFAOYSA-N Miogatrial Natural products O=CCC(C=O)=CCC1C(C=O)CCC2C(C)(C)CCCC21C VOEKGBXENFNRQW-UHFFFAOYSA-N 0.000 description 1
- 208000029549 Muscle injury Diseases 0.000 description 1
- 206010073713 Musculoskeletal injury Diseases 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- QVLMCRFQGHWOPM-ZKWNWVNESA-N N-arachidonoyl vanillylamine Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCC1=CC=C(O)C(OC)=C1 QVLMCRFQGHWOPM-ZKWNWVNESA-N 0.000 description 1
- QQBPLXNESPTPNU-KTKRTIGZSA-N N-oleoyldopamine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)NCCC1=CC=C(O)C(O)=C1 QQBPLXNESPTPNU-KTKRTIGZSA-N 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- AZJUJOFIHHNCSV-KCQAQPDRSA-N Polygodial Polymers C[C@@]1([C@H](C(C=O)=CC2)C=O)[C@@H]2C(C)(C)CCC1 AZJUJOFIHHNCSV-KCQAQPDRSA-N 0.000 description 1
- 229920000388 Polyphosphate Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001219 Polysorbate 40 Polymers 0.000 description 1
- 235000009827 Prunus armeniaca Nutrition 0.000 description 1
- 244000018633 Prunus armeniaca Species 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
- 240000001890 Ribes hudsonianum Species 0.000 description 1
- 235000016954 Ribes hudsonianum Nutrition 0.000 description 1
- 235000001466 Ribes nigrum Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UHFFFAOYSA-N Rohrzucker Natural products OCC1OC(CO)(OC2OC(CO)C(O)C(O)C2O)C(O)C1O CZMRCDWAGMRECN-UHFFFAOYSA-N 0.000 description 1
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
- 244000151637 Sambucus canadensis Species 0.000 description 1
- 235000018735 Sambucus canadensis Nutrition 0.000 description 1
- XQTQSUUULVXJPG-JTCWOHKRSA-N Scutigeral Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC1=C(C)C(C=O)=C(O)C(O)=C1O XQTQSUUULVXJPG-JTCWOHKRSA-N 0.000 description 1
- XQTQSUUULVXJPG-UHFFFAOYSA-N Scutigeral Natural products CC(C)=CCCC(C)=CCCC(C)=CCC1=C(C)C(C=O)=C(O)C(O)=C1O XQTQSUUULVXJPG-UHFFFAOYSA-N 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 108010025083 TRPV1 receptor Proteins 0.000 description 1
- 244000145580 Thalia geniculata Species 0.000 description 1
- 235000012419 Thalia geniculata Nutrition 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- STEQPJJDFVFRGX-UHFFFAOYSA-N Tinyatoxin Natural products CC1CC2(CC34OC(Cc5ccccc5)(O2)OC13C6C=C(C)C(=O)C6(O)CC(=C4)COC(=O)Cc7ccc(O)cc7)C(=C)C STEQPJJDFVFRGX-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 240000001717 Vaccinium macrocarpon Species 0.000 description 1
- 235000012545 Vaccinium macrocarpon Nutrition 0.000 description 1
- 235000002118 Vaccinium oxycoccus Nutrition 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical class [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- ZEWSMOFWZCBFSU-OAMUUVBCSA-N [(e)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enyl] (e)-8-methylnon-6-enoate Chemical compound COC1=CC(\C=C\COC(=O)CCCC\C=C\C(C)C)=CC=C1O ZEWSMOFWZCBFSU-OAMUUVBCSA-N 0.000 description 1
- MPGLKHMQOVOUKA-CSKARUKUSA-N [(e)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enyl] 8-methylnonanoate Chemical compound COC1=CC(\C=C\COC(=O)CCCCCCC(C)C)=CC=C1O MPGLKHMQOVOUKA-CSKARUKUSA-N 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010358 acesulfame potassium Nutrition 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- ZAWCPGMKVKTLKI-UHFFFAOYSA-N afromodial Natural products C1CC2C(C)(C)CCCC2(C)C(CC=C(CC=O)C=O)C21CO2 ZAWCPGMKVKTLKI-UHFFFAOYSA-N 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 235000010081 allicin Nutrition 0.000 description 1
- JDLKFOPOAOFWQN-UHFFFAOYSA-N allicin Chemical compound C=CCSS(=O)CC=C JDLKFOPOAOFWQN-UHFFFAOYSA-N 0.000 description 1
- 235000016720 allyl isothiocyanate Nutrition 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000010407 ammonium alginate Nutrition 0.000 description 1
- 239000000728 ammonium alginate Substances 0.000 description 1
- KPGABFJTMYCRHJ-YZOKENDUSA-N ammonium alginate Chemical compound [NH4+].[NH4+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O KPGABFJTMYCRHJ-YZOKENDUSA-N 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 description 1
- 239000010362 annatto Substances 0.000 description 1
- 235000012665 annatto Nutrition 0.000 description 1
- 229930014669 anthocyanidin Natural products 0.000 description 1
- 235000008758 anthocyanidins Nutrition 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- XADJWCRESPGUTB-UHFFFAOYSA-N apigenin Natural products C1=CC(O)=CC=C1C1=CC(=O)C2=CC(O)=C(O)C=C2O1 XADJWCRESPGUTB-UHFFFAOYSA-N 0.000 description 1
- 235000008714 apigenin Nutrition 0.000 description 1
- KZNIFHPLKGYRTM-UHFFFAOYSA-N apigenin Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 KZNIFHPLKGYRTM-UHFFFAOYSA-N 0.000 description 1
- 229940117893 apigenin Drugs 0.000 description 1
- 235000015197 apple juice Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 235000007123 blue elder Nutrition 0.000 description 1
- 150000003842 bromide salts Chemical class 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 1
- 235000010410 calcium alginate Nutrition 0.000 description 1
- 239000000648 calcium alginate Substances 0.000 description 1
- 229960002681 calcium alginate Drugs 0.000 description 1
- 230000009460 calcium influx Effects 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=O)[C@H]1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 description 1
- 239000001511 capsicum annuum Substances 0.000 description 1
- 235000013736 caramel Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 230000009084 cardiovascular function Effects 0.000 description 1
- 239000004106 carminic acid Substances 0.000 description 1
- 235000012730 carminic acid Nutrition 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- CEZCCHQBSQPRMU-UHFFFAOYSA-L chembl174821 Chemical compound [Na+].[Na+].COC1=CC(S([O-])(=O)=O)=C(C)C=C1N=NC1=C(O)C=CC2=CC(S([O-])(=O)=O)=CC=C12 CEZCCHQBSQPRMU-UHFFFAOYSA-L 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015111 chews Nutrition 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 239000001752 chlorophylls and chlorophyllins Substances 0.000 description 1
- 235000012698 chlorophylls and chlorophyllins Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 229940080423 cochineal Drugs 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 208000004209 confusion Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- 235000004634 cranberry Nutrition 0.000 description 1
- 229960003624 creatine Drugs 0.000 description 1
- 239000006046 creatine Substances 0.000 description 1
- 235000003373 curcuma longa Nutrition 0.000 description 1
- 235000007336 cyanidin Nutrition 0.000 description 1
- 229940109275 cyclamate Drugs 0.000 description 1
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 235000007242 delphinidin Nutrition 0.000 description 1
- FFNDMZIBVDSQFI-UHFFFAOYSA-N delphinidin chloride Chemical compound [Cl-].[O+]=1C2=CC(O)=CC(O)=C2C=C(O)C=1C1=CC(O)=C(O)C(O)=C1 FFNDMZIBVDSQFI-UHFFFAOYSA-N 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- XJQPQKLURWNAAH-UHFFFAOYSA-N dihydrocapsaicin Chemical compound COC1=CC(CNC(=O)CCCCCCC(C)C)=CC=C1O XJQPQKLURWNAAH-UHFFFAOYSA-N 0.000 description 1
- MPGLKHMQOVOUKA-UHFFFAOYSA-N dihydrocapsiconiate Natural products COC1=CC(C=CCOC(=O)CCCCCCC(C)C)=CC=C1O MPGLKHMQOVOUKA-UHFFFAOYSA-N 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 229960004242 dronabinol Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 235000007124 elderberry Nutrition 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- LPTRNLNOHUVQMS-UHFFFAOYSA-N epicatechin Natural products Cc1cc(O)cc2OC(C(O)Cc12)c1ccc(O)c(O)c1 LPTRNLNOHUVQMS-UHFFFAOYSA-N 0.000 description 1
- 235000012734 epicatechin Nutrition 0.000 description 1
- 230000002270 ergogenic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 229960004667 ethyl cellulose Drugs 0.000 description 1
- 239000004715 ethylene vinyl alcohol Substances 0.000 description 1
- 235000008995 european elder Nutrition 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930182497 flavan-3-ol Natural products 0.000 description 1
- 150000002206 flavan-3-ols Chemical class 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002213 flavones Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- YTAQZPGBTPDBPW-UHFFFAOYSA-N flavonoid group Chemical class O1C(C(C(=O)C2=CC=CC=C12)=O)C1=CC=CC=C1 YTAQZPGBTPDBPW-UHFFFAOYSA-N 0.000 description 1
- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Natural products O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 description 1
- 150000002216 flavonol derivatives Chemical class 0.000 description 1
- 235000011957 flavonols Nutrition 0.000 description 1
- NWKFECICNXDNOQ-UHFFFAOYSA-N flavylium Chemical compound C1=CC=CC=C1C1=CC=C(C=CC=C2)C2=[O+]1 NWKFECICNXDNOQ-UHFFFAOYSA-N 0.000 description 1
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 1
- 229960004369 flufenamic acid Drugs 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000000245 forearm Anatomy 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000019674 grape juice Nutrition 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 239000012676 herbal extract Substances 0.000 description 1
- AIONOLUJZLIMTK-AWEZNQCLSA-N hesperetin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O)=CC(O)=C2C(=O)C1 AIONOLUJZLIMTK-AWEZNQCLSA-N 0.000 description 1
- 229960001587 hesperetin Drugs 0.000 description 1
- RZXDTJIXPSCHCI-UHFFFAOYSA-N hexa-1,5-diene-2,5-diol Chemical compound OC(=C)CCC(O)=C RZXDTJIXPSCHCI-UHFFFAOYSA-N 0.000 description 1
- MLJGZARGNROKAC-VQHVLOKHSA-N homocapsaicin Chemical compound CCC(C)\C=C\CCCCC(=O)NCC1=CC=C(O)C(OC)=C1 MLJGZARGNROKAC-VQHVLOKHSA-N 0.000 description 1
- JKIHLSTUOQHAFF-UHFFFAOYSA-N homocapsaicin Natural products COC1=CC(CNC(=O)CCCCCC=CC(C)C)=CC=C1O JKIHLSTUOQHAFF-UHFFFAOYSA-N 0.000 description 1
- JZNZUOZRIWOBGG-UHFFFAOYSA-N homocapsaicin-II Natural products COC1=CC(CNC(=O)CCCCC=CCC(C)C)=CC=C1O JZNZUOZRIWOBGG-UHFFFAOYSA-N 0.000 description 1
- GOBFKCLUUUDTQE-UHFFFAOYSA-N homodihydrocapsaicin-II Natural products CCC(C)CCCCCCC(=O)NCC1=CC=C(O)C(OC)=C1 GOBFKCLUUUDTQE-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical class II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- IZQSVPBOUDKVDZ-UHFFFAOYSA-N isorhamnetin Chemical compound C1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 IZQSVPBOUDKVDZ-UHFFFAOYSA-N 0.000 description 1
- 235000008800 isorhamnetin Nutrition 0.000 description 1
- 235000008777 kaempferol Nutrition 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000012680 lutein Nutrition 0.000 description 1
- 239000001656 lutein Substances 0.000 description 1
- 229960005375 lutein Drugs 0.000 description 1
- KBPHJBAIARWVSC-RGZFRNHPSA-N lutein Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\[C@H]1C(C)=C[C@H](O)CC1(C)C KBPHJBAIARWVSC-RGZFRNHPSA-N 0.000 description 1
- ORAKUVXRZWMARG-WZLJTJAWSA-N lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C ORAKUVXRZWMARG-WZLJTJAWSA-N 0.000 description 1
- LRDGATPGVJTWLJ-UHFFFAOYSA-N luteolin Natural products OC1=CC(O)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 LRDGATPGVJTWLJ-UHFFFAOYSA-N 0.000 description 1
- 235000009498 luteolin Nutrition 0.000 description 1
- IQPNAANSBPBGFQ-UHFFFAOYSA-N luteolin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(O)C(O)=C1 IQPNAANSBPBGFQ-UHFFFAOYSA-N 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000009584 malvidin Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229960003476 methylparaben sodium Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- MEFBJEMVZONFCJ-UHFFFAOYSA-N molybdate Chemical class [O-][Mo]([O-])(=O)=O MEFBJEMVZONFCJ-UHFFFAOYSA-N 0.000 description 1
- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- 208000015001 muscle soreness Diseases 0.000 description 1
- 239000008164 mustard oil Substances 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 229940117954 naringenin Drugs 0.000 description 1
- WGEYAGZBLYNDFV-UHFFFAOYSA-N naringenin Natural products C1(=O)C2=C(O)C=C(O)C=C2OC(C1)C1=CC=C(CC1)O WGEYAGZBLYNDFV-UHFFFAOYSA-N 0.000 description 1
- 235000007625 naringenin Nutrition 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 229960004036 nonivamide Drugs 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- FATBGEAMYMYZAF-KTKRTIGZSA-N oleamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(N)=O FATBGEAMYMYZAF-KTKRTIGZSA-N 0.000 description 1
- FATBGEAMYMYZAF-UHFFFAOYSA-N oleicacidamide-heptaglycolether Natural products CCCCCCCCC=CCCCCCCCC(N)=O FATBGEAMYMYZAF-UHFFFAOYSA-N 0.000 description 1
- BOWVQLFMWHZBEF-KTKRTIGZSA-N oleoyl ethanolamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)NCCO BOWVQLFMWHZBEF-KTKRTIGZSA-N 0.000 description 1
- OPZKBPQVWDSATI-UHFFFAOYSA-N oleoyl vanillylamide Natural products CCCCCCCCC=CCCCCCCCC(=O)NCC1=CC=C(O)C(OC)=C1 OPZKBPQVWDSATI-UHFFFAOYSA-N 0.000 description 1
- 229950010717 olvanil Drugs 0.000 description 1
- 235000015205 orange juice Nutrition 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 235000015206 pear juice Nutrition 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- 235000013997 pineapple juice Nutrition 0.000 description 1
- 235000019100 piperine Nutrition 0.000 description 1
- WVWHRXVVAYXKDE-UHFFFAOYSA-N piperine Natural products O=C(C=CC=Cc1ccc2OCOc2c1)C3CCCCN3 WVWHRXVVAYXKDE-UHFFFAOYSA-N 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- FPGPDEPMWUWLOV-UHFFFAOYSA-N polygodial Natural products CC1(C)CCCC2(C)C(C=O)C(=CC(O)C12)C=O FPGPDEPMWUWLOV-UHFFFAOYSA-N 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940101027 polysorbate 40 Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000010408 potassium alginate Nutrition 0.000 description 1
- 239000000737 potassium alginate Substances 0.000 description 1
- MZYRDLHIWXQJCQ-YZOKENDUSA-L potassium alginate Chemical compound [K+].[K+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O MZYRDLHIWXQJCQ-YZOKENDUSA-L 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 238000012910 preclinical development Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229960005359 propylparaben sodium Drugs 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 235000011962 puddings Nutrition 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- DSDNAKHZNJAGHN-UHFFFAOYSA-N resinferatoxin Natural products C1=C(O)C(OC)=CC(CC(=O)OCC=2CC3(O)C(=O)C(C)=CC3C34C(C)CC5(OC(O4)(CC=4C=CC=CC=4)OC5C3C=2)C(C)=C)=C1 DSDNAKHZNJAGHN-UHFFFAOYSA-N 0.000 description 1
- DSDNAKHZNJAGHN-MXTYGGKSSA-N resiniferatoxin Chemical compound C1=C(O)C(OC)=CC(CC(=O)OCC=2C[C@]3(O)C(=O)C(C)=C[C@H]3[C@@]34[C@H](C)C[C@@]5(O[C@@](O4)(CC=4C=CC=CC=4)O[C@@H]5[C@@H]3C=2)C(C)=C)=C1 DSDNAKHZNJAGHN-MXTYGGKSSA-N 0.000 description 1
- 229940073454 resiniferatoxin Drugs 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 235000019192 riboflavin Nutrition 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000013974 saffron Nutrition 0.000 description 1
- 239000004248 saffron Substances 0.000 description 1
- 150000003902 salicylic acid esters Chemical class 0.000 description 1
- MCAHWIHFGHIESP-UHFFFAOYSA-L selenite(2-) Chemical class [O-][Se]([O-])=O MCAHWIHFGHIESP-UHFFFAOYSA-L 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
- 229940048086 sodium pyrophosphate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- PESXGULMKCKJCC-UHFFFAOYSA-M sodium;4-methoxycarbonylphenolate Chemical compound [Na+].COC(=O)C1=CC=C([O-])C=C1 PESXGULMKCKJCC-UHFFFAOYSA-M 0.000 description 1
- IXMINYBUNCWGER-UHFFFAOYSA-M sodium;4-propoxycarbonylphenolate Chemical compound [Na+].CCCOC(=O)C1=CC=C([O-])C=C1 IXMINYBUNCWGER-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 229940075554 sorbate Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- 235000008118 thearubigins Nutrition 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- 230000001550 time effect Effects 0.000 description 1
- WWZMXEIBZCEIFB-ACAXUWNGSA-N tinyatoxin Chemical compound C([C@@]12O[C@]3(C[C@H]([C@@]4([C@H]5[C@](C(C(C)=C5)=O)(O)CC(COC(=O)CC=5C=CC(O)=CC=5)=C[C@H]4[C@H]3O2)O1)C)C(C)=C)C1=CC=CC=C1 WWZMXEIBZCEIFB-ACAXUWNGSA-N 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 235000015193 tomato juice Nutrition 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- KBPHJBAIARWVSC-XQIHNALSSA-N trans-lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C KBPHJBAIARWVSC-XQIHNALSSA-N 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
- 235000013976 turmeric Nutrition 0.000 description 1
- 210000001170 unmyelinated nerve fiber Anatomy 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- FJHBOVDFOQMZRV-XQIHNALSSA-N xanthophyll Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C=C(C)C(O)CC2(C)C FJHBOVDFOQMZRV-XQIHNALSSA-N 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
- 239000011701 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 239000011686 zinc sulphate Substances 0.000 description 1
- YKPUWZUDDOIDPM-VURMDHGXSA-N zucapsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C/C(C)C)=CC=C1O YKPUWZUDDOIDPM-VURMDHGXSA-N 0.000 description 1
- 229960002860 zucapsaicin Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/11—Aldehydes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/67—Piperaceae (Pepper family), e.g. Jamaican pepper or kava
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
Definitions
- compositions that include activators of TRP and ASIC channels may be useful to improve or preserve exercise performance and exercise recovery.
