EP3758798A1 - Zusammensetzung mit myo-inositol und d-chiro-inositol zur verwendung in verfahren zur gewichtsreduktion, zur verbesserung metabolischer und hormoneller parameter und zur verbesserung des hautzustandes bei frauen mit polyzystischem ovarialsyndrom - Google Patents
Zusammensetzung mit myo-inositol und d-chiro-inositol zur verwendung in verfahren zur gewichtsreduktion, zur verbesserung metabolischer und hormoneller parameter und zur verbesserung des hautzustandes bei frauen mit polyzystischem ovarialsyndromInfo
- 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
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- 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
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Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
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- 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
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- 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
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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
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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 (de) | 2021-01-06 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP19719363.4A Pending EP3758798A1 (de) | 2018-02-28 | 2019-02-28 | Zusammensetzung mit myo-inositol und d-chiro-inositol zur verwendung in verfahren zur gewichtsreduktion, zur verbesserung metabolischer und hormoneller parameter und zur verbesserung des hautzustandes bei frauen mit polyzystischem ovarialsyndrom |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP3758798A1 (de) |
| PL (1) | PL238919B1 (de) |
| WO (1) | WO2019166984A1 (de) |
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| EP4000626A1 (de) * | 2020-11-16 | 2022-05-25 | concrete flowers GmbH | Pharmazeutisches präparat |
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| 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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- 2019-02-28 EP EP19719363.4A patent/EP3758798A1/de active Pending
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| Publication number | Publication date |
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| PL424713A1 (pl) | 2019-09-09 |
| WO2019166984A1 (en) | 2019-09-06 |
| PL238919B1 (pl) | 2021-10-18 |
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