TWI504392B - A medical composition or food and drink for hyperthyroidism - Google Patents
A medical composition or food and drink for hyperthyroidism Download PDFInfo
- Publication number
- TWI504392B TWI504392B TW097111617A TW97111617A TWI504392B TW I504392 B TWI504392 B TW I504392B TW 097111617 A TW097111617 A TW 097111617A TW 97111617 A TW97111617 A TW 97111617A TW I504392 B TWI504392 B TW I504392B
- Authority
- TW
- Taiwan
- Prior art keywords
- lactic acid
- compound
- phenyl lactic
- activity
- formula
- Prior art date
Links
- 235000013305 food Nutrition 0.000 title claims description 48
- 206010020850 Hyperthyroidism Diseases 0.000 title claims description 7
- 239000000203 mixture Substances 0.000 title description 26
- VOXXWSYKYCBWHO-QMMMGPOBSA-N (S)-3-phenyllactic acid Chemical compound OC(=O)[C@@H](O)CC1=CC=CC=C1 VOXXWSYKYCBWHO-QMMMGPOBSA-N 0.000 claims description 83
- 244000005700 microbiome Species 0.000 claims description 44
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 42
- 239000008194 pharmaceutical composition Substances 0.000 claims description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 34
- 201000010099 disease Diseases 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 25
- 238000004519 manufacturing process Methods 0.000 claims description 24
- 230000001734 parasympathetic effect Effects 0.000 claims description 22
- 239000004310 lactic acid Substances 0.000 claims description 21
- 235000014655 lactic acid Nutrition 0.000 claims description 21
- 241000894006 Bacteria Species 0.000 claims description 19
- 239000012228 culture supernatant Substances 0.000 claims description 18
- 239000000047 product Substances 0.000 claims description 18
- 206010020772 Hypertension Diseases 0.000 claims description 13
- 230000036737 immune function Effects 0.000 claims description 9
- 239000000654 additive Substances 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 241000186660 Lactobacillus Species 0.000 claims description 7
- 230000000996 additive effect Effects 0.000 claims description 5
- 241000186000 Bifidobacterium Species 0.000 claims description 4
- 240000001929 Lactobacillus brevis Species 0.000 claims description 4
- 235000013957 Lactobacillus brevis Nutrition 0.000 claims description 4
- 241000194036 Lactococcus Species 0.000 claims description 4
- 241000202221 Weissella Species 0.000 claims description 4
- 206010013781 dry mouth Diseases 0.000 claims description 4
- 241000201860 Abiotrophia Species 0.000 claims description 3
- 241000422409 Alkalibacterium Species 0.000 claims description 3
- 241000193818 Atopobium Species 0.000 claims description 3
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 3
- 206010013774 Dry eye Diseases 0.000 claims description 3
- 241000194033 Enterococcus Species 0.000 claims description 3
- 241000235796 Granulicatella Species 0.000 claims description 3
- 241001584954 Lactobacillus brevis ATCC 14869 = DSM 20054 Species 0.000 claims description 3
- 241000192132 Leuconostoc Species 0.000 claims description 3
- 241001468189 Melissococcus Species 0.000 claims description 3
- 241000202223 Oenococcus Species 0.000 claims description 3
- 241000927544 Olsenella Species 0.000 claims description 3
- 241000192001 Pediococcus Species 0.000 claims description 3
- 241000500334 Tetragenococcus Species 0.000 claims description 3
- 241001635318 Trichococcus Species 0.000 claims description 3
- 241000207194 Vagococcus Species 0.000 claims description 3
- 229940039696 lactobacillus Drugs 0.000 claims description 3
- 230000003340 mental effect Effects 0.000 claims description 3
- 241000206594 Carnobacterium Species 0.000 claims description 2
- 241000219823 Medicago Species 0.000 claims 1
- 235000017587 Medicago sativa ssp. sativa Nutrition 0.000 claims 1
- 229910052797 bismuth Inorganic materials 0.000 claims 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 claims 1
- 201000001421 hyperglycemia Diseases 0.000 claims 1
- 230000000694 effects Effects 0.000 description 78
- NWCHELUCVWSRRS-SECBINFHSA-N (2r)-2-hydroxy-2-phenylpropanoic acid Chemical compound OC(=O)[C@@](O)(C)C1=CC=CC=C1 NWCHELUCVWSRRS-SECBINFHSA-N 0.000 description 59
- 230000002889 sympathetic effect Effects 0.000 description 53
- 206010029216 Nervousness Diseases 0.000 description 29
- 239000000126 substance Substances 0.000 description 29
- 230000002567 autonomic effect Effects 0.000 description 28
- 230000008035 nerve activity Effects 0.000 description 27
- 238000000034 method Methods 0.000 description 25
- 241000700159 Rattus Species 0.000 description 18
- 230000036772 blood pressure Effects 0.000 description 18
- 230000028327 secretion Effects 0.000 description 17