- compositions comprising activators of TRP and ASIC channels and methods of use thereof to improve or preserve exercise performance and exercise recovery.
- the present invention features a method of improving or preserving physical performance during exercise in a subject, wherein the method comprises orally administering to the subject a composition (e.g., a beverage) comprising a TRP channel activator and an excipient.
- a composition e.g., a beverage
- the TRP channel activator is selected from a capsaicinoid, a gingerol, or cinnamaldehyde.
- improving or preserving the physical performance comprises shortening the time to complete an exercise, e.g., a sprint or cycling exercise by the subject, e.g., relative to a reference standard.
- improving or preserving the physical performance comprises an increase in the maximal oxygen consumption (VO 2 max) in the subject, e.g., relative to a reference standard.
- improving or preserving the physical performance comprises a decrease in the fatigue of the subject, e.g., as measured by the Fatigue Index, e.g., relative to a reference standard.
- improving or preserving the physical performance comprises exhibiting a greater mean power, total power, or interval power during a test (e.g., a sprint test, e.g., as described in Example 1).
- improving or preserving the physical performance comprises improving the time trial distance of a subject (e.g., as described in Example 1).
- improving or preserving the physical performance comprises increasing the energy (e.g., the mental energy), improving the mood, or reducing the exertion and pain (e.g., perceived exertion and pain) of a subject, e.g., relative to a reference standard.
- the present invention features a method of improving or preserving recovery after exercise in a subject, wherein the method comprises orally administering to the subject a composition (e.g., a beverage) comprising a TRP channel activator and an excipient.
- a composition e.g., a beverage
- the TRP channel activator is selected from a capsaicinoid, a gingerol, or cinnamaldehyde.
- improving or preserving recovery comprises reducing pain in a subject (e.g., reducing leg pain).
- the present invention features a method of reducing inflammation in a subject, wherein the method comprises orally administering to the subject a composition (e.g., a beverage) comprising a TRP channel activator and an excipient.
- a composition e.g., a beverage
- the TRP channel activator is selected from a capsaicinoid, a gingerol, or cinnamaldehyde.
- the inflammation occurs as a result of exercise.
- the TRP channel activator comprises a TRPA1 channel activator or a TRPV1 channel activator.
- the capsaicinoid comprises capsaicin.
- the composition comprises at least two of a capsaicinoid, a gingerol, or cinnamaldehyde and an excipient.
- the composition comprises each of a capsaicinoid, a gingerol, or cinnamaldehyde and an excipient.
- the amount of the TRP channel activator in the composition e.g., beverage
- the amount of the TRP channel activator in the composition is between about 0.001% to 1% weight/weight (w/w) of TRPA1 channel activator per weight of the composition (e.g., beverage).
- the excipient comprises a disintegrant, a binder, a surfactant, an emulsifier, a viscosity modifier, a lubricant, a sweetener, a pH-adjusting agent, a preservative, a flavoring agent, a coloring agent, or an antioxidant.
- the excipient comprises an emulsifier, a sweetener, a pH-adjusting agent, a preservative, or a flavoring agent.
- the excipient is selected from gellan gum, carob bean gum, locust bean gum, carrageenan, alginates, agar, guar gum, xanthan gum, carboxymethyl cellulose, clear starch, pectin, gelatin, cornstarch, katakuri starch, potato starch, and gum arabic.
- the excipient comprises a sweetener selected from high fructose corn syrup, mannose, maltose, glucose polymers, sucrose, glucose, dextrose, lactose, galactose, fructose, polysaccharides, rice syrup, honey, saccharin, cyclamates, acetosulfam, sorbitol, sucralose, xylitol, erythritol, Stevia extract, L-aspartyl-L-phenyl-alanine ester, L-aspartyl-D-alanine alkyl amides, L-aspartyl-L-1-hydroxymethylalkaneamide, and L-aspartyl-1-hydroxyethylalkaneamide.
- a sweetener selected from high fructose corn syrup, mannose, maltose, glucose polymers, sucrose, glucose, dextrose, lactose, galactose, fructose, polysaccharides, rice syrup, honey
- the excipient comprises a pH-adjusting agent selected from hydrochloric acid, citric acid, sodium hydrogen carbonate, potassium hydroxide, sodium hydroxide, and sodium carbonate.
- the excipient comprises a preservative selected from sorbic acid, benzoic acid, sodium benzoate, sodium chloride, calcium benzoate, potassium benzoate, potassium sorbate, calcium sorbate, and sodium sorbate.
- the excipient comprises a flavoring agent selected from almond oil, amaretto oil, anethole, anise oil, benzaldehyde, blackberry, black walnut oil, blueberry, caraway, caraway oil, cardamom oil, cardamom seed, cherry juice, cherry syrup, cinnamon, cinnamon oil, cinnamon water, citric acid, citric acid syrup, clove oil, cocoa, coriander oil, dextrose, eriodictyon, ethyl acetate, ethyl vanillin, fennel oil, ginger, glucose, glycerin, glycyrrhiza, grape, honey, lavender oil, lemon oil, lemon juice, lime, lime juice, mannitol, methyl salicylate, myristica oil, orange oil, orange peel, orange syrup, peppermint, peppermint oil, peppermint water, phenylethyl alcohol, pineapple, raspberry juice, raspberry syrup, rosemary oil, rose oil, rose water, sarsaparilla
- the composition e.g., beverage
- the composition is bottled or packaged in a unit that contains between 10 mL and 1000 mL of the composition (e.g., beverage).
- the beverage is bottled or packaged in a unit that contains 50 mL or 100 mL of the beverage.
- the composition is administered to the subject prior to commencement of exercise (e.g., at least about 1 minute, about 2 minutes, about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 30 minutes, about 45 minutes, about 1 hour, about 1.5 hours, about 2 hours, or more).
- FIGS. 1 A- 1 B are figures outlining the overall study design ( FIG. 1 A ) and the measurement timeline during experimental sessions 1 and 2 ( FIG. 1 B ) as set forth in Example 1.
- FIG. 2 is a table summarizing exemplary subject characteristics of the participants in the study outlined in Example 1.
- FIGS. 3 A- 3 B are charts comparing the results of the 30-second maximal sprint in subjects that received either the experimental (STA) or vehicle (PLA) drink as mean power output ( FIG. 3 A ) or total power output ( FIG. 3 B ).
- FIG. 4 is a graph comparing the results of the mean power during each 5-second interval of the 30-second maximal sprint in subjects that received either the experimental (STA) or vehicle (PLA) drink.
- FIG. 5 is a chart comparing the results of the distance covered by subjects that received either the experimental (STA) or vehicle (PLA) drink in the 30-second maximal sprint.
- FIG. 6 is a graph showing the individual time trial distance by treatment for each subject in the study outlined in Example 1.
- compositions of the present invention are directed to improving or preserving exercise performance and exercise recovery in a subject in need thereof.
- exemplary compositions comprise a TRP channel activator or an ASIC channel activator formulated for oral consumption.
- the term “acidulant” as used herein refers to an acidic compound (e.g., an acid) used to lower the pH of a composition.
- the pH can be lowered in the range of about 2.5 to about 6.5 (e.g., pH of 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, or 6.5).
- the pH can be lowered in the range of about 1.5 to about 5.0 (e.g., pH of 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0), for example, in the range of about 1.5 to about 4.4 (e.g., pH of 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.4).
- “Directly acquiring” means performing a process (e.g., applying or measuring a current to or from a subject, or capturing a signal from a subject or sample or performing a synthetic or analytical method) to obtain the value or physical entity.
- “Indirectly acquiring” refers to receiving the value or physical entity from another party or source (e.g., a third party laboratory that directly acquired the physical entity or value).
- Directly acquiring a value or physical entity includes performing a process that includes a physical change in a physical substance or the use of a machine or device.
- agonist refers to a molecule that stimulates a biological response.
- an agonist is an activator.
- the agonists and activators referred to herein may activate a TRP ion channel (e.g., TRPV1 or TRPA1) or an ASIC ion channel.
- administering and “administration” refers to a mode of delivery.
- a daily dosage can be divided into one, two, three or more doses in a suitable form to be administered one, two, three or more times throughout a time period.
- compositions and solutions are administered orally.
- analog or “related analogs” as used herein in regard to a compound or compounds refer to a substance that has a similar chemical structure to another compound, but differs from it with respect to a certain component or components.
- derivative refers to a substance produced from another substance either directly or by modification or partial substitution.
- Muscle cramp as used herein is a muscle cramp which is treated with the composition described herein. In some embodiments, it is not induced but rather arises spontaneously either from activity or underlying disease etiology, e.g., exercise. In some embodiments, the muscle cramp can be a contraction of a skeletal muscle or the smooth muscle. In some embodiments, the muscle cramp is a contraction of a skeletal muscle, e.g., the flexor hallucis brevis muscle.
- the terms “prevent” or “preventing” as used in the context of a disorder or disease refer to administration of an agent to a subject such that the onset of at least one symptom of the disorder or disease is delayed as compared to what would be seen in the absence of administration of said agent. As compared with an equivalent untreated control, such prevention is at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100%, as measured by any standard technique.
- subject refers to a mammal, including, but not limited to, a human or non-human mammal, such as a bovine, equine, canine, ovine, or feline mammal.
- subject refers to a human (e.g., a human male or female).
- substantially pure refers to a composition that is free of organic and/or inorganic species that do not activate the TRPV1, TRPA1, or/or ASIC channels, and where 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% (w/w) of the composition is comprised of a single chemical species.
- substantially pure compositions can be prepared and analyzed using standard methods known in the art (e.g., chromatographic separation, extractions, and the like).
- substantially pure compositions do not include isomeric impurities (e.g., geometric isomers) and/or salts or solvates of a particular chemical species.
- Treat” or “treating” as used herein refers to administering a composition for therapeutic purposes or administering treatment to a subject to improve at least one symptom of already suffering from a disorder to improve the subject's condition.
- treating a condition or disorder or “alleviating a condition or disorder” is meant that the condition or disorder and the symptoms associated with the condition or disorder are, e.g., prevented, alleviated, reduced, cured, or placed in a state of remission.
- alleviation or degree of treatment is at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100%, as measured by any standard technique.
- viscosity refers to a measurement of a fluid's internal resistance to flow (e.g., “thickness”). Viscosity is generally expressed in centipoise (cP) or pascal-seconds.
- compositions described herein are suitable for oral consumption by a subject (e.g., by a human) and include an activator of a TRP channel (e.g., TRPV1, TRPA1) or an activator of an ASIC channel, as well as one or more optional excipients as described herein.
- a subject e.g., by a human
- an activator of a TRP channel e.g., TRPV1, TRPA1
- an activator of an ASIC channel e.g., a TRP channel
- exemplary, non-limiting compositions include those that are solids (e.g., chews or chewing gums), liquids (e.g., beverages), and gels.
- TRPV1 Compounds that activate TRPV1 that may be used in the compositions of the present invention include, for example, capsaicin, capsaicin analogs and derivatives (e.g., capsaicinoids), and any other compound that activates TRPV1, examples of which are described herein.
- Modulators of TRPV1 activity are known in the art (see, e.g., Harteneck et al., Adv Exp Med Biol. 704:87-106, 2011, and other references described herein).
- the TRPV1 channel activator is a capsaicinoid (e.g., capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide)).
- capsaicin 8-methyl-N-vanillyl-trans-6-nonenamide
- Exemplary capsaicinoids are provided in Table 1.
- Suitable capsaicinoids and capsaicinoid analogs and derivatives for use in the compositions and methods of the present invention include naturally occurring and synthetic capsaicin derivatives and analogs including, e.g., vanilloids (e.g., N-vanillyl-alkanedienamides, N-vanillyl-alkanedienyls, and N-vanillyl-cis-monounsaturated alkenamides), capsiate, dihydrocapsiate, nordihydrocapsiate and other capsinoids, capsiconiate, dihydrocapsiconiate and other coniferyl esters, capsiconinoid, resiniferatoxin, tinyatoxin, civamide, N-phenylmethylalkenamide capsaicin derivatives, olvanil, N-[4-(2-aminoethoxy)-3-methoxyphenyl)methyl]-9Z-octa-decanamide, N-oleyl-homovanillamide
- TRPV1 channel activators include oleoylethanolamide, N-oleoyldopamine, 3-methyl-N-oleoyldopamine, oleamide, capsiate, 1-monoacylglycerols having C18 and C20 unsaturated and C8-C12 saturated fatty acid, 2-monoacylglycerols having C18 and C20 unsaturated fatty acids, miogadial, miogatrial, polygodial, and other terpenoids with an alpha, beta-unsaturated 1,4-dialdehyde moiety, sanshools, evodiamine, acesulfame-K, cyclamate, sulfates (e.g., CuSO 4 , ZnSO 4 , and FeSO 4 ), arvanil, anandamide, N-arachidonoyl-dopamine, flufenamic acid dopamide and other dopamine amides of fenamic acids, 4-hydroxyn
- TRPV1 channel activator may be an analog or derivative of any of the TRPV1 channel activators described herein.
