WO2013016742A1 - Composition for obesity treatment - Google Patents
Composition for obesity treatment Download PDFInfo
- Publication number
- WO2013016742A1 WO2013016742A1 PCT/ZA2011/000054 ZA2011000054W WO2013016742A1 WO 2013016742 A1 WO2013016742 A1 WO 2013016742A1 ZA 2011000054 W ZA2011000054 W ZA 2011000054W WO 2013016742 A1 WO2013016742 A1 WO 2013016742A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- insulin
- fat
- composition according
- energy
- weight
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 11
- 238000011282 treatment Methods 0.000 title claims description 9
- 208000008589 Obesity Diseases 0.000 title abstract description 18
- 235000020824 obesity Nutrition 0.000 title abstract description 13
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims abstract description 84
- 102000004877 Insulin Human genes 0.000 claims abstract description 43
- 108090001061 Insulin Proteins 0.000 claims abstract description 43
- 229940125396 insulin Drugs 0.000 claims abstract description 43
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 22
- 230000036651 mood Effects 0.000 claims abstract description 14
- 230000002093 peripheral effect Effects 0.000 claims abstract description 12
- 239000003623 enhancer Substances 0.000 claims abstract description 11
- 230000004580 weight loss Effects 0.000 claims description 23
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims description 15
- 229960000367 inositol Drugs 0.000 claims description 15
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims description 15
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 9
- 102000004882 Lipase Human genes 0.000 claims description 8
- 108090001060 Lipase Proteins 0.000 claims description 8
- 239000004367 Lipase Substances 0.000 claims description 8
- 235000019421 lipase Nutrition 0.000 claims description 8
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 7
- 239000011701 zinc Substances 0.000 claims description 7
- 229910052725 zinc Inorganic materials 0.000 claims description 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 6
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 claims description 6
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 claims description 6
- 229940093265 berberine Drugs 0.000 claims description 6
- 239000011777 magnesium Substances 0.000 claims description 6
- 229910052749 magnesium Inorganic materials 0.000 claims description 6
- 102000004366 Glucosidases Human genes 0.000 claims description 5
- 108010056771 Glucosidases Proteins 0.000 claims description 5
- 244000042430 Rhodiola rosea Species 0.000 claims description 5
- 235000003713 Rhodiola rosea Nutrition 0.000 claims description 5
- 239000003112 inhibitor Substances 0.000 claims description 5
- 241000647991 Salacia reticulata Species 0.000 claims description 4
- 235000013824 polyphenols Nutrition 0.000 claims description 4
- 150000008442 polyphenolic compounds Chemical class 0.000 claims description 3
- 240000001972 Gardenia jasminoides Species 0.000 claims 1
- 229940086609 Lipase inhibitor Drugs 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000003925 fat Substances 0.000 description 29
- 230000000694 effects Effects 0.000 description 23
- 235000013305 food Nutrition 0.000 description 22
- 208000016261 weight loss Diseases 0.000 description 18
- 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 16
- 239000008280 blood Substances 0.000 description 16
- 210000004369 blood Anatomy 0.000 description 16
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 16
- 239000008103 glucose Substances 0.000 description 16
- 239000000284 extract Substances 0.000 description 12
- 235000019786 weight gain Nutrition 0.000 description 11
- 230000009471 action Effects 0.000 description 10
- 150000001720 carbohydrates Chemical class 0.000 description 10
- 235000014633 carbohydrates Nutrition 0.000 description 10
- 235000014113 dietary fatty acids Nutrition 0.000 description 10
- 230000029087 digestion Effects 0.000 description 10
- 229930195729 fatty acid Natural products 0.000 description 10
- 239000000194 fatty acid Substances 0.000 description 10
- 150000004665 fatty acids Chemical class 0.000 description 10
- 230000007246 mechanism Effects 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 230000004584 weight gain Effects 0.000 description 10
- 206010022489 Insulin Resistance Diseases 0.000 description 9
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 9
- 241000196324 Embryophyta Species 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 241000282414 Homo sapiens Species 0.000 description 7
- 102000003746 Insulin Receptor Human genes 0.000 description 7
- 108010001127 Insulin Receptor Proteins 0.000 description 7
- 206010012601 diabetes mellitus Diseases 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 230000006872 improvement Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 210000002784 stomach Anatomy 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 210000001789 adipocyte Anatomy 0.000 description 6
- 229940077731 carbohydrate nutrients Drugs 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 150000003626 triacylglycerols Chemical class 0.000 description 6
- 208000019901 Anxiety disease Diseases 0.000 description 5
- 241001165494 Rhodiola Species 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 210000000577 adipose tissue Anatomy 0.000 description 5
- 235000021407 appetite control Nutrition 0.000 description 5
- 235000019577 caloric intake Nutrition 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 102000038379 digestive enzymes Human genes 0.000 description 5
- 108091007734 digestive enzymes Proteins 0.000 description 5
- 210000000936 intestine Anatomy 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 208000011688 Generalised anxiety disease Diseases 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical group OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 description 4
- 241000220225 Malus Species 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 4
- 235000004458 antinutrient Nutrition 0.000 description 4
- 230000036506 anxiety Effects 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 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 4
- 210000004556 brain Anatomy 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 229940088597 hormone Drugs 0.000 description 4
- 239000005556 hormone Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 235000002949 phytic acid Nutrition 0.000 description 4
- 229940068041 phytic acid Drugs 0.000 description 4
- 239000000467 phytic acid Substances 0.000 description 4
- 239000000902 placebo Substances 0.000 description 4
- 229940068196 placebo Drugs 0.000 description 4
- 230000001603 reducing effect Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 210000000813 small intestine Anatomy 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 239000013589 supplement Substances 0.000 description 4
- 230000009469 supplementation Effects 0.000 description 4
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 3
- SEBIKDIMAPSUBY-ARYZWOCPSA-N Crocin Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)OC(=O)C(C)=CC=CC(C)=C\C=C\C=C(/C)\C=C\C=C(C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)O1)O)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SEBIKDIMAPSUBY-ARYZWOCPSA-N 0.000 description 3
- SEBIKDIMAPSUBY-JAUCNNNOSA-N Crocin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C(=O)OC1OC(COC2OC(CO)C(O)C(O)C2O)C(O)C(O)C1O)C=CC=C(/C)C(=O)OC3OC(COC4OC(CO)C(O)C(O)C4O)C(O)C(O)C3O SEBIKDIMAPSUBY-JAUCNNNOSA-N 0.000 description 3
- 229930091371 Fructose Natural products 0.000 description 3
- 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 3
- 208000019022 Mood disease Diseases 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 3
- 235000019789 appetite Nutrition 0.000 description 3
- 230000036528 appetite Effects 0.000 description 3
- 230000031018 biological processes and functions Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 150000002016 disaccharides Chemical class 0.000 description 3
- 230000002996 emotional effect Effects 0.000 description 3
- 229960002737 fructose Drugs 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000006377 glucose transport Effects 0.000 description 3
- 150000004676 glycans Chemical class 0.000 description 3
- 229960004801 imipramine Drugs 0.000 description 3
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000004130 lipolysis Effects 0.000 description 3
- 230000003340 mental effect Effects 0.000 description 3
- 150000002772 monosaccharides Chemical class 0.000 description 3
- 239000002858 neurotransmitter agent Substances 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 235000016709 nutrition Nutrition 0.000 description 3
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229940076279 serotonin Drugs 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 2
- PANKHBYNKQNAHN-JTBLXSOISA-N Crocetin Natural products OC(=O)C(\C)=C/C=C/C(/C)=C\C=C\C=C(\C)/C=C/C=C(/C)C(O)=O PANKHBYNKQNAHN-JTBLXSOISA-N 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 102000000853 LDL receptors Human genes 0.000 description 2
- 108010001831 LDL receptors Proteins 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
- 101710184309 Probable sucrose-6-phosphate hydrolase Proteins 0.000 description 2
- 241000545263 Salacia <hydroid> Species 0.000 description 2
- 102000000019 Sterol Esterase Human genes 0.000 description 2
- 108010055297 Sterol Esterase Proteins 0.000 description 2
- 102400000472 Sucrase Human genes 0.000 description 2
- 101710112652 Sucrose-6-phosphate hydrolase Proteins 0.000 description 2
- 208000028552 Treatment-Resistant Depressive disease Diseases 0.000 description 2
- 235000021068 Western diet Nutrition 0.000 description 2
- OMKXVFDVAGCPBS-GTEYUELZSA-N [(2s,3s,4r,5r,6s)-1-[(2r,3s,4s)-3,4-dihydroxy-2-(hydroxymethyl)thiolan-1-ium-1-yl]-2,4,5,6,7-pentahydroxyheptan-3-yl] sulfate Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](OS([O-])(=O)=O)[C@H](O)C[S+]1C[C@@H](O)[C@H](O)[C@H]1CO OMKXVFDVAGCPBS-GTEYUELZSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 102000016679 alpha-Glucosidases Human genes 0.000 description 2
- 108010028144 alpha-Glucosidases Proteins 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 239000000883 anti-obesity agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- PANKHBYNKQNAHN-JUMCEFIXSA-N carotenoid dicarboxylic acid Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C(=O)O)C=CC=C(/C)C(=O)O PANKHBYNKQNAHN-JUMCEFIXSA-N 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- PANKHBYNKQNAHN-MQQNZMFNSA-N crocetin Chemical compound OC(=O)C(/C)=C/C=C/C(/C)=C/C=C/C=C(\C)/C=C/C=C(\C)C(O)=O PANKHBYNKQNAHN-MQQNZMFNSA-N 0.000 description 2
- 230000000994 depressogenic effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- 235000013367 dietary fats Nutrition 0.000 description 2
- 235000013681 dietary sucrose Nutrition 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 235000005686 eating Nutrition 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 208000029364 generalized anxiety disease Diseases 0.000 description 2
- 235000009200 high fat diet Nutrition 0.000 description 2
- 230000003054 hormonal effect Effects 0.000 description 2
- 235000003642 hunger Nutrition 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 210000003405 ileum Anatomy 0.000 description 2