- 210000000467 autonomic pathway Anatomy 0.000 description 16
- 239000002609 medium Substances 0.000 description 14
- 210000005037 parasympathetic nerve Anatomy 0.000 description 14
- 208000024891 symptom Diseases 0.000 description 13
- 230000002496 gastric effect Effects 0.000 description 12
- 210000001186 vagus nerve Anatomy 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 230000033228 biological regulation Effects 0.000 description 10
- 230000001105 regulatory effect Effects 0.000 description 10
- 206010020751 Hypersensitivity Diseases 0.000 description 9
- 208000008035 Back Pain Diseases 0.000 description 8
- 208000008930 Low Back Pain Diseases 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 8
- 201000011510 cancer Diseases 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 210000003296 saliva Anatomy 0.000 description 8
- 240000006024 Lactobacillus plantarum Species 0.000 description 7
- 235000013965 Lactobacillus plantarum Nutrition 0.000 description 7
- 206010037888 Rash pustular Diseases 0.000 description 7
- 208000007107 Stomach Ulcer Diseases 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 210000003403 autonomic nervous system Anatomy 0.000 description 7
- 230000001684 chronic effect Effects 0.000 description 7
- 229940072205 lactobacillus plantarum Drugs 0.000 description 7
- 210000005036 nerve Anatomy 0.000 description 7
- 208000029561 pustule Diseases 0.000 description 7
- 208000006820 Arthralgia Diseases 0.000 description 6
- 206010009900 Colitis ulcerative Diseases 0.000 description 6
- 206010028391 Musculoskeletal Pain Diseases 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 208000007613 Shoulder Pain Diseases 0.000 description 6
- 201000006704 Ulcerative Colitis Diseases 0.000 description 6
- 210000001198 duodenum Anatomy 0.000 description 6
- 201000005917 gastric ulcer Diseases 0.000 description 6
- 208000024765 knee pain Diseases 0.000 description 6
- 210000004698 lymphocyte Anatomy 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- 239000000825 pharmaceutical preparation Substances 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 208000026935 allergic disease Diseases 0.000 description 5
- 230000007815 allergy Effects 0.000 description 5
- 235000013361 beverage Nutrition 0.000 description 5
- 230000004531 blood pressure lowering effect Effects 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 229940127557 pharmaceutical product Drugs 0.000 description 5
- 230000004215 skin function Effects 0.000 description 5
- -1 sucrose fatty acid esters Chemical class 0.000 description 5
- VOXXWSYKYCBWHO-UHFFFAOYSA-M 3-phenyllactate Chemical compound [O-]C(=O)C(O)CC1=CC=CC=C1 VOXXWSYKYCBWHO-UHFFFAOYSA-M 0.000 description 4
- VOXXWSYKYCBWHO-UHFFFAOYSA-N 3-phenyllactic acid Chemical compound OC(=O)C(O)CC1=CC=CC=C1 VOXXWSYKYCBWHO-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 230000009471 action Effects 0.000 description 4
- 208000030961 allergic reaction Diseases 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 208000013403 hyperactivity Diseases 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 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 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 206010033557 Palpitations Diseases 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 235000013334 alcoholic beverage Nutrition 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000012790 confirmation Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 208000002173 dizziness Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 206010016256 fatigue Diseases 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 210000003128 head Anatomy 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 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
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010003840 Autonomic nervous system imbalance Diseases 0.000 description 2
- 244000063299 Bacillus subtilis Species 0.000 description 2
- 235000014469 Bacillus subtilis Nutrition 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 208000008454 Hyperhidrosis Diseases 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- 208000001431 Psychomotor Agitation Diseases 0.000 description 2
- 206010038743 Restlessness Diseases 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 241000194017 Streptococcus Species 0.000 description 2
- 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 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 230000000843 anti-fungal effect Effects 0.000 description 2