- TRPV1 channel activators are described, for example, in U.S. Pat. Nos. 7,632,519; 7,446,226; 7,429,673; 7,407,950; 6,022,718; 5,962,532; 5,762,963; 5,403,868; 5,290,816; 5,221,692; 4,812,446; 4,599,342; 4,564,633; 4,544,669; 4,544,668; 4,532,139; 4,493,848; 4,424,205; 4,313,958; in U.S. Patent Application Publication Nos. 2007/0293703; 2007/0167524; 2006/0240097; and 2005/0085652; and in WO 00/50387, each of which is incorporated by reference.
- the TRPV1 channel activator may be an acidulant (e.g., acetic acid, phosphoric acid, citric acid, malic acid, succinic acid, tartaric acid, fumaric acid, or ascorbic acid) maintaining a low pH in the range of 2.5-6.5 (e.g., pH of 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, or 6.5).
- an acidulant e.g., acetic acid, phosphoric acid, citric acid, malic acid, succinic acid, tartaric acid, fumaric acid, or ascorbic acid
- 2.5-6.5 e.g., pH of 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, or 6.5.
- TRPV1 channel activators for use in the compositions and methods described herein can be identified using standard methodology, as described, for example, in U.S. Patent Application Publication No. 2003/0104085, which is hereby incorporated by reference.
- Exemplary assays for identification of TRPV1 channel activators include, without limitation, receptor binding assays; functional assessments of stimulation of calcium influx or membrane potential in cells expressing the TRPV1 receptor; assays for the ability to induce cell death in such cells (e.g., selective ablation of C-fiber neurons); and other assays known in the art.
- a TRPV1 channel activator may be present in a composition of the invention at a concentration range of about 0.001% to about 50% weight by weight (w/w) based on the total weight or total volume of the composition (e.g., 0.005%, 0.01%, 0.05%, 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 30%, 40% or 50%).
- a TRPV1 channel activator is present between 0.001% to 1% weight/weight (w/w) per weight of the composition.
- a composition described herein comprises between about 0.0001 to about 0.1 mg TRPV1 channel activator (e.g., about 0.0001 to about 0.01 mg, or about 0.001 mg to about 0.01 mg, or about 0.01 mg to about 0.1 mg TRPV1 channel activator per mL or mg of composition.
- TRPA1 channels are activated by naturally occurring substances including, e.g., mustard oil, isothiocyanate compounds (e.g., allyl isothiocyanate), acrolein, farnesyl thiosalicylic acid, ⁇ 9 -tetrahydrocannabinol (THC), eugenol, ginger, gingerol, gingerols, shogaols, nicotine, nicotine derivatives and analogs, methyl salicylate, cinnamaldehyde, cinnamon oil, wintergreen oil, clove oil, allicin, diallyl sulfide, diallyl disulfide, diallyl trisulfide, sanshools, farnesyl thiosalicylic acid, and farnesyl thioacetic acid.
- mustard oil isothiocyanate compounds (e.g., allyl isothiocyanate), acrolein, farnesyl thiosalicylic acid, ⁇
- the TRPA1 channel activator may also be an analog or derivative of any of the TRPA1 channel activators described herein, and additional TRPA1 channel activators are identified in WO 2009/071631, hereby incorporated by reference. Still other modulators of TRPA1 are described in, e.g., Harteneck et al., “Synthetic modulators of TRP channel activity,” Adv Exp Med Biol. 704:87-106, 2011; Viana et al. “TRPA1 modulators in preclinical development,” Expert Opin. Ther. Pat. 19(12):1787-99, 2009).
- TRPA1 channel activators are known in the art and are described, for example, in U.S. Pat. No. 7,674,594.
- a TRPA1 channel activator may be present in a composition of the invention at a concentration range of about 0.001% to about 50% weight by weight (w/w) based on the total weight or total volume of the composition (e.g., 0.005%, 0.01%, 0.05%, 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 30%, 40% or 50%).
- a TRPA1 channel activator is present between 0.001% to 1% weight/weight (w/w) per weight of the composition.
- a composition described herein comprises between about 0.0001 to about 0.1 mg TRPA1 channel activator (e.g., about 0.0001 to about 0.01 mg, or about 0.001 mg to about 0.01 mg, or about 0.01 mg to about 0.1 mg TRPA1 channel activator per mL or mg of composition.
- ASIC channels are activated by low pH.
- the pH of a composition of the present invention that includes an ASIC channel activator may be in the range of 2.5-6.5 (e.g., pH of 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, or 6.5).
- the pH may be adjusted within this range by any means acceptable for compositions that are intended to be ingested by a subject.
- Exemplary acidulants are acetic acid, phosphoric acid, citric acid, malic acid, succinic acid, tartaric acid, fumaric acid, and ascorbic acid.
- the ASIC channel activator may be present in a composition of the invention at a concentration range of about 0.001% to about 50% weight by weight (w/w) based on the total weight or total volume of the composition (e.g., 0.005%, 0.01%, 0.05%, 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 30%, 40% or 50%).
- an ASIC channel activator is present between 0.001% to 1% weight/weight (w/w) per weight of the composition.
- a composition described herein comprises between about 0.0001 to about 0.1 mg an ASIC channel activator (e.g., about 0.0001 to about 0.01 mg, or about 0.001 mg to about 0.01 mg, or about 0.01 mg to about 0.1 mg an ASIC channel activator per mL or mg of composition.
- an ASIC channel activator e.g., about 0.0001 to about 0.01 mg, or about 0.001 mg to about 0.01 mg, or about 0.01 mg to about 0.1 mg an ASIC channel activator per mL or mg of composition.
- the composition of the present invention comprises a TRP channel activator or an ASIC channel activator and an excipient.
- excipient include electrolytes (e.g., potassium salt or other salts), buffering agents, sweeteners, flavoring and coloring agents, vitamins, minerals, preservatives, viscosity modifiers, thickening agents, dissolving agents, solvents, and antioxidants as described below.
- electrolytes e.g., potassium salt or other salts
- buffering agents e.g., sweeteners, flavoring and coloring agents
- Other exemplary excipients are described in Handbook of Pharmaceutical Excipients, 6 th Edition, Rowe et al., Eds., Pharmaceutical Press (2009).
- Viscosity is the ratio of shear stress to shear rate, expressed as dynes-second/cm 2 , or poise.
- a centipoise (cP) is one one-hundredth of a poise.
- the composition of the present invention may have a viscosity greater than water (i.e., about 1.0 cP at 20° C.), e.g., about 100, 200, 300, 400, 500, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 6000, 7000, 8000, 9000 cP or more. If a consistency of corn syrup is desired, viscosities in the range of about 2500 cP are suitable. If a consistency of a soft gel or honey is desired, viscosities in the range of about 10000 cP to about 15000 cP are suitable. For pudding-like products, viscosities in the range of about 30000 cP to about 38000 cP are desirable. Viscosity of the compositions of the present invention may be measured with, e.g., a rheometer or viscometer, though additional methods of measuring viscosity are known in the art.
- Viscosity modifiers and thickening agents may be added to compositions of the present invention.
- Such viscosity modifiers and thickening agents include, for example, collagen, gellan gum, carbohydrate gel-forming polymers, carob bean gum, locust bean gum, carrageenan, alginates (e.g., alginic acid, sodium alginate, potassium alginate, ammonium alginate, and calcium alginate), agar, guar gum, xanthan gum, microcrystalline cellulose, carboxymethyl cellulose, ethyl cellulose, clear starch, pectin, gelatin, arrowroot, cornstarch, katakuri starch, potato starch, sago, tapioca, furcellaran, karo syrup (e.g., light karo syrup and dark karo syrup), glycerin, and sodium pyrophosphate.
- alginates e.g., alginic acid, sodium alginate, potassium alginate, am
- a viscosity modifier or thickening agent may be present in the composition in an amount of from about 0.01% to about 10% by weight based on the total weight or volume of the composition (e.g., about 0.01, about 0.1, about 0.5, about 1, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%), though the viscosity modifier or thickening agent may be present in lower or higher concentrations (e.g., about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 90%). In some embodiments, the viscosity modifier or thickening agent is present in the composition from about 40% to about 60% (e.g, about 50%).
- Exemplary electrolytes and buffering agents include potassium salts, chloride salts, bromide salts, sodium salts, magnesium salts, calcium salts, citrate salts, acetate salts, phosphate salts, salicylates, bicarbonate salts (e.g., sodium bicarbonate), lactate salts, sulphate salts, tartrate salts, benzoate salts, selenite salts, molybdate salts, iodide salts, oxides, and combinations thereof.
- potassium salts chloride salts, bromide salts, sodium salts, magnesium salts, calcium salts, citrate salts, acetate salts, phosphate salts, salicylates, bicarbonate salts (e.g., sodium bicarbonate), lactate salts, sulphate salts, tartrate salts, benzoate salts, selenite salts, molybdate salts, iodide salts, oxides, and combinations thereof.
- bicarbonate salts e
- An electrolyte or buffering agent may be present in a composition of the invention at a concentration range of about 0.01% to about 10% by weight based on the total weight or volume of the composition (e.g., about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%), though an electrolyte or buffering agent may be present in lower or higher concentrations.
- the compositions of the present invention include high concentrations of potassium (e.g., potassium chloride).
- concentration of potassium in the composition may be, e.g., about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, or about 7% or more by weight based on the total weight or volume of the composition.
- the compositions of the present invention include high concentrations of magnesium (e.g., magnesium chloride).
- concentration of magnesium in the composition may be, e.g., about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, or about 7% or more by weight based on the total weight or volume of the composition.
- an electrolyte or buffering agent may be added to the compositions of the present invention to affect the pH level.
- the pH of the composition e.g., with the addition of an electrolyte or buffering agent, is e.g., about 1.5, about 2.0, about 2.5, about 3.0, about 3.5, about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, about 7.0, about 7.5, about 8.0, or about 8.5.
- Sweeteners may be included in the compositions of the invention.
- Exemplary sweeteners include corn syrup (e.g., high fructose corn syrup or karo syrup), mannose, maltose, glucose polymers, sucrose (e.g., cane sugar or beet sugar), glucose, dextrose, lactose, galactose, fructose, polysaccharides (e.g., malodextrins), rice syrup, honey, and natural fruit juices (e.g., orange juice, papaya juice, pineapple juice, apple juice, grape juice, apricot juice, pear juice, tomato juice, agave nectar, or cranberry juice).
- corn syrup e.g., high fructose corn syrup or karo syrup
- mannose maltose
- glucose polymers e.g., cane sugar or beet sugar
- sucrose e.g., cane sugar or beet sugar
- glucose dextrose
- lactose gal
- non- or low-caloric sweeteners can be used in the compositions of the invention.
- non-caloric or low-caloric sweeteners include, but are not limited to, saccharin, sodium saccharin, cyclamates, acetosulfam, sorbitol, mannitol, sucralose, xylitol, erythritol, Stevia extract, L-aspartyl-L-phenyl-alanine ester (e.g., aspartame), L-aspartyl-D-alanine alkyl amides, L-aspartyl-L-1-hydroxymethylalkaneamide, and L-aspartyl-1-hydroxyethylalkaneamide.
- sweeteners may be present in a composition of the invention at a concentration range of about 2% to about 20% by weight based on the total weight or volume of the composition (e.g., about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20%), though sweeteners may be present in lower or higher concentrations.
- Exemplary flavors and flavoring agents include almond oil, amaretto oil, anethole, anise oil, apple, benzaldehyde, blackberry, black walnut oil, blueberry, caraway, caraway oil, cardamom oil, cardamom seed, cherry juice, cherry syrup, chocolate, cinnamon, cinnamon oil, cinnamon water, citric acid, citric acid syrup, clove oil, cocoa, coriander oil, dextrose, eriodictyon, ethyl acetate, ethyl vanillin, fennel oil, ginger, glucose, glycerin, glycyrrhiza, grape, honey, lavender oil, lemon oil, lime, mannitol, methyl salicylate, mint (e.g., peppermint, spearmint), myristica oil, orange oil, orange peel, orange syrup, peppermint, peppermint oil, peppermint water, phenylethyl alcohol, pineapple, raspberry juice, raspberry syrup, rosemary oil, rose oil, rose water,
- Flavoring agents may be present in a composition of the invention at a concentration range of about 0.01% to about 20% by weight based on the total weight or volume of the composition (e.g., about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 7.5%, about 10%, about 12.5%, about 15%, about 17.5%, or about 20%), though flavoring agents may be present in lower or higher concentrations.
- Coloring agents include, e.g., beta-carotene, riboflavin dyes, FD&C dyes (e.g., Yellow No. 5, Blue No. 1, Blue No. 2, and Red No. 40), FD&C lakes, chlorophylls and chlorophyllins, caramel coloring, annatto, cochineal, turmeric, saffron, paprika, and fruit, vegetable, and/or plant extracts (e.g., grape, black currant, aronia, carrot, beetroot, red cabbage, elderberry, and hibiscus extracts).
- FD&C dyes e.g., Yellow No. 5, Blue No. 1, Blue No. 2, and Red No. 40
- FD&C lakes e.g., Yellow No. 5, Blue No. 1, Blue No. 2, and Red No. 40
- chlorophylls and chlorophyllins e.g., caramel coloring, annatto, cochineal, turmeric, saffron, paprika
- Coloring agents will vary depending on the agents used in the composition and the color intensity desired in the finished product. Coloring agents may be present in a composition of the invention at a concentration range of about 0.01% to about 20% by weight based on the total weight or volume of the composition (e.g., about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 7.5%, about 10%, about 12.5%, about 15%, about 17.5%, or about 20%), though coloring agents may be present in lower or higher concentrations.
- Non-limiting examples of vitamins and minerals that may be included in the compositions of the present invention include, e.g., choline bitartate, niacinamide, thiamin, folic acid, d-calcium pantothenate, biotin, vitamin A, vitamin C, vitamin Bi hydrochloride, vitamin B 2 , vitamin B 3 , vitamin B 6 hydrochloride, vitamin B 12 , vitamin D, vitamin E acetate, vitamin K, and salts of calcium, potassium, magnesium, zinc, iodine, iron, and copper.
- vitamins and minerals include, e.g., choline bitartate, niacinamide, thiamin, folic acid, d-calcium pantothenate, biotin, vitamin A, vitamin C, vitamin Bi hydrochloride, vitamin B 2 , vitamin B 3 , vitamin B 6 hydrochloride, vitamin B 12 , vitamin D, vitamin E acetate, vitamin K, and salts of calcium, potassium, magnesium, zinc, iod
- vitamins and minerals may be present in a composition of the invention at a concentration range of about 0.01% to about 50% by weight based on the total weight or volume of the composition (e.g., about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 7.5%, about 10%, about 12.5%, about 15%, about 17.5%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50%), though vitamins and minerals may be present in lower or higher concentrations.
- the composition when included in a composition of the invention, may contain at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50% of the U.S. recommended daily intake (RDI) for such vitamins and minerals.
