EP3758798A1 - Composition containing myo-inositol and d-chiro-inositol for use in method of weight reduction, improvement of metabolic and hormonal parameters and improvement of condition of skin in women with polycystic ovary syndrome - Google Patents
Composition containing myo-inositol and d-chiro-inositol for use in method of weight reduction, improvement of metabolic and hormonal parameters and improvement of condition of skin in women with polycystic ovary syndromeInfo
- Publication number
- EP3758798A1 EP3758798A1 EP19719363.4A EP19719363A EP3758798A1 EP 3758798 A1 EP3758798 A1 EP 3758798A1 EP 19719363 A EP19719363 A EP 19719363A EP 3758798 A1 EP3758798 A1 EP 3758798A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- inositol
- chiro
- myo
- improvement
- composition containing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 title claims abstract description 115
- 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 title claims abstract description 61
- 229960000367 inositol Drugs 0.000 title claims abstract description 60
- CDAISMWEOUEBRE-LKPKBOIGSA-N 1D-chiro-inositol Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O CDAISMWEOUEBRE-LKPKBOIGSA-N 0.000 title claims abstract description 51
- 201000010065 polycystic ovary syndrome Diseases 0.000 title claims abstract description 46
- 239000000203 mixture Substances 0.000 title claims abstract description 43
- 230000006872 improvement Effects 0.000 title claims abstract description 21
- 230000003054 hormonal effect Effects 0.000 title claims abstract description 11
- 230000002503 metabolic effect Effects 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 title claims abstract description 6
- 239000013585 weight reducing agent Substances 0.000 title claims abstract description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 claims description 4
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 4
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 4
- 230000004580 weight loss Effects 0.000 claims description 4
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 claims description 2
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 2
- 229930003779 Vitamin B12 Natural products 0.000 claims description 2
- 229930003316 Vitamin D Natural products 0.000 claims description 2
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 2
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 claims description 2
- 229960000304 folic acid Drugs 0.000 claims description 2
- 235000019152 folic acid Nutrition 0.000 claims description 2
- 239000011724 folic acid Substances 0.000 claims description 2
- 229940055726 pantothenic acid Drugs 0.000 claims description 2
- 235000019161 pantothenic acid Nutrition 0.000 claims description 2
- 239000011713 pantothenic acid Substances 0.000 claims description 2
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 claims description 2
- 235000019163 vitamin B12 Nutrition 0.000 claims description 2
- 239000011715 vitamin B12 Substances 0.000 claims description 2
- 235000019158 vitamin B6 Nutrition 0.000 claims description 2
- 239000011726 vitamin B6 Substances 0.000 claims description 2
- 235000019166 vitamin D Nutrition 0.000 claims description 2
- 239000011710 vitamin D Substances 0.000 claims description 2
- 150000003710 vitamin D derivatives Chemical class 0.000 claims description 2
- 229940011671 vitamin b6 Drugs 0.000 claims description 2
- 229940046008 vitamin d Drugs 0.000 claims description 2
- 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 description 18
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 14
- 206010022489 Insulin Resistance Diseases 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 12
- 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 description 11
- 102000004877 Insulin Human genes 0.000 description 9
- 108090001061 Insulin Proteins 0.000 description 9
- 229940125396 insulin Drugs 0.000 description 9
- 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 8
- 230000000694 effects Effects 0.000 description 8
- 239000008103 glucose Substances 0.000 description 8
- 208000002874 Acne Vulgaris Diseases 0.000 description 6
- 206010000496 acne Diseases 0.000 description 6
- 238000009826 distribution Methods 0.000 description 6
- 238000002604 ultrasonography Methods 0.000 description 6
- 206010033307 Overweight Diseases 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 201000010066 hyperandrogenism Diseases 0.000 description 4
- 201000008980 hyperinsulinism Diseases 0.000 description 4
- 238000007410 oral glucose tolerance test Methods 0.000 description 4
- 210000001672 ovary Anatomy 0.000 description 4
- 206010002659 Anovulatory cycle Diseases 0.000 description 3
- 108010089417 Sex Hormone-Binding Globulin Proteins 0.000 description 3
- 102100030758 Sex hormone-binding globulin Human genes 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000003098 androgen Substances 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
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- 239000000843 powder Substances 0.000 description 3
- 230000033458 reproduction Effects 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- 201000005670 Anovulation Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 238000000729 Fisher's exact test Methods 0.000 description 2