- 238000000222 aromatherapy Methods 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- NWCHELUCVWSRRS-UHFFFAOYSA-N atrolactic acid Chemical compound OC(=O)C(O)(C)C1=CC=CC=C1 NWCHELUCVWSRRS-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 230000036760 body temperature Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 235000013353 coffee beverage Nutrition 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 235000015243 ice cream Nutrition 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000000622 liquid--liquid extraction Methods 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000006872 mrs medium Substances 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- VOXXWSYKYCBWHO-MRVPVSSYSA-N (R)-3-phenyllactic acid Chemical compound OC(=O)[C@H](O)CC1=CC=CC=C1 VOXXWSYKYCBWHO-MRVPVSSYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UAJRSHJHFRVGMG-UHFFFAOYSA-N 1-ethenyl-4-methoxybenzene Chemical compound COC1=CC=C(C=C)C=C1 UAJRSHJHFRVGMG-UHFFFAOYSA-N 0.000 description 1
- 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 1
- FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 1
- LIOSZYBFCUDMNY-UHFFFAOYSA-N 2-hydroxy-2-phenylpropanoic acid 2-hydroxy-3-phenylpropanoic acid Chemical compound OC(=O)C(O)(C)C1=CC=CC=C1.OC(=O)C(O)CC1=CC=CC=C1 LIOSZYBFCUDMNY-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 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 1
- 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 1
- 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 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000194032 Enterococcus faecalis Species 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 244000004281 Eucalyptus maculata Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 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 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000033830 Hot Flashes Diseases 0.000 description 1
- 206010060800 Hot flush Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 239000002211 L-ascorbic acid Substances 0.000 description 1
- 235000000069 L-ascorbic acid Nutrition 0.000 description 1
- 240000001046 Lactobacillus acidophilus Species 0.000 description 1
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 description 1
- 241000186715 Lactobacillus alimentarius Species 0.000 description 1
- 241000186685 Lactobacillus hilgardii Species 0.000 description 1
- 241000218588 Lactobacillus rhamnosus Species 0.000 description 1
- 244000025090 Lactobacillus sanfrancisco Species 0.000 description 1
- 235000013864 Lactobacillus sanfrancisco Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 241001468192 Leuconostoc citreum Species 0.000 description 1
- 241000192130 Leuconostoc mesenteroides Species 0.000 description 1
- 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 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000017657 Menopausal disease Diseases 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 208000006550 Mydriasis Diseases 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 241001093501 Rutaceae Species 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[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 UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
- 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 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 241001416177 Vicugna pacos Species 0.000 description 1
- 241000219094 Vitaceae Species 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000004855 amber Substances 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 208000003464 asthenopia Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 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 1
- 238000011325 biochemical measurement Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004556 brain Anatomy 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
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 210000000750 endocrine system Anatomy 0.000 description 1
- 229940032049 enterococcus faecalis Drugs 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 235000021021 grapes Nutrition 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 230000000423 heterosexual effect Effects 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 230000037315 hyperhidrosis Effects 0.000 description 1
- 230000000521 hyperimmunizing effect Effects 0.000 description 1
- 230000001660 hyperkinetic effect Effects 0.000 description 1
- 230000000393 hypersympathetic effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910001410 inorganic ion Inorganic materials 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 229940039695 lactobacillus acidophilus Drugs 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000008558 metabolic pathway by substance Effects 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 238000009629 microbiological culture Methods 0.000 description 1