- RDI U.S. recommended daily intake
- a preservative may additionally be utilized in the compositions described herein.
- exemplary preservatives include, for example, sorbate, polysorbate (e.g., polysorbate 20, polysorbate 40, polysorbate 80), a paraben (e.g., methylparaben sodium, propylparaben sodium), benzoate, and polyphosphate preservatives (e.g., sorbic acid, benzoic acid, calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, and mixtures thereof).
- sorbate e.g., polysorbate 20, polysorbate 40, polysorbate 80
- paraben e.g., methylparaben sodium, propylparaben sodium
- benzoate e.g., sorbic acid, benzoic acid, calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, and mixtures thereof.
- the preservative may be present in a composition of the invention at a concentration range of about 0.0005% to about 0.5% (e.g., about 0.0005%, about 0.001%, about 0.005%, about 0.01%, about 0.05%, about 0.1%, or about 0.5%) by weight based on the total weight or volume of the composition, though preservatives may be present in lower or higher concentrations.
- a preservative may be added to the compositions of the present invention to affect the pH.
- the pH of the composition e.g., with the addition of a preservative, is e.g., about 1.5, about 2.0, about 2.5, about 3.0, about 3.5, about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, about 7.0, about 7.5, about 8.0, or about 8.5.
- the pH of the composition e.g., with the addition of a preservative
- the pH of the composition is within the range of about 1.5 to about 7.5, about 1.75 to about 7.0, about 2.0 to about 6.5, about 2.1 to about 6.0, about 2.2 to about 5.5, about 2.3 to about 5.0, about 2.4 to about 4.5, about 2.5 to about 4.0, about 2.6 to about 3.5.
- the pH of the composition e.g., with the addition of a preservative, is within the range of about 1.5 to about 4.0.
- antioxidant agent may also be included in the compositions to, for example, reduce exercise-induced oxidative stress.
- exemplary antioxidants include vitamin C and vitamin E; beta-carotene, lutein, or other carotenoids; cyanidin, delphinidin, malvidin, or other anthocyanidins; apigenin, luteolin, or other flavones; hesperitin, naringenin, or other flavonones; isorhamnetin, quercetin, kaempferol or other flavonols; butylated hydroxyanisole and butylated hydroxytoluene; and epigallocatechin-3-gallate, epicatechin, thearubigins, or other flavan-3-ols.
- an antioxidant may be present in a composition of the invention at a concentration range of about 0.0005% to about 0.5% (e.g., about 0.0005%, about 0.001%, about 0.005%, about 0.01%, about 0.05%, about 0.1%, or about 0.5%) by weight based on the total weight or volume of the composition, though antioxidants may be present in lower or higher concentrations.
- a dissolving agent or solvent may also be included in the compositions to, for example, improve the suspension or emulsification of particular components.
- certain dissolving agents or solvents may have a preservative function.
- Exemplary dissolving agents or solvents include acetic acid, acetone, butanol, dimethyl sulfoxide, ethanol, ethyl acetate, isopropanol, methanol, petroleum ether and the like.
- a dissolving agent or solvent may be present in a composition of the invention at a concentration range of about 0.0005% to about 0.5% (e.g., about 0.0005%, about 0.001%, about 0.005%, about 0.01%, about 0.05%, about 0.1%, or about 0.5%) by weight based on the total weight or volume of the composition, though dissolving agents or solvents may be present in lower or higher concentrations.
- compositions described herein may include amino acids (e.g., leucine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine), stimulants (e.g., caffeine), emulsifying agents, carbon dioxide (e.g., to carbonate a liquid composition), stabilizers, humectants, anticaking agents, or herbal extracts.
- amino acids e.g., leucine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine
- stimulants e.g., caffeine
- emulsifying agents e.g., carbon dioxide (e.g., to carbonate a liquid composition)
- carbon dioxide e.g., to carbonate a liquid composition
- stabilizers e.g., to carbonate a liquid composition
- humectants e.g., to carbon
- These components may be included at levels from about 0.0005% to about 25% (e.g., about 0.0005%, about 0.001%, about 0.005%, about 0.01%, about 0.05%, about 0.1%, about 0.5%, about 1%, about 5%, about 10%, about 15%, about 20%, or about 25%) by weight based on the total volume of the composition, though an additional component may be present in lower or higher concentrations.
- an additional therapeutic agent may be administered with compositions of the present invention, e.g., to improve or preserve exercise performance or exercise recovery.
- the additional therapeutic agent can be administered as a separate formulation or may be combined with any of the compositions described herein.
- an additional therapeutic agent may be administered to improve or preserve exercise performance, prevent or treat muscle cramps, muscle soreness, or pain, or enhance mood.
- Such therapeutic agents include, for example, muscle relaxants (e.g., diazepam), anti-inflammatory agents (e.g., ibuprofen), steroids, hormones, diuretics, nutritional supplements (e.g., creatine), vitamins, stimulants (e.g., caffeine, amphetamines), and anti-depressants.
- compositions and solutions of the present invention may be formulated as ready-to-drink beverages, concentrates (e.g., syrups), dry compositions (e.g., powders, granules, or tablets that may be reconstituted with a liquid (e.g., with water), gels, solids, semi-solids (e.g., ice cream, pudding, or yogurt), frozen liquids (e.g., ice pops), lozenges or hard candies, dissolving strips (e.g., an edible strip containing pullulan and compositions of the invention), and chewing gum.
- concentrates e.g., syrups
- dry compositions e.g., powders, granules, or tablets that may be reconstituted with a liquid (e.g., with water), gels, solids, semi-solids (e.g., ice cream, pudding, or yogurt), frozen liquids (e.g., ice pops), lozenges or hard candies, dissolving strips (e
- the compositions may be in the form of a dry powder, granule, or tablet that may be reconstituted in a specified amount of a liquid.
- the dried components may be mixed together and milled (e.g., to create a homogenous powder) or mixed in aqueous solution and dried by using methods known to one of skill in the art. Dried powders or granules may be “loose” or fashioned into tablets.
- compositions described herein can be ingested, for example, by a subject before, during, or after exercise.
- the compositions and solutions described herein can be ingested (e.g., through eating or drinking) before the onset of muscle cramping, when muscle cramping begins, any time after the onset of muscle cramping, or after muscle cramping has subsided.
- the compositions of the solution can also be ingested after exercise to accelerate nerve-muscle recovery from exercise fatigue, or to reduce inflammation.
- compositions and solutions of the present invention are in the form of a ready-to-drink beverage
- a ready-to-drink beverage e.g., 1, 2, 4, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30, or 32 ounces of the beverage may be consumed as needed (e.g., once, twice, three, four, five, six times per day; once per week; or once per month).
- compositions and solutions of the present invention may be prepared using methods known to one of skill in the art. Such methods include dissolving, dispersing, or otherwise mixing all components singularly or in suitable combinations and agitating with, for example, a mechanical stirrer until all of the ingredients have been solubilized or adequately dispersed. Where a shelf-stable composition or solution is desired, the final mixture can be pasteurized, ultra-pasteurized, sterilized, or filled aseptically at appropriate process conditions. Where required for mutual stability of two or more components (for example if a component is unstable at low pH), multiple components can be mixed shortly before ingestion.
- compositions and solutions described herein may be bottled or packaged in, for example, glass bottles, plastic bottles and containers (e.g., polyethylene terephthalate or foil-lined ethylene vinyl alcohol), metal cans (e.g., coated aluminum or steel), lined cardboard containers, pouches, packs, wrappers, or any other packaging known to one of skill in the art.
- a ready-to-drink beverage can be bottled or packaged in a unit that contains between 10-1000 mL of the beverage.
- the packaging can contain 10, 20, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 mL of the beverage.
- the packaging can contain 200, 250, 330, 350, 355, 375, 440, or 500 mL of the beverage.
- a ready-to-drink beverage can also be bottled or packaged in a unit that contains between 1-32 fluid ounces of beverage (e.g., the unit may contain 1, 2, 5, 6.75, 8, 8.3, 8.4, 8.45, 9.6, 10, 12, 15, 15.5, 16, 18.6, 20, 23, 24, or 32 fluid ounces).
- the packaging is appropriately sterilized before being filled by the pasteurized, ultra-pasteurized, or sterilized composition or solution.
- the packaging may feature multiple containers that can be mixed shortly before ingestion or that can be consumed serially.
- compositions of the present invention are formulated into acceptable dosage forms by conventional methods known to those of skill in the art. Actual dosage levels of the active ingredients in the compositions of the present invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular subject, composition, and mode of administration, without being toxic to the subject.
- the selected dosage level will depend upon a variety of pharmacokinetic factors including the activity of the particular compositions of the present invention employed, the route of administration, the time of administration, the rate of absorption of the particular agent being employed, the duration of the treatment, other drugs, substances, and/or materials used in combination with the particular compositions employed, the age, sex, weight, condition, general health and prior medical history of the subject being treated, and like factors well known in the medical arts.
- a physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the composition required. For example, the physician or veterinarian can start doses of the substances of the invention employed in the composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved.
- a suitable daily dose of a composition of the invention will be that amount of the substance which is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above.
- the effective daily dose of a therapeutic composition may be administered as one, two, three, four, five, six or more sub-doses administered separately at appropriate intervals throughout the day, optionally, in unit dosage forms.
- the frequency of treatment may also vary.
- the subject can be treated one or more times per day (e.g., once, twice, three, four or more times) or every so-many hours (e.g., about every 2, 4, 6, 8, 12, or 24 hours).
- the composition can be administered 1, 2, or 3 times per 24 hours.
- the time course of treatment may be of varying duration, e.g., for two, three, four, five, six, seven, eight, nine, ten, or more days, two weeks, 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, or more than one year.
- the treatment can be twice a day for three days, twice a day for seven days, twice a day for ten days.
- Treatment cycles can be repeated at intervals, for example weekly, bimonthly or monthly, which are separated by periods in which no treatment is given.
- the treatment can be a single treatment or can last as long as the life span of the subject (e.g., many years).
- compositions of the invention may be useful for improving or preserving exercise performance or recovery from exercise.
- Improving or preserving physical performance may comprise shortening the time to complete an exercise, e.g., a sprint or cycling exercise by the subject, increasing the maximal oxygen consumption (VO 2 max) in the subject, decreasing the fatigue of the subject, e.g., as measured by the Fatigue Index, or improving the energy level, improving the mood, or reducing the exertion and pain (e.g., perceived exertion and pain) of a subject.
- the aforementioned improvement or preservation targets are determined relative to a reference standard.
- the present invention features a method of improving recovery after exercise in a subject. Improving recovery may comprise reducing pain in a subject (e.g., reducing leg pain) or reducing inflammation in a subject.
- the present invention features a method of reducing inflammation in a subject.
- the inflammation occurs as a result of exercise.
- Performance improvement may be associated with improved energy level, mental energy, and mood, and reduced perceived exertion and pain, with little or no effects on cardiovascular and/or metabolic function.
- Subjects Twenty healthy, active, but untrained male and female subjects between the ages of 18 and 30 were recruited to participate in this study. Subjects were required to be in good general health with no recent musculoskeletal injuries, and absence of cardiovascular, respiratory, and metabolic disorders. Subjects were further required to maintain a normal state of hydration, e.g., by avoiding changes in caffeine consumption and dehydration-inducing substances (e.g., alcohol), maintain a normal diet, and avoid rigorous exercise 24 hours prior to the study. Subjects were screened using a health history questionnaire and signed an Informed Consent Form prior to participation. University of South Carolina Institutional Review Board approval was obtained prior initiation of the study for any cases requiring additional review.
- caffeine consumption and dehydration-inducing substances e.g., alcohol
- the drinks were given to the participants immediately prior to the start of the exercise protocol (i.e., the initial sprint performance test). A second drink was provided during the rest period after the IHE session, 5 min prior to the time trial.
- VO 2 max Maximal Oxygen Consumption
- IHE Intermittent High Intensity Exercise Protocol: After the maximal sprint test (10 min), subjects completed a controlled IHE exercise session on a stationary bicycle ergometer (Monark) in a well-controlled laboratory setting (environmental chamber). The temperature and humidity was set at ambient conditions (i.e., 20° C. and 40% relative humidity).
- the controlled exercise protocol consisted of 45 min of repeated 5-minute bouts of 4-minute at ⁇ 60% VO 2 max followed by 1-minute at ⁇ 125% VO 2 max (sprints).
- Cycling Time Trial After a 15-min rest period following completion of the IHE, subjects completed an approximately 10-minute time trial (e.g., race to the finish line) to complete a prescribed amount of work (i.e., distance) as fast as possible.
- Body Weight Nude body weight was measured using a precisely calibrated weighing scale before and after completion of each exercise trial to estimate of overall dehydration level.
- Body Composition The 7-site skinfolds technique was used to assess percent body fat and lean body mass during the preliminary session.
- Heart Rate and Blood Pressure In order to ensure subjects remain at safe limits and determine any benefits from the cooling towel, heart rate was continuously monitored using a heart rate monitor, and blood pressure was assessed at 10-minute intervals using an aneroid sphygmomanometer.
- Body Core Temperature Body core temperature (Tc) was recorded continuously throughout the exercise trial using rectal temperature (model 4600, YSI Precision Temperature Group, Dayton, Ohio). Subjects were not allowed to exceed a Tc>40° C./104° F.
- Rectal temperature is accepted as a valid and reliable measure of Tc. Ratings of Perceived Exertion: Perceived exertion ratings were assessed using a 20-point Borg scale at a 10-minute interval throughout the exercise session. Leg Muscle Pain: Leg-muscle pain intensity was measured immediately after each of the initial sprint performance test, at the end of the 1 min sprints during IHE, and immediately after TT using a validated 10- point scale. Mood State: The Profile of Mood State (POMS) questionnaire was used to assess the mood states prior to taking the supplement and immediately before IHE and TT. The self-report scales are a collection of tools that allow for the quick assessment of transient, fluctuating feelings, and enduring affect states.
- POMS Profile of Mood State
- Exemplary scale scores include: Anger-Hostility, Confusion-Bewilderment, Depression-Dejection, Fatigue-Inertia, Tension-Anxiety, and Vigor-Activity. Each was determined separately and a Total Mood Disturbance score was assigned, which is a function of these six scale scores.
- Blood collection An intravenous catheter was inserted into a forearm vein prior to testing. Then 5-min prior to experimental testing, 10 ml of blood was collected via the catheter and then again at 15-minute intervals through the exercise session.
- Blood samples were analyzed for markers of metabolic function (e.g., glucose, lactate), muscle damage (e.g., creatine kinase) and inflammation (e.g., inflammatory cytokines IL-6, IL-10, IL-lra protein and leukocyte gene expression).
- markers of metabolic function e.g., glucose, lactate
- muscle damage e.g., creatine kinase
- inflammation e.g., inflammatory cytokines IL-6, IL-10, IL-lra protein and leukocyte gene expression.
- Preliminary Session Before starting the protocol, subjects attended a meeting with the study coordinator to complete informed consent and health history questionnaire. Preliminary Session: Both preliminary and experimental sessions were held in the laboratory of Public Health Research Center located at the University of South Carolina. Subjects first attended the preliminary session for height, weight and body composition assessment followed by a maximal VO 2 test on a stationary cycle ergometer. For the second preliminary session, 60% and 125% VO 2 max workloads were set and validated on the bicycle ergometer, and participants became familiarized with the exercise protocol and experimental procedures. Experimental Sessions I Data Collection: Qualified subjects were then randomized and counterbalanced to either experimental (STA) or control (PLA) treatments for the 1st trial. The 2nd trial (opposite treatment) was done within 5-7 days after the first trial.