- 206010020112 Hirsutism Diseases 0.000 description 2
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 206010036049 Polycystic ovaries Diseases 0.000 description 2
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 2
- 229940030486 androgens Drugs 0.000 description 2
- 231100000552 anovulation Toxicity 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
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- 238000012937 correction Methods 0.000 description 2
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- 230000003451 hyperinsulinaemic effect Effects 0.000 description 2
- 208000030159 metabolic disease Diseases 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 230000016087 ovulation Effects 0.000 description 2
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- 150000003905 phosphatidylinositols Chemical class 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
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- 229960003604 testosterone Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 201000004384 Alopecia Diseases 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- NMJREATYWWNIKX-UHFFFAOYSA-N GnRH Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CC(C)C)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 NMJREATYWWNIKX-UHFFFAOYSA-N 0.000 description 1
- 108050000048 Gonadoliberin Proteins 0.000 description 1
- 102000009165 Gonadoliberin Human genes 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
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- 206010020772 Hypertension Diseases 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- 206010027339 Menstruation irregular Diseases 0.000 description 1
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- 241000699670 Mus sp. Species 0.000 description 1
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- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
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- 206010068168 androgenetic alopecia Diseases 0.000 description 1
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- 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 1
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- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
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- 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
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- 229940067626 phosphatidylinositols Drugs 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
Definitions
- composition containing myo-inositol and D-chiro-inositol for use in method of weight reduction, improvement of metabolic and hormonal parameters and improvement of condition of skin in women with polycystic ovary syndrome
- the subject matter of the invention is a composition containing myo-inositol and D-chiro-inositol for use in method of weight reduction, improvement of metabolic and hormonal parameters and improvement of condition of skin in women with polycystic ovary syndrome (PCOS).
- PCOS polycystic ovary syndrome
- PCOS Polycystic ovary syndrome
- PCOS is usually manifested by irregular menstrual cycles, infertility, and clinical signs of hyperandrogenism, including hirsutism, acne and androgenetic alopecia (Helvaci N. Polycystic ovary syndrome and the risk of obstructive sleep apnea: a meta-analysis and review of the literature. Endocr Connect. 2017, 6(7):437-445, Jakimiuk A, Szamatowicz J. Rola niedoboru inozytolu w patofizjologii zaburzeh wyst ⁇ pujqcych w zespole policystycznych jajnikow. Ginekol Pol, 2014, 85, 54-57).
- Insulin resistance determines also an increased exposure to cardiovascular and metabolic disorders, such as obesity, resistance to insulin, impaired glucose metabolism, type 2 diabetes, dyslipidemia, hypertension, metabolic syndrome, and cardiovascular diseases (Dunaif A et al. Insulin Resistance and the Polycystic Ovary Syndrome Revisited: An Update on Mechanisms and Implications. Endocr Rev., 2012; 33(6): 981 -1030; Dunaif A et al. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989; 38(9):1 165-1 174).
- Insulin resistance is thought to be associated with an altered insulin signaling, possibly as a result of disruption of the inositol phosphoglycan (IPG) pathway, which are mediators of intracellular insulin action and cell signal transducers (Baillargeon JP et al. Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome. Diabetes Care. 2006; 29(2):300-5; Lamer J. D-chiro-inositol— its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res. 2002;3(1 ):47-60).
- IPG inositol phosphoglycan
- Inositol is a glucose isomer, also called a sugar alcohol, a hexahydric alcohol, and vitamin B8. Inositol is involved in a number of functions, including cell membrane formation, cell growth, morphogenesis, cytoskeleton rearrangements, proliferation regulation, intracellular signaling, peripheral nerve development and function, osteogenesis, and reproduction (Unfer V et al. Updates on the myo-inositol plus D-chiro-inositol combined therapy in polycystic ovary syndrome. Expert Rev Clin Pharmacol. 2014;7(5): 623-31 ; 31 Carlomagno G., Unfer V. Inositol safety: clinical evidences. Eur Rev Med Pharmacol Sci.
- inositol is present both in free form and as a structural element of membrane phosphatidylinositols.
- the epimerization of six hydroxyl groups causes that the inositol has nine isomeric forms, with myo-inositol (Ml) and D-(+)-chiro-inositol (DCI) being the most important.
- Myo-inositol is a phosphatidylinositol cycle precursor and a component of phospholipids and cell membranes.
- Ml is a precursor in the synthesis of secondary hormonal transmitters such as gonadoliberin (GnRH), TSH, and insulin.
- DCI is involved in the insulin-mediated synthesis of androgens, while Ml mediates the glucose uptake and FSH signaling (Unfer V et al. Effects of Inositol(s) in Women with PCOS: A Systematic Review of Randomized Controlled Trials. J Endocrinol 2016: 1849162).
- the most common form in the ovaries is the myo-inositol (> 99%), followed by D-chiro-inositol (Carlomagno G., Unfer V. Inositol safety: clinical evidences. Eur Rev Med Pharmacol Sci. 201 1 ; 15 (8):931 -6).
- Insulin resistance has been shown to be associated with an MI/DCI imbalance in the cell (Lamer J. D-chiro-inositol in insulin action and insulin resistance - old-fashioned biochemistry still at work. IUBMB Life. 2001 ;51 (3):139-48; Sun TH et al. Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls. Biochem Biophys Res Commun. 2002; 293(3): 1092-8).
- EP1052997 describes compositions containing DCI for use in the treatment of e.g., PCOS.
- Japanese patent application JP2006213684 describes the use of a combination of myo-inositol and D-chiro-inositol in mice, in different weight ratios of these two components, and the effect of such a combination on lowering glucose and triglyceride level in blood and reducing insulin resistance. In experimental results it has been shown that it is preferable to increase the ratio of myo-inositol to D-chiro-inositol.
- European patent application EP2782559 discloses the use of myo-inositol and D-chiro-inositol compositions in PCOS. This application was related to compositions containing myo-inositol and D-chiro-inositol in a ratio in the range above 10:1 and below 100:1 (w/w), with the application description showing only that for myo-inositol and D-chiro-inositol in a ratio of 40:1 w/w (so in the normal ratio observed in blood plasma, see Dinicola S, Chiu TT, Unfer V, Carlomagno G, Bizzarri M.
- compositions containing myo-inositol and D-chiro-inositol in a weight ratio of 10:1 or lower in patients with PCOS allow not only to obtain known therapeutic effects of the composition of these two forms of inositol (this is, i.a., hormonal parameter improvement, blood glucose reduction and insulin resistance decrease), but also provides additional beneficial effects: weight loss and skin condition improvement, not observed with the state of the art recommended ratio of myo-inositol to D-chiro-inositol of 40:1 .
- the subject matter of the present invention is therefore a composition containing myo-inositol and D-chiro-inositol for use in method of weight reduction, improvement of metabolic and hormonal parameters and improvement of condition of skin in women with polycystic ovary syndrome (PCOS), wherein myo-inositol and D-chiro-inositol are in a weight ratio of 10:1 or lower, respectively.
- PCOS polycystic ovary syndrome
- the weight loss in a woman is observed no later than 3 months after the beginning of the composition intake.
- the composition is administered twice a day for at least 3 months, preferably at least 6 months.
- myo-inositol and D-chiro-inositol are in a weight ratio of 10:1 , respectively.
- myo-inositol and D-chiro-inositol are in a weight ratio of 9:1 , respectively.
- the daily dose of myo-inositol and D-chiro-inositol in combination is 1 100 mg.
- the composition further comprises additional active ingredients, preferably selected from the group consisting of folic acid, vitamin B6, pantothenic acid, vitamin B12, and vitamin D.
- the improvement of the condition of the patient’s skin is observed no later than 6 months after the beginning of composition intake, preferably no later than 3 months after the beginning of the composition intake.
- the condition of skin By improving the condition of skin, as used herein, it is meant to reduce or attenuate or suppress skin symptoms associated with PCOS, e.g., acne symptoms.
- the improvement of the condition of skin can be evaluated in any manner known in the art, for example by self-assessment by the patient receiving the composition (e.g., in a survey), doctor's assessment, scoring on a point scale (e.g., Acne Global Severity Scale).
- Fig. 1 shows the results for body weight analysis.
- Fig. 2 shows the results for fT (free testosterone) analysis.
- Fig. 3 shows the results for SHBG analysis.
- Fig. 4 shows the results for FSH analysis.
- Fig. 5 shows the results for LH analysis.
- Fig. 6 shows the results for LDL analysis.
- Fig. 7 shows the results for HDL analysis.
- Fig. 8 shows the results for triglyceride analysis.
- Fig. 9 shows the results for an OGTT analysis after administration of 75 g of glucose.
- Fig. 10 shows the results for OGTT analysis after administration of 75 g of glucose (after 1 hour).
- Fig. 1 1 shows the results for OGTT analysis after administration of 75 g of glucose (after 2 hours).
- Fig. 12 shows the results for fasting insulin analysis.
- Example 1 Composition A containing myo-inositol and D-chiro-inositol
- the composition was prepared in tablets, with the active ingredient content listed in Table 1 below.
- the technology of product manufacture is based on the combination of the granule production process (MIO + DCI) with the powder mixture of other substances (actives and excipients).
- the raw materials used for production are suitably sieved and homogenized so that the mixture is as homogeneous as possible. For this purpose, parameters such as humidity, bulk volume, grain size distribution of both powder mixture and granulate are tested.
- the tablets are then manufactured by pressing the mixture of powder and granules.
- the substances are poured into a mould, where they are crushed by the lower and upper punch.
- the mould volume determines the weight of the tablet and is adjusted by the height of the initial setting of the lower punch.
- the compression pressure regulated by the distance between the punches, determines the tablet parameters: hardness, thickness, mechanical resistance, as well as their disintegration time and release rate of active substances.
- composition A Active ingredients of composition A (values for one tablet)
- Example 2 Composition B containing myo-inositol and D-chiro-inositol
- composition was prepared in an analogous manner to Example 1 , with the active ingredient content listed in Table 2 below.
- composition B (values for one tablet)
- composition A prepared as in Example 1.
- the median value is statistically significantly higher at the second and the third visit in relation to the first visit.
- the median values are statistically significantly lower at the second and third visit compared to the first visit.
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL424713A PL238919B1 (pl) | 2018-02-28 | 2018-02-28 | Kompozycja farmaceutyczna zawierająca mio-inozytol i D-chiro- inozytol, do zastosowania w terapeutycznym sposobie obniżania masy ciała u kobiet z zespołem policystycznych jajników |
| PCT/IB2019/051618 WO2019166984A1 (en) | 2018-02-28 | 2019-02-28 | Composition containing myo-inositol and d-chiro-inositol for use in method of weight reduction, improvement of metabolic and hormonal parameters and improvement of condition of skin in women with polycystic ovary syndrome |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP3758798A1 true EP3758798A1 (en) | 2021-01-06 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP19719363.4A Pending EP3758798A1 (en) | 2018-02-28 | 2019-02-28 | Composition containing myo-inositol and d-chiro-inositol for use in method of weight reduction, improvement of metabolic and hormonal parameters and improvement of condition of skin in women with polycystic ovary syndrome |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP3758798A1 (pl) |
| PL (1) | PL238919B1 (pl) |
| WO (1) | WO2019166984A1 (pl) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP4000626A1 (en) * | 2020-11-16 | 2022-05-25 | concrete flowers GmbH | Pharmaceutical preparation |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5906979A (en) | 1998-01-27 | 1999-05-25 | Insmed Pharmaceuticals, Inc. | Compositions and methods for treating metabolic diseases characterized by hyperandrogenism and/or anovulation and/or infertility |
| JP2006213684A (ja) | 2005-02-07 | 2006-08-17 | Hokko Chem Ind Co Ltd | インスリン抵抗性改善に用いられる組成物及び健康用食品 |
| ITFI20110252A1 (it) | 2011-11-22 | 2013-05-23 | Lo Li Pharma Srl | Composizione farmaceutica comprendente myo-inositolo e d-chiro-inositolo. |
-
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- 2018-02-28 PL PL424713A patent/PL238919B1/pl unknown
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2019
- 2019-02-28 EP EP19719363.4A patent/EP3758798A1/en active Pending
- 2019-02-28 WO PCT/IB2019/051618 patent/WO2019166984A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL424713A1 (pl) | 2019-09-09 |
| WO2019166984A1 (en) | 2019-09-06 |
| PL238919B1 (pl) | 2021-10-18 |
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