- 239000011785 micronutrient Substances 0.000 description 1
- 235000013369 micronutrients Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 235000019809 paraffin wax Nutrition 0.000 description 1
- 210000001002 parasympathetic nervous system Anatomy 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000223 polyglycerol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000010248 power generation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 235000011962 puddings Nutrition 0.000 description 1
- 230000010349 pulsation Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000004320 sodium erythorbate Substances 0.000 description 1
- 235000010352 sodium erythorbate Nutrition 0.000 description 1
- RBWSWDPRDBEWCR-RKJRWTFHSA-N sodium;(2r)-2-[(2r)-3,4-dihydroxy-5-oxo-2h-furan-2-yl]-2-hydroxyethanolate Chemical compound [Na+].[O-]C[C@@H](O)[C@H]1OC(=O)C(O)=C1O RBWSWDPRDBEWCR-RKJRWTFHSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 1
- 229940013618 stevioside Drugs 0.000 description 1
- 235000019202 steviosides Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 210000002820 sympathetic nervous system Anatomy 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000001331 thermoregulatory effect Effects 0.000 description 1
- 230000035922 thirst Effects 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000007371 visceral function Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 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 1
- 239000002076 α-tocopherol Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/745—Bifidobacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Dermatology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Non-Alcoholic Beverages (AREA)
Description
本發明係關於一種醫藥組成物或飲食物,係含苯乳酸、具有調節自律神經作用。本發明另外還關於一種苯乳酸係D-苯乳酸及/或L-苯乳酸之上述醫藥組成物或飲食物。進一步本發明係關於上述醫藥組成物或飲食物,係具有亢進副交感神經活動作用、用於處置自律神經活動相關之疾病或狀態。
為了維持生物體之恆定性,於生物體具備有自律神經系統、內分泌系統、免疫系統。於其中,因為自律神經系統係由大腦支配而較為獨立,尤其與意志無關而自動地工作,故以此為命名,主要為調節內臟機能。在自律神經系統方面,有交感神經系統與副交感神經系統之2種系統,藉由兩者之平衡而作控制。亦即,在身體正在活動時,交感神經活動成為優位,全身變成緊張之狀態。相反地,副交感神經活動優位時身體緊張消除,而成為放鬆狀態(非專利文獻1)。另外,交感神經活動亢進之情況,會引起瞳孔之擴大、頻脈、血壓上昇、物質代謝‧高血糖)等,副交感神經活動亢進之情況,會引起消化吸收系之活性化、汗或唾液之分泌等。
若自律神經活動之平衡發生異常,則出現不定愁訴等之健康障礙(非專利文獻2)。
就著眼於自律神經之健康障礙處置而言,揭示有例如使用芸香科或桉樹科等之精油亢進副交感神經活動產生放鬆作用(專利文獻1)、使用4-甲氧基苯乙烯亢進副交感神經活動進行之芳香療法(專利文獻2)及使用胜肽對副交感神經產生作用造成淚液分泌作用(專利文獻3)以及使用n-3系高度不飽和脂肪酸之交感神經抑制劑產生之對紅面症、不安症等自律神經失調症之效果(專利文獻4)。
另一方面,關於已知存在有2種光學異構物之苯乳酸(phenyl lactic acid, 2-hydroxy-3-Phenyl propionic acid),係藉由Lactobacilus屬進行生產,僅已知對Aspergillus niger等有防霉活性,若於培養中添加***酸則培養上清液中之濃度會上昇(非專利文獻3)、使用乳酸菌所產生之苯乳酸對病原性大腸菌0-157、耐甲氧西林金黃色葡萄球菌會有抗菌效果(專利文獻5)等之抗菌‧防霉作用。
[專利文獻1]特開2005-272445
[專利文獻2]特開2004-131436
[專利文獻3]特開平11-209294
[專利文獻4]特開2004-067537
[專利文獻5]特開2000-300284
[非專利文獻1]萩原俊男等:岩波講座「現代醫學之基礎」第4卷生體之調節系統,1999
[非專利文獻2]久保木書房:醫學之進展VOl.181
No.12, 1013-1015, 1997
[非專利文獻3]FEMS microbiology Letters 233: 289-295, 2004
自律神經失調及起因於此之健康障礙係以例如不定愁訴為首而多數存在著,然而對每個該等症狀進行治療,卻沒有採取對根本原因之自律神經活動本身作控制之方法。即使依照症狀種類之療法可暫時改善其症狀,再發之可能性或自律神經失調導致其他之症狀發病之可能性亦高。於是,對根本原因之自律神經活動本身作控制之醫藥品或飲食物為大眾所需求。
另外還有需兼顧其效果與低副作用、高安全性之課題,或對於醫藥品之合成而言,有必要經過其他階段程序、為了進一步成為容易地攝取有必要加工為錠劑等之形態,而有變成高成本之課題。於是,由自然界所存在之天然而來之物質經過簡便程序所得到之具有調節自律神經作用之物質正強烈地被大眾所需求。
本發明之課題在於提供一種醫藥組成物或飲食物,係具有自律神經活動之調節作用、尤其是抑制交感神經活動作用或亢進副交感神經活動作用、對於處置自律神經活動相關之疾病或狀態為有用。
關於特定之乳酸菌菌體,已確認有抑制腎臟之交感神經活動,亢進胃之副交感神經活動作用(Tanida M, et al: Neuroscience Letters 389:109-114, 2005)。
本發明人等為了解決上述課題努力進行研究,將使用大鼠之對自律神經直接之作用當作指標,確認了特定之乳酸菌培養上清液中含苯乳酸、進一步確認了在2個光學異構物之內係含L-苯乳酸作為主成分。其次,藉由使用大鼠之實驗,調查L-苯乳酸及D-苯乳酸分別對腎臟交感神經活動之作用、對血壓之影響、對胃迷走神經之副交感神經活動之作用,而完成本發明。
亦即,本發明係關於一種醫藥組成物或飲食物,係含臨床上有效量之下式(I):
之化合物(苯乳酸)、及容許作為醫藥或食品之添加劑,具有調節自律神經作用。
本發明另外還關於上述醫藥組成物或飲食物,其中上述式(I)之化合物係以下式所表示者:
(亦即D-苯乳酸及/或L-苯乳酸)。
本發明另外還關於上述醫藥組成物或飲食物,係用於處置自律神經活動相關之疾病或狀態。
本發明另外還關於上述醫藥組成物或飲食物,其中上述自律神經活動相關之疾病或狀態,係選自血壓降低、身心緊張、眼睛乾燥、口腔乾燥、免疫機能調整不全、皮膚機能不全及血糖降低所構成之群。
本發明另外還關於上述醫藥組成物或飲食物,其中上述調節自律神經作用係抑制交感神經活動作用及/或亢進副交感神經活動作用。
本發明另外還關於上述醫藥組成物或飲食物,其中上述化合物係以下式所表示之化合物:
,上述調節自律神經作用係亢進胃迷走神經(副交感神經)活動作用。
本發明另外還關於上述醫藥組成物或飲食物,其中含有具有式(I)之化合物生產能力之微生物或其加工品。
本發明另外還關於上述醫藥組成物或飲食物,其中含有具有式(I)之化合物之生產能力之微生物之培養上清液或其加工品。
本發明另外還關於上述醫藥組成物或飲食物,其中上述微生物係乳酸菌。
本發明另外還關於上述醫藥組成物或飲食物,其中上述乳酸菌係屬於鏈球菌屬(Storeptococcus)、乳桿菌屬(Lactobacillus)、白念珠球菌屬(Leuconostoc)、小球菌屬(Pediococcus)、雙叉桿菌屬(Bifidobacterium)、四體球菌屬(Tetragenococcus)、魏斯氏菌屬(Weissella)、腸球菌屬(Enterococcus)、蜜蜂球菌屬(Melissococcus)、乳球菌屬(Lactococcus)、肉品桿菌屬(Carnobacteriurn)、徘徊球菌屬(Vagococcus)、奇異菌屬(Atopobium)、乳球形菌屬(Lactosphaera)、酒球菌屬(Oenococcus)、乏養球菌屬(Abiotrophia)、副乳桿菌屬(Paralactobacillus)、顆粒鏈菌屬(Granulicatella)、奇異桿菌屬(Atopobactor)、嗜鹽嗜鹼菌屬(Alkalibacterium)或奧爾森氏菌屬(Olsenella)。
本發明另外還關於上述醫藥組成物或飲食物,其中上述微生物係胚芽乳酸桿菌(宜為胚芽乳酸桿菌SAM2446株(FERM ABP-10438))或短毛乳酸桿菌(宜為短毛乳酸桿菌ATCC14869)。