- STA experimental
- PDA control
- compositions e.g., STA and others described herein
- STA may work through stimulation of the CNS, as no differences were seen between STA and PLA on markers of cardiovascular, metabolic, and inflammatory function.
- these results suggest that subjects consuming the exemplary compositions described herein (e.g., STA) comprising TRPV1 and TRPA1 agonists may improve performance during exercise (e.g., intermittent, high-intensity exercise) with no apparent adverse side effects.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Nutrition Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Physiology (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Pain & Pain Management (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Described herein are compositions comprising activators of TRP and ASIC channels that may be useful to improve or preserve exercise performance and exercise recovery.
Description
- This application is a continuation of U.S. patent application Ser. No. 16/479,748, filed on Jul. 22, 2019, which is a U.S. National Phase Application under 35 U.S.C. § 371 of International Application No. PCT/US2018/014872, filed Jan. 23, 2018, titled COMPOSITIONS AND METHODS AFFECTING EXERCISE PERFORMANCE, which claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 62/449,411, filed Jan. 23, 2017, titled COMPOSITIONS AND METHODS AFFECTING EXERCISE PERFORMANCE, both of which are hereby incorporated by reference in their entirety for all purposes.
- Athletes often seek nutritional ergogenic aids to maintain optimal physical performance and mental function during exercise as well as to enhance recovery between bouts of exercise. As shown herein, compositions that include activators of TRP and ASIC channels may be useful to improve or preserve exercise performance and exercise recovery.
- Described herein are compositions comprising activators of TRP and ASIC channels and methods of use thereof to improve or preserve exercise performance and exercise recovery. In one aspect, the present invention features a method of improving or preserving physical performance during exercise in a subject, wherein the method comprises orally administering to the subject a composition (e.g., a beverage) comprising a TRP channel activator and an excipient. In some embodiments, the TRP channel activator is selected from a capsaicinoid, a gingerol, or cinnamaldehyde.
- In some embodiments, improving or preserving the physical performance comprises shortening the time to complete an exercise, e.g., a sprint or cycling exercise by the subject, e.g., relative to a reference standard. In some embodiments, improving or preserving the physical performance comprises an increase in the maximal oxygen consumption (VO2 max) in the subject, e.g., relative to a reference standard. In some embodiments, improving or preserving the physical performance comprises a decrease in the fatigue of the subject, e.g., as measured by the Fatigue Index, e.g., relative to a reference standard. In some embodiments, improving or preserving the physical performance comprises exhibiting a greater mean power, total power, or interval power during a test (e.g., a sprint test, e.g., as described in Example 1). In some embodiments, improving or preserving the physical performance comprises improving the time trial distance of a subject (e.g., as described in Example 1). In some embodiments, improving or preserving the physical performance comprises increasing the energy (e.g., the mental energy), improving the mood, or reducing the exertion and pain (e.g., perceived exertion and pain) of a subject, e.g., relative to a reference standard.
- In another aspect, the present invention features a method of improving or preserving recovery after exercise in a subject, wherein the method comprises orally administering to the subject a composition (e.g., a beverage) comprising a TRP channel activator and an excipient. In some embodiments, the TRP channel activator is selected from a capsaicinoid, a gingerol, or cinnamaldehyde. In some embodiments, improving or preserving recovery comprises reducing pain in a subject (e.g., reducing leg pain).
- In another aspect, the present invention features a method of reducing inflammation in a subject, wherein the method comprises orally administering to the subject a composition (e.g., a beverage) comprising a TRP channel activator and an excipient. In some embodiments, the TRP channel activator is selected from a capsaicinoid, a gingerol, or cinnamaldehyde. In some embodiments, the inflammation occurs as a result of exercise.
- In any and all embodiments, in some aspects, the TRP channel activator comprises a TRPA1 channel activator or a TRPV1 channel activator. In some embodiments, the capsaicinoid comprises capsaicin. In some embodiments, the composition comprises at least two of a capsaicinoid, a gingerol, or cinnamaldehyde and an excipient. In some embodiments, the composition comprises each of a capsaicinoid, a gingerol, or cinnamaldehyde and an excipient. In some embodiments, the amount of the TRP channel activator in the composition (e.g., beverage) is between about 0.001% to 1% weight/weight (w/w) of TRPA1 channel activator per weight of the composition (e.g., beverage).
- In some embodiments, the excipient comprises a disintegrant, a binder, a surfactant, an emulsifier, a viscosity modifier, a lubricant, a sweetener, a pH-adjusting agent, a preservative, a flavoring agent, a coloring agent, or an antioxidant. In some embodiments, the excipient comprises an emulsifier, a sweetener, a pH-adjusting agent, a preservative, or a flavoring agent. In some embodiments, the excipient is selected from gellan gum, carob bean gum, locust bean gum, carrageenan, alginates, agar, guar gum, xanthan gum, carboxymethyl cellulose, clear starch, pectin, gelatin, cornstarch, katakuri starch, potato starch, and gum arabic. In some embodiments, the excipient comprises a sweetener selected from high fructose corn syrup, mannose, maltose, glucose polymers, sucrose, glucose, dextrose, lactose, galactose, fructose, polysaccharides, rice syrup, honey, saccharin, cyclamates, acetosulfam, sorbitol, sucralose, xylitol, erythritol, Stevia extract, L-aspartyl-L-phenyl-alanine ester, L-aspartyl-D-alanine alkyl amides, L-aspartyl-L-1-hydroxymethylalkaneamide, and L-aspartyl-1-hydroxyethylalkaneamide. In some embodiments, the excipient comprises a pH-adjusting agent selected from hydrochloric acid, citric acid, sodium hydrogen carbonate, potassium hydroxide, sodium hydroxide, and sodium carbonate. In some embodiments, the excipient comprises a preservative selected from sorbic acid, benzoic acid, sodium benzoate, sodium chloride, calcium benzoate, potassium benzoate, potassium sorbate, calcium sorbate, and sodium sorbate. In some embodiments, the excipient comprises a flavoring agent selected from almond oil, amaretto oil, anethole, anise oil, benzaldehyde, blackberry, black walnut oil, blueberry, caraway, caraway oil, cardamom oil, cardamom seed, cherry juice, cherry syrup, cinnamon, cinnamon oil, cinnamon water, citric acid, citric acid syrup, clove oil, cocoa, coriander oil, dextrose, eriodictyon, ethyl acetate, ethyl vanillin, fennel oil, ginger, glucose, glycerin, glycyrrhiza, grape, honey, lavender oil, lemon oil, lemon juice, lime, lime juice, mannitol, methyl salicylate, myristica oil, orange oil, orange peel, orange syrup, peppermint, peppermint oil, peppermint water, phenylethyl alcohol, pineapple, raspberry juice, raspberry syrup, rosemary oil, rose oil, rose water, sarsaparilla syrup, salt (e.g., sea salt), sorbitol, spearmint, spearmint oil, strawberry, sucrose, thyme oil, tolu balsam, vanilla, vanillin, and wild cherry syrup.
- In some embodiments, the composition (e.g., beverage) is bottled or packaged in a unit that contains between 10 mL and 1000 mL of the composition (e.g., beverage). In some embodiments, the beverage is bottled or packaged in a unit that contains 50 mL or 100 mL of the beverage.
- In some embodiments, the composition is administered to the subject prior to commencement of exercise (e.g., at least about 1 minute, about 2 minutes, about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 30 minutes, about 45 minutes, about 1 hour, about 1.5 hours, about 2 hours, or more).
-
FIGS. 1A-1B are figures outlining the overall study design (FIG. 1A ) and the measurement timeline duringexperimental sessions 1 and 2 (FIG. 1B ) as set forth in Example 1. -
FIG. 2 is a table summarizing exemplary subject characteristics of the participants in the study outlined in Example 1. -
FIGS. 3A-3B are charts comparing the results of the 30-second maximal sprint in subjects that received either the experimental (STA) or vehicle (PLA) drink as mean power output (FIG. 3A ) or total power output (FIG. 3B ). -
FIG. 4 is a graph comparing the results of the mean power during each 5-second interval of the 30-second maximal sprint in subjects that received either the experimental (STA) or vehicle (PLA) drink. -
FIG. 5 is a chart comparing the results of the distance covered by subjects that received either the experimental (STA) or vehicle (PLA) drink in the 30-second maximal sprint. -
FIG. 6 is a graph showing the individual time trial distance by treatment for each subject in the study outlined in Example 1. - The methods and compositions of the present invention are directed to improving or preserving exercise performance and exercise recovery in a subject in need thereof. Exemplary compositions comprise a TRP channel activator or an ASIC channel activator formulated for oral consumption.
- The use of the words “a” or “an” when used in conjunction with the term “comprising” herein may mean “one,” but are also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.”
- The term “acidulant” as used herein refers to an acidic compound (e.g., an acid) used to lower the pH of a composition. In some embodiments, the pH can be lowered in the range of about 2.5 to about 6.5 (e.g., pH of 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, or 6.5). In some embodiments, the pH can be lowered in the range of about 1.5 to about 5.0 (e.g., pH of 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0), for example, in the range of about 1.5 to about 4.4 (e.g., pH of 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.4).
- “Acquire” or “acquiring” as the terms are used herein, refer to obtaining possession of a value, e.g., a numerical value, or image, or a physical entity (e.g., a sample), by “directly acquiring” or “indirectly acquiring” the value or physical entity. “Directly acquiring” means performing a process (e.g., applying or measuring a current to or from a subject, or capturing a signal from a subject or sample or performing a synthetic or analytical method) to obtain the value or physical entity. “Indirectly acquiring” refers to receiving the value or physical entity from another party or source (e.g., a third party laboratory that directly acquired the physical entity or value). Directly acquiring a value or physical entity includes performing a process that includes a physical change in a physical substance or the use of a machine or device.
- The term “agonist,” as used herein, refers to a molecule that stimulates a biological response. In some embodiments, an agonist is an activator. In some embodiments, the agonists and activators referred to herein may activate a TRP ion channel (e.g., TRPV1 or TRPA1) or an ASIC ion channel.
- The term “administering” and “administration” refers to a mode of delivery. A daily dosage can be divided into one, two, three or more doses in a suitable form to be administered one, two, three or more times throughout a time period. In preferred embodiments of the present invention, compositions and solutions are administered orally.
- The terms “analog” or “related analogs” as used herein in regard to a compound or compounds refer to a substance that has a similar chemical structure to another compound, but differs from it with respect to a certain component or components.
- The term “derivative” as used herein refers to a substance produced from another substance either directly or by modification or partial substitution.
- “Muscle cramp” as used herein is a muscle cramp which is treated with the composition described herein. In some embodiments, it is not induced but rather arises spontaneously either from activity or underlying disease etiology, e.g., exercise. In some embodiments, the muscle cramp can be a contraction of a skeletal muscle or the smooth muscle. In some embodiments, the muscle cramp is a contraction of a skeletal muscle, e.g., the flexor hallucis brevis muscle.
- As used herein, the terms “prevent” or “preventing” as used in the context of a disorder or disease, refer to administration of an agent to a subject such that the onset of at least one symptom of the disorder or disease is delayed as compared to what would be seen in the absence of administration of said agent. As compared with an equivalent untreated control, such prevention is at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100%, as measured by any standard technique.
- The term “subject” as used herein refers to a mammal, including, but not limited to, a human or non-human mammal, such as a bovine, equine, canine, ovine, or feline mammal. In some embodiments, the term subject refers to a human (e.g., a human male or female).
- As used herein, the term “substantially pure” refers to a composition that is free of organic and/or inorganic species that do not activate the TRPV1, TRPA1, or/or ASIC channels, and where 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% (w/w) of the composition is comprised of a single chemical species. Substantially pure compositions can be prepared and analyzed using standard methods known in the art (e.g., chromatographic separation, extractions, and the like). In some embodiments, substantially pure compositions do not include isomeric impurities (e.g., geometric isomers) and/or salts or solvates of a particular chemical species.
- “Treat” or “treating” as used herein refers to administering a composition for therapeutic purposes or administering treatment to a subject to improve at least one symptom of already suffering from a disorder to improve the subject's condition. By “treating a condition or disorder” or “alleviating a condition or disorder” is meant that the condition or disorder and the symptoms associated with the condition or disorder are, e.g., prevented, alleviated, reduced, cured, or placed in a state of remission. As compared with an equivalent untreated control, such alleviation or degree of treatment is at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100%, as measured by any standard technique.
- The term “viscosity” as used herein refers to a measurement of a fluid's internal resistance to flow (e.g., “thickness”). Viscosity is generally expressed in centipoise (cP) or pascal-seconds.
- Other features and advantages of the invention will be apparent from the Detailed Description, Examples, and Claims.
- The compositions described herein are suitable for oral consumption by a subject (e.g., by a human) and include an activator of a TRP channel (e.g., TRPV1, TRPA1) or an activator of an ASIC channel, as well as one or more optional excipients as described herein. Exemplary, non-limiting compositions include those that are solids (e.g., chews or chewing gums), liquids (e.g., beverages), and gels.
- Compounds that activate TRPV1 that may be used in the compositions of the present invention include, for example, capsaicin, capsaicin analogs and derivatives (e.g., capsaicinoids), and any other compound that activates TRPV1, examples of which are described herein. Modulators of TRPV1 activity are known in the art (see, e.g., Harteneck et al., Adv Exp Med Biol. 704:87-106, 2011, and other references described herein).
- In one embodiment, the TRPV1 channel activator is a capsaicinoid (e.g., capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide)). Exemplary capsaicinoids are provided in Table 1.
- Suitable capsaicinoids and capsaicinoid analogs and derivatives for use in the compositions and methods of the present invention include naturally occurring and synthetic capsaicin derivatives and analogs including, e.g., vanilloids (e.g., N-vanillyl-alkanedienamides, N-vanillyl-alkanedienyls, and N-vanillyl-cis-monounsaturated alkenamides), capsiate, dihydrocapsiate, nordihydrocapsiate and other capsinoids, capsiconiate, dihydrocapsiconiate and other coniferyl esters, capsiconinoid, resiniferatoxin, tinyatoxin, civamide, N-phenylmethylalkenamide capsaicin derivatives, olvanil, N-[4-(2-aminoethoxy)-3-methoxyphenyl)methyl]-9Z-octa-decanamide, N-oleyl-homovanillamide, triprenyl phenols (e.g., scutigeral), gingerols, piperines, shogaols, guaiacol, eugenol, zingerone, nuvanil, NE-19550, NE-21610, and NE-28345.
- Other suitable TRPV1 channel activators include oleoylethanolamide, N-oleoyldopamine, 3-methyl-N-oleoyldopamine, oleamide, capsiate, 1-monoacylglycerols having C18 and C20 unsaturated and C8-C12 saturated fatty acid, 2-monoacylglycerols having C18 and C20 unsaturated fatty acids, miogadial, miogatrial, polygodial, and other terpenoids with an alpha, beta-unsaturated 1,4-dialdehyde moiety, sanshools, evodiamine, acesulfame-K, cyclamate, sulfates (e.g., CuSO4, ZnSO4, and FeSO4), arvanil, anandamide, N-arachidonoyl-dopamine, flufenamic acid dopamide and other dopamine amides of fenamic acids, 4-hydroxynonenal, SA13353 (i.e., 1-[2-(1-adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea), gingerol or salts of magnesium.
- In addition, the TRPV1 channel activator may be an analog or derivative of any of the TRPV1 channel activators described herein.
- Additional TRPV1 channel activators are described, for example, in U.S. Pat. Nos. 7,632,519; 7,446,226; 7,429,673; 7,407,950; 6,022,718; 5,962,532; 5,762,963; 5,403,868; 5,290,816; 5,221,692; 4,812,446; 4,599,342; 4,564,633; 4,544,669; 4,544,668; 4,532,139; 4,493,848; 4,424,205; 4,313,958; in U.S. Patent Application Publication Nos. 2007/0293703; 2007/0167524; 2006/0240097; and 2005/0085652; and in WO 00/50387, each of which is incorporated by reference.