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 235000011073 invertase Nutrition 0.000 description 2
- 235000019626 lipase activity Nutrition 0.000 description 2
- 238000009140 magnesium supplementation Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 235000013372 meat Nutrition 0.000 description 2
- 230000008450 motivation Effects 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 229960001243 orlistat Drugs 0.000 description 2
- 208000019906 panic disease Diseases 0.000 description 2
- 239000000419 plant extract Substances 0.000 description 2
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000036186 satiety Effects 0.000 description 2
- 235000019627 satiety Nutrition 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 description 1
- DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- CWVRJTMFETXNAD-FWCWNIRPSA-N 3-O-Caffeoylquinic acid Natural products O[C@H]1[C@@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-FWCWNIRPSA-N 0.000 description 1
- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 1
- 206010054196 Affect lability Diseases 0.000 description 1
- 208000008811 Agoraphobia Diseases 0.000 description 1
- 241000707825 Argyrosomus regius Species 0.000 description 1
- 240000000724 Berberis vulgaris Species 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- JMGZEFIQIZZSBH-UHFFFAOYSA-N Bioquercetin Natural products CC1OC(OCC(O)C2OC(OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5)C(O)C2O)C(O)C(O)C1O JMGZEFIQIZZSBH-UHFFFAOYSA-N 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- PZIRUHCJZBGLDY-UHFFFAOYSA-N Caffeoylquinic acid Natural products CC(CCC(=O)C(C)C1C(=O)CC2C3CC(O)C4CC(O)CCC4(C)C3CCC12C)C(=O)O PZIRUHCJZBGLDY-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241001503987 Clematis vitalba Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 244000247747 Coptis groenlandica Species 0.000 description 1
- 235000002991 Coptis groenlandica Nutrition 0.000 description 1
- 241000086550 Dinosauria Species 0.000 description 1
- 208000027534 Emotional disease Diseases 0.000 description 1
- 244000111489 Gardenia augusta Species 0.000 description 1
- IBFYXTRXDNAPMM-BVTMAQQCSA-N Geniposide Chemical compound O([C@@H]1OC=C([C@@H]2[C@H]1C(=CC2)CO)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O IBFYXTRXDNAPMM-BVTMAQQCSA-N 0.000 description 1
- IBFYXTRXDNAPMM-FZEIBHLUSA-N Geniposide Natural products COC(=O)C1=CO[C@@H](O[C@H]2O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]2O)[C@H]2[C@@H]1CC=C2CO IBFYXTRXDNAPMM-FZEIBHLUSA-N 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 102100031004 Histidine-tRNA ligase, cytoplasmic Human genes 0.000 description 1
- 101000843187 Homo sapiens Histidine-tRNA ligase, cytoplasmic Proteins 0.000 description 1
- 241000735432 Hydrastis canadensis Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 1
- 206010020710 Hyperphagia Diseases 0.000 description 1
- 108010059881 Lactase Proteins 0.000 description 1
- 244000198896 Lagerstroemia speciosa Species 0.000 description 1
- 241000134253 Lanka Species 0.000 description 1
- 229940127470 Lipase Inhibitors Drugs 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 208000008167 Magnesium Deficiency Diseases 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- SNIXRMIHFOIVBB-UHFFFAOYSA-N N-Hydroxyl-tryptamine Chemical compound C1=CC=C2C(CCNO)=CNC2=C1 SNIXRMIHFOIVBB-UHFFFAOYSA-N 0.000 description 1
- CWVRJTMFETXNAD-KLZCAUPSSA-N Neochlorogenin-saeure Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O CWVRJTMFETXNAD-KLZCAUPSSA-N 0.000 description 1
- YCUKGYWMYZBCGT-MJYKKNOESA-N OC[C@H](O)[C@@H](O)[C@H](OS([O-])(=O)=O)[C@H](O)C[S@@+]1C[C@@H](O)[C@H](O)[C@H]1CO Chemical compound OC[C@H](O)[C@@H](O)[C@H](OS([O-])(=O)=O)[C@H](O)C[S@@+]1C[C@@H](O)[C@H](O)[C@H]1CO YCUKGYWMYZBCGT-MJYKKNOESA-N 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 206010033664 Panic attack Diseases 0.000 description 1
- CWEZAWNPTYBADX-UHFFFAOYSA-N Procyanidin Natural products OC1C(OC2C(O)C(Oc3c2c(O)cc(O)c3C4C(O)C(Oc5cc(O)cc(O)c45)c6ccc(O)c(O)c6)c7ccc(O)c(O)c7)c8c(O)cc(O)cc8OC1c9ccc(O)c(O)c9 CWEZAWNPTYBADX-UHFFFAOYSA-N 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 230000011759 adipose tissue development Effects 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000002929 anti-fatigue Effects 0.000 description 1
- 230000003579 anti-obesity Effects 0.000 description 1
- 229940125710 antiobesity agent Drugs 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 235000021016 apples Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- VGLLGNISLBPZNL-RBUKDIBWSA-N arborescoside Natural products O=C(OC)C=1[C@@H]2C([C@H](O[C@H]3[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O3)OC=1)=C(CO)CC2 VGLLGNISLBPZNL-RBUKDIBWSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 208000014679 binge eating disease Diseases 0.000 description 1
- 231100000693 bioaccumulation Toxicity 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 1
- 235000005487 catechin Nutrition 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007987 cellular zinc ion homeostasis Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940074393 chlorogenic acid Drugs 0.000 description 1
- CWVRJTMFETXNAD-JUHZACGLSA-N chlorogenic acid Chemical compound O[C@@H]1[C@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-JUHZACGLSA-N 0.000 description 1
- FFQSDFBBSXGVKF-KHSQJDLVSA-N chlorogenic acid Natural products O[C@@H]1C[C@](O)(C[C@@H](CC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O FFQSDFBBSXGVKF-KHSQJDLVSA-N 0.000 description 1
- 235000001368 chlorogenic acid Nutrition 0.000 description 1
- 229950001002 cianidanol Drugs 0.000 description 1
- BMRSEYFENKXDIS-KLZCAUPSSA-N cis-3-O-p-coumaroylquinic acid Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)cc2)[C@@H]1O)C(=O)O BMRSEYFENKXDIS-KLZCAUPSSA-N 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 235000011850 desserts Nutrition 0.000 description 1
- 235000021196 dietary intervention Nutrition 0.000 description 1
- 235000001916 dieting Nutrition 0.000 description 1
- 230000037228 dieting effect Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- IVTMALDHFAHOGL-UHFFFAOYSA-N eriodictyol 7-O-rutinoside Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC=2C=C3C(C(C(O)=C(O3)C=3C=C(O)C(O)=CC=3)=O)=C(O)C=2)O1 IVTMALDHFAHOGL-UHFFFAOYSA-N 0.000 description 1
- 235000021321 essential mineral Nutrition 0.000 description 1
- 235000013410 fast food Nutrition 0.000 description 1
- 229960001582 fenfluramine Drugs 0.000 description 1
- 229960004038 fluvoxamine Drugs 0.000 description 1
- CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 235000012020 french fries Nutrition 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 150000002303 glucose derivatives Chemical class 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 230000035929 gnawing Effects 0.000 description 1
- 235000005679 goldenseal Nutrition 0.000 description 1
- 230000036433 growing body Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000007407 health benefit Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 1
- 201000008980 hyperinsulinism Diseases 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 230000003585 interneuronal effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000001596 intra-abdominal fat Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229930013397 isoquinoline alkaloid Natural products 0.000 description 1
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 229940116108 lactase Drugs 0.000 description 1
- 239000008141 laxative Substances 0.000 description 1
- 229940125722 laxative agent Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 150000002681 magnesium compounds Chemical class 0.000 description 1
- 235000004764 magnesium deficiency Nutrition 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000036997 mental performance Effects 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000004050 mood stabilizer Substances 0.000 description 1
- 229940127237 mood stabilizer Drugs 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000009251 neurologic dysfunction Effects 0.000 description 1
- 208000015015 neurological dysfunction Diseases 0.000 description 1
- 230000007658 neurological function Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 230000003557 neuropsychological effect Effects 0.000 description 1
- 235000008935 nutritious Nutrition 0.000 description 1
- 235000020830 overeating Nutrition 0.000 description 1
- 230000000624 ovulatory effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000003119 painkilling effect Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000004526 pharmaceutical effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- -1 phorodzin Chemical compound 0.000 description 1
- 235000017807 phytochemicals Nutrition 0.000 description 1
- 229930000223 plant secondary metabolite Natural products 0.000 description 1
- 150000004804 polysaccharides Polymers 0.000 description 1
- 210000000229 preadipocyte Anatomy 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 229920002414 procyanidin Polymers 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- FDRQPMVGJOQVTL-UHFFFAOYSA-N quercetin rutinoside Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 FDRQPMVGJOQVTL-UHFFFAOYSA-N 0.000 description 1
- 230000003893 regulation of appetite Effects 0.000 description 1
- 230000001020 rhythmical effect Effects 0.000 description 1
- JZCPYUJPEARBJL-UHFFFAOYSA-N rimonabant Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JZCPYUJPEARBJL-UHFFFAOYSA-N 0.000 description 1
- 229960003015 rimonabant Drugs 0.000 description 1
- IKGXIBQEEMLURG-BKUODXTLSA-N rutin Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@@H]1OC[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-BKUODXTLSA-N 0.000 description 1
- ALABRVAAKCSLSC-UHFFFAOYSA-N rutin Natural products CC1OC(OCC2OC(O)C(O)C(O)C2O)C(O)C(O)C1OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5 ALABRVAAKCSLSC-UHFFFAOYSA-N 0.000 description 1
- 235000005493 rutin Nutrition 0.000 description 1
- 229960004555 rutoside Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229960004425 sibutramine Drugs 0.000 description 1
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000007593 synaptic transmission, glutaminergic Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 229940002552 xenical Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- 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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- 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
- A23L33/30—Dietetic or nutritional methods, e.g. for losing weight
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
-
- 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)
-
- 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)
- A61K36/29—Berberidaceae (Barberry family), e.g. barberry, cohosh or mayapple
-
- 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)
- A61K36/37—Celastraceae (Staff-tree or Bittersweet family), e.g. tripterygium or spindletree
-
- 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)
- A61K36/41—Crassulaceae (Stonecrop family)
-
- 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)
- A61K36/74—Rubiaceae (Madder family)
- A61K36/744—Gardenia
-
- 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
-
- 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
Definitions
- This invention relates to the unique combination of three novel dietary supplements for use in a weight loss program.