本發明還關於上述之醫藥品組成物或飲食物之製造方法,包含培養具有式(I)之化合物之生產能力之微生物之步驟。
本發明進一步關於上述醫藥組成物或飲食物,其中上述調節自律神經作用,係選自亢進腎臟交感神經活動作用、抑制腎臟交感神經活動作用、亢進胃迷走神經(副交感神經)活動作用所構成之群中之1種以上之作用,宜為抑制腎臟交感神經活動作用及/或亢進胃迷走神經(副交感神經)活動作用。
本發明進一步關於上述醫藥組成物或飲食物,其中上述調節自律神經作用係伴隨血壓降低。
本發明進一步關於一種具有緩和過敏症狀之作用之上述醫藥組成物或飲食物。
本發明進一步關於上述醫藥組成物或飲食物,其中上述自律神經活動相關之疾病或狀態係選自癌、胃潰瘍、潰瘍性大腸炎、高血壓、膿皰、腰痛、肩膀酸痛、膝痛及慢性關節風濕所構成之群。
本發明進一步關於上述醫藥組成物或飲食物,其中上述苯乳酸係來自乳酸菌,D-苯乳酸:L-苯乳酸=5:1~0:1,宜為1:1~1:20、較佳為1:1~1:10程度。
本發明進一步關於一種醫藥組成物或飲食物,係含亢進交感神經活動有效量之D-苯乳酸,用於處置過敏症狀。
本發明進一步關於一種醫藥組成物或飲食物,係含抑
制交感神經活動有效量之D-苯乳酸及/或L-苯乳酸,用於處置選自癌、胃潰瘍、潰瘍性大腸炎、高血壓、膿皰、腰痛、肩膀酸痛、膝痛及慢性關節風濕所構成之群之疾病或狀態。
本發明進一步關於一種醫藥組成物或飲食物,係含、亢進副交感神經活動有效量之L-苯乳酸,用於亢進免疫機能、血壓降低、身心之放鬆、促進唾液分泌、淚液分泌、皮膚機能改善及/或血糖降低。
本發明進一步關於上述醫藥組成物,係經口服用。
本發明進一步關於一種自律神經調節劑,係將苯乳酸定為有效成分。
本發明進一步關於一種血壓調節劑,係包含將苯乳酸定為有效成分。
本發明進一步關於一種苯乳酸之使用,係用於處置自律神經活動相關疾病或狀態之醫藥組成物或飲食物之製造。
本發明進一步關於一種自律神經活動相關之疾病或狀態之處置方法,係包含投予苯乳酸。
本發明進一步關於一種自律神經活動之調節方法,係包含投予苯乳酸。
在本說明書中,苯乳酸係指以下式(I):
所表示之化合物(亦稱為2-hydroxy-3-Phenyl propionic acid、β-3-Phenyl lactic acid,MW 166.17)。就苯乳酸而言,存在有以下2個異性體:
,D-苯乳酸及L-苯乳酸,各自皆為已知之化合物。在本說明書中,簡單稱為「苯乳酸」時,包含上述D-苯乳酸及L-苯乳酸各自單獨,以及兩者之混合物全部。苯乳酸係已知含於牛乳、乳酪、蜂蜜等,亦已知含於微生物培養培養基中。另外,D-苯乳酸及L-苯乳酸各自有標準品作為試藥而被販售。雖然為如此取得容易、安全性非常高之化合物,然而關於苯乳酸僅有抗菌、防霉作用被報導出(專利文獻5、非專利文獻3),其對自律神經之作用、目標為處置自律神經活動相關疾病或狀態之作用則完全沒有被報導出來。本發明人等發現含苯乳酸之醫藥組成物或飲食物(以下
,亦簡單稱為「組成物」),係具有自律神經活動之調節作用,對於自律神經活動相關之疾病或狀態之處置為有用。
另外如後述之實施例所記載,本發明人等亦發現乳酸菌(Lactobacillus plantarum SAM 2446株(FERM ABP-10438))之培養後培養基上清液中含苯乳酸,且主要含L-苯乳酸(D:L=1:9程度)。
關於由上述之原料或培養上清液等分離苯乳酸之方法,可藉由將該原料等直接分離、或在分離操作之前作冷凍乾燥,再使用有機溶劑作液液分配萃取等進行濃縮。其後之分離操作,係可依照需要以超過濾處理等進行粗分離後,藉由使用逆相管柱、光學分割管柱等之處理進行。上述液液分配萃取、超過濾處理、逆相管柱處理、光學分割管柱處理等,係可使用業界人士一般所使用之方法進行。由分離所得到之苯乳酸,為D-苯乳酸與L-苯乳酸之混合物或各自之單體皆可。得到混合物之情況,可依照需要進一步藉由光學分割操作得到單體。
藉由上述方法得到苯乳酸之確認,係可藉由與標準品比較,以MS圖譜、NMR圖譜等測定來進行。
另外,使用市售標準品(BACHEM公司等)之苯乳酸亦可,亦可藉由合成得到苯乳酸。合成方法方面並無特別限制。
本發明之組成物所含之苯乳酸,係亦可使用例如鹽酸鹽般,藥學上所容許之鹽之形式,亦可使用在體內會變為苯乳酸之鹽(藥物前體)之形式。
另外,本發明提供上述醫藥組成物或飲食物,係含有具有苯乳酸(式(I)之化合物)生產能力之微生物或其加工品、該微生物之培養上清液或其加工品。
在本說明書中,「具有苯乳酸之生產能力」係指在以有效之條件培養時可生產苯乳酸。該有效之條件,只要是業界人士即可適宜決定。微生物之苯乳酸生產能力,係在將微生物(含微生物本身、微生物之乾燥物、微生物之培養液、微生物之萃取物等)使用例如LC、MS、NMR等在依照既定方法分析之情況下,可確認含苯乳酸等。就具有如此生產能力之微生物而言,亦包含使培養條件(培養基之組成、培養時之溫度條件、培養時之pH條件、培養密度等)適宜調整之情況下會成為具有苯乳酸生產能力之微生物。
上述之微生物亦可為由天然採取而得者,另外,以成為具有苯乳酸生產能力而設計之突變體及/或重組體,亦包含在本發明之範圍內。如此之突變體及/或重組體係包含目標為在使用同組成之培養基培養時,與野性株相比苯乳酸之生產能力變高而設計者。
再者,上述之微生物產生之苯乳酸,係D-苯乳酸或L-苯乳酸或該等之混合物皆可,由參照例如後述之實施例之記載,可按照作為處置對象之疾病或狀態,適宜地選擇具有所希望之苯乳酸產生能力之微生物來使用。
如此之具有苯乳酸生產能力之微生物,係可為例如乳酸菌、酵母、枯草菌等。就乳酸菌而言,可列舉例如屬於
鏈球菌屬(Storeptococcus)、乳桿菌屬(Lactobacillus)、白念珠球菌屬(Leuconostoc)、小球菌屬(Pediococcus)、雙叉桿菌屬(Bifidobacterium)、四體球菌屬(Tetragenococcus)、魏斯氏菌屬(Weissella)、腸球菌屬(Enterococcus)、蜜蜂球菌屬(Melissococcus)、乳球菌屬(Lactococcus)、肉品桿菌屬(Carnobacterium)、徘徊球菌屬(Vagococcus)、奇異菌屬(Atopobium)、乳球形菌屬(Lactosphaera)、酒球菌屬(Oenococcus)、乏養球菌屬(Abiotrophia)、副乳桿菌屬(Paralactobacillus)、顆粒鏈菌屬(Granulicatella)、奇異桿菌屬(Atopobactor)、嗜鹽嗜鹼菌屬(Alkalibacterium)或奧爾森氏菌屬(Olsenella)之微生物;就酵母而言,可列舉例如屬於念珠菌屬(Candida)或酵母菌屬(Saccharomyces)之微生物;就枯草菌而言,可列舉屬於枯草桿菌屬(B.subutilis)之微生物。
就適宜之微生物而言,可列舉例如非專利文獻3所記載之Lactobacillus plantarum、Lactobacillus alimentarius、Lactobacillus rhamnosus、Lactobacillus sanfranciscensis、Lactobacillus hilgardii、Leuconostoc citreum、Lactobacillus brevis之某株、Lactobacillus acidophilus之某株、Leuconostoc mesenteroides subsp. mesenteroides,或專利文獻5所記載之Enterococcus faecalis等。特別適宜之微生物,係乳酸菌之胚芽乳酸桿菌(Lactobacillus plantarum)(若較為特定而言,胚芽乳酸桿菌SAM 2446
株(FERM ABP-10438))及短毛乳酸桿菌(Lactobacillus brevis)(若較為特定而言,短毛乳酸桿菌ATCC14869)。
本發明另外還提供上述之醫藥品組成物或飲食物之製造方法,其中包含以培養基培養具有上述之苯乳酸生產能力之微生物之步驟。該微生物之培養,係可將微生物接種至適當之培養基,依照微生物之種類、使用業界人士周知之手法進行。
關於例如微生物為乳酸菌之情況時之培養,於以下簡潔地敘述。就培養基而言,可使用例如洋菜培養基及/或液體培養基。於培養基中,以所期望之濃度適宜添加業界人士周知之碳源、氮源,進一步因應必要添加無機離子、維生素類等微量營養源。較簡便地使用例如MRS培養基等市售之培養基,可進一步於其中加上添加物而使用。培養時,可以業界人士所周知之手段加上適宜使苯乳酸生成量增加之操作,例如非專利文獻3所記載之方式,於Lactobacilus屬培養中藉由添加***酸使培養基中之苯乳酸量增加亦可。調製培養基之後,使用適當之酸或鹼調製使pH在6.0~7.0之範圍,可使用高壓滅菌釜等進行滅菌。
其後,將乳酸菌接種至培養基,於培養溫度10℃~45℃、通常1~2天,藉由振動培養、靜置培養、在槽中進行之工業培養、在洋菜培養基等之固態培養基之培養等,於培養基中可使微生物增殖。培養條件,係依照所使用之
微生物而相異,而在使用例如Lactobacillus Plantarum之情況,可在37℃左右、1天、pH6.5左右之MRS培養基中靜置培養。將如此之方式培養之微生物,依照需要進行離心分離,進一步因應必要而過濾,可得到培養上清液。
由後述之實施例看來明顯地,苯乳酸在分別單獨以D-苯乳酸及L-苯乳酸經由十二指腸投予至大鼠時,會對大鼠之腎臟交感神經活動、血壓、胃迷走神經(副交感神經)活動起作用。
較詳細而言,對腎臟交感神經活動,在投予量10μg/隻時,D-苯乳酸被認為有亢進腎臟交感神經活動作用,L-苯乳酸對於腎臟交感神經活動幾乎不被認為有影響。在投予量100μg/隻時,D-苯乳酸、L-苯乳酸皆被認為有抑制腎臟交感神經活動作用。
對血壓而言,尤其是在投予量100μg時,L-苯乳酸及D-苯乳酸皆被認為有降低血壓作用。
再者,對於胃迷走神經(副交感神經)活動而言,在投予量100μg/隻時,L-苯乳酸被認為有亢進胃迷走神經(副交感神經)活動作用。
就評估自律神經活動之方法而言,可列舉心電計、血壓計、皮膚電氣反射、瞳孔徑測定等之生物理學方面的測定法,或血中兒茶酚胺濃度測定等之生化學方面的測定法等。尤其使用心電計之心跳變動解析為經常利用之方法,而本發明人等如於後述之實施例所記載之方式,藉由使用大鼠之方法(可直接評估投予物質對自律神經活動之影響
),評估上述苯乳酸對自律神經活動之作用。本方法之特徵點,係在於可個別地調查投予物質對支配各臟器、組織等之自律神經之神經活動產生之作用。進一步而言,亦為一種具有實驗動物只要生存,即可逐次測定相異投予物質對調節自律神經作用之優點之方法。
關於被認為與自律神經活動有關之器官、荷爾蒙、生物體活動,與對應於該等而言被認為自律神經所涉及到之影響及預測之效果之一例,表示於以下之表。