- In addition, the TRPV1 channel activator may be an acidulant (e.g., acetic acid, phosphoric acid, citric acid, malic acid, succinic acid, tartaric acid, fumaric acid, or ascorbic acid) maintaining a low pH in the range of 2.5-6.5 (e.g., pH of 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, or 6.5).
- TRPV1 channel activators for use in the compositions and methods described herein can be identified using standard methodology, as described, for example, in U.S. Patent Application Publication No. 2003/0104085, which is hereby incorporated by reference. Exemplary assays for identification of TRPV1 channel activators include, without limitation, receptor binding assays; functional assessments of stimulation of calcium influx or membrane potential in cells expressing the TRPV1 receptor; assays for the ability to induce cell death in such cells (e.g., selective ablation of C-fiber neurons); and other assays known in the art.
- A TRPV1 channel activator may be present in a composition of the invention at a concentration range of about 0.001% to about 50% weight by weight (w/w) based on the total weight or total volume of the composition (e.g., 0.005%, 0.01%, 0.05%, 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 30%, 40% or 50%). In some embodiments, a TRPV1 channel activator is present between 0.001% to 1% weight/weight (w/w) per weight of the composition. In some embodiments, a composition described herein comprises between about 0.0001 to about 0.1 mg TRPV1 channel activator (e.g., about 0.0001 to about 0.01 mg, or about 0.001 mg to about 0.01 mg, or about 0.01 mg to about 0.1 mg TRPV1 channel activator per mL or mg of composition.
- TRPA1 channels are activated by naturally occurring substances including, e.g., mustard oil, isothiocyanate compounds (e.g., allyl isothiocyanate), acrolein, farnesyl thiosalicylic acid, Δ9-tetrahydrocannabinol (THC), eugenol, ginger, gingerol, gingerols, shogaols, nicotine, nicotine derivatives and analogs, methyl salicylate, cinnamaldehyde, cinnamon oil, wintergreen oil, clove oil, allicin, diallyl sulfide, diallyl disulfide, diallyl trisulfide, sanshools, farnesyl thiosalicylic acid, and farnesyl thioacetic acid. The TRPA1 channel activator may also be an analog or derivative of any of the TRPA1 channel activators described herein, and additional TRPA1 channel activators are identified in WO 2009/071631, hereby incorporated by reference. Still other modulators of TRPA1 are described in, e.g., Harteneck et al., “Synthetic modulators of TRP channel activity,” Adv Exp Med Biol. 704:87-106, 2011; Viana et al. “TRPA1 modulators in preclinical development,” Expert Opin. Ther. Pat. 19(12):1787-99, 2009).
- Methods for identifying TRPA1 channel activators are known in the art and are described, for example, in U.S. Pat. No. 7,674,594.
- A TRPA1 channel activator may be present in a composition of the invention at a concentration range of about 0.001% to about 50% weight by weight (w/w) based on the total weight or total volume of the composition (e.g., 0.005%, 0.01%, 0.05%, 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 30%, 40% or 50%). In some embodiments, a TRPA1 channel activator is present between 0.001% to 1% weight/weight (w/w) per weight of the composition. In some embodiments, a composition described herein comprises between about 0.0001 to about 0.1 mg TRPA1 channel activator (e.g., about 0.0001 to about 0.01 mg, or about 0.001 mg to about 0.01 mg, or about 0.01 mg to about 0.1 mg TRPA1 channel activator per mL or mg of composition.
- ASIC channels are activated by low pH. The pH of a composition of the present invention that includes an ASIC channel activator may be in the range of 2.5-6.5 (e.g., pH of 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, or 6.5). The pH may be adjusted within this range by any means acceptable for compositions that are intended to be ingested by a subject. Exemplary acidulants are acetic acid, phosphoric acid, citric acid, malic acid, succinic acid, tartaric acid, fumaric acid, and ascorbic acid. The ASIC channel activator may be present in a composition of the invention at a concentration range of about 0.001% to about 50% weight by weight (w/w) based on the total weight or total volume of the composition (e.g., 0.005%, 0.01%, 0.05%, 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 30%, 40% or 50%). In some embodiments, an ASIC channel activator is present between 0.001% to 1% weight/weight (w/w) per weight of the composition. In some embodiments, a composition described herein comprises between about 0.0001 to about 0.1 mg an ASIC channel activator (e.g., about 0.0001 to about 0.01 mg, or about 0.001 mg to about 0.01 mg, or about 0.01 mg to about 0.1 mg an ASIC channel activator per mL or mg of composition.
- The composition of the present invention comprises a TRP channel activator or an ASIC channel activator and an excipient. Exemplary excipient include electrolytes (e.g., potassium salt or other salts), buffering agents, sweeteners, flavoring and coloring agents, vitamins, minerals, preservatives, viscosity modifiers, thickening agents, dissolving agents, solvents, and antioxidants as described below. Other exemplary excipients are described in Handbook of Pharmaceutical Excipients, 6th Edition, Rowe et al., Eds., Pharmaceutical Press (2009).
- Viscosity is the ratio of shear stress to shear rate, expressed as dynes-second/cm2, or poise. A centipoise (cP) is one one-hundredth of a poise.
- The composition of the present invention may have a viscosity greater than water (i.e., about 1.0 cP at 20° C.), e.g., about 100, 200, 300, 400, 500, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 6000, 7000, 8000, 9000 cP or more. If a consistency of corn syrup is desired, viscosities in the range of about 2500 cP are suitable. If a consistency of a soft gel or honey is desired, viscosities in the range of about 10000 cP to about 15000 cP are suitable. For pudding-like products, viscosities in the range of about 30000 cP to about 38000 cP are desirable. Viscosity of the compositions of the present invention may be measured with, e.g., a rheometer or viscometer, though additional methods of measuring viscosity are known in the art.
- Viscosity modifiers and thickening agents may be added to compositions of the present invention. Such viscosity modifiers and thickening agents include, for example, collagen, gellan gum, carbohydrate gel-forming polymers, carob bean gum, locust bean gum, carrageenan, alginates (e.g., alginic acid, sodium alginate, potassium alginate, ammonium alginate, and calcium alginate), agar, guar gum, xanthan gum, microcrystalline cellulose, carboxymethyl cellulose, ethyl cellulose, clear starch, pectin, gelatin, arrowroot, cornstarch, katakuri starch, potato starch, sago, tapioca, furcellaran, karo syrup (e.g., light karo syrup and dark karo syrup), glycerin, and sodium pyrophosphate. A viscosity modifier or thickening agent may be present in the composition in an amount of from about 0.01% to about 10% by weight based on the total weight or volume of the composition (e.g., about 0.01, about 0.1, about 0.5, about 1, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%), though the viscosity modifier or thickening agent may be present in lower or higher concentrations (e.g., about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 90%). In some embodiments, the viscosity modifier or thickening agent is present in the composition from about 40% to about 60% (e.g, about 50%).
- Exemplary electrolytes and buffering agents include potassium salts, chloride salts, bromide salts, sodium salts, magnesium salts, calcium salts, citrate salts, acetate salts, phosphate salts, salicylates, bicarbonate salts (e.g., sodium bicarbonate), lactate salts, sulphate salts, tartrate salts, benzoate salts, selenite salts, molybdate salts, iodide salts, oxides, and combinations thereof. An electrolyte or buffering agent may be present in a composition of the invention at a concentration range of about 0.01% to about 10% by weight based on the total weight or volume of the composition (e.g., about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%), though an electrolyte or buffering agent may be present in lower or higher concentrations.
- In certain embodiments, the compositions of the present invention include high concentrations of potassium (e.g., potassium chloride). The concentration of potassium in the composition may be, e.g., about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, or about 7% or more by weight based on the total weight or volume of the composition.
- In certain embodiments, the compositions of the present invention include high concentrations of magnesium (e.g., magnesium chloride). The concentration of magnesium in the composition may be, e.g., about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, or about 7% or more by weight based on the total weight or volume of the composition.
- In some embodiments, an electrolyte or buffering agent may be added to the compositions of the present invention to affect the pH level. In some embodiments, the pH of the composition, e.g., with the addition of an electrolyte or buffering agent, is e.g., about 1.5, about 2.0, about 2.5, about 3.0, about 3.5, about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, about 7.0, about 7.5, about 8.0, or about 8.5.
- Sweeteners may be included in the compositions of the invention. Exemplary sweeteners include corn syrup (e.g., high fructose corn syrup or karo syrup), mannose, maltose, glucose polymers, sucrose (e.g., cane sugar or beet sugar), glucose, dextrose, lactose, galactose, fructose, polysaccharides (e.g., malodextrins), rice syrup, honey, and natural fruit juices (e.g., orange juice, papaya juice, pineapple juice, apple juice, grape juice, apricot juice, pear juice, tomato juice, agave nectar, or cranberry juice). Additionally, non- or low-caloric sweeteners can be used in the compositions of the invention. Examples of such non-caloric or low-caloric sweeteners include, but are not limited to, saccharin, sodium saccharin, cyclamates, acetosulfam, sorbitol, mannitol, sucralose, xylitol, erythritol, Stevia extract, L-aspartyl-L-phenyl-alanine ester (e.g., aspartame), L-aspartyl-D-alanine alkyl amides, L-aspartyl-L-1-hydroxymethylalkaneamide, and L-aspartyl-1-hydroxyethylalkaneamide. In some embodiments, sweeteners may be present in a composition of the invention at a concentration range of about 2% to about 20% by weight based on the total weight or volume of the composition (e.g., about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20%), though sweeteners may be present in lower or higher concentrations.
- Exemplary flavors and flavoring agents include almond oil, amaretto oil, anethole, anise oil, apple, benzaldehyde, blackberry, black walnut oil, blueberry, caraway, caraway oil, cardamom oil, cardamom seed, cherry juice, cherry syrup, chocolate, cinnamon, cinnamon oil, cinnamon water, citric acid, citric acid syrup, clove oil, cocoa, coriander oil, dextrose, eriodictyon, ethyl acetate, ethyl vanillin, fennel oil, ginger, glucose, glycerin, glycyrrhiza, grape, honey, lavender oil, lemon oil, lime, mannitol, methyl salicylate, mint (e.g., peppermint, spearmint), myristica oil, orange oil, orange peel, orange syrup, peppermint, peppermint oil, peppermint water, phenylethyl alcohol, pineapple, raspberry juice, raspberry syrup, rosemary oil, rose oil, rose water, sarsaparilla syrup, sorbitol, spearmint oil, strawberry, sucrose, thyme oil, tolu balsam, vanilla, vanillin, watermelon, and wild cherry syrup. Additional flavoring agents may be found in Food Chemicals Codex and Fenaroli's Handbook of Flavor Ingredients. Flavoring agents may be present in a composition of the invention at a concentration range of about 0.01% to about 20% by weight based on the total weight or volume of the composition (e.g., about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 7.5%, about 10%, about 12.5%, about 15%, about 17.5%, or about 20%), though flavoring agents may be present in lower or higher concentrations.
- Small amounts of a coloring agent may be utilized in the compositions of the present invention. Coloring agents include, e.g., beta-carotene, riboflavin dyes, FD&C dyes (e.g., Yellow No. 5, Blue No. 1, Blue No. 2, and Red No. 40), FD&C lakes, chlorophylls and chlorophyllins, caramel coloring, annatto, cochineal, turmeric, saffron, paprika, and fruit, vegetable, and/or plant extracts (e.g., grape, black currant, aronia, carrot, beetroot, red cabbage, elderberry, and hibiscus extracts). The amount of coloring agent used will vary depending on the agents used in the composition and the color intensity desired in the finished product. Coloring agents may be present in a composition of the invention at a concentration range of about 0.01% to about 20% by weight based on the total weight or volume of the composition (e.g., about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 7.5%, about 10%, about 12.5%, about 15%, about 17.5%, or about 20%), though coloring agents may be present in lower or higher concentrations.
- Non-limiting examples of vitamins and minerals that may be included in the compositions of the present invention include, e.g., choline bitartate, niacinamide, thiamin, folic acid, d-calcium pantothenate, biotin, vitamin A, vitamin C, vitamin Bi hydrochloride, vitamin B2, vitamin B3, vitamin B6 hydrochloride, vitamin B12, vitamin D, vitamin E acetate, vitamin K, and salts of calcium, potassium, magnesium, zinc, iodine, iron, and copper. In some embodiments, vitamins and minerals may be present in a composition of the invention at a concentration range of about 0.01% to about 50% by weight based on the total weight or volume of the composition (e.g., about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 7.5%, about 10%, about 12.5%, about 15%, about 17.5%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50%), though vitamins and minerals may be present in lower or higher concentrations. In some embodiments, when included in a composition of the invention, the composition may contain at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50% of the U.S. recommended daily intake (RDI) for such vitamins and minerals.
- A preservative may additionally be utilized in the compositions described herein. Exemplary preservatives include, for example, sorbate, polysorbate (e.g.,
polysorbate 20, polysorbate 40, polysorbate 80), a paraben (e.g., methylparaben sodium, propylparaben sodium), benzoate, and polyphosphate preservatives (e.g., sorbic acid, benzoic acid, calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, and mixtures thereof). In some embodiments, the preservative may be present in a composition of the invention at a concentration range of about 0.0005% to about 0.5% (e.g., about 0.0005%, about 0.001%, about 0.005%, about 0.01%, about 0.05%, about 0.1%, or about 0.5%) by weight based on the total weight or volume of the composition, though preservatives may be present in lower or higher concentrations. - In some embodiments, a preservative may be added to the compositions of the present invention to affect the pH. In some embodiments, the pH of the composition, e.g., with the addition of a preservative, is e.g., about 1.5, about 2.0, about 2.5, about 3.0, about 3.5, about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, about 7.0, about 7.5, about 8.0, or about 8.5. In some embodiments, the pH of the composition, e.g., with the addition of a preservative, is within the range of about 1.5 to about 7.5, about 1.75 to about 7.0, about 2.0 to about 6.5, about 2.1 to about 6.0, about 2.2 to about 5.5, about 2.3 to about 5.0, about 2.4 to about 4.5, about 2.5 to about 4.0, about 2.6 to about 3.5. In some embodiments, the pH of the composition, e.g., with the addition of a preservative, is within the range of about 1.5 to about 4.0.
- An antioxidant agent may also be included in the compositions to, for example, reduce exercise-induced oxidative stress. Exemplary antioxidants include vitamin C and vitamin E; beta-carotene, lutein, or other carotenoids; cyanidin, delphinidin, malvidin, or other anthocyanidins; apigenin, luteolin, or other flavones; hesperitin, naringenin, or other flavonones; isorhamnetin, quercetin, kaempferol or other flavonols; butylated hydroxyanisole and butylated hydroxytoluene; and epigallocatechin-3-gallate, epicatechin, thearubigins, or other flavan-3-ols. In some embodiments, an antioxidant may be present in a composition of the invention at a concentration range of about 0.0005% to about 0.5% (e.g., about 0.0005%, about 0.001%, about 0.005%, about 0.01%, about 0.05%, about 0.1%, or about 0.5%) by weight based on the total weight or volume of the composition, though antioxidants may be present in lower or higher concentrations.