- this invention relates to a usage in combination of three novel nutritional agents simultaneously, with each agent targeting a different obesity-promoting category.
- each of the three nutritional agents displays a unique weight-loss benefit within its own distinctive category and can effectively be used to treat or prevent obesity as a single or standalone treatment strategy.
- CATEGORY A BEHAVIOUR [0009] Most people gain weight because they eat too much. This could merely be because of bad habits, but often over-eating stems from emotional and medical conditions that make appetite control very difficult.
- the inventor has demonstrated that large numbers of obese individuals had undiagnosed psychological disorders such as the Binge Eating Disorder (Obsessive Compulsive Disorder), Attention Deficit Disorder (ADHD/ADD) and other mood disorders, (such as depression) and anxiety disorders (such as Generalised Anxiety Disorder), conditions that all lower levels of compliance and motivation. Giving these individuals a meal-plan of whatever kind without helping them address their underlying perceptive emotional disorder sets them up for failure right from the start and is therefore a futile exercise.
- Binge Eating Disorder Obsessive Compulsive Disorder
- ADHD/ADD Attention Deficit Disorder
- other mood disorders such as depression
- anxiety disorders such as Generalised Anxiety Disorder
- Insulin has several different effects that lead to fat accumulation in adipose tissue. Firstly, insulin promotes fat synthesis. When the quantity of glucose that enters the liver cells is more than what can be stored as glycogen, insulin promotes the conversion of excess glucose into fatty acids. These fatty acids are subsequently packaged as triglycerides in very low density lipoproteins and transported to the adipose tissue where they are deposited as fat. However, insulin also increases the utilisation of glucose by most of the body's tissues, which automatically decreases the utilisation of fat, thus functioning as a "fat sparer". [0014] Secondly, insulin plays a role in fat storage.
- insulin By inhibiting the action of hormone-sensitive lipase, an enzyme that causes hydrolysis of the triglycerides already stored in the fat cells, insulin inhibits the release of fatty acids into the circulating blood stream, thereby promoting obesity. Insulin also promotes glucose transport through the cell membrane into the fat cells in the same way that it promotes glucose transport into the muscle cells. Although some of this glucose is then utilized to synthesize small amounts of fatty acids, the glucose also forms large quantities of glycerophosphate which supplies the glycerol backbone that combines with fatty acids to form triglycerides molecules which are a dominant storage form of fat in adipose cells. Therefore, when insulin is not available, storage of a large amount of fatty acids transported from the liver via lipoproteins is almost totally blocked.
- Fat cells have historically been accredited with two main functions, namely that of storing energy and preserving body temperature via insulation.
- fat cells once filled with fat, also assume a hormonal function by manufacturing and releasing various chemical substances called inflammatory cytokines, able to mimic or interfere with normal hormonal functions.
- inflammatory cytokines able to mimic or interfere with normal hormonal functions.
- some of these inflammatory cytokines disrupt insulin's role on cellular level (at the insulin receptor that regulates the glucose portal across the cell membrane) and render insulin less effective.
- the medical term for this condition is 'insulin resistance'. To get the same task done as before, the body compensates by producing even more insulin, and insulin levels rise above the norm.
- the invention in this category is based on the proposition that aspects of fat breakdown and use for providing energy are enhanced in the absence of insulin. This can occur normally between meals when secretion of insulin is minimal but the effect becomes extreme in diabetes mellitus when secretion of insulin, is almost absent. When this happens, the aforementioned effects of insulin causing the production and storage of fat, are reversed.
- a dominant effect is that the enzyme hormone-sensitive lipase in the fat cells becomes strongly activated. This causes hydrolysis of stored triglycerides, releasing large quantities of fatty acids and glycerol from the adipose tissue into the circulating blood. The net effect is significant weight- loss.
- a goal in this respect is a strategy in which the insulin level is lowered to a value which is still healthy but which does not promote fat deposition and fat storage, thereby counteracting insulin's obesity-promoting effects.
- the invention is inter alia based on the use of a combination of naturally derived compounds and plant extracts that display complementary and synergistic pharmaceutical effects, all of which have been proven to be useful for the treatment or alleviation of insulin resistance.
- the mode of action is via an unique mechanism, which optimises catabolic metabolism by lowering insulin levels and increasing the usage of fat for energy purposes, thereby assisting with weight loss.
- Fat contains more than twice the amount of energy as the same quality of carbohydrate and protein.
- the human intestine is able to absorb 95% of all dietary fat, and it is therefore not surprising that a high fat diet is readily converted into fatty tissue, especially in individuals with a slow metabolic rate.
- each triglyceride consist of three smaller building blocks, called fatty acids, bonded together by a larger carrier molecule called glycerol. Triglyceride molecules are far too large to be absorbed through the intestinal wall, and therefore need to be broken down into smaller particles. This happens during the process of digestion, when fat-digesting enzymes split the bonds between fatty acids and set them free. Once released, each individual fatty acid freely passes through the wall of the small intestine and enters the body.
- Fats are medically called 'lipids'. Fat digestion is therefore called 'lipolysis' and the fat-digesting enzymes responsible for this process are the 'lipases". There are several different lipases, released throughout the gastro-intestinal tract. Lipolysis takes place via the combined action of different lipases. The rate at which lipolysis takes place and the consequent supply of free fatty acids to the body can be affected by various factors. These include certain biochemical agents, many of which are naturally occurring or derived from nature.
- carbohydrates are too large to be absorbed into the system without the splicing action of digestive enzymes. All carbohydrates are constructed from the elements carbon, hydrogen and oxygen, arranged in a three dimensional ring-like structure. A single ring is called a monosaccharide, two rings are a disaccharide, whilst those with more than two rings are the polysaccharides. For obvious reasons, monosaccharides are the smallest carbohydrate molecules and can be absorbed directly into the body without the need for digestion. Monosaccharides include glucose, the dominant energy molecule of the body, as well as fructose or 'fruit sugar', naturally found in fruit and fruit juice.
- the disaccharides include table sugar and milk sugar, whilst the polysaccharides form the various starches. These two groups are the most important source of calories consumed in the average Western diet. Being too large to be absorbed, both disaccharides and polysaccharides require reduction through digestion into smaller molecules like glucose and fructose which can be absorbed and utilised as energy.
- Nutrients are essential to health and the dominant reason all living creatures must eat a variety of nutritious food. Nutrients enter the body and are absorbed via the intestines. Antinutrients, however, are agents that block or interfere with the absorption of nutrients. Antinutrients are either natural or synthetic compounds and are found at some level in almost all foods for a variety of reasons, including food items that we consume on a daily basis. A common example is phytic acid, found abundantly in sodas and junk food. Phytic acid has the ability to form insoluble complexes with calcium, zinc, iron and copper, thereby reducing their absorption in the intestines and potentially causing a shortage.
- each of the three nutritional agents displays a unique weight-loss benefit within its own distinctive category and can effectively be used to treat or prevent obesity as a single or standalone treatment strategy.
- the invention is based, however, on the premise that the use of three anti- obesity products, each targeting different obesity promoting mechanisms, will have a synergistic weight loss effect in subjects.
- a premise is that the use of a mood enhancer, included in a weight loss program, may be beneficial. It is believed that the effects of a mood enhancer, such as increased endurance and diminished fatigue as well as a heightened sense of emotional and mental wellbeing, would help a subject to be more inclined to begin with, and adhere to, an exercise and diet program.
- a mood enhancer identified as being suitable for use in a weight-loss program, consists of a composition of a plant extract, neutraceutical food extract and two essential minerals, namely inositol, rhodiola rosea, magnesium and zinc, respectively.
- Rhodiola rosea is a plant that grows in cold regions around the world. These regions include the Arctic, the mountainous areas of central Asia, the Alps, Scandinavia and Iceland. Traditionally, Rhodiola rosea was used by Siberians and Scandinavians to improve vitality in harsh conditions presented by bitter cold climates and high altitude areas. To improve physical and mental endurance while persevering under stressful conditions, Rhodiola was routinely given to Soviet cosmonauts, KGB secret agents and special force soldiers. Various studies have assessed Rhodiola extract's effect on the neurological function of humans and animals In particular, studies on human subjects have shown that it improves mood by displaying the rare quality of alleviating both the symptoms of depression and anxiety.
- Rhodiola's mode of action appears to be mediated by its influence on the levels of the two most important "happiness” neurotransmitters, namely serotonin and dopamine.
- Rhodiola rosea extract exerts an anti-fatigue effect that improves general mental performance and increases the ability to concentrate in healthy subjects.
- One such double-blind, cross-over study examined this effect in healthy physicians during night duty. During this trial, a statistically significant improvement in perceptive and cognitive cerebral functions was measured in all the doctors that participated in the trail.
- Inositol occurs naturally as phytic acid in the fibre component of certain plant foods, and as myo-inositol in meat. Myo-inositol is found to bio-accumulate most abundantly in the central nervous system, where it plays an important role as the structural basis for numerous signalling and secondary messenger molecules. These play a crucial role in a number of biological processes, including nerve guidance, the modulation of serotonin's activity, gene expression and the assembly of the cytoskeleton of neurons.
- inositol supplementation shows promising results for people suffering from neuro-psychological conditions such as generalised anxiety disorder, panic disorder, obsessive-compulsive disorder, bulimia, agoraphobia and depression.
- inositol proved superior to fluvoxamine, a popular antidepressant belonging to the class of SSRI drugs, (serotonin selective reuptake inhibitors), for decreasing the number of panic attacks.
- TRD treatment-resistant depression
- Magnesium-deficiency is known to lead to the dysfunctional opening of specialised calcium channels (N-methyl-d-aspartate /NMDA coupled), thereby causing neuronal injury and subsequent neurological dysfunction. It is postulated that this pathological development may present in humans with the symptom of depression. Evidence from several studies strongly links magnesium with the intracellular and interneuronal processes associated with certain mood disorders, especially depression.
- magnesium supplementation was comparable to the anti-depressant drug imipramine.
- Zinc stimulates the activity of about 100 different enzymatic reactions in the body and, like magnesium, is an important modulator of glutaminergic transmission in the brain.
- a growing body of evidence implicates a derangement of zinc homeostasis in the psychopathology as well as treatment of mood disorders.
- Zinc's antidepressant-like activity has been examined in a variety of tests and models in laboratory animals as well as human studies.
- zinc supplementation significantly reduced depression scores and facilitated the treatment outcome in antidepressant treatment resistant patients.
- a premise is that the use of an insulin sparing agent, included in a weight loss program, may be beneficial. It is believed that the effect of lowering insulin levels, via a unique triple action mechanism, is beneficial to weight loss for the reasons mentioned hereinbefore.
- the dietary insulin sparing component of the invention is a combination agent indicated for the treatment of insulin resistance, obesity and metabolic syndrome. It contains three biological actives, namely berberine , banaba leaf and inositol.
- Berberine is a quaternary ammonium salt from the group of isoquinoline alkaloids found in plants such as Berberis, Hydrastis canadensis and Coptis chinenses. Berberine has demonstrated the property of being able to up-regulate activity on both low-density-lipoprotein receptors (LDLR), as well as insulin receptors (InsR). To explain how this mechanism works, one has to touch on the topic of two common biological processes that happen throughout the body and which, to a large degree, control how the body communicates with cells. These processes are called 'downregulation' and 'upregulation'.
- LDLR low-density-lipoprotein receptors
- InsR insulin receptors
- Each cell contains a certain amount of receptors on its surface membrane.
- the number of receptors can be increased (“upregulate”) or decreased (“downregulated”). If a cell has fewer receptors on its surface membrane, it is less sensitive to a chemical messenger that is attempting to communicate with the cell. Examples of chemical messengers are hormones and neurotransmitters. Pharmaceutical drugs, however, or toxins, for that matter, may also occupy these receptors and act as chemical messengers.
- An example of downregulation can be illustrated by the insulin receptor sites on the cells of a person with type 2 diabetes. If the number of receptors on the surface membrane decreases, the sensitivity of the membrane to insulin will also decrease. The body will compensate for this by releasing more insulin to complete the same task.
- Insulin levels drop by up-regulating activity on insulin receptors (InsR).
- InsR insulin receptors
- Studies on berberine demonstrate berberine's ability to stimulate glucose transport across the cell membrane to lower elevated blood glucose levels, to prevent or alleviate insulin resistance, to increase insulin receptor expression and to inhibit adipogenesis in human white preadipocytes.
- Banaba (Lagerstroemia speciosa) is a medicinal plant that grows naturally in India, Southeast Asia and the Philippines. Tea brewed from the leaves is traditionally used to treat diabetes in Eastern medicine and has been in use for over a century. The hypoglycaemic effect of banaba leaf extract has been shown to be similar to that of insulin. The blood sugar regulating properties of banaba and its ability to increase insulin sensitivity have scientifically been demonstrated in cell culture, animal and human studies. Tighter blood sugar control and a reduction in insulin levels have also demonstrated weight-loss in trials, even in the absence of dietary alterations.
- inositol occurs naturally as phytic acid in the fibre component of certain plant foods, and as myo-inositol in meat. It has an important role as a structural basis for numerous signalling and secondary messenger molecules that play a crucial role in a number of biological processes, including insulin signal transduction.
- PCOS polycystic ovary syndrome
- inositol increases the action of insulin by improving insulin sensitivity.
- study subjects benefited by showing improved ovulatory function, decreased blood pressure and plasma triglyceride concentrations.
- a premise is that the use of a peripheral energy blocker, included in a weight loss program, may be beneficial. It is believed that the effects will assist obese individuals by preventing the digestion of excess fat and refined carbohydrates in their diet, thereby allowing it to pass through their systems without getting absorbed.
- apple extracts inhibited lipase activity by more than 70%. Apples contain several different phenolic substances, which include chlorogenic acid, catechin, phorodzin, rutin and some procyanidins. Other studies have also demonstrated that apple polyphenols display highly effective lipase blocking activity.
- Salacia reticulata is a climber found in Sri Lanka and India. Its roots and stems have been used to treat diabetes for centuries. In Japan, Salacia is consumed as a food supplement for the purposes of suppressing high blood sugar levels. Pharmacological studies have demonstrated that various multi-target actions contribute to Salicia root-extract's improvement of type 2 diabetes, high blood sugar and cholesterol levels, conditions commonly associated with obesity. scientistss have found that Salacia's effects are mainly due to the presence of highly potent glucosidase inhibitors.
- the main compounds responsible for a-glucosidase inhibition are salicinol, kotalanol and ponkoranol.
- kotalanol demonstrated more potent inhibitory activity against sucrase, the enzyme that digests sucrose (table sugar), than the diabetic drug acarbose.
- sucrase the enzyme that digests sucrose (table sugar)
- Various studies have shown that the oral administration of a Salacia reticulata extract suppressed body weight gain without affecting food intake.
- a peripheral energy blocker containing all the above agents in a proprietary blend, assists obese individuals by preventing the digestion of excess fat and refined carbohydrates. But, besides blocking calorie intake, the peripheral energy blocker has also been designed to assist with appetite control.
- the stomach also plays a role in the regulation of appetite. If one has not had food for a while, the stomach undergoes a series of rhythmic contractions, which present as gnawing, cramp-like sensations in the pit of the stomach. These are commonly referred to as 'hunger pangs'.
- signals from the stomach suppress the feeding centre in the brain, thereby reducing the desire to eat. This mechanism is controlled by nerves which link the stomach with the feeding centre, as well as various chemical messengers, the dominant player being the hormones cholecystokinen and grehlin, released by the intestines when food enters the stomach.
- Salacia reticulata 50 10 - 450 [0071] A daily dosage constitutes between 1-2 tablet of each product between 1-3 times per day.
- Group I and Group II each consisted of 5 subjects.
- Group I was administered a placebo for the first 15 weeks and then switched to a supplement of the three products for the remainder of the 30 week period.
- Group II was administered a supplement of the three products for the duration of the 30 week period.
- Table 4 indicates that the average total weight loss and average weekly weight loss recorded for Group II is more than double that of Group I.
- the cholesterol and glucose content of the blood substantially decreased for the Group II, whereas the cholesterol content of Group I had increased and the glucose decrease was significantly less in this group.
- the average BMI and waist circumference reduction were also significantly more in Group II.
- Table 5 indicates that Group I results for the last 15 weeks of the trial showed a significant increase in average weight loss and BMI and waist circumference reduction. It also indicates a substantial decrease in the blood cholesterol content and blood glucose content in the subjects in the final 15 weeks compared to the first 15 weeks.
- Table 6 compares the results of the final 15 weeks of both groups. The results show similar weight loss and similar BMI and waist circumference reductions. The reductions in blood cholesterol and blood glucose content are significantly more in Group I compared to Group II. [0083] The results in Table 5 and 6 are an indication that the supplements administered to the subjects are a likely cause of the weight reduction and blood cholesterol and blood glucose content reduction observed.
- Table 7 indicates a smaller decrease in the blood cholesterol and glucose content in the final 15 weeks compared to the first 15 weeks.
- the average weight loss and BMI reduction and waist circumference reduction remained more or less unchanged. This indicates that weight loss, blood cholesterol and glucose reduction, as well as BMI and waist measurements, reached respective plateaux.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Inorganic Chemistry (AREA)
- Hematology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
A composition for treating obesity which includes a mood enhancer, an insulin sparing agent, and a peripheral energy blocker
Description
COMPOSITION FOR OBESITY TREATMENT
BACKGROUND OF THE INVENTION
[0001] This invention relates to the unique combination of three novel dietary supplements for use in a weight loss program.
[0002] The worldwide phenomenon of weight gain, despite various attempts at dietary intervention and exercise, indicates that the current mechanisms of regulating energy balance and body weight are not able to cope with obesity-promoting genetic makeup as well as the modern food environment, where calories are abundant and relatively inexpensive.
[0003] Moderate weight loss achievements, however, are recognised to have major health benefits for overweight individuals, and increases life-expectancy in those with obesity-related complications. A reduced energy intake combined with increased energy expenditure is known to be an effective weight-loss strategy. Research however has documented that only one third of those trying to lose weight reported eating fewer calories and exercising more. In addition, it has been estimated that 90% of those who lose weight through dieting will return to their original weight within 2-5 years.
[0004] This suggests that mono-therapy to reduce body weight cannot cope with the level of over-consumption triggered by modern society. It has therefore been proposed that combination therapies might provide a better future solution.
[0005] Rather than the current single-product/single-programme approach to treat obesity, this invention relates to a usage in combination of three novel nutritional agents simultaneously, with each agent targeting a different obesity-promoting category.
[0006] Used on their own, each of the three nutritional agents displays a unique weight-loss benefit within its own distinctive category and can effectively be used to treat or prevent obesity as a single or standalone treatment strategy.
[0007] This patent application, however, is based on the strategy that the combination of the three agents simultaneously is novel, synergistic and unique, and presents an improvement to prior models. This postulation is supported by original research that demonstrates that the combination of the three products simultaneously, achieves better results, compared to each agent used as a standalone agent during testing. [0008] Numerous mechanisms control appetite, behaviour and energy regulation.
For clarification purposes, these factors will be divided into three broad categories, namely: A - behaviour B - metabolism and C - food environment, and will be discussed in this sequence in this specification.
CATEGORY A: BEHAVIOUR [0009] Most people gain weight because they eat too much. This could merely be because of bad habits, but often over-eating stems from emotional and medical conditions that make appetite control very difficult. The inventor has demonstrated that large numbers of obese individuals had undiagnosed psychological disorders such as the Binge Eating Disorder (Obsessive Compulsive Disorder), Attention Deficit Disorder (ADHD/ADD) and other mood disorders, (such as depression) and anxiety disorders (such as Generalised Anxiety Disorder), conditions that all lower levels of compliance and motivation. Giving these individuals a meal-plan of whatever kind without helping them address their underlying perceptive emotional disorder sets them up for failure right from the start and is therefore a futile exercise.
[0010] Successful weight-loss requires sustained effort, fuelled by motivation, which in turn is dependent on many other factors, including mood. Happiness and contentment are not static processes and it is difficult to maintain positive emotions like optimism, self-confidence and emotional tranquillity. Many persons must deal with difficult people on a daily basis, and can become emotionally drained and physically exhausted by numerous responsibilities. A successful solution to this problem has led the inventor to develop a mood stabiliser.
CATEGORY B: METABOLISM
[0011] The phenomenon where some individuals can consume significantly more food calories than others, without gaining weight, is well known. This has been attributed to differences, some genetic and others acquired, which are numerous and complex, but can in many instances be explained on the basis of an acquired medical condition called 'insulin resistance', of which obesity is a major precipitating factor.
[0012] The single most important controller of organic metabolism is the hormone insulin, and not the thyroid hormone, as what is often mistakenly stated.
[0013] Insulin has several different effects that lead to fat accumulation in adipose tissue. Firstly, insulin promotes fat synthesis. When the quantity of glucose that enters the liver cells is more than what can be stored as glycogen, insulin promotes the conversion of excess glucose into fatty acids. These fatty acids are subsequently packaged as triglycerides in very low density lipoproteins and transported to the adipose tissue where they are deposited as fat. However, insulin also increases the utilisation of glucose by most of the body's tissues, which automatically decreases the utilisation of fat, thus functioning as a "fat sparer".
[0014] Secondly, insulin plays a role in fat storage. By inhibiting the action of hormone-sensitive lipase, an enzyme that causes hydrolysis of the triglycerides already stored in the fat cells, insulin inhibits the release of fatty acids into the circulating blood stream, thereby promoting obesity. Insulin also promotes glucose transport through the cell membrane into the fat cells in the same way that it promotes glucose transport into the muscle cells. Although some of this glucose is then utilized to synthesize small amounts of fatty acids, the glucose also forms large quantities of glycerophosphate which supplies the glycerol backbone that combines with fatty acids to form triglycerides molecules which are a dominant storage form of fat in adipose cells. Therefore, when insulin is not available, storage of a large amount of fatty acids transported from the liver via lipoproteins is almost totally blocked.
[0015] Various studies have investigated the role that insulin plays in weight gain. In the United Kingdom Prospective Diabetes Study (UKPDS), for example, increased weight gain was directly related to improved glycaemic control and intensification of therapy with all pharmacotherapies, (with the exception of the diabetic drug metformin). However, weight gain was greatest in a group treated with insulin, where patients gained on average 6.5 kg. In addition, data from the Diabetes Control and Complication Trial (DCCT) demonstrated that insulin-associated weight gain was significantly greater in patients receiving intensified insulin intervention, compared to conventional intervention.
[0016] Fat cells have historically been accredited with two main functions, namely that of storing energy and preserving body temperature via insulation. In the presence of excess intra-abdominal (visceral) fat, however, fat cells, once filled with fat, also assume a hormonal function by manufacturing and releasing various
chemical substances called inflammatory cytokines, able to mimic or interfere with normal hormonal functions. For reasons not completely understood, some of these inflammatory cytokines disrupt insulin's role on cellular level (at the insulin receptor that regulates the glucose portal across the cell membrane) and render insulin less effective. The medical term for this condition is 'insulin resistance'. To get the same task done as before, the body compensates by producing even more insulin, and insulin levels rise above the norm.
[0017] Because of insulin's obesity-promoting effects, insulin resistance makes one more prone to gaining weight than before. In addition, it also makes it more difficult for one to lose weight. Once this condition sets in, a vicious cycle begins, explaining why many obese individuals, once burdened with excess visceral fat, experience that their metabolism has effectively slowed down.
[0018] The invention in this category is based on the proposition that aspects of fat breakdown and use for providing energy are enhanced in the absence of insulin. This can occur normally between meals when secretion of insulin is minimal but the effect becomes extreme in diabetes mellitus when secretion of insulin, is almost absent. When this happens, the aforementioned effects of insulin causing the production and storage of fat, are reversed. A dominant effect is that the enzyme hormone-sensitive lipase in the fat cells becomes strongly activated. This causes hydrolysis of stored triglycerides, releasing large quantities of fatty acids and glycerol from the adipose tissue into the circulating blood. The net effect is significant weight- loss.
[0019] A goal in this respect is a strategy in which the insulin level is lowered to a value which is still healthy but which does not promote fat deposition and fat storage, thereby counteracting insulin's obesity-promoting effects.
[0020] The invention is inter alia based on the use of a combination of naturally derived compounds and plant extracts that display complementary and synergistic pharmaceutical effects, all of which have been proven to be useful for the treatment or alleviation of insulin resistance. The mode of action is via an unique mechanism, which optimises catabolic metabolism by lowering insulin levels and increasing the usage of fat for energy purposes, thereby assisting with weight loss.
CATEGORY C: THE FOOD ENVIRONMENT
[0021] Our caveman forefathers used considerable amounts of energy and covered great distances on foot in search of food. Their meals, consisting mainly of low energy-dense foods, were often infrequent and interrupted by regular periods of famine. They also utilized large amounts of energy to maintain their body heat, especially in colder climates and in meagre habitats. In order to survive periods of starvation, the caveman's body perfected ways to store excess energy in the form of body fat. Those with more efficient storage systems had a significant advantage over their less padded friends during periods of famine.
[0022] Besides the caveman's body developing more efficient storage systems, the caveman's mind was also gearing for survival, and evolved to prevent weight loss at all costs. This basic instinct comes from the dinosaurs, inherited by cavemen (Homo erectus) and passed along to humans (Homo sapiens). If excess calories are available, appetite promotes weight gain by ensuring that the individual rather eats "too much" than "too little". Matching energy intake and energy expenditure is extremely difficult. A small mismatch of, for example, 1 % can lead to the accumulation of 10 000 calories per year, resulting in a weight gain of 1-2 kg per annum.
[0023] Modem day man, unlike cavemen, does not experience periods of famine, but still has the same ability to store energy very efficiently. The paradigm has however changed considerably and current lifestyles are vastly different. Food, now significantly more energy-dense for cavemen, has become abundant and many modern lives and social activities revolve around eating. Whilst genetics may permit the problem to occur, the food environment in the form of energy-rich food that is freely available at fast-food restaurants that line our roadways, and the rows of candies at checkout counters drive it.
[0024] The worldwide phenomenon of weight gain therefore indicates that the current mechanisms of regulating energy balance are clearly not able to cope with the prevailing obesity-promoting environment. Various mechanisms control appetite and energy intake and much attention has been focused upon the development of anti-obesity drugs that act on the central nervous system and reduce appetite. The withdrawal of numerous central working appetite suppressant drugs, however, such as fenfluramine, rimonabant and sibutramine (in Europe and under consideration in the US), suggest that targeting this pathway is not without problems.
[0025] Alternative options are agents that act on the periphery, namely the gastrointestinal system, to block or prevent calorie absorption. The fat blocker orlistat, marketed under the trade name Xenical and Alii, falls into this category and is currently the only drug registered for the treatment of obesity in Europe.
[0026] It is well known that diets high in fat lead to weight gain because of energy overconsumption. This is mainly due to fat's high energy content and low potential for producing satiety. On the other hand, the excess consumption of refined carbohydrates found in sweet snack foods, sodas and desserts is also a major cause
for weight gain. Fat, like refined carbohydrates, is rarely eaten in isolation, but more likely in combination. Good examples are French fries and ice cream.
[0027] Fat contains more than twice the amount of energy as the same quality of carbohydrate and protein. The human intestine is able to absorb 95% of all dietary fat, and it is therefore not surprising that a high fat diet is readily converted into fatty tissue, especially in individuals with a slow metabolic rate.
[0028] In the typical Western diet the dominant source (90%) of fat comes packaged as triglycerides. Each triglyceride consist of three smaller building blocks, called fatty acids, bonded together by a larger carrier molecule called glycerol. Triglyceride molecules are far too large to be absorbed through the intestinal wall, and therefore need to be broken down into smaller particles. This happens during the process of digestion, when fat-digesting enzymes split the bonds between fatty acids and set them free. Once released, each individual fatty acid freely passes through the wall of the small intestine and enters the body.
[0029] Fats are medically called 'lipids'. Fat digestion is therefore called 'lipolysis' and the fat-digesting enzymes responsible for this process are the 'lipases". There are several different lipases, released throughout the gastro-intestinal tract. Lipolysis takes place via the combined action of different lipases. The rate at which lipolysis takes place and the consequent supply of free fatty acids to the body can be affected by various factors. These include certain biochemical agents, many of which are naturally occurring or derived from nature.
[0030] Like triglycerides, most carbohydrates are too large to be absorbed into the system without the splicing action of digestive enzymes. All carbohydrates are constructed from the elements carbon, hydrogen and oxygen, arranged in a three dimensional ring-like structure. A single ring is called a monosaccharide, two rings
are a disaccharide, whilst those with more than two rings are the polysaccharides. For obvious reasons, monosaccharides are the smallest carbohydrate molecules and can be absorbed directly into the body without the need for digestion. Monosaccharides include glucose, the dominant energy molecule of the body, as well as fructose or 'fruit sugar', naturally found in fruit and fruit juice.
[0031] The disaccharides include table sugar and milk sugar, whilst the polysaccharides form the various starches. These two groups are the most important source of calories consumed in the average Western diet. Being too large to be absorbed, both disaccharides and polysaccharides require reduction through digestion into smaller molecules like glucose and fructose which can be absorbed and utilised as energy.
[0032] Like fat, the digestion of carbohydrate begins in the mouth and continues in the small intestines by the action of various digestive enzymes, mostly produced by the pancreas. This process is completed by another group of enzymes found in the intestines, which include maltase, sucrase, and lactase, collectively known as the aplha-glucosidases.
[0033] Nutrients are essential to health and the dominant reason all living creatures must eat a variety of nutritious food. Nutrients enter the body and are absorbed via the intestines. Antinutrients, however, are agents that block or interfere with the absorption of nutrients. Antinutrients are either natural or synthetic compounds and are found at some level in almost all foods for a variety of reasons, including food items that we consume on a daily basis. A common example is phytic acid, found abundantly in sodas and junk food. Phytic acid has the ability to form insoluble complexes with calcium, zinc, iron and copper, thereby reducing their absorption in the intestines and potentially causing a shortage.
[0034] Numerous antinutrients are also known to inhibit the action of digestive enzymes, including the lipases and alpha-glucosidases. In this field the inventor based his research and developed a novel unique product which is able to block carbohydrate and fat digestion simultaneously, thereby blocking the absorption of calories from both these sources after consumption.
SUMMARY OF THE INVENTION
[0035] Used on its own, each of the three nutritional agents displays a unique weight-loss benefit within its own distinctive category and can effectively be used to treat or prevent obesity as a single or standalone treatment strategy.
[0036] The invention is based, however, on the premise that the use of three anti- obesity products, each targeting different obesity promoting mechanisms, will have a synergistic weight loss effect in subjects.
[0037] The novel products developed in each individual category will be referred to according to the following schedule: A) behaviour - 'MOOD ENHANCER' B) metabolism - 'INSULIN SPARING AGENT' and C) the food environment - 'PERIPHERAL ENERGY BLOCKER'
DESCRIPTION OF PREFERRED EMBODIMENTS A - MOOD ENHANCER
[0038] A premise is that the use of a mood enhancer, included in a weight loss program, may be beneficial. It is believed that the effects of a mood enhancer, such as increased endurance and diminished fatigue as well as a heightened sense of emotional and mental wellbeing, would help a subject to be more inclined to begin with, and adhere to, an exercise and diet program.
[0039] A mood enhancer, identified as being suitable for use in a weight-loss program, consists of a composition of a plant extract, neutraceutical food extract and two essential minerals, namely inositol, rhodiola rosea, magnesium and zinc, respectively.
[0040] Rhodiola rosea is a plant that grows in cold regions around the world. These regions include the Arctic, the mountainous areas of central Asia, the Alps, Scandinavia and Iceland. Traditionally, Rhodiola rosea was used by Siberians and Scandinavians to improve vitality in harsh conditions presented by bitter cold climates and high altitude areas. To improve physical and mental endurance while persevering under stressful conditions, Rhodiola was routinely given to Soviet cosmonauts, KGB secret agents and special force soldiers. Various studies have assessed Rhodiola extract's effect on the neurological function of humans and animals In particular, studies on human subjects have shown that it improves mood by displaying the rare quality of alleviating both the symptoms of depression and anxiety.
[0041] Rhodiola's mode of action appears to be mediated by its influence on the levels of the two most important "happiness" neurotransmitters, namely serotonin and dopamine.
[0042] Trials done with Rhodiola extract on patients suffering from mild to moderate depression showed a significant improvement regarding scores of insomnia and emotional instability as compared to placebo.
[0043] During another trial, participants with generalized anxiety disorder (GAD) showed a significant improvement in anxiety-related symptoms with Rhodiola extract, as measured via three different psychometric scales, namely the Hamilton Anxiety
Rating Scale (HARS), the Four-Dimensional Anxiety and Depression Scale and the Clinical Global Impressions of Severity/Improvement Scale.
[0044] Various studies have also demonstrated that Rhodiola rosea extract exerts an anti-fatigue effect that improves general mental performance and increases the ability to concentrate in healthy subjects. One such double-blind, cross-over study, examined this effect in healthy physicians during night duty. During this trial, a statistically significant improvement in perceptive and cognitive cerebral functions was measured in all the doctors that participated in the trail.
[0045] Inositol occurs naturally as phytic acid in the fibre component of certain plant foods, and as myo-inositol in meat. Myo-inositol is found to bio-accumulate most abundantly in the central nervous system, where it plays an important role as the structural basis for numerous signalling and secondary messenger molecules. These play a crucial role in a number of biological processes, including nerve guidance, the modulation of serotonin's activity, gene expression and the assembly of the cytoskeleton of neurons.
[0046] Studies on inositol supplementation show promising results for people suffering from neuro-psychological conditions such as generalised anxiety disorder, panic disorder, obsessive-compulsive disorder, bulimia, agoraphobia and depression. In a double-blind, controlled trial, inositol proved superior to fluvoxamine, a popular antidepressant belonging to the class of SSRI drugs, (serotonin selective reuptake inhibitors), for decreasing the number of panic attacks.
[0047] Research has also indicated that many patients suffering from clinical depression have decreased levels of inositol in their cerebrospinal fluid, the liquid medium that encapsulates the brain. It has been postulated that inositol produces positive clinical results in patients with depression due to the important role that it
plays as a messenger molecule for the mood controlling neurotransmitter, 5-HTP (Hydroxytryptamine).
[0048] In another double-blind, placebo-controlled study of depressed patients, inositol supplementation resulted in the significant improvement of symptoms
[0049] Magnesium, in its ionic form, is crucial to the function of all living cells, playing a major role in regulating biological compounds like ATP, DNA and RNA. Over 300 enzymes require the presence of magnesium ions for their catalytic action. Historically, magnesium compounds are commonly used medicinally as laxatives, antacids and, until recently, treatment-resistant depression (TRD).
[0050] Magnesium-deficiency is known to lead to the dysfunctional opening of specialised calcium channels (N-methyl-d-aspartate /NMDA coupled), thereby causing neuronal injury and subsequent neurological dysfunction. It is postulated that this pathological development may present in humans with the symptom of depression. Evidence from several studies strongly links magnesium with the intracellular and interneuronal processes associated with certain mood disorders, especially depression.
[0051] Studies have also demonstrated the mental benefits of magnesium supplementation. In one animal study, magnesium supplementation was comparable to the anti-depressant drug imipramine. A randomized clinical trial done on humans, however, also showed that magnesium was as effective as imipramine when treating depression.
[0052] Zinc stimulates the activity of about 100 different enzymatic reactions in the body and, like magnesium, is an important modulator of glutaminergic transmission
in the brain. A growing body of evidence implicates a derangement of zinc homeostasis in the psychopathology as well as treatment of mood disorders.
[0053] Zinc's antidepressant-like activity has been examined in a variety of tests and models in laboratory animals as well as human studies. A placebo-controlled, double-blind study of zinc supplementation in imipramine therapy, an antidepressant drug, was conducted in sixty depressed patients fulfilling the DSM-IV criteria for major depression without psychotic symptoms. During this trial zinc supplementation significantly reduced depression scores and facilitated the treatment outcome in antidepressant treatment resistant patients.
B - INSULIN SPARING AGENT
[0054] A premise is that the use of an insulin sparing agent, included in a weight loss program, may be beneficial. It is believed that the effect of lowering insulin levels, via a unique triple action mechanism, is beneficial to weight loss for the reasons mentioned hereinbefore.
[0055] The dietary insulin sparing component of the invention is a combination agent indicated for the treatment of insulin resistance, obesity and metabolic syndrome. It contains three biological actives, namely berberine , banaba leaf and inositol.
[0056] Berberine is a quaternary ammonium salt from the group of isoquinoline alkaloids found in plants such as Berberis, Hydrastis canadensis and Coptis chinenses. Berberine has demonstrated the property of being able to up-regulate activity on both low-density-lipoprotein receptors (LDLR), as well as insulin receptors (InsR). To explain how this mechanism works, one has to touch on the topic of two common biological processes that happen throughout the body and which, to a large
degree, control how the body communicates with cells. These processes are called 'downregulation' and 'upregulation'.
[0057] Each cell contains a certain amount of receptors on its surface membrane. The number of receptors can be increased ("upregulate") or decreased ("downregulated"). If a cell has fewer receptors on its surface membrane, it is less sensitive to a chemical messenger that is attempting to communicate with the cell. Examples of chemical messengers are hormones and neurotransmitters. Pharmaceutical drugs, however, or toxins, for that matter, may also occupy these receptors and act as chemical messengers.
[0058] An example of downregulation can be illustrated by the insulin receptor sites on the cells of a person with type 2 diabetes. If the number of receptors on the surface membrane decreases, the sensitivity of the membrane to insulin will also decrease. The body will compensate for this by releasing more insulin to complete the same task.
[0059] Insulin levels drop by up-regulating activity on insulin receptors (InsR). Studies on berberine demonstrate berberine's ability to stimulate glucose transport across the cell membrane to lower elevated blood glucose levels, to prevent or alleviate insulin resistance, to increase insulin receptor expression and to inhibit adipogenesis in human white preadipocytes.
[0060] Banaba (Lagerstroemia speciosa) is a medicinal plant that grows naturally in India, Southeast Asia and the Philippines. Tea brewed from the leaves is traditionally used to treat diabetes in Eastern medicine and has been in use for over a century. The hypoglycaemic effect of banaba leaf extract has been shown to be similar to that of insulin. The blood sugar regulating properties of banaba and its ability to increase insulin sensitivity have scientifically been demonstrated in cell
culture, animal and human studies. Tighter blood sugar control and a reduction in insulin levels have also demonstrated weight-loss in trials, even in the absence of dietary alterations.
[0061] As mentioned, inositol occurs naturally as phytic acid in the fibre component of certain plant foods, and as myo-inositol in meat. It has an important role as a structural basis for numerous signalling and secondary messenger molecules that play a crucial role in a number of biological processes, including insulin signal transduction. Studies in patients with the polycystic ovary syndrome (PCOS), a condition known to be associated with insulin resistance and hyperinsulinemia, have demonstrated that inositol increases the action of insulin by improving insulin sensitivity. As a result, study subjects benefited by showing improved ovulatory function, decreased blood pressure and plasma triglyceride concentrations.
C - PERIPHERAL ENERGY BLOCKER
[0062]A premise is that the use of a peripheral energy blocker, included in a weight loss program, may be beneficial. It is believed that the effects will assist obese individuals by preventing the digestion of excess fat and refined carbohydrates in their diet, thereby allowing it to pass through their systems without getting absorbed.
[0063] In the continual search for novel anti-obesity agents, scientists have screened numerous plant-derived 'phytochemicals' for potential lipase and glucosidase inhibition. One such study examined 132 extracts from 106 plant species, used either as food sources or as medicinal plants, screening them for digestive enzyme inhibition potential. Because of their antinutrient content, the majority of extracts exhibited some degree of digestive enzyme inhibition. Whilst some of these effects were mild, others proved remarkably potent, especially when compared to synthetic
drugs. Twenty six extracts, for example, inhibited lipase activity by at least 40%, of which 10 exhibited more than 70% inhibitory activity.
[0064] Certain apple extracts inhibited lipase activity by more than 70%. Apples contain several different phenolic substances, which include chlorogenic acid, catechin, phorodzin, rutin and some procyanidins. Other studies have also demonstrated that apple polyphenols display highly effective lipase blocking activity.
[0065] Gardeniae fructus is an ancient Chinese medicine used for its painkilling, fever reducing and neuroprotective effects. Its main components are geniposide and crocin. Research has demonstrated that crocin and its metabolite, crocetin, potently inhibit the effect of lipase. In mice fed on a high fat diet, crocetin and crocin significantly reduced fat deposits, and their potency at a dose of 50 mg/kg was found to be comparable with that of orlistat at a dose of 10 mg/kg.
[0066]Salacia reticulata is a climber found in Sri Lanka and India. Its roots and stems have been used to treat diabetes for centuries. In Japan, Salacia is consumed as a food supplement for the purposes of suppressing high blood sugar levels. Pharmacological studies have demonstrated that various multi-target actions contribute to Salicia root-extract's improvement of type 2 diabetes, high blood sugar and cholesterol levels, conditions commonly associated with obesity. Scientists have found that Salacia's effects are mainly due to the presence of highly potent glucosidase inhibitors.
[0067]The main compounds responsible for a-glucosidase inhibition are salicinol, kotalanol and ponkoranol. In one study, kotalanol demonstrated more potent inhibitory activity against sucrase, the enzyme that digests sucrose (table sugar), than the diabetic drug acarbose. Various studies have shown that the oral
administration of a Salacia reticulata extract suppressed body weight gain without affecting food intake. A peripheral energy blocker, containing all the above agents in a proprietary blend, assists obese individuals by preventing the digestion of excess fat and refined carbohydrates. But, besides blocking calorie intake, the peripheral energy blocker has also been designed to assist with appetite control.
[0069] Besides the brain, the stomach also plays a role in the regulation of appetite. If one has not had food for a while, the stomach undergoes a series of rhythmic contractions, which present as gnawing, cramp-like sensations in the pit of the stomach. These are commonly referred to as 'hunger pangs'. Once the stomach becomes distended or filled with food, signals from the stomach suppress the feeding centre in the brain, thereby reducing the desire to eat. This mechanism is controlled by nerves which link the stomach with the feeding centre, as well as various chemical messengers, the dominant player being the hormones cholecystokinen and grehlin, released by the intestines when food enters the stomach.
[0070] Research has identified a new mechanism called the 'ileal brake' as a novel way to assist with appetite control. Normally, dietary fat is digested and absorbed in the first part of the small intestine, called the duodenum. However, it has long been known that if digestion and absorption of fats take place in the ileum, the second part of the small intestine, a strong feedback signal is activated which slows the gastrointestinal transit time and releases various satiety hormones including cholecystokinen. Thus, the fat digestion in the ileum caused by the peripheral energy blocker applies a 'brake' on the digestive processes by slowing it down, an additional strategy to help reduce calorie intake by reducing appetite.
TABLE OF PREFERRED EMBODIMENTS
Table 1- Mood enhancer
Table 2 - Insulin sparing agent
Table 3 - Peripheral energy blocker
SUBSTANCE DOSAGE (mg) DOSAGE RANGE
(mg)
Lipase inhibitors
Gardenia fructus 250 25 - 500
Apple polyphenols 150 20 - 550
Glucosidase inhibitors
Salacia reticulata 50 10 - 450
[0071] A daily dosage constitutes between 1-2 tablet of each product between 1-3 times per day.
Trials
[0072]A 25 week trial was conducted. 22 Subjects were divided into two groups designated Group I and Group II. Group I and Group II each consisted of 5 subjects.
[0073] Group I was administered a placebo for the first 15 weeks and then switched to a supplement of the three products for the remainder of the 30 week period.
[0074] Group II was administered a supplement of the three products for the duration of the 30 week period.
[0075]The results achieved, in the first 15 weeks, by Group I and Group II can be compared as follows;
[0076] Table 4 indicates that the average total weight loss and average weekly weight loss recorded for Group II is more than double that of Group I. The cholesterol and glucose content of the blood substantially decreased for the Group II, whereas the cholesterol content of Group I had increased and the glucose decrease was significantly less in this group. The average BMI and waist circumference reduction were also significantly more in Group II.
[0077] In the final 15 weeks Group I was administered with the supplement.
[0078]This was done to rule out genetic differences and environmental circumstances as the cause of the diverse results obtained for the two groups in the first 15 weeks.
[0079] The results recorded for Group I for the last 15 weeks, compared to the results for the first 15 weeks, are as follows;
[0081] Table 5 indicates that Group I results for the last 15 weeks of the trial showed a significant increase in average weight loss and BMI and waist circumference reduction. It also indicates a substantial decrease in the blood cholesterol content and blood glucose content in the subjects in the final 15 weeks compared to the first 15 weeks.
[0082]Table 6 compares the results of the final 15 weeks of both groups. The results show similar weight loss and similar BMI and waist circumference reductions. The reductions in blood cholesterol and blood glucose content are significantly more in Group I compared to Group II.
[0083] The results in Table 5 and 6 are an indication that the supplements administered to the subjects are a likely cause of the weight reduction and blood cholesterol and blood glucose content reduction observed.
[0084]The results of the first 15 weeks for Group II, were compared to the results of the final 15 weeks for Group II;
[0085] Table 7 indicates a smaller decrease in the blood cholesterol and glucose content in the final 15 weeks compared to the first 15 weeks. The average weight loss and BMI reduction and waist circumference reduction remained more or less unchanged. This indicates that weight loss, blood cholesterol and glucose reduction, as well as BMI and waist measurements, reached respective plateaux.
Claims
1. A pharmaceutical composition comprising a mood enhancer, an insulin sparing agent, and a peripheral energy blocker.
2. A composition according to claim 1 wherein the mood enhancer contains inositol, rhodiola rosea, magnesium and zinc.
3. A composition according to claim 1 wherein the insulin sparing agent includes berberine, banaba leaf and inositol
4. A composition according to claim 1 wherein the peripheral energy blocker contains a combination of a lipase and a glucosidase inhibitor
5. A composition according to claim 4 wherein the lipase inhibitor comprises gardenia fructus and apple polyphenols.
6. A composition according to claim 4 or 5 wherein the glucosidase inhibitor comprises salacia reticulata.
7. A method of treatment in a weight loss program, comprising simultaneous, sequential or separate administration of a therapeutically effective amount of a mood enhancer, an insulin sparing agent and a peripheral energy blocker.
8. A method according to claim 7 wherein the mood enhancer, and the insulin sparing agent and the peripheral energy blocker are included in a composition according to claim 6.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/ZA2011/000054 WO2013016742A1 (en) | 2011-07-22 | 2011-07-22 | Composition for obesity treatment |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/ZA2011/000054 WO2013016742A1 (en) | 2011-07-22 | 2011-07-22 | Composition for obesity treatment |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2013016742A1 true WO2013016742A1 (en) | 2013-01-31 |
Family
ID=44543899
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/ZA2011/000054 WO2013016742A1 (en) | 2011-07-22 | 2011-07-22 | Composition for obesity treatment |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2013016742A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ITUA20163025A1 (en) * | 2016-04-29 | 2017-10-29 | Sochim Int S P A | COMPOSITION FOR THE TREATMENT OF THE POLICISTIC OVARIAN SYNDROME |
US9849151B2 (en) | 2013-11-19 | 2017-12-26 | OmniActive Health Technologies (Canada) Limited | Salacia compositions, methods of treatment by their administration, and methods of their preparation |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005107779A2 (en) * | 2004-04-30 | 2005-11-17 | New Hc Formulations Ltd. | Weight loss composition and method of inducing weight loss |
US20060040003A1 (en) * | 2004-08-10 | 2006-02-23 | Alvin Needleman | Dietary supplement for supressing appetite, enhancing and extending satiety, improving glycemic control, and stimulant free |
US7476406B1 (en) * | 2004-05-17 | 2009-01-13 | Nse Products, Inc. | Multifaceted weight control system |
EP2070926A1 (en) * | 2006-09-30 | 2009-06-17 | Shanghai Institute of Materia Medica, Chinese Academy of Sciences | 13,13a-DIHYDROBERBERINE DERIVATIVES, THEIR PHARMACEUTICAL COMPOSITION AND USE |
WO2010104595A1 (en) * | 2009-03-11 | 2010-09-16 | Xintria Pharmaceutical Corporation, Inc. | Methods and compositions for the treatment of metabolic and cardiovascular disorders |
JP2010202634A (en) * | 2008-06-05 | 2010-09-16 | Green Kanpo Seiyaku Kk | Crude drug-containing composition and use thereof |
-
2011
- 2011-07-22 WO PCT/ZA2011/000054 patent/WO2013016742A1/en active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005107779A2 (en) * | 2004-04-30 | 2005-11-17 | New Hc Formulations Ltd. | Weight loss composition and method of inducing weight loss |
US7476406B1 (en) * | 2004-05-17 | 2009-01-13 | Nse Products, Inc. | Multifaceted weight control system |
US20060040003A1 (en) * | 2004-08-10 | 2006-02-23 | Alvin Needleman | Dietary supplement for supressing appetite, enhancing and extending satiety, improving glycemic control, and stimulant free |
EP2070926A1 (en) * | 2006-09-30 | 2009-06-17 | Shanghai Institute of Materia Medica, Chinese Academy of Sciences | 13,13a-DIHYDROBERBERINE DERIVATIVES, THEIR PHARMACEUTICAL COMPOSITION AND USE |
JP2010202634A (en) * | 2008-06-05 | 2010-09-16 | Green Kanpo Seiyaku Kk | Crude drug-containing composition and use thereof |
WO2010104595A1 (en) * | 2009-03-11 | 2010-09-16 | Xintria Pharmaceutical Corporation, Inc. | Methods and compositions for the treatment of metabolic and cardiovascular disorders |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9849151B2 (en) | 2013-11-19 | 2017-12-26 | OmniActive Health Technologies (Canada) Limited | Salacia compositions, methods of treatment by their administration, and methods of their preparation |
ITUA20163025A1 (en) * | 2016-04-29 | 2017-10-29 | Sochim Int S P A | COMPOSITION FOR THE TREATMENT OF THE POLICISTIC OVARIAN SYNDROME |
WO2017187375A1 (en) * | 2016-04-29 | 2017-11-02 | Sochim International S.P.A. | Composition for the treatment of polycystic ovary syndrome |
EP3448370B1 (en) | 2016-04-29 | 2020-10-21 | Sochim International SpA | Composition for the treatment of polycystic ovary syndrome |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Peuhkuri et al. | Diet promotes sleep duration and quality | |
AU2002364213B2 (en) | Compositions incorporating (-)-hydroxycitric acid, chromium, and gymnemic acid, and related methods for promoting healthy body weight and improving related health factors | |
US20140017337A1 (en) | Therapeutic methods | |
WO2005023021A1 (en) | Diet food | |
KR101341475B1 (en) | Healthy diet food composite without adverse effect and manufacturing method thereof | |
CN103520179B (en) | Hyperlipidemia improving agent, anemia improve compositions, uric acid level reduces compositions and beverage/food | |
US8420131B2 (en) | Composition for obesity treatment | |
Blum et al. | Genotrim™, a DNA-customized nutrigenomic product, targets genetic factors of obesity: Hypothesizing a dopamine–glucose correlation demonstrating reward deficiency syndrome (RDS) | |
RU2449600C1 (en) | Biologically active food additive | |
KR101447760B1 (en) | Dietary and pharmaceutical compositions comprising a sage extract containing a mixture of tricyclic diterpenes and their derivatives and their uses | |
CN102613461B (en) | Rapidly beautifying and weight losing nourishment and preparation method thereof | |
WO2013016742A1 (en) | Composition for obesity treatment | |
US20230180810A1 (en) | Dosage forms and methods of preparation and use thereof | |
CN102228117A (en) | Chicory tea | |
Emmons | The chemistry of joy: A three-step program for overcoming depression through western science and eastern wisdom | |
US20070298057A1 (en) | Composition and method for modulating addictive behaviors | |
CN101703249A (en) | Health care product with functions of regulating incretion and increasing immunity and preparation method thereof | |
CN106255502A (en) | Satiety continues agent and makes the lasting method of satiety | |
US8349373B1 (en) | Dietary supplement for use in a weight loss program | |
Sagar et al. | An survey on obesity stigma and its assessment with update: a review | |
CN105106310A (en) | Health product for auxiliary reduction of blood sugar | |
WO2013016741A1 (en) | Dietary supplement for use in a weight loss program | |
KR20040097813A (en) | Composition containing Diet Neurotrophic Factor having anti-fatness functions | |
Premlata et al. | Role of Vidangadi Kwatha in Madhumeha (Diabetes Mellitus Type II) | |
CN102630945A (en) | Health preserving composition |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 11751784 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 11751784 Country of ref document: EP Kind code of ref document: A1 |