由上述表明顯地可知,自律神經活動密切地影響血糖調節、血壓調節、荷爾蒙分泌調節、糖代謝調節、胃液分泌調節、血流量調節、體溫調節等、生物體之各式各樣之調節機構。若自律神經活動之平衡發生異常,則出現例如不定愁訴等之身體不適。不定愁訴之症狀種類繁多,可列舉全身疲勞感、睡眠障礙、心悸、口渴(口腔乾燥)、性無能、口內乾燥感、眼睛疲勞等(非專利文獻2)。另外,就過度之交感神經優位之疾病而言,可列舉癌‧胃潰瘍‧潰瘍性大腸炎‧高血壓‧膿皰‧腰痛‧肩膀酸痛‧膝痛‧慢性關節風濕等,就過度之副交感神經優位之疾病而言,可列舉淋巴球增殖而成為對抗原過敏反應結果之過敏症狀等。藉由亢進副交感神經活動,能預測有淋巴球數增加造成免疫機能之亢進、降低血壓、身心之放鬆、唾液之分泌、促進淚液之分泌、降低血糖等作用、改善皮膚機能產生之美容效果或美肌效果。
在本說明書中,調節自律神經作用,係指包含亢進交感神經活動作用、交感神經活動亢進之抑制作用、抑制交感神經活動作用、亢進副交感神經活動作用、副交感神經活動亢進之抑制作用、抑制副交感神經活動作用。
本發明之組成物係由於含上述苯乳酸,故可使用於上述自律神經活動相關之疾病或狀態之處置。可使用於例如由於自律神經失調所容易引起之症狀(有時亦總稱為不定愁訴)如呼氣困難、心悸、肩膀酸痛、頭痛、眩暈、不安感、食慾不振、倦怠感、失眠等(亦稱為自律神經失調症
)或認為起因於自律神經活動失調之體溫調節障礙所造成者、更年期障礙時之頭暈‧熱潮紅‧冷感‧急劇發汗等之處置。
特別是認為對於以抑制交感神經活動之可作處置之疾病或狀態,例如交感神經活動優位之情況時之疾病、對人緊張症、紅面症、多汗症、心悸、脈搏不整、下痢、站起時頭暈、胃不舒服、疲勞感、癌‧胃潰瘍‧潰瘍性大腸炎‧高血壓‧膿皰‧腰痛‧肩膀酸痛‧膝痛‧慢性關節風濕等之處置,或為副交感神經活動優位之情況下之疾病如淋巴球增殖而成為對抗原過敏反應結果之過敏症狀等之處置為有用。另外,可認為本發明之組成物對於高血壓之處置為有用。進一步認為本發明之組成物係藉由亢進副交感神經活動,可具有淋巴球數增加造成免疫機能之亢進、降低血壓、身心之放鬆、唾液之分泌、促進淚液之分泌、降低血糖等之作用,故認為對於降低血壓、身心緊張、眼睛乾燥、口腔乾燥、免疫機能調整不全、皮膚機能不全、血糖降低等之處置為有用。
在本說明書中,處置疾病或狀態,係指包含防止該疾病或狀態惡化,改善該疾病或狀態,以及預防該疾病或狀態。含上述苯乳酸之本發明之組成物,由後述之實施例之結果判斷,只要投予5μg/kg以上之苯乳酸即可得到充分之效果。苯乳酸之投予量並無特別存在上限,而若考慮毒性、經濟性,則一般以不超過50mg/kg程度為佳。為了充分地發揮本發明之組成物其效果,苯乳酸每1次服用為
5μg/kg~50mg/kg(宜為10μg/kg~20mg/kg、較佳為20μg/kg~10mg/kg),較具體而言,在將人類成人當作對象之情況時,希望含有每1次服用300μg~3000mg之量(宜為600μg~1200mg,較佳為1200μg~600mg)。另外,本發明之組成物中,每單位製品重量(g)可含有0.5μg~5mg苯乳酸(宜為1μg~2mg,較佳為2μg~1mg)。另外,由其他觀點看來,每單位製品重量(g)可含有4μg以上苯乳酸(宜為25μg以上,較佳為75μg以上),此時上限值任一者皆可定為例如每單位製品重量(g)1mg、2mg、或5mg。
另外,決定投予量時,藉由參照例如後述實施例之記載,可按照作為處置對象之疾病或狀態,適宜地設定D-苯乳酸及/或L-苯乳酸之投予量。在本說明書中,臨床上有效量係指為了調節自律神經臨床上有效之量,亢進交感神經活動有效量係指為了亢進交感神經活動有效之量,抑制交感神經活動有效量係指為了抑制交感神經活動有效之量,亢進副交感神經活動有效量係指為了亢進副交感神經活動有效之量,該等之有效量係以例如後述之實施例所記載之手法測定,可將對自律神經活動之物質之作用及該作用時之投予量設定為判斷指標。
本發明之組成物,係可將含苯乳酸之原料、具有苯乳酸產生能力之微生物、該微生物之培養上清液、含該微生物之培養物本身等以其原樣使用、或使用進行萃取‧分離操作等之處理而純化分離、精製者,而並無特別限制。另
外,亦可使用通常之殺菌、減壓濃縮、冷凍乾燥等之手法,將該等製成濃縮物或乾燥粉體等之加工品而使用。就不容易乾燥粉體化之濃縮物之情況而言,使用常用之糊精、高分子澱粉水解物或高分子胜肽等作為賦形劑可進行乾燥粉體化。由作業性、保存性之觀點看來係以粉體化者為佳。
本發明之組成物,可因應目的成為飲食物(亦含食品、飲料、調味料、酒精飲料、機能食品等)及醫藥組成物之各種之形態。例如使用苯乳酸、具有苯乳酸生產能力之微生物、該微生物之培養上清液、加工品等,可提供飲食物、醫藥品。
就本發明所提供之飲食物而言,可列舉糖果、喉錠、口香糖、酸凝酪、冰淇淋、布丁、果凍、水羊羹、酒精飲料、咖啡飲料、果汁、果實飲料、碳酸飲料、清涼水飲料、牛乳、乳清飲料、乳酸菌飲料等各種物品。
另外,該等之飲食物係可依照必要配合各種添加劑,依據常法調製。具體而言,在調製該等之飲食品之情況,可適宜地配合例如葡萄糖、果糖、蔗糖、麥芽糖、山梨醇、甜菊素、甜茶素、玉米糖漿、乳糖、檸檬酸、酒石酸、蘋果酸、琥珀酸、乳酸、L-抗壞血酸、d1-α-生育酚、異抗壞血酸鈉、甘油、丙二醇、脂肪酸甘油酯、聚脂肪酸甘油酯、脂肪酸蔗糖酯、脂肪酸去水山梨醇酯、脂肪酸丙二醇酯、***膠、鹿角菜膠、酪蛋白、明膠、果膠、洋菜、維生素B類、菸鹼酸醯胺、泛酸鈣、胺基酸類、鈣鹽類
、色素、香料、保存劑等使用作為通常之食品原料者,而依照常法製造。
進一步,在調製本發明所提供之醫藥品之情況時,還可依照必要配合各種添加劑而調製為各種劑形之醫藥品。可提供作為例如錠劑、膠囊劑、顆粒劑、藥粉、糖漿劑、萃取精華劑等之口服醫藥品,或軟膏、眼用軟膏、洗劑、乳膏、貼附劑、栓劑、點眼藥、點鼻藥、注射劑之非口服醫藥品。
該等醫藥品係使用各種添加劑依照常法製造即可。所使用之添加劑方面係並無特別限制,可使用通常使用者,而就其例而言可列舉澱粉、乳糖、白糖、甘露醇、羧甲基纖維素、玉米澱粉、無機鹽等之固態擔體;蒸餾水、生理食鹽水、葡萄糖水溶液、乙醇等之醇、丙二醇、聚乙二醇等之液態擔體;各種之動植物油、白色凡士林、石蠟、蠟類等之油性擔體等。
本發明之組成物係含苯乳酸作為有效成分,依照需要,亦可進一步含以往所使用在醫藥組成物或飲食物方面之其他有效成分。
例如,具有調節自律神經作用之物質(交感神經作用物質、副交感神經作用物質等)、亢進交感神經活動作用物質、處置過敏症狀之相關物質、抑制交感神經活動物質、處置選自癌、胃潰瘍、潰瘍性大腸炎、高血壓、膿皰、腰痛、肩膀酸痛、膝痛及慢性關節風濕所構成之群之疾病或狀態相關之物質、具有降低血壓作用之物質、亢進副交
感神經活動作用物質(含具有芳香療法效果‧放鬆效果之物質)、具有亢進免疫機能、降低血壓、身心之放鬆、唾液之分泌、促進淚液之分泌、改善皮膚機能及/或降低血糖作用之物質等,可將業界人士所周知之物質1種或複數種加以組合而包含在內。
再者,在本發明之組成物含有具有苯乳酸生產能力之微生物或其加工品、其培養上清液或加工品之情況下,亦可含有尤其是由該微生物而來之上述物質(具有調節自律神經作用之物質、亢進交感神經活動作用之物質、抑制交感神經活動之物質、具有降低血壓作用之物質、亢進副交感神經活動相關物質等)。
尤其在本發明之組成物含亢進交感神經活動有效量之D-苯乳酸之情況下,上述之其他之有效成分係以亢進交感神經活動作用物質或過敏症狀之處置相關之物質者為佳。特別是本發明之組成物含亢進交感神經活動有效量之D-苯乳酸及/或L-苯乳酸之情況下,上述之其他之有效成分係以亢進交感神經活動作用物質,或選自癌、胃潰瘍、潰瘍性大腸炎、高血壓、膿皰、腰痛、肩膀酸痛、腰痛及慢性關節風濕所構成之群之疾病或狀態之處置相關之物質者為佳。特別是本發明之組成物含亢進副交感神經活動有效量之L-苯乳酸之情況下,上述之其他之有效成分係以亢進副交感神經活動作用物質,或具有亢進免疫機能、降低血壓、身心之放鬆、唾液之分泌、促進淚液之分泌、改善皮膚機能及/或降低血糖作用之物質為佳。
另外,關於本發明之醫藥組成物或飲食品,可表示其具體的用途(例如用於調節自律神經、調節交感神經、調節副交感神經、緩和過敏症狀、高血壓之治療/預防、亢進免疫機能、身心之放鬆、降低血糖之對策、唾液之分泌、促進淚液之分泌、美容效果‧美肌效果、維持健康等)及/或其具體的使用方法(例如攝取量、攝取次數、攝取方法)。
如以上詳細地說明般,依據本發明,提供一種醫藥組成物或飲食物,係對自律神經活動相關之疾病或狀態之根本原因之自律神經活動其本身進行調節。特別是,提供上述之醫藥組成物或飲食物,係不會伴隨血壓上昇,具備高安全性,並可簡便地製造。
以下,根據實施例對本發明作詳細地說明,而本發明並非受到該等所限定者。
實施例1,係對乳酸菌Lactobacilus plantarum SAM 2446株(FERM ABP-10438)培養上清液中所含之苯乳酸進行掌性分析。另外,實施例2~4係使用BACHEM公司之試藥L-苯乳酸(L-β-3-Phenyl lactic acid (Q1375))、及D-苯乳酸(D-β-3-phenyl lactic acid (Q1670)
)調查苯乳酸含有組成物對大鼠自律神經活動之效果。
將Lactobacilus plantarum SAM 2446株培養上清液之冷凍乾燥品定為初始材料,使用Develosil C30-UG-5管柱,回收相當於苯乳酸之峰。接著,將該峰溶解於含0.1%TFA及5%2-丙醇之己烷,載入Chiralpak AD(DAICEL化學工業製),等位(isocratic)地使用含0.1%TFA及5%2-丙醇之己烷作為移動相而進行分析。
其結果,在Lactobacilus plantarum SAM2446株培養上清液中之苯乳酸中,判斷出含L-苯乳酸作為主成分(D:L=約1:9)(圖1)。另外,收率在大約90%之程度。
本實驗中,使用體重300~350g之Wistar系雄性大鼠,使用在1天12小時(7:00-19:00)點燈之24℃恆溫動物室預先進行1週間以上飼養之動物。對各個神經實驗每次使用1隻大鼠。使其自由攝食飼料(MF:Oriental酵母公司製)及水。實驗當日使其絕食5小時後在胺甲酸乙酯(1g/kg,ip)麻醉下開腹,投予L-苯乳酸及D-苯乳酸(10μg或100μg)至十二指腸內所產生對腎臟交感神經活動
之效果,使用T. Yamano et al., Neurosci. Lett. 313:78-82 (2001)、A.Niijima et al., Autonom. Neurosci.: Basic & Clinical 97:99-102 (2002)及M. Tanida et al., Am. J. Physiol:Regulatory, Integrative and Comerative Physiology 288:R447-R455 (2005)所記載之方法作測定。亦即將投射至腎臟之交感神經在臟器前方切斷,將其中樞側載置於銀製電極上,測定其電氣活動變化。為了防止乾燥,電極係預先以液體石蠟與石油膠之混合物充分浸泡。另外,由手術開始至測定終了為止將管子***氣管以確保氣道,以保溫裝置將體溫(大鼠直腸溫)保持於35.0±0.5℃。十二指腸內投予,係將L-苯乳酸或D-苯乳酸分別以生理食鹽水調製為10μg/2ml或100μg/2ml,使用***十二指腸之聚乙烯tube,以每1隻為2ml、1ml/min之投予速度進行。所得到之神經電氣活動係以電容式差動增幅器作增幅,以示波器監視,並記錄於磁帶。對於全部之神經活動,為了將其原始資料與背景雜訊分離,係使用雙向限幅器與窗形鑑別器變換為標準脈動之後進行解析。放電頻率係藉由速率計以5秒鐘之重置時間表示於筆式記錄器上。資料係每5分鐘以每5秒之發電頻率(pulse/5sec)平均值作解析,將投予前之值定為100%以百分率表示。將投予生理食鹽水之實驗定為控制組。