- A dissolving agent or solvent may also be included in the compositions to, for example, improve the suspension or emulsification of particular components. In addition, certain dissolving agents or solvents may have a preservative function. Exemplary dissolving agents or solvents include acetic acid, acetone, butanol, dimethyl sulfoxide, ethanol, ethyl acetate, isopropanol, methanol, petroleum ether and the like. In some embodiments, a dissolving agent or solvent may be present in a composition of the invention at a concentration range of about 0.0005% to about 0.5% (e.g., about 0.0005%, about 0.001%, about 0.005%, about 0.01%, about 0.05%, about 0.1%, or about 0.5%) by weight based on the total weight or volume of the composition, though dissolving agents or solvents may be present in lower or higher concentrations.
- Additional components of the compositions described herein may include amino acids (e.g., leucine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine), stimulants (e.g., caffeine), emulsifying agents, carbon dioxide (e.g., to carbonate a liquid composition), stabilizers, humectants, anticaking agents, or herbal extracts. These components may be included at levels from about 0.0005% to about 25% (e.g., about 0.0005%, about 0.001%, about 0.005%, about 0.01%, about 0.05%, about 0.1%, about 0.5%, about 1%, about 5%, about 10%, about 15%, about 20%, or about 25%) by weight based on the total volume of the composition, though an additional component may be present in lower or higher concentrations.
- In certain embodiments, an additional therapeutic agent may be administered with compositions of the present invention, e.g., to improve or preserve exercise performance or exercise recovery. When combination therapy is employed, the additional therapeutic agent can be administered as a separate formulation or may be combined with any of the compositions described herein. For example, an additional therapeutic agent may be administered to improve or preserve exercise performance, prevent or treat muscle cramps, muscle soreness, or pain, or enhance mood. Such therapeutic agents include, for example, muscle relaxants (e.g., diazepam), anti-inflammatory agents (e.g., ibuprofen), steroids, hormones, diuretics, nutritional supplements (e.g., creatine), vitamins, stimulants (e.g., caffeine, amphetamines), and anti-depressants.
- The compositions and solutions of the present invention may be formulated as ready-to-drink beverages, concentrates (e.g., syrups), dry compositions (e.g., powders, granules, or tablets that may be reconstituted with a liquid (e.g., with water), gels, solids, semi-solids (e.g., ice cream, pudding, or yogurt), frozen liquids (e.g., ice pops), lozenges or hard candies, dissolving strips (e.g., an edible strip containing pullulan and compositions of the invention), and chewing gum.
- In some embodiments, the compositions may be in the form of a dry powder, granule, or tablet that may be reconstituted in a specified amount of a liquid. The dried components may be mixed together and milled (e.g., to create a homogenous powder) or mixed in aqueous solution and dried by using methods known to one of skill in the art. Dried powders or granules may be “loose” or fashioned into tablets.
- The compositions described herein can be ingested, for example, by a subject before, during, or after exercise. In addition, the compositions and solutions described herein can be ingested (e.g., through eating or drinking) before the onset of muscle cramping, when muscle cramping begins, any time after the onset of muscle cramping, or after muscle cramping has subsided. The compositions of the solution can also be ingested after exercise to accelerate nerve-muscle recovery from exercise fatigue, or to reduce inflammation. When the compositions and solutions of the present invention are in the form of a ready-to-drink beverage, e.g., 1, 2, 4, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30, or 32 ounces of the beverage may be consumed as needed (e.g., once, twice, three, four, five, six times per day; once per week; or once per month).
- The compositions and solutions of the present invention may be prepared using methods known to one of skill in the art. Such methods include dissolving, dispersing, or otherwise mixing all components singularly or in suitable combinations and agitating with, for example, a mechanical stirrer until all of the ingredients have been solubilized or adequately dispersed. Where a shelf-stable composition or solution is desired, the final mixture can be pasteurized, ultra-pasteurized, sterilized, or filled aseptically at appropriate process conditions. Where required for mutual stability of two or more components (for example if a component is unstable at low pH), multiple components can be mixed shortly before ingestion.
- The compositions and solutions described herein may be bottled or packaged in, for example, glass bottles, plastic bottles and containers (e.g., polyethylene terephthalate or foil-lined ethylene vinyl alcohol), metal cans (e.g., coated aluminum or steel), lined cardboard containers, pouches, packs, wrappers, or any other packaging known to one of skill in the art. For example, a ready-to-drink beverage can be bottled or packaged in a unit that contains between 10-1000 mL of the beverage. For example, the packaging can contain 10, 20, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 mL of the beverage. Alternatively, the packaging can contain 200, 250, 330, 350, 355, 375, 440, or 500 mL of the beverage. A ready-to-drink beverage can also be bottled or packaged in a unit that contains between 1-32 fluid ounces of beverage (e.g., the unit may contain 1, 2, 5, 6.75, 8, 8.3, 8.4, 8.45, 9.6, 10, 12, 15, 15.5, 16, 18.6, 20, 23, 24, or 32 fluid ounces). Where a shelf-stable composition or solution is desired, the packaging is appropriately sterilized before being filled by the pasteurized, ultra-pasteurized, or sterilized composition or solution. Where required for mutual stability of two or more components (for example if a component is unstable at low pH), the packaging may feature multiple containers that can be mixed shortly before ingestion or that can be consumed serially.
- The compositions of the present invention are formulated into acceptable dosage forms by conventional methods known to those of skill in the art. Actual dosage levels of the active ingredients in the compositions of the present invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular subject, composition, and mode of administration, without being toxic to the subject. The selected dosage level will depend upon a variety of pharmacokinetic factors including the activity of the particular compositions of the present invention employed, the route of administration, the time of administration, the rate of absorption of the particular agent being employed, the duration of the treatment, other drugs, substances, and/or materials used in combination with the particular compositions employed, the age, sex, weight, condition, general health and prior medical history of the subject being treated, and like factors well known in the medical arts. A physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the composition required. For example, the physician or veterinarian can start doses of the substances of the invention employed in the composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. In general, a suitable daily dose of a composition of the invention will be that amount of the substance which is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above. Preferably, the effective daily dose of a therapeutic composition may be administered as one, two, three, four, five, six or more sub-doses administered separately at appropriate intervals throughout the day, optionally, in unit dosage forms.
- The frequency of treatment may also vary. The subject can be treated one or more times per day (e.g., once, twice, three, four or more times) or every so-many hours (e.g., about every 2, 4, 6, 8, 12, or 24 hours). The composition can be administered 1, 2, or 3 times per 24 hours. The time course of treatment may be of varying duration, e.g., for two, three, four, five, six, seven, eight, nine, ten, or more days, two weeks, 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, or more than one year. For example, the treatment can be twice a day for three days, twice a day for seven days, twice a day for ten days. Treatment cycles can be repeated at intervals, for example weekly, bimonthly or monthly, which are separated by periods in which no treatment is given. The treatment can be a single treatment or can last as long as the life span of the subject (e.g., many years).
- The compositions of the invention may be useful for improving or preserving exercise performance or recovery from exercise. Improving or preserving physical performance may comprise shortening the time to complete an exercise, e.g., a sprint or cycling exercise by the subject, increasing the maximal oxygen consumption (VO2 max) in the subject, decreasing the fatigue of the subject, e.g., as measured by the Fatigue Index, or improving the energy level, improving the mood, or reducing the exertion and pain (e.g., perceived exertion and pain) of a subject. In some embodiments, the aforementioned improvement or preservation targets are determined relative to a reference standard.
- In another aspect, the present invention features a method of improving recovery after exercise in a subject. Improving recovery may comprise reducing pain in a subject (e.g., reducing leg pain) or reducing inflammation in a subject.
- In another aspect, the present invention features a method of reducing inflammation in a subject. In some embodiments, the inflammation occurs as a result of exercise.
- In order to study the effects of exemplary compositions on exercise performance and recovery, a study involving intermittent high intensity exercise was carried out on 20 healthy, active, college-aged men and women administered a beverage described herein.
- The goals of this study include determining of the effects of an exemplary composition on intense exercise performance, as well as to identify possible mechanisms responsible for the effects of said composition on exercise performance. Performance improvement may be associated with improved energy level, mental energy, and mood, and reduced perceived exertion and pain, with little or no effects on cardiovascular and/or metabolic function.
- Twenty healthy, active, but untrained male and female subjects between the ages of 18 and 30 were recruited to participate in this study. Subjects were required to be in good general health with no recent musculoskeletal injuries, and absence of cardiovascular, respiratory, and metabolic disorders. Subjects were further required to maintain a normal state of hydration, e.g., by avoiding changes in caffeine consumption and dehydration-inducing substances (e.g., alcohol), maintain a normal diet, and avoid rigorous exercise 24 hours prior to the study. Subjects were screened using a health history questionnaire and signed an Informed Consent Form prior to participation. University of South Carolina Institutional Review Board approval was obtained prior initiation of the study for any cases requiring additional review.
- The study was a randomized and counterbalanced, double-blind, placebo-controlled, cross-over design in which participants took part in both experimental (STA) and placebo conditions (PLA). The experimental treatment (STA) contained a mixture of ginger, cinnamon, capsicum in 50 ml (1.7 ounce) of a lime-juice vehicle. The placebo (PLA) was a vehicle control with no TRP activating component (1.7 ounce). The drinks were given to the participants immediately prior to the start of the exercise protocol (i.e., the initial sprint performance test). A second drink was provided during the rest period after the IHE session, 5 min prior to the time trial.
- The following tests and analyses were carried out on each subject:
- Maximal Oxygen Consumption (VO2 max): This test was conducted on a bicycle ergometer to determine the overall aerobic fitness level of subject and to set the individual workloads (% VO2 max) for each subject during the controlled 45 min intermittent high intensity exercise session. The cycle test, which lasts between 8 to 15 minutes, progressively increased in difficulty during which inspired and expired air was analyzed for oxygen and carbon dioxide content. Subjects with a VO2 max value between 40 ml/kg/min and 55 ml/kg/min were qualified for this study.
Maximal Sprint Cycling Performance After a specified 5-min warm-up period, the overall exercise protocol began with a 30-s maximal sprint effort. Measurements was made from mean power output for 0-30 sec, peak power output (i.e., the maximum power output in Watts over a 5 s period), and mean power output for 0-10 s, 10-20 sec, and 20-30 s. The Fatigue Index, which is the rate of power decline during the test, was also calculated.
Intermittent High Intensity Exercise (IHE) Protocol: After the maximal sprint test (10 min), subjects completed a controlled IHE exercise session on a stationary bicycle ergometer (Monark) in a well-controlled laboratory setting (environmental chamber). The temperature and humidity was set at ambient conditions (i.e., 20° C. and 40% relative humidity). The controlled exercise protocol consisted of 45 min of repeated 5-minute bouts of 4-minute at −60% VO2 max followed by 1-minute at −125% VO2 max (sprints).
Cycling Time Trial (IT): After a 15-min rest period following completion of the IHE, subjects completed an approximately 10-minute time trial (e.g., race to the finish line) to complete a prescribed amount of work (i.e., distance) as fast as possible. - The following experimental measurements were taken for each subject prior to, during, and/or after each exercise protocol.
- Body Weight: Nude body weight was measured using a precisely calibrated weighing scale before and after completion of each exercise trial to estimate of overall dehydration level.
Body Composition: The 7-site skinfolds technique was used to assess percent body fat and lean body mass during the preliminary session.
Heart Rate and Blood Pressure: In order to ensure subjects remain at safe limits and determine any benefits from the cooling towel, heart rate was continuously monitored using a heart rate monitor, and blood pressure was assessed at 10-minute intervals using an aneroid sphygmomanometer.
Body Core Temperature: Body core temperature (Tc) was recorded continuously throughout the exercise trial using rectal temperature (model 4600, YSI Precision Temperature Group, Dayton, Ohio). Subjects were not allowed to exceed a Tc>40° C./104° F. Rectal temperature is accepted as a valid and reliable measure of Tc.
Ratings of Perceived Exertion: Perceived exertion ratings were assessed using a 20-point Borg scale at a 10-minute interval throughout the exercise session.
Leg Muscle Pain: Leg-muscle pain intensity was measured immediately after each of the initial sprint performance test, at the end of the 1 min sprints during IHE, and immediately after TT using a validated 10- point scale.
Mood State: The Profile of Mood State (POMS) questionnaire was used to assess the mood states prior to taking the supplement and immediately before IHE and TT. The self-report scales are a collection of tools that allow for the quick assessment of transient, fluctuating feelings, and enduring affect states. Exemplary scale scores include: Anger-Hostility, Confusion-Bewilderment, Depression-Dejection, Fatigue-Inertia, Tension-Anxiety, and Vigor-Activity. Each was determined separately and a Total Mood Disturbance score was assigned, which is a function of these six scale scores.
Blood collection: An intravenous catheter was inserted into a forearm vein prior to testing. Then 5-min prior to experimental testing, 10 ml of blood was collected via the catheter and then again at 15-minute intervals through the exercise session. Blood samples were analyzed for markers of metabolic function (e.g., glucose, lactate), muscle damage (e.g., creatine kinase) and inflammation (e.g., inflammatory cytokines IL-6, IL-10, IL-lra protein and leukocyte gene expression). - Information Session: Before starting the protocol, subjects attended a meeting with the study coordinator to complete informed consent and health history questionnaire.
Preliminary Session: Both preliminary and experimental sessions were held in the laboratory of Public Health Research Center located at the University of South Carolina. Subjects first attended the preliminary session for height, weight and body composition assessment followed by a maximal VO2 test on a stationary cycle ergometer. For the second preliminary session, 60% and 125% VO2 max workloads were set and validated on the bicycle ergometer, and participants became familiarized with the exercise protocol and experimental procedures.
Experimental Sessions I Data Collection: Qualified subjects were then randomized and counterbalanced to either experimental (STA) or control (PLA) treatments for the 1st trial. The 2nd trial (opposite treatment) was done within 5-7 days after the first trial. - Prior to the testing day, subjects were instructed to maintain normal exercise habits and refrain from vigorous exercise 24 hours prior to the session. They were also asked to abstain from consumption of any caffeinated beverage and dehydration-inducing substances such as alcohol 12 hours prior to the trial and to fully hydrate themselves (16 oz water) 1-2 hr before reporting to the lab the day of the trial Immediately prior to the start of exercise trial, the STA or PLA drink (1.7 oz) was given to the subjects. They were asked to consume the drink within 2 min, first swishing the solution around their mouth and then swallowing. Subjects were provided water to consume every 15 min (3.5 ml/kg body weight) during IHE to maintain adequate hydration.
- Data Analysis: Statistical analysis was performed with SPSS for Windows (SPSS, Chicago, Ill.). A two-way repeated measures ANOVA was used to determine the significance of differences between means by condition, time and their interaction. A two-tailed alpha level of 0.05 was used for all significance tests.
- Consistent beneficial trends were observed for subjects that received the experimental drink (STA) across several tested variables. For example, subjects that drank STA exhibited greater mean power (p=0.09), total power (p=0.09), and 5 s interval power (p=0.09) during the 30 s maximal sprint test. In addition, 14 of 19 subjects (p=0.20) demonstrated a greater time trial distance, and overall, the subjects that consumed STA had lower ratings of leg muscle pain sensation during the course of the experimental sessions (treatment x time effect, p=0.17). In addition, subjects receiving STA had improved mood over the course of the test (p=0.20).
- These results support a central finding that exemplary compositions (e.g., STA and others described herein) may work through stimulation of the CNS, as no differences were seen between STA and PLA on markers of cardiovascular, metabolic, and inflammatory function. In addition, these results suggest that subjects consuming the exemplary compositions described herein (e.g., STA) comprising TRPV1 and TRPA1 agonists may improve performance during exercise (e.g., intermittent, high-intensity exercise) with no apparent adverse side effects.