其結果關於控制組,所評估全部之自律神經活動之影響皆沒有顯現,亦沒有顯現對血壓之影響。另一方面,在投予群中,10μg之投予量之下,D-苯乳酸方面雖然腎臟
交感神經活動受到亢進,然而L-苯乳酸對於腎臟交感神經活動幾乎不被認為有影響(圖2)。100μg之投予量之下,D-苯乳酸和L-苯乳酸皆抑制腎臟交感神經活動,尤其以L-苯乳酸抑制效果為高(圖3)。
使用與實施例2同樣之手法,投予L-苯乳酸及D-苯乳酸(10μg或100μg)至十二指腸內對血壓之影響,以實施例2中列記之文獻所記載之方法進行調查。亦即,於左大腿動脈***套管,使用變換器測定血壓。對各個化合物之各投予量每次使用1隻大鼠。十二指腸內投予,係藉由與實施例2同樣之手法進行。其結果,判斷出L-苯乳酸及D-苯乳酸,尤其在100μg之投予量之下皆具有血壓降低作用(圖4)。
使用與實施例2同樣之手法,將L-苯乳酸(100μg)投予至大鼠十二指腸內,調查對胃迷走神經(副交感神經)活動之影響。其結果認為有胃迷走神經(副交感神經)活動之亢進(圖5)。
錠劑:
依照以下所示之方法,製造含有苯乳酸之醫藥品(錠劑)。
將市售之苯乳酸5g,與乳糖293.7g及硬脂酸鎂1.3g一起混合,藉由以單發式打錠機進行打錠,製造直徑10mm、重量300mg之錠劑。
顆粒劑:將市售之苯乳酸5g,加入乳糖293.7g及硬脂酸鎂1.3g,壓縮、粉碎、分粒、篩選而得到20~50網目之顆粒劑。
製造例2:含有苯乳酸之飲食物
依照常法製造以下之配方之含有苯乳酸之各種食品。
冰淇淋:
果汁:
乳酸菌飲料:
酸凝酪:
咖啡飲料:
酒精飲料:
由該等之結果明顯可知,2-苯乳酸係以光學異構物之L-苯乳酸及D-苯乳酸之形式而含於乳酸菌Lactobacilus plantarum SAM 2446株培養上清液中,而主要為L-苯乳酸。
其次,調查該等化合物對腎臟交感神經活動之影響,結果,在投予量為10μg/隻時,認為D-苯乳酸有亢進腎臟交感神經活動作用,而L-苯乳酸對於腎臟交感神經活動幾乎不被認為有影響,故認為D-苯乳酸在低濃度之有效用量時,對於副交感神經活動優位之情況下之疾病如淋巴球增殖而成為對抗原過敏反應結果之過敏症狀為有效。另外,由於認為在投予量為100μg/隻時,D-苯乳酸和L-苯乳酸皆有腎臟交感神經活動抑制作用,故認為L-苯乳酸及D-苯乳酸在高濃度之有效用量時,對於交感神經優位之疾病如癌‧胃潰瘍‧潰瘍性大腸炎‧高血壓‧膿皰‧腰痛‧肩膀酸痛‧膝痛‧慢性關節風濕等為有效。
由於L-苯乳酸及D-苯乳酸係具有降低血壓作用,因此認為對於改善高血壓為有效。
進一步顯示出L-苯乳酸尤其在投予量為100μg/隻時認為有亢進胃迷走神經(副交感神經)活動作用,而具有亢進副交感神經活動之作用。因此,認為在淋巴球數增加造成免疫機能之亢進、血壓降低、身心之放鬆、唾液之分泌、促進淚液之分泌、改善皮膚之機能、降低血糖等方面為有效。
圖1係確認實施例1中乳酸菌培養上清液中之2-苯乳酸之掌性之圖。
圖2係表示在實施例2中投予10μg之L-苯乳酸及D-苯乳酸之情況下對於大鼠腎臟交感神經活動之影響之圖。
圖3係表示在實施例2中投予100μg之L-苯乳酸及D-苯乳酸之情況下對於大鼠腎臟交感神經活動之影響之圖。
圖4係表示在實施例3中投予100μg之L-苯乳酸及D-苯乳酸之情況下對於大鼠血壓之影響之圖。
圖5係表示實施例4中投予100μg之L-苯乳酸之情況下對於大鼠胃迷走神經(副交感神經)活動之影響之圖。
Claims (15)
- 一種下式(I)之化合物用於製造亢進副交感神經活動的醫藥組成物的用途,其特徵在於:該醫藥組成物含有臨床上有效量之下式(I)之化合物
- 一種下式(I)之化合物用於製造亢進副交感神經活動的飲食物的用途,其特徵在於:該飲食物含有臨床上有效量之下式(I)之化合物
- 如申請專利範圍第1或2項之用途,其中,該式(I)之化合物係以下式所表示者:
- 如申請專利範圍第1或2項之用途,其中,亢進副交感神經活動係包含處置藉由亢進副交感神經活動被改善之疾病或狀態。
- 如申請專利範圍第4項之用途,其中,該疾病或狀態,係選自高血壓、身心緊張、眼睛乾燥、口腔乾燥、免疫機能調整不全、皮膚之機能不全及高血糖所構成之群。
- 如申請專利範圍第1或2項之用途,其中,該副交感神經活動之亢進係胃迷走神經活動之亢進。
- 如申請專利範圍第1項之用途,該醫藥組成物係含有具有式(I)之化合物之生產能力之微生物或其加工品。
- 如申請專利範圍第2項之用途,該飲食物係含有具有式(I)之化合物之生產能力之微生物或其加工品。
- 如申請專利範圍第1項之用途,該醫藥組成物係含有具有式(I)之化合物之生產能力之微生物之培養上清液或其加工品。
- 如申請專利範圍第2項之用途,該飲食物係含有具有式(I)之化合物之生產能力之微生物之培養上清液 或其加工品。
- 如申請專利範圍第7~10項中任一項之用途,其中,該微生物係乳酸菌。
- 如申請專利範圍第11項之用途,其中,該乳酸菌係屬於鏈球菌屬(storeptococcus)、乳桿菌屬(Lactobacillus)、白念珠球菌屬(Leuconostoc)、小球菌屬(Pediococcus)、雙叉桿菌屬(Bifidobacterium)、四體球菌屬(Tetragenococcus)、魏斯氏菌屬(Weissella)、腸球菌屬(Enterococcus)、蜜蜂球菌屬(Melissococcus)、乳球菌屬(Lactococcus)、肉品桿菌屬(Carnobacterium)、徘徊球菌屬(Vagococcus)、奇異菌屬(Atopobium)、乳球形菌屬(Lactosphaera)、酒球菌屬(Oenococcus)、乏養球菌屬(Abiotrophia)、副乳桿菌屬(Paralactobacillus)、顆粒鏈菌屬(Granulicatella)、奇異桿菌屬(Atopobactor)、嗜鹽嗜鹼菌屬(Alkalibacterium)或奧爾森氏菌屬(Olsenella)。
- 如申請專利範圍第12項之用途,其中,該乳酸菌係胚芽乳酸桿菌或短毛乳酸桿菌。
- 如申請專利範圍第12項之用途,其中,該乳酸菌為短毛乳酸桿菌ATCC14869。
- 如申請專利範圍第1或2項之用途,前述製造係包含培養具有式(I)之化合物之生產能力之微生物之步驟。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2007092528 | 2007-03-30 |
Publications (2)
Publication Number | Publication Date |
---|---|
TW200906385A TW200906385A (en) | 2009-02-16 |
TWI504392B true TWI504392B (zh) | 2015-10-21 |
Family
ID=39808293
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW097111617A TWI504392B (zh) | 2007-03-30 | 2008-03-28 | A medical composition or food and drink for hyperthyroidism |
Country Status (10)
Country | Link |
---|---|
US (1) | US8492442B2 (zh) |
EP (1) | EP2143427A1 (zh) |
JP (1) | JP5770425B2 (zh) |
KR (1) | KR20100016101A (zh) |
CN (1) | CN101657192B (zh) |
AU (1) | AU2008233633B2 (zh) |
CA (1) | CA2682375A1 (zh) |
SG (1) | SG182959A1 (zh) |
TW (1) | TWI504392B (zh) |
WO (1) | WO2008120713A1 (zh) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008120712A1 (ja) * | 2007-03-30 | 2008-10-09 | Suntory Holdings Limited | 交感神経活動亢進作用を有する医薬組成物又は飲食物 |
JP5923238B2 (ja) * | 2010-07-07 | 2016-05-24 | アサヒグループホールディングス株式会社 | 迷走神経活性化剤 |
JP5943342B2 (ja) | 2012-03-02 | 2016-07-05 | 国立研究開発法人産業技術総合研究所 | 概日リズム改善剤 |
JP6067292B2 (ja) * | 2012-03-19 | 2017-01-25 | サッポロビール株式会社 | セロトニン分泌促進剤 |
KR20170045247A (ko) * | 2014-08-29 | 2017-04-26 | 와카모토 세이야꾸 가부시끼가이샤 | 유산균 함유 조성물 |
JP6402016B2 (ja) * | 2014-12-10 | 2018-10-10 | 国立大学法人岐阜大学 | 神経機能改善剤 |
CN105274023A (zh) * | 2015-09-30 | 2016-01-27 | 厦门和美科盛生物技术有限公司 | 植物乳杆菌L.plantarum HM6055及其用途 |
CN108624533B (zh) * | 2018-05-10 | 2021-03-09 | 浙江工商大学 | 一种植物乳杆菌中分离纯化苯基乳酸的方法 |
TWI754126B (zh) * | 2018-07-19 | 2022-02-01 | 大江生醫股份有限公司 | 益生質組合物用於改善女性***內的菌相的用途及外用衛生用品 |
JP7369992B2 (ja) * | 2019-05-13 | 2023-10-27 | 株式会社明治 | 自律神経機能改善用の発酵乳 |
KR102317304B1 (ko) * | 2019-05-14 | 2021-10-26 | 한국식품연구원 | 락토바실러스 아시도필루스를 포함하는 갱년기 여성의 신경과민, 개미환각, 불면증, 현기증, 또는 피로의 예방, 개선, 또는 치료용 조성물 |
JP7063514B2 (ja) * | 2019-12-02 | 2022-05-09 | 株式会社ライフ・クオリティ研究所 | 起立性低血圧の予防又は改善用剤及びそれを含む組成物 |
EP4104844A4 (en) * | 2019-12-13 | 2024-02-14 | Meiji Co., Ltd | COMPOSITION FOR LOWERING HEART RATE |
KR102201544B1 (ko) * | 2020-04-20 | 2021-01-12 | 주식회사 휴온스내츄럴 | 페닐락틱산을 생산하는 페디오코쿠스 에시디락티시 hbt 균주 및 이를 배양한 페닐락티산의 생산방법 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04352720A (ja) * | 1991-05-30 | 1992-12-07 | Tanabe Seiyaku Co Ltd | 癌患者用アミノ酸製剤 |
JPH092959A (ja) | 1995-06-16 | 1997-01-07 | Yakult Honsha Co Ltd | IgE抗体産生抑制剤および抗アレルギー剤 |
US5648389A (en) * | 1995-10-27 | 1997-07-15 | Medicis Pharmaceutical, Inc. | Compositions for the treatment of dermatological disorders and methods for their use |
JP4065038B2 (ja) * | 1996-08-07 | 2008-03-19 | カルピス株式会社 | 計算作業負荷ストレス緩和剤 |
JPH10139674A (ja) * | 1996-11-11 | 1998-05-26 | Yakult Honsha Co Ltd | インターロイキン12産生促進剤 |
JPH11209294A (ja) | 1998-01-20 | 1999-08-03 | Karita Takahisa | 精油を有効成分とする副交感神経作用剤 |
JP2000300284A (ja) | 1999-04-20 | 2000-10-31 | Seibutsu Kassei Kenkyusho:Kk | 乳酸菌を用いて作られたフェニル乳酸およびその生産方法 |
AU2058702A (en) * | 2000-10-06 | 2002-04-15 | Nestle Sa | Use of probiotic lactic acid bacteria for balancing the skin's immune system |
JP2004067537A (ja) | 2002-08-02 | 2004-03-04 | Asahi Kasei Chemicals Corp | 交感神経の興奮抑制剤 |
JP2004131436A (ja) | 2002-10-11 | 2004-04-30 | Kanebo Ltd | 香料組成物 |
JP4653516B2 (ja) | 2004-02-27 | 2011-03-16 | 扶桑薬品工業株式会社 | 涙液分泌促進ペプチドおよびその組成物 |
JP4891255B2 (ja) | 2005-10-31 | 2012-03-07 | サントリーホールディングス株式会社 | ワイン発酵もろみ由来の免疫調節作用を有する乳酸菌 |
-
2008
- 2008-03-28 KR KR1020097022792A patent/KR20100016101A/ko not_active Application Discontinuation
- 2008-03-28 JP JP2009507515A patent/JP5770425B2/ja active Active
- 2008-03-28 EP EP08739194A patent/EP2143427A1/en not_active Withdrawn
- 2008-03-28 CA CA002682375A patent/CA2682375A1/en not_active Abandoned
- 2008-03-28 WO PCT/JP2008/056076 patent/WO2008120713A1/ja active Application Filing
- 2008-03-28 TW TW097111617A patent/TWI504392B/zh active
- 2008-03-28 US US12/593,468 patent/US8492442B2/en active Active
- 2008-03-28 AU AU2008233633A patent/AU2008233633B2/en not_active Ceased
- 2008-03-28 CN CN200880011024XA patent/CN101657192B/zh active Active
- 2008-03-28 SG SG2012047569A patent/SG182959A1/en unknown
Non-Patent Citations (3)
Title |
---|
Naruszewicz, M et al,"Effect of Lactobacillus plantarum 299v on cardiovascular disease risk factors in smokers", AMERICAN JOURNAL OF CLINICAL NUTRITION, 2002, 76: 1249-1255. * |
Valerio F. et al,"Production of phenyllactic acid by lactic bacteria: an approach to the selection of strains contributing to food quality and preservation", FEMS MICROBIOL. LETT. , 2004, 233: 289-295. * |
Yamano, T et al,"Effects of the probiotic strain Lactobacillus johnsonii strain La1 on autonomic nerves and blood glucose in rats", LIFE SCIENCES, 2006, 79: 1963-1967. * |
Also Published As
Publication number | Publication date |
---|---|
US20100150891A1 (en) | 2010-06-17 |
EP2143427A1 (en) | 2010-01-13 |
JPWO2008120713A1 (ja) | 2010-07-15 |
TW200906385A (en) | 2009-02-16 |
CA2682375A1 (en) | 2008-10-09 |
CN101657192B (zh) | 2013-01-23 |
AU2008233633A1 (en) | 2008-10-09 |
WO2008120713A1 (ja) | 2008-10-09 |
US8492442B2 (en) | 2013-07-23 |
SG182959A1 (en) | 2012-08-30 |
CN101657192A (zh) | 2010-02-24 |
KR20100016101A (ko) | 2010-02-12 |
AU2008233633B2 (en) | 2013-11-14 |
JP5770425B2 (ja) | 2015-08-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI504392B (zh) | A medical composition or food and drink for hyperthyroidism | |
JP5923238B2 (ja) | 迷走神経活性化剤 | |
WO1998005343A1 (fr) | Medicaments anti-stress et aliments fonctionnels ayant des effets anti-stress | |
TW200911775A (en) | Pharmaceutical composition, food or beverage capable of enhancing sympathetic nerve activity | |
JP6664315B2 (ja) | セロトニン分泌促進剤 | |
TW201642753A (zh) | 茶發酵物 | |
KR101614929B1 (ko) | 인지장애 및 기억장애 치료용 약학 조성물 | |
JP6471145B2 (ja) | 鎮静用の自律神経調整剤及び日周リズム改善剤 | |
US10004769B2 (en) | Lactobacillus brevis G-101 strain and use thereof | |
KR101690175B1 (ko) | 고본 추출물을 유효성분으로 포함하는 불면증의 예방 또는 치료용 약학적 조성물 | |
JP2002241305A (ja) | 高血圧症予防・治療剤 | |
JP2007126399A (ja) | グルタチオン増加用組成物 | |
KR101998821B1 (ko) | 황칠 발효물 및 l-세린을 이용한 수면 장애 개선용 조성물 | |
JP7007798B2 (ja) | 概日リズム改善剤 | |
KR102279034B1 (ko) | 아연 및 nac를 포함하는 신경계 질환을 예방하거나 치료하는 약학적 조성물 | |
KR20200134446A (ko) | 시계꽃 추출물을 함유하는 수면 유도용 조성물 | |
KR20240088051A (ko) | 한약재 추출물을 유효성분으로 포함하는 스트레스 완화, 피로 개선 또는 숙면 유도용 조성물 | |
KR20220097225A (ko) | 발효숙성노니 및 깔라만시를 유효성분으로 포함하는 스트레스 완화용 조성물 | |
KR20230120695A (ko) | 항균, 항산화 또는 면역 강화용 조성물 | |
JP2020002051A (ja) | 糖尿病性末梢神経障害の予防又は治療用組成物 |