- The disclosures of each and every patent, patent application, and publication cited herein are hereby incorporated herein by reference in their entirety. While this disclosure has been described with reference to specific aspects, it is apparent that other aspects and variations may be devised by others skilled in the art without departing from the true spirit and scope of the disclosure. The appended claims are intended to be construed to include all such aspects and equivalent variations. Any patent, publication, or other disclosure material, in whole or in part, that is said to be incorporated by reference herein is incorporated herein only to the extent that the incorporated material does not conflict with existing definitions, statements, or other disclosure material set forth in this disclosure. As such, and to the extent necessary, the disclosure as explicitly set forth herein supersedes any conflicting material incorporated herein by reference.
- While this disclosure has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the disclosure encompassed by the appended claims.
Claims (8)
1. A method of improving or preserving physical performance during exercise in a subject, wherein the method comprises orally administering to the subject a composition comprising capsicum, ginger, cinnamon and an excipient, wherein improving or preserving physical performance during exercise in a subject is a decrease in the fatigue of the subject.
2.-20. (Canceled)
21. The method of claim 1 , wherein:
(a) the amount of capsicum in the composition is in the range of 0.001% (w/w) to 1% (w/w); or
(b) the amount of ginger in the composition is in the range of 0.001% (w/w) to 1% (w/w); or
(c) the amount of cinnamon in the composition is in the range of 0.001% (w/w) to 1% (w/w).
22. The method of claim 1 , wherein the excipient is selected from the group consisting of an antioxidant, a binder, a coloring agent, a disintegrant, an emulsifier, a flavoring agent, a lubricant, a pH-adjusting agent, a preservative, a surfactant, a sweetener, and viscosity modifier.
23. The method of claim 1 , wherein the method further comprises administering to the subject an amount of composition in the range of 10 mL to 1000 mL.
24. The method of claim 1 , wherein the composition is administered to the subject prior to commencement of exercise.
25. The method of claim 1 , wherein the composition is a beverage.
26. The method of claim 1 , wherein improving or preserving physical performance during exercise in a subject is a decrease in the fatigue of the subject as measured by the Fatigue Index.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US17/577,505 US20220401387A1 (en) | 2017-01-23 | 2022-01-18 | Compositions and methods affecting exercise performance |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762449411P | 2017-01-23 | 2017-01-23 | |
PCT/US2018/014872 WO2018136943A1 (en) | 2017-01-23 | 2018-01-23 | Compositions and methods affecting exercise performance |
US201916479748A | 2019-07-22 | 2019-07-22 | |
US17/577,505 US20220401387A1 (en) | 2017-01-23 | 2022-01-18 | Compositions and methods affecting exercise performance |
Related Parent Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US16/479,748 Continuation US11253493B2 (en) | 2017-01-23 | 2018-01-23 | Compositions and methods affecting exercise performance |
PCT/US2018/014872 Continuation WO2018136943A1 (en) | 2017-01-23 | 2018-01-23 | Compositions and methods affecting exercise performance |
Publications (1)
Publication Number | Publication Date |
---|---|
US20220401387A1 true US20220401387A1 (en) | 2022-12-22 |
Family
ID=62909020
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US16/479,748 Active US11253493B2 (en) | 2017-01-23 | 2018-01-23 | Compositions and methods affecting exercise performance |
US17/577,505 Abandoned US20220401387A1 (en) | 2017-01-23 | 2022-01-18 | Compositions and methods affecting exercise performance |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US16/479,748 Active US11253493B2 (en) | 2017-01-23 | 2018-01-23 | Compositions and methods affecting exercise performance |
Country Status (3)
Country | Link |
---|---|
US (2) | US11253493B2 (en) |
EP (1) | EP3570861A4 (en) |
WO (1) | WO2018136943A1 (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3570861A4 (en) | 2017-01-23 | 2020-11-18 | Flex Pharma, Inc. | Compositions and methods affecting exercise performance |
Family Cites Families (56)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4313958A (en) | 1980-10-24 | 1982-02-02 | The Procter & Gamble Company | Method of producing analgesia |
US4424205A (en) | 1982-03-18 | 1984-01-03 | The Procter & Gamble Company | Hydroxyphenylacetamides having analgesic and anti-irritant activity |
US4493848A (en) | 1983-07-14 | 1985-01-15 | The Procter & Gamble Company | Compositions and methods useful for producing analgesia |
US4564633A (en) | 1983-07-14 | 1986-01-14 | The Procter & Gamble Company | Compositions and methods useful for producing analgesia |
US4544669A (en) | 1983-07-14 | 1985-10-01 | The Procter & Gamble Company | Compounds and compositions useful for producing analgesia |
US4544668A (en) | 1983-07-14 | 1985-10-01 | The Procter & Gamble Company | Compounds and compositions useful for producing analgesia |
US4532139A (en) | 1983-07-14 | 1985-07-30 | The Procter & Gamble Company | Compounds and compositions useful for producing analgesia |
US4681897A (en) | 1984-01-16 | 1987-07-21 | The Procter & Gamble Company | Pharmaceutical products providing enhanced analgesia |
US4599342A (en) | 1984-01-16 | 1986-07-08 | The Procter & Gamble Company | Pharmaceutical products providing enhanced analgesia |
US4939149A (en) | 1988-10-24 | 1990-07-03 | The United States Of America As Represented By The Department Of Health And Human Services | Resiniferatoxin and analogues thereof to cause sensory afferent C-fiber and thermoregulatory desensitization |
US5403868A (en) | 1988-12-23 | 1995-04-04 | Sandoz Ltd. | Capsaicin derivatives |
US5221692A (en) | 1991-08-22 | 1993-06-22 | National Science Council | Ether linked and relatively nonpungent analogues of N-nonanoyl vanillylamide |
US7404967B2 (en) | 1994-12-21 | 2008-07-29 | Cosmederm, Inc. | Topical product formulations containing strontium for reducing skin irritation |
US5762963A (en) | 1995-06-07 | 1998-06-09 | Emory University | Method and compositions for controlling oral and pharyngeal pain using capsaicinoids |
JPH09176002A (en) | 1995-12-27 | 1997-07-08 | Kureha Chem Ind Co Ltd | Gingerol-containing agent for suppressing synthesis of protein of hsp27 family |
ES2179473T5 (en) | 1997-03-13 | 2006-03-01 | James N. Campbell | COMPOSITIONS CONTAINING CAPSAICINE OR CAPSAICINE ANALOGS AND A LOCAL ANESTHETIC. |
JP4043605B2 (en) | 1998-07-02 | 2008-02-06 | 丸善製薬株式会社 | Method for producing capsaicin analogs |
AU1648600A (en) | 1998-12-04 | 2000-06-26 | Neurosearch A/S | Use of isatin derivatives as ion channel activating agents |
CN1210254C (en) | 1999-02-22 | 2005-07-13 | 株式会社太平洋 | Vanilloid analogues containing resiniferatoxin pharmacophores as potent vannilloid receptor agonists and analgesics, compositions and uses thereof |
US6534086B1 (en) | 2000-03-06 | 2003-03-18 | Metagenics, Inc. | Composition and method for treatment of inflammation and pain in mammals |
US6274177B1 (en) | 2000-08-26 | 2001-08-14 | National Science Council | Method of preparing an extract potent in anti-inflammation and anti-platelet aggregation from Zingiber officinale and pharmaceutical compositions containing said extract |
US6592896B2 (en) | 2001-08-06 | 2003-07-15 | The Quigley Corporation | Medicinal composition and method of using it |
US20030104085A1 (en) | 2001-12-05 | 2003-06-05 | Yeomans David C. | Methods and compositions for treating back pain |
US20030180226A1 (en) | 2002-01-23 | 2003-09-25 | Haughton Pauline A. | Anti-bacterial sneeze spray |
EP1615880A4 (en) | 2003-04-08 | 2007-03-07 | Algorx Pharmaceuticals Inc | Preparation and purification of synthetic trans capsaicin |
TW200509882A (en) | 2003-08-29 | 2005-03-16 | Kanebo Cosmetics Inc | Beauty method |
NO20034069L (en) | 2003-09-12 | 2005-03-14 | Aximed As | Preparation and use of capsaicin derivatives |
ITMI20041566A1 (en) | 2004-07-30 | 2004-10-30 | Indena Spa | "TRPV1 AGONISTS, FORMULATIONS THAT CONTAIN THEM AND THEIR USES" |
US8097271B2 (en) | 2004-08-11 | 2012-01-17 | Kraft Foods Global Brands Llc | Warming compositions and delivery systems therefor |
DE102004047087A1 (en) | 2004-09-29 | 2006-03-30 | Robert Bosch Gmbh | Method for object verifaction in radar systems for motor vehicles |
FR2880625B1 (en) | 2005-01-07 | 2007-03-09 | Sanofi Aventis Sa | N- (HETEROARYL) -1H-INDOLE-2-CARBOXAMIDE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC USE |
KR20080007378A (en) | 2005-04-25 | 2008-01-18 | 노이로제스엑스, 인코포레이티드 | Trpv1 agonist compounds and methods for making and using the same |
WO2007044748A2 (en) | 2005-10-11 | 2007-04-19 | University Of Pittsburgh | Sphingomyelin liposomes for the treatment of hyperactive bladder disorders |
WO2007056176A2 (en) | 2005-11-03 | 2007-05-18 | Southwest Immunology, Inc. | Compositions for preventing and reducing delayed onset muscle soreness |
GB2436063A (en) | 2006-03-16 | 2007-09-19 | Nicholas John Larkins | Pharmaceutical composition for the treatment of excess mucous production |
CN101040720A (en) | 2006-03-24 | 2007-09-26 | 沈华立 | Spiced salted soup of torfu |
US20080021034A1 (en) | 2006-04-10 | 2008-01-24 | Painceptor Pharma Corporation | Compositions and methods for modulating gated ion channels |
US7674594B2 (en) | 2006-07-27 | 2010-03-09 | Redpoint Bio Corporation | Screening assay for inhibitors of TRPA1 activation by a lower alkyl phenol |
US8227603B2 (en) | 2006-08-01 | 2012-07-24 | Cytokinetics, Inc. | Modulating skeletal muscle |
ES2402789T3 (en) | 2006-11-20 | 2013-05-08 | President And Fellows Of Harvard College | Methods, compositions and kits to treat pain and pruritus |
ES2535730T3 (en) | 2007-12-05 | 2015-05-14 | Janssen Pharmaceutica, N.V. | TRPA1 agonists of dibenzoazepines and dibenzooxazepines |
KR100951656B1 (en) | 2008-02-25 | 2010-04-07 | 고려대학교 산학협력단 | Activator for transient receptor potential vanilloid 2 comprising probenecids |
EP2271329A4 (en) | 2008-03-11 | 2013-01-09 | Harvard College | Methods, compositions, and kits for treating pain and pruritis |
WO2009137686A1 (en) | 2008-05-08 | 2009-11-12 | University Of Utah Research Foundation | Sensory receptors for chronic fatigue and pain and uses thereof |
US20090304827A1 (en) | 2008-05-08 | 2009-12-10 | Kim Darrick S H L | Combinations of Ingredients Having Synergistic Anti-Inflammatory Effects |
CN102215857B (en) | 2008-11-19 | 2015-06-17 | 庆熙大学校产学协力团 | Pharmaceutical composition containing ginger extract or shogaol |
US20110305779A1 (en) * | 2010-06-10 | 2011-12-15 | Cowan Fred M | Phytochemical combinations that regulate pathological immunity |
EP3295794A1 (en) | 2010-07-27 | 2018-03-21 | Flex Pharma, Inc. | Methods and compositions for preventing and relieving muscle cramps and for recovery from neuromuscular irritability and fatigue following exercise |
US8840938B2 (en) | 2011-04-13 | 2014-09-23 | W. Matthew Warnock | Bioavailability enhancing composition |
US9211274B2 (en) | 2012-02-01 | 2015-12-15 | Warsaw Orthopedic, Inc. | TRPV1 compounds in a biodegradable polymer carrier |
WO2013155365A1 (en) | 2012-04-12 | 2013-10-17 | University Of Maryland | Markers for diagnosing amyotrophic lateral sclerosis |
BR112015017176A2 (en) | 2013-01-18 | 2017-07-11 | Tonix Pharmaceuticals Inc | isometeptide isomer |
WO2015160842A1 (en) | 2014-04-14 | 2015-10-22 | Flex Pharma, Inc. | Methods and formulatiions of capsaicinoids and capsinoids |
CA2945795A1 (en) | 2014-04-14 | 2015-10-22 | Flex Pharma, Inc. | Ion channel activators and methods of use |
MX2018004274A (en) | 2015-10-06 | 2018-06-22 | Flex Pharma Inc | Methods and compositions for unwanted or abnormal muscle contractions. |
EP3570861A4 (en) | 2017-01-23 | 2020-11-18 | Flex Pharma, Inc. | Compositions and methods affecting exercise performance |
-
2018
- 2018-01-23 EP EP18742227.4A patent/EP3570861A4/en not_active Withdrawn
- 2018-01-23 WO PCT/US2018/014872 patent/WO2018136943A1/en active Application Filing
- 2018-01-23 US US16/479,748 patent/US11253493B2/en active Active
-
2022
- 2022-01-18 US US17/577,505 patent/US20220401387A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
WO2018136943A9 (en) | 2019-10-10 |
EP3570861A4 (en) | 2020-11-18 |
US20200261382A1 (en) | 2020-08-20 |
WO2018136943A1 (en) | 2018-07-26 |
EP3570861A1 (en) | 2019-11-27 |
US11253493B2 (en) | 2022-02-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20220387539A1 (en) | Methods of treating muscle cramping and related compositions | |
JP3907964B2 (en) | Mental fatigue reducing composition, concentration maintenance enhancing composition and mental vitality maintenance enhancing composition | |
SG185133A1 (en) | Compositions and methods for enhancing physiological performance and recovery time | |
JP2004520065A (en) | Hypoglycemic reaction composition | |
O’Connor et al. | Grape consumption’s effects on fitness, muscle injury, mood, and perceived health | |
JP2021528420A (en) | Compositions for treatment and health containing bitter amino acids | |
KR20180029963A (en) | Amino acid supplement | |
KR20060022668A (en) | Compositions and foods and drinks contiaing higher fatty acid derivative | |
US20220401387A1 (en) | Compositions and methods affecting exercise performance | |
CN106659430A (en) | Method for monitoring swallowing | |
EP1402788B1 (en) | Body temperature-raising agent of amino acids for eating or drinking and for medical use | |
EP3422938B1 (en) | Personalized food for dysphagia management | |
JPWO2020130146A1 (en) | Muscle quality improver | |
CN105792819A (en) | Methods and compositions for increasing energy expenditure using cinnamaldehyde | |
Lan et al. | Citrus reticulata peel improves patient tolerance of low-volume polyethylene glycol for colonoscopy preparation | |
EP0206240A2 (en) | Solid pharmaceutical composition for oral use | |
US10307435B2 (en) | Exercise performance enhancers | |
JP2008127371A (en) | Stable internal liquid medicine composition | |
US11304967B2 (en) | Compounds and compositions for improving power output and oxygen efficiency | |
Kumbharkar et al. | FORMULATION AND EVALUATION OF ANTIULCER SYRUP | |
Junior et al. | Effect of microencapsulated cocoa intake on muscle recovery, inflammation, and oxidative stress after exercise-induced muscle damage | |
Trexler | PERFORMANCE EFFECTS OF CITRULLINE MALATE AND BEETROOT JUICE SUPPLEMENTATION | |
GB2479748A (en) | Carnitine containing nutritional composition | |
JP2022505270A (en) | Oral galactose composition and its use | |
Caravalho et al. | Grape Consumption's Effects on Fitness, Muscle Injury, Mood, and Perceived Health. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STPP | Information on status: patent application and granting procedure in general |
Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NON FINAL ACTION MAILED |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |