WO2024089078A1 - Depigmentation composition comprising l-cysteamine, ascorbic acid and phytic acid - Google Patents
Depigmentation composition comprising l-cysteamine, ascorbic acid and phytic acid Download PDFInfo
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- WO2024089078A1 WO2024089078A1 PCT/EP2023/079731 EP2023079731W WO2024089078A1 WO 2024089078 A1 WO2024089078 A1 WO 2024089078A1 EP 2023079731 W EP2023079731 W EP 2023079731W WO 2024089078 A1 WO2024089078 A1 WO 2024089078A1
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- WO
- WIPO (PCT)
- Prior art keywords
- composition
- weight
- cysteamine
- depigmentation
- ascorbic acid
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims abstract description 200
- 230000035614 depigmentation Effects 0.000 title claims abstract description 36
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 title claims description 80
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0241—Containing particulates characterized by their shape and/or structure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/55—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9771—Ginkgophyta, e.g. Ginkgoaceae [Ginkgo family]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/41—Particular ingredients further characterized by their size
- A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns
Definitions
- the present patent application relates to a depigmentation composition, a depigmentation composition for use as a medicine, as well as the non-therapeutic use of a depigmentation composition.
- melanin a macromolecule synthesized in melanocytes located in the stratum basale, the innermost layer of the epidermis. Once synthesized, melanin accumulates in melanosomes. These melanosomes are transported to the surface of the skin by the action of dendrites which link melanocytes to keratinocytes, thus protecting the genetic integrity in cells against the mutagenic effects of UV rays.
- the depigmentation compositions can have a medical action, to prevent or treat a pigmentation disorder, or purely cosmetic, to lighten the natural coloring of black or tanned skin.
- a pigmentation disorder or purely cosmetic, to lighten the natural coloring of black or tanned skin.
- melasma or chloasma spots which generally appear during or after pregnancy, but which can also be caused by medications, particularly hormonal ones, or acne.
- lentigo lentigo (solar or senile) which manifests itself on parts of the skin exposed to the sun in a predominantly elderly population.
- post-inflammatory hyperpigmentation can occur as a result of any inflammatory condition of the skin, such as photoallergic reactions or laser therapy.
- hydroquinone The molecule most used today to reduce skin pigmentation is hydroquinone. This molecule is generally formulated at between 0.5 and 10% in creams or lotions. However, the irritant and cytotoxic properties of hydroquinone limit its use in many countries. Indeed, even at concentrations below 2% hydroquinone is both irritating and cytotoxic to melanocytes, notably causing exogenous ochronosis.
- Sulfur molecules such as cysteamine (L-cysteamine) having a strong reducing action are among the most effective.
- Cysteamine (beta-mercaptoethylamine) is an aminothiolated compound with antioxidant and depigmenting properties. It is produced naturally in mammals by intracellular degradation of L-cysteine.
- a method proposed to overcome these problems consists of encapsulating or derivatizing cysteamine (Atallah, C. et al. Challenges for cysteamine stabilization, quantification, and biological effects improvement. Journal of Pharmaceutical Analysis. 2020; 10: 499-516 ).
- these techniques are complex to implement and can affect the therapeutic or cosmetic activity of cysteamine.
- ascorbic acid is also known for its depigmenting properties by inhibiting the migration of melanosomes through dendrites towards the surface of the skin.
- ascorbic acid is also rapidly oxidized in aqueous solution, causing a yellow color, which limits its cosmetic and/or therapeutic action (Boo Y.C. Ascorbic Acid (Vitamin C) as a Cosmeceutical to Increase Dermal Collagen for Skin Antiaging Purposes : Emerging Combination Therapies.
- the present invention relates to a depigmentation composition [composition (D), hereinafter] in the form of a serum comprising, relative to the total weight of the composition (D): from 0.2 to 10, 0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts, from 1.0 to 20.0% by weight of ascorbic acid, preferably from 2.0 to 20.0% by weight of acid ascorbic acid, and 0.1 to 5.0% by weight of phytic acid, in which the pH of said composition is less than 5.0.
- composition (D) in the form of a serum comprising, relative to the total weight of the composition (D): from 0.2 to 10, 0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts, from 1.0 to 20.0% by weight of ascorbic acid, preferably from 2.0 to 20.0% by weight of acid ascorbic acid, and 0.1 to 5.0% by weight of phytic acid, in which the pH of said composition is less than 5.0.
- the present invention relates to the depigmentation composition (D) for use as a medicament, in particular for use in the treatment or prevention of at least one skin pigmentation disorder linked to excessive production of melanin and/or or an abnormally high number of melanocytes.
- the present invention also relates to the non-therapeutic use of the depigmentation composition (D) to reduce normal pigmentation of the skin and/or hair.
- composition comprising A and B
- the scope of the expression "a composition comprising A and B” should not be limited to the composition composed only of A and B. This means that, in the context of the present invention, the only relevant elements are A and B Consequently, the terms “comprising” and “including” encompass the more restrictive terms “consisting essentially of” and “consisting of”.
- the term "subject" is used here to designate a mammal, preferably a human.
- the subject is a subject in need of treatment or a subject having a skin pigmentation disease or disorder, such as hyperpigmentation.
- the subject is a normal subject who has healthy, normal skin and needs to lighten their skin and/or healthy, normal hair and needs to lighten their hair.
- the term “depigmentation” is used to refer to the lightening of the skin and/or hair, or the loss of pigments.
- Depigmentation compositions are generally called “lighteners”, “whiteners” or “equalizers”. Regardless of the terminology used, the general principle is that they relate to a reduction in melanization or the rate of melanization of the skin and/or hair, resulting in loss of pigment.
- composition (D), hereinafter in the form of a serum comprising, relative to the total weight of the composition (D): from 0.2 to 10.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts, from 1.0 to 20.0% by weight of ascorbic acid, preferably from 2.0 to 20.0% by weight of ascorbic acid and from 0.0% by weight of ascorbic acid, 1 to 5.0% by weight of phytic acid, wherein the pH of said composition is less than 5.0.
- L-cysteamine and ascorbic acid are generally known for their depigmenting properties.
- these two active molecules are unstable in aqueous solution, which until now prevents their combined use in cosmetic formulations.
- the inventors have surprisingly found that, in composition (D) as described above, L-cysteamine and ascorbic acid are both stable during storage under commercial conditions. This allows composition (D) to have a pleasant odor and clear coloring over an extended period, and also to develop a depigmenting action superior to that of the gold standard in the matter which is hydroquinone.
- composition (D) It appears in fact that, when ascorbic acid and cysteamine are stabilized in composition (D), a synergy develops between their depigmenting activities.
- composition (D) comprises, relative to the total weight of composition (D), from 0.2 to 10.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts.
- cysteamine and “L-cysteamine” are used interchangeably to refer to the compound which can be synthesized by mammals by degradation of Coenzyme A, of general formula C2N7NS and also known as name beta-mercaptoethylamine.
- the term "pharmaceutically acceptable salt” refers to the relatively non-toxic inorganic or organic acid salts of cysteamine. These salts can be prepared in situ during the preparation or isolation of the cysteamine, or by separately reacting the purified cysteamine with a suitable organic or inorganic acid, and isolating the salt thus formed.
- pharmaceutically acceptable salts include hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, valerate, oxalate, benzoate, lactate, phosphate, tosylate, citrate, fumarate, tartrate, succinate.
- the pharmaceutically acceptable salt of cysteamine is cysteamine hydrochloride.
- said composition (D) comprises, relative to the total weight of the composition (D), at least 0.5% by weight, preferably at least 1.0% by weight, even more preferably at least 2.0% by weight. weight, preferably at least 3.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts.
- said composition (D) comprises, relative to the total weight of the composition (D), at most 9.0% by weight, preferably at most 8.0% by weight, even more preferably at most 7.0% by weight. weight, preferably at most 6.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts.
- said composition (D) comprises, relative to the total weight of the composition (D), at least 0.5% by weight and at most 9.0% by weight, preferably at least 1, 0% by weight and at most 8.0% by weight, even more preferably at least 2.0% by weight and at most 7.0% by weight weight, preferably at least 3.0% by weight and at most 6.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts.
- said composition (D) comprises, relative to the total weight of the composition (D), from 2.0 to 20.0% by weight of ascorbic acid.
- ascorbic acid refers to the organic compound of general formula CeHsOe also known under the name hexuronic acid. Ascorbic acid exists in two enantiomeric forms (L and D). Preferably, ascorbic acid is the L-enantiomer of ascorbic acid.
- said composition (D) comprises, relative to the total weight of the composition (D), at least 3.0% by weight, preferably at least 4.0% by weight, even more preferably at least 5.0% by weight. weight, preferably at least 6.0% by weight of ascorbic acid.
- said composition (D) comprises, relative to the total weight of the composition (D), at most 15.0% by weight, preferably at most 12.0% by weight, even more preferably at most 10.0% by weight. weight, preferably at most 8.0% by weight of ascorbic acid.
- said composition (D) comprises, relative to the total weight of the composition (D), at least 3.0% by weight and at most 15.0% by weight, preferably at least 4, 0% by weight and at most 12.0% by weight, even more preferably at least 5.0% by weight and at most 10.0% by weight, preferably at least 6.0% by weight and at most 8 .0% by weight of ascorbic acid.
- said composition (D) comprises, relative to the total weight of the composition (D), from 0.1 to 5.0% by weight of phytic acid.
- the term “phytic acid” refers to inositol hexaphosphate (IP6).
- IP6 inositol hexaphosphate
- the term also encompasses inositol phosphates that are catabolites of I P6, including inositol pentaphosphate (IP5), inositol tetraphosphate inositol (IP4), inositol triphosphate (IP3), inositol diphosphate (IP2) and inositol monophosphate (IP1), their salts and their mixtures.
- IP5 inositol pentaphosphate
- IP4 inositol tetraphosphate inositol
- IP3 inositol triphosphate
- IP2 inositol diphosphate
- IP1 inositol monophosphate
- the term “phytic acid” encompasses catabolites, hydrolysis products, salts, and analogs (e.g., esters and salts).
- IP6, IP5, IP4, IP3, IP2, IP1, and salts thereof refer to any isomer of that particular inositol phosphate.
- IP6, IP5, IP4, IP3, IP2 and IP1 in salt form are typically called “phytates”
- the term “phytic acid” used herein also includes these phytates.
- An example of a counterion to phytate is sodium (such as sodium phytate).
- the counterion can be, for example, calcium, magnesium, iron, copper or zinc.
- the term "phytic acid” as used herein includes both the acid form and the salt form of phytic acid.
- the phytic acid is the acidic form or combinations of acidic forms.
- phytic acid is the salt form or combinations of salt forms.
- phytic acid is a combination of the acid form (or combinations of acid forms) and the salt form (or combinations of salt forms).
- said composition (D) comprises, relative to the total weight of the composition (D), at least 0.2% by weight, preferably at least 0.3% by weight, even more preferably at least 0.4% by weight. weight, preferably at least 0.5% by weight of phytic acid.
- said composition (D) comprises, relative to the total weight of the composition (D), at most 4.0% by weight, preferably at most 3.0% by weight, even more preferably at most 2.0% by weight. weight, preferably at most 1.5% by weight of phytic acid.
- said composition (D) comprises, relative to the total weight of the composition (D), at least 0.2% by weight and at most 4.0% by weight, preferably at least 0. 3% by weight and at most 3.0% by weight, even more preferably at least 0.4% by weight and at most 2.0% by weight, preferably at least 0.5% by weight and at most 1 .5% by weight of phytic acid.
- said composition (D) has a pH less than 5.0.
- the inventors have surprisingly discovered that the presence of phytic acid in combination with a pH less than 5.0 makes it possible to stabilize both cysteamine and ascorbic acid in a composition, and thus produce a depigmentation composition having a powerful, rapid and selective activity on melanocytes, while not presenting harmful side effects, not having the unpleasant odor characteristic of cysteamine and having an acceptable shelf life.
- the pH of composition (D) is at most 4.5, preferably at most 4.0.
- the pH of composition (D) is at least 3.0, preferably at least 3.2.
- the pH of composition (D) is at least 3.2 and at most 4.0.
- the pH of composition (D) is approximately 3.8.
- composition (D) is buffered using a weak acid present in composition (D).
- the weak acid comprises citric acid.
- composition (D) maintains its pleasant odor several hours after application.
- compositions of the prior art are not buffered and must be washed from the treated area quickly (so-called “fleeting” applications) after application in order to avoid the development of the unpleasant odor characteristic of the degradation of the L -cysteamine.
- the composition (D) according to the invention therefore has great stability after application to the area to be treated, in particular great skin stability.
- said composition (D) is in the form of a serum.
- serum refers to an essentially liquid composition having the ability to be easily absorbed by the skin.
- serums are marketed in the form of bottles fitted with a dropper.
- serums allow better skin penetration of active ingredients.
- said composition (D) in the form of a serum comprises, relative to the total weight of said composition (D): from 3.0 to 6.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts, from 6.0 to 8.0% by weight of ascorbic acid, and from 0.5 to 1.5% by weight of phytic acid, in which the pH of said composition is between 3.2 and 4.0.
- said composition (D) further comprises, relative to the total weight of said composition (D), from 1.0 to 20.0% by weight of an extract of Ginkgo biloba leaves.
- Ginkgo biloba leaf extract corresponds to its usual meaning known in the state of the technical.
- Ginkgo biloba leaf extract can be obtained by extraction using an organic solvent (such as propylene glycol and/or ethanol) from Ginkgo biloba leaves. The extraction process may also contain additional steps.
- organic solvent such as propylene glycol and/or ethanol
- Ginkgo biloba leaf extracts are rich in flavone glycosides and terpene lactones, and contain bilobalides, Ginkgolides (A, B and C), quercetin and kaempferol.
- Extracts are generally obtained by solvent extraction and are then concentrated and/or dried. Therefore, in the context of the present invention, the term “extract” includes both solid and liquid extracts.
- the Ginkgo biloba leaf extract is a liquid extract.
- said composition (D) comprises, relative to the total weight of the composition (D), at least 2.0% by weight, even more advantageously at least 4.0% by weight, even more advantageously at least 5, 0% by weight of Ginkgo biloba leaf extract.
- said composition (D) comprises, relative to the total weight of the composition (D), at most 15.0% by weight, even more advantageously at most 12.0% by weight, even more advantageously at most 10, 0% by weight of Ginkgo biloba leaf extract.
- said composition (D) comprises, relative to the total weight of said composition (D), from 5.0 to 10.0% by weight of an extract of Ginkgo biloba leaves.
- said composition (D) in the form of a serum comprises, relative to the total weight of said composition (D): from 3.0 to 6.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts, from 6.0 to 8.0% by weight of ascorbic acid, from 0.5 to 1.5% by weight of phytic acid, and from 5.0 to 10.0 % by weight of an extract of Ginkgo biloba leaves, in which the pH of said composition is between 3.2 and 4.0.
- said composition (D) further comprises, relative to the total weight of said composition (D), from 0.1 to 5.0% by weight, more advantageously from 0.3 to 3.0% by weight, even more advantageously from 0.5% to 2.0% by weight of a depigmenting peptide.
- said depigmenting peptide is acetyl glycyl beta-alanine.
- said composition (D) further comprises, relative to the total weight of said composition (D), from 10.0 to 60.0% by weight, more advantageously from 20.0 to 50.0% by weight, even more advantageously 30.0 % to 40.0% by weight of a thickener.
- said thickener is propylene glycol and/or a polyethylene glycol glycein ether.
- said composition (D) further comprises, relative to the total weight of said composition (D), from 5.0 to 30.0% by weight, more advantageously from 10.0 to 20.0% by weight, even more advantageously from 12.0% to 18.0% by weight of water.
- said composition (D) further comprises, relative to the total weight of said composition (D), from 10.0 to 40.0% by weight, more advantageously from 12.0 to 30.0% by weight, even more preferably from 15.0% to 25.0% by weight of an organic solvent miscible in water.
- said water-miscible organic solvent is isopentyldiol and/or ethoxydiglycol.
- said composition (D) further comprises, relative to the total weight of said composition (D), from 0.1 to 50% by weight, more advantageously from 0.2 to 3.0% by weight, even more advantageously from 0.5% to 2.0% by weight of a silicone emollient agent.
- said silicone emollient agent is PEG-8 dimethicone.
- said composition (D) further comprises, relative to the total weight of said composition (D), from 0.1 to 50% by weight, more advantageously from 0.2 to 3.0% by weight, even more advantageously from 0.5% to 2.0% by weight of an alkanolamine.
- said alkanolamine is aminomethyl propanol.
- composition (D) according to the invention is intended for topical administration, preferably on the skin and/or hair.
- the present invention relates to the composition (D) according to the invention for use as a medicine.
- composition (D) according to the invention also apply mutatis mutandis for its use as a medicine.
- composition (D) according to the invention is used in the treatment and/or prevention of at least one skin pigmentation disorder, preferably a skin pigmentation disorder linked to excessive production of melanin and /or an abnormally high number of melanocytes.
- the present invention therefore relates to the composition (D) according to the invention for use in the treatment and/or prevention of at least one pigmentation disorder.
- pigmentation disorder such as conditions, non-cosmetic lesions or damage, are linked to excessive production of melanin or an abnormally high number of melanocytes.
- the present invention also relates to a method for reducing and/or preventing at least one pigmentation disorder, comprising the topical administration of the depigmentation composition (D), to a subject in need thereof.
- alpha-MSH alpha melanoctye stimulating hormone
- Non-limiting examples of such pigmentation disorders include hyperpigmentation, melasma, postinflammatory hyperpigmentations, radiodermatitis, solar or senile lentigo, hyperpigmentation induced by light, and hyperpigmentation induced by chemical exposure. .
- the inventors have surprisingly discovered that such pigmentation disorders can be treated effectively by the complex or composition according to the invention, and this with an activity greater than that of the gold standard in the matter that is hydroquinone.
- the present invention relates to the non-therapeutic, cosmetic use of the composition (D) according to the invention to reduce normal pigmentation of the skin and/or hair.
- the expression “normal pigmentation of the skin and/or hair” refers to healthy skin and/or healthy hair, not presenting a pigmentation disorder.
- composition (D) according to the invention.
- composition (D) according to the invention can be used to make hair lighter compared to the natural color of the hair. For example, it can make hair brown, red or blonde compared to the natural hair color.
- Said composition (D) according to the invention can be used to reduce the normal pigmentation of the skin and/or hair, preferably the skin and/or hair of the face.
- Said composition (D) according to the invention can be used to treat and/or prevent dark circles.
- the present invention also relates to a method for reducing normal pigmentation of the skin and/or hair, comprising the topical administration of the depigmentation composition (D), to a subject in need thereof.
- composition (D) according to the invention also apply mutatis mutandis for their non-therapeutic use in the reduction of the natural pigmentation of the skin and/or hair.
- the present invention further relates to a method for producing said composition (D) according to the invention, said method comprising the steps of: contacting from 1.0 to 20.0% by weight of ascorbic acid, preferably 2 0 to 20.0% by weight of ascorbic acid; and from 0.5 to 2.0% by weight of phytic acid, relative to the total weight of said composition, so as to obtain a first mixture, and contact said first mixture with from 0.2 to 20.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts.
- composition (D) according to the invention also apply mutatis mutandis for the method of producing said composition.
- a depigmentation composition (D) according to the invention was prepared by mixing the different ingredients listed in Table 1, below. The formulation of the composition is detailed below and comes in the form of a serum. Table 1
- the citrate buffer consists of a mixture of 0.7 M citric acid and 0.7 M trisodium citrate.
- the pH of composition (D) is measured at 3.8.
- Ginkgo biloba leaf extract comes in the form of a brownish liquid composed of 75.0% propylene glycol and 25.0% dry extract of Ginkgo biloba leaves.
- the specifications of said dry extract of Ginkgo biloba leaves are given in Table 2, below.
- Cysteamine is a very smelly compound that gives a rotten egg smell to cosmetic formulations that contain it. Although some formulations containing cysteamine with reduced odor exist, they still have a certain odor which is bothersome to users. On the other hand, composition (D) above does not produce any odor, which is an undeniable advantage over other topical formulations containing cysteamine.
- Example 2 Evaluation of the stability of composition (D) according to the invention.
- composition (D) described in Example 1 The stability of the composition (D) described in Example 1 is evaluated over a period of 6 months.
- a calibration curve was produced by dissolving cysteamine hydrochloride in milliQ water at concentrations of 0.1, 0.2, 1.0 and 2.0 mg/mL.
- the calibration curve was produced from these four points by reporting the areas under the peaks measured in HPLC at 215 nm as a function of the mass of cysteamine injected onto the HPLC column and the concentrations of the standards respectively.
- Each standard solution was analyzed three times by HPLC in order to average the integrations of the area under the signal corresponding to cysteamine.
- composition (D) of 136.9 mg was weighed into a 10 mL flask and then diluted in 5 mL of milliQ water. The aqueous solution obtained is transferred to a separatory funnel and the aqueous phase is washed twice with 2 mL of diethyl ether. The aqueous phase is recovered and centrifuged 10 minutes at 4,500 rpm. Finally, 1 mL of the centrifuged solution is placed in a pillbox for HPLC analysis.
- the mobile phase is an aqueous solution (4mM) of sodium 1-heptanesulfonate containing 0.1% by weight of HCOOH
- composition (D) The cysteamine content in composition (D) was evaluated over a period of 6 months. For this purpose, the quantity of cysteamine was measured at regular intervals. Stability was evaluated under normal storage conditions (25°C and 60% relative humidity).
- composition (D) according to the invention presents a consistent quantity of cysteamine (> 90%) over the entire duration of the stability study, i.e. 6 months under commercial conditions. Furthermore, over the entire duration of the test no alteration in the coloring or odor of composition (D) could be observed. These observations are surprising given that the Cysteamine and ascorbic acid are generally oxidized within a few hours in cosmetic formulations of this type.
- composition (D) according to the invention Clinical evaluation of the depigmentation activity of composition (D) according to the invention on melasma in comparison with a serum dosed at 4% hydroquinone.
- composition (D) The treatment of choice (“gold standard”) for skin pigmentation disorders is hydroquinone, generally dosed at 4%.
- composition (D) is applied to the right side of the face and the serum dosed at 4% hydroquinone to the left side of the patient.
- the results are evaluated 3 times by a practitioner on days 0, 60 and 120 with standard photographs, Wood lamp photographs, and colorimetry for the mMasi and MELASqol indices.
- the Global Aesthetic Improvement Scale is also used to assess the difference in skin appearance using standardized photographs. This study is being conducted in the Northern Hemisphere.
- Exclusion criteria are pregnancy, sensitivity to some of the active ingredients, facial skin conditions (skin infections, eczema, psoriasis, rosacea, herpes, etc.) or severe allergies.
- the products are applied once a day, in the evening, to the specified area.
- the treated area is not washed after application.
- 20 patients are enrolled in the study, for a period of 4 months.
- Each operator receives two batches of twenty treatments each for twenty patients labeled “Right side product” and “Left side product”. He gives the patient an evaluation sheet as well as a treatment kit. He fills out the practitioner observation form himself.
- the practitioner takes a photo of the face and carries out a colorimetric evaluation of the visits, on the day of the start (T0 marking), after 2 months (T60 marking) and a final photo after 4 months of intervention (T120 marking).
- the photographs are both standard and under Wood light to classify melasma between superficial, medium, and dermal.
- a fragrance-free moisturizing preparation called is provided to each patient and a 50+ SPF sunscreen is used each morning.
- composition (D) reduces hyperpigmentation (mMasi and MELASqol indices) of the skin in a homogeneous manner and without side effects, with superior performance to the hydroquinone treatment. as well as other alternatives containing cysteamine. Furthermore, the odor of the product remains acceptable over the duration of the study, despite the fact that composition (D) is not washed after application to the treated area. Comparative tests of compositions according to the invention with the compositions described in document CH706226B1. a) The following compositions were compared in terms of stability over time:
- Formulation according to example 1 of document CH706226B1 3% L-cysteamine + 1% sodium ascorbyl phosphate + 0.5% citric acid + 95.5% water;
- Formulation according to the invention 3% L-cysteamine + 1% ascorbic acid + 0.5% phytic acid + 95.5% water.
- composition according to the invention has increased stability compared to that determined for a formulation according to Example 1 of document CH706226B1.
- Formulation according to the invention 4.8% L-cysteamine + 1% ascorbic acid + 0.2% phytic acid + 94% water.
- composition according to the invention has increased stability compared to that determined for a formulation according to Example 2 of document CH706226B1.
- composition compared to those described in the state of the art.
- compositions were compared in terms of stability over time:
- Formulation according to example 3 of document CH706226B1 8% L-cysteamine + 1% sodium ascorbyl phosphate + 1.5% ascorbyl palmilate + 0.5% lactic acid + 89% water;
- Formulation according to the invention 8% L-cysteamine + 2.5% ascorbic acid + 0.5% phytic acid + 89% water.
- composition according to the invention has increased stability compared to that determined for a formulation according to Example 3 of document CH706226B1.
Abstract
The present application relates to a depigmentation composition, a depigmentation composition for use as a drug, and the non-therapeutic use of a depigmentation composition.
Description
COMPOSITION DE DÉPIGMENTATION COMPRENANT DE LA L-CYSTÉAMINE, DE LACIDE ASCORBIQUE ET DE LACIDE PHYTIQUE DEPIGMENTATION COMPOSITION COMPRISING L-CYSTEAMINE, ASCORBIC ACID AND PHYTIC ACID
Domaine de l’invention Field of the invention
La présente demande de brevet concerne une composition de dépigmentation, une composition de dépigmentation pour utilisation comme médicament, ainsi que l’utilisation non-thérapeutique d’une composition de dépigmentation. The present patent application relates to a depigmentation composition, a depigmentation composition for use as a medicine, as well as the non-therapeutic use of a depigmentation composition.
Arrière-
Back-
La pigmentation de la peau humaine est très variable et provient de la mélanine, une macromolécule synthétisée dans les mélanocytes situés dans le stratum basale, la couche la plus interne de l’épiderme. Une fois synthétisée, la mélanine s’accumule dans les mélanosomes. Ces mélanosomes sont transportés vers la surface de la peau par l’action des dendrites qui lient les mélanocytes aux kératinocytes, protégeant ainsi l’intégrité génétique dans cellules contre les effets mutagènes des rayons UV. The pigmentation of human skin is very variable and comes from melanin, a macromolecule synthesized in melanocytes located in the stratum basale, the innermost layer of the epidermis. Once synthesized, melanin accumulates in melanosomes. These melanosomes are transported to the surface of the skin by the action of dendrites which link melanocytes to keratinocytes, thus protecting the genetic integrity in cells against the mutagenic effects of UV rays.
Les compositions de dépigmentation peuvent avoir une action médicale, pour prévenir ou traiter un trouble de la pigmentation, ou purement cosmétique, pour éclaircir la coloration naturelle de la peau noire ou basanée. Parmi les applications médicales, nous pouvons notamment citer l’éclaircissement des taches sombres sur la peau et l’homogénéisation des irrégularités de la coloration de la peau. Ceci concerne notamment l’hyperpigmentation qui se manifeste sous la forme de taches sombres et irrégulières sur la peau. Sont également concernés les mélasma ou chloasma, des taches qui apparaissent généralement durant ou après la grossesse, mais qui peuvent également être provoquées par des médicaments, notamment hormonaux, ou de l’acné. Nous pouvons également citer le lentigo (solaire ou sénile) qui se manifeste sur les parties de la peau exposées au soleil chez une population majoritairement âgée. Enfin, l’hyperpigmentation post-inflammatoire peut se produire à la suite de tout état inflammatoire de la peau, tel que des réactions photo-allergiques ou une thérapie au laser. The depigmentation compositions can have a medical action, to prevent or treat a pigmentation disorder, or purely cosmetic, to lighten the natural coloring of black or tanned skin. Among the medical applications, we can cite in particular the lightening of dark spots on the skin and the homogenization of irregularities in the coloring of the skin. This particularly concerns hyperpigmentation which manifests itself in the form of dark and irregular spots on the skin. Also affected are melasma or chloasma, spots which generally appear during or after pregnancy, but which can also be caused by medications, particularly hormonal ones, or acne. We can also cite lentigo (solar or senile) which manifests itself on parts of the skin exposed to the sun in a predominantly elderly population. Finally, post-inflammatory hyperpigmentation can occur as a result of any inflammatory condition of the skin, such as photoallergic reactions or laser therapy.
La molécule la plus utilisée aujourd’hui pour réduire pigmentation de la peau est l’hydroquinone. Cette molécule est généralement formulée à entre 0,5 et 10 % dans des crèmes ou des lotions. Cependant, les propriétés irritantes et cytotoxiques de l’hydroquinone limitent son utilisation dans de nombreux pays. En effet, même à
des concentrations inférieures à 2 % l’hydroquinone est à la fois irritante et cytotoxique pour les mélanocytes, provoquant notamment l’ochronose exogène. The molecule most used today to reduce skin pigmentation is hydroquinone. This molecule is generally formulated at between 0.5 and 10% in creams or lotions. However, the irritant and cytotoxic properties of hydroquinone limit its use in many countries. Indeed, even at concentrations below 2% hydroquinone is both irritating and cytotoxic to melanocytes, notably causing exogenous ochronosis.
De nombreuses compositions de dépigmentation alternatives ont été développées pour surmonter ces problèmes d’irritation, mais avec des résultats peu satisfaisants. Many alternative depigmentation compositions have been developed to overcome these irritation problems, but with unsatisfactory results.
Les molécules soufrées comme la cystéamine (L-cystéamine) ayant une forte action réductrice sont parmi les plus efficaces. Sulfur molecules such as cysteamine (L-cysteamine) having a strong reducing action are among the most effective.
La cystéamine (beta-mercaptoethylamine) est un composé aminothiolé avec des propriétés antioxydantes et dépigmentantes. Il est produit naturellement chez les mammifères par dégradation intracellulaire de la L-cystéine. Cysteamine (beta-mercaptoethylamine) is an aminothiolated compound with antioxidant and depigmenting properties. It is produced naturally in mammals by intracellular degradation of L-cysteine.
Cependant, un désavantage majeur de ces molécules soufrées est que, dû à leur instabilité en solution aqueuse, ces molécules développent une odeur désagréable et une coloration brune, qui limite fortement leur utilisation pour la préparation de compositions cosmétiques ou thérapeutiques. However, a major disadvantage of these sulfur molecules is that, due to their instability in aqueous solution, these molecules develop an unpleasant odor and a brown color, which strongly limits their use for the preparation of cosmetic or therapeutic compositions.
Une méthode proposée pour s’affranchir de ces problèmes consiste à encapsuler ou à dérivatiser la cystéamine (Atallah, C. et al. Challenges for cysteamine stabilization, quantification, and biological effects improvement. Journal of Pharmaceutical Analysis. 2020 ; 10 : 499-516). Cependant, ces techniques sont complexes à mettre en œuvre et peuvent affecter l’activité thérapeutique ou cosmétique de la cystéamine. A method proposed to overcome these problems consists of encapsulating or derivatizing cysteamine (Atallah, C. et al. Challenges for cysteamine stabilization, quantification, and biological effects improvement. Journal of Pharmaceutical Analysis. 2020; 10: 499-516 ). However, these techniques are complex to implement and can affect the therapeutic or cosmetic activity of cysteamine.
Par ailleurs, l’acide ascorbique est également connue pour ses propriétés dépigmentantes en inhibant la migration des mélanosomes par les dendrites vers la surface de la peau. Cependant, l’acide ascorbique est lui aussi rapidement oxydé en solution aqueuse, provoquant une coloration jaune, ce qui limite son action cosmétique et/ou thérapeutique (Boo Y.C. Ascorbic Acid (Vitamin C) as a Cosmeceutical to Increase Dermal Collagen for Skin Antiaging Purposes : Emerging Combination Therapies. Antioxidants. 2022 ; 11, 1663). Furthermore, ascorbic acid is also known for its depigmenting properties by inhibiting the migration of melanosomes through dendrites towards the surface of the skin. However, ascorbic acid is also rapidly oxidized in aqueous solution, causing a yellow color, which limits its cosmetic and/or therapeutic action (Boo Y.C. Ascorbic Acid (Vitamin C) as a Cosmeceutical to Increase Dermal Collagen for Skin Antiaging Purposes : Emerging Combination Therapies.
Une méthode alternative décrite dans le brevet CH706226B1 consiste à combiner la cystéamine avec des dérivés de l’acide ascorbique (sodium ascrobyl phosphate, magnésium ascorbyl phopshate, ascorbyl palmitate). Selon les inventeurs, ces dérivés chimiques de l’acide ascorbique ont permis de stabiliser la cystéamine tout en évitant les problèmes de stabilité de l’acide ascorbique pur, et ainsi obtenir des formulations ayant une bonne odeur et une coloration claire. An alternative method described in patent CH706226B1 consists of combining cysteamine with ascorbic acid derivatives (sodium ascrobyl phosphate, magnesium ascorbyl phopshate, ascorbyl palmitate). According to the inventors, these chemical derivatives of ascorbic acid made it possible to stabilize cysteamine while avoiding the stability problems of pure ascorbic acid, and thus obtain formulations having a good odor and a light color.
Cependant, l’efficacité clinique de ces formulations s’est révélée inférieure à celle de l’hydroquinone à dosage équivalent (Lima P. B. et al. A comparative study of topical 5% cysteamine versus 4% hydroquinone in the treatment of facial melasma in women). Ceci s’explique notamment par le fait que les dérivés chimiques de l’acide
ascorbique ne présentent pas les mêmes propriétés dépigmentantes que l’acide ascorbique en tant que tel. However, the clinical effectiveness of these formulations was found to be lower than that of hydroquinone at equivalent dosage (Lima PB et al. A comparative study of topical 5% cysteamine versus 4% hydroquinone in the treatment of facial melasma in women) . This is explained in particular by the fact that the chemical derivatives of the acid ascorbic acid does not have the same depigmenting properties as ascorbic acid itself.
Il existe donc un besoin pour la mise à disposition de formulations peu ou pas irritantes (et n’ayant pas d’autre effet secondaire indésirable) et qui présentent malgré tout une activité de dépigmentation comparable voir supérieure à celle de l’hydroquinone. Ces formulations doivent pouvoir être produites à l’échelle industrielle et présenter une odeur agréable, une coloration claire et être stables dans des conditions de stockage commerciales (avoir une durée de conservation acceptable). There is therefore a need for the provision of formulations that are little or not irritating (and have no other undesirable side effects) and which nevertheless have depigmentation activity comparable or even greater than that of hydroquinone. These formulations must be able to be produced on an industrial scale and have a pleasant odor, a light color and be stable under commercial storage conditions (have an acceptable shelf life).
Résumé de l’invention Summary of the invention
Les inventeurs ont découvert de manière surprenante que la présente invention répond aux problèmes mentionnés ci-dessus. The inventors have surprisingly discovered that the present invention addresses the problems mentioned above.
Selon un premier aspect, la présente invention concerne une composition de dépigmentation [composition (D), ci-après] sous la forme d’un sérum comprenant, relatif au poids total de la composition (D) : de 0,2 à 10,0 % en poids de L-cystéamine ou l’un de ses sels pharmaceutiquement acceptables, de 1 ,0 à 20,0 % en poids d’acide ascorbique, de préférence de 2,0 à 20,0 % en poids d’acide ascorbique, et de 0,1 à 5,0 % en poids d’acide phytique, dans laquelle le pH de ladite composition est inférieur à 5,0. According to a first aspect, the present invention relates to a depigmentation composition [composition (D), hereinafter] in the form of a serum comprising, relative to the total weight of the composition (D): from 0.2 to 10, 0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts, from 1.0 to 20.0% by weight of ascorbic acid, preferably from 2.0 to 20.0% by weight of acid ascorbic acid, and 0.1 to 5.0% by weight of phytic acid, in which the pH of said composition is less than 5.0.
Selon un autre aspect, la présente invention concerne la composition de dépigmentation (D) pour utilisation comme médicament, en particulier pour utilisation dans le traitement ou le prévention d’au moins un trouble de la pigmentation cutanée lié à une production excessive de mélanine et/ou un nombre anormalement élevé de mélanocytes. According to another aspect, the present invention relates to the depigmentation composition (D) for use as a medicament, in particular for use in the treatment or prevention of at least one skin pigmentation disorder linked to excessive production of melanin and/or or an abnormally high number of melanocytes.
Selon un autre aspect, la présente invention concerne également l’utilisation non-thérapeutique de la composition de dépigmentation (D) pour réduire la pigmentation normale de la peau et/ou des cheveux. According to another aspect, the present invention also relates to the non-therapeutic use of the depigmentation composition (D) to reduce normal pigmentation of the skin and/or hair.
Description détaillée de l’invention Detailed description of the invention
Le terme “comprenant”, tel qu’utilisé dans le contexte de l’invention, ne doit pas être interprété comme étant limité aux moyens énumérés par après ; il n’exclut pas la présence d’autres éléments ou étapes. Il doit être interprété comme précisant la présence des caractéristiques énumérées, les éléments, étapes ou composants
auxquels il est fait référence, mais n’exclut pas la présence ou l’ajout d’une ou plusieurs autres caractéristiques, éléments, étapes, ou composants, ou des groupes de ceux-ci. Ainsi, la portée de l’expression « une composition comprenant A et B » ne doit pas être limitée à la composition composée uniquement A et B. Cela signifie que, dans le contexte de la présente invention, les seuls éléments pertinents sont A et B. En conséquence, les termes « comprenant » et « incluant » englobent les termes plus restrictifs que sont « consistant essentiellement de » et « consistant en ». The term “comprising”, as used in the context of the invention, should not be interpreted as being limited to the means listed below; it does not exclude the presence of other elements or stages. It should be interpreted as specifying the presence of the listed characteristics, elements, steps or components referred to, but does not exclude the presence or addition of one or more other features, elements, steps, or components, or groups thereof. Thus, the scope of the expression "a composition comprising A and B" should not be limited to the composition composed only of A and B. This means that, in the context of the present invention, the only relevant elements are A and B Consequently, the terms “comprising” and “including” encompass the more restrictive terms “consisting essentially of” and “consisting of”.
Dans le contexte de la présente invention, le terme « sujet » est utilisé pour désigner ici un mammifère, de préférence un humain. Dans certains modes de réalisation, le sujet est un sujet nécessitant un traitement ou un sujet présentant une maladie ou un trouble de la pigmentation de la peau, tel que l’hyperpigmentation. Cependant, dans d’autres modes de réalisation, le sujet est un sujet normal qui a une peau saine et normale et qui a besoin d’éclaircir sa peau et/ou une chevelure saine et normale et qui a besoin d’éclaircir ses cheveux. In the context of the present invention, the term "subject" is used here to designate a mammal, preferably a human. In some embodiments, the subject is a subject in need of treatment or a subject having a skin pigmentation disease or disorder, such as hyperpigmentation. However, in other embodiments, the subject is a normal subject who has healthy, normal skin and needs to lighten their skin and/or healthy, normal hair and needs to lighten their hair.
Dans le contexte de la présente invention, le terme « dépigmentation » est utilisé pour désigner l’éclaircissement de la peau et/ou des cheveux, ou la perte de pigments. Les compositions de dépigmentation sont généralement appelés « éclaircisseurs », « blanchisseurs » ou « égaliseurs ». Quelle que soit la terminologie utilisée, le principe général est qu’ils ont trait à une réduction de la mélanisation ou de la vitesse de mélanisation de la peau et/ou des cheveux, entrainant une perte de pigments. In the context of the present invention, the term "depigmentation" is used to refer to the lightening of the skin and/or hair, or the loss of pigments. Depigmentation compositions are generally called “lighteners”, “whiteners” or “equalizers”. Regardless of the terminology used, the general principle is that they relate to a reduction in melanization or the rate of melanization of the skin and/or hair, resulting in loss of pigment.
La présente invention concerne une composition de dépigmentation [composition (D), ci-après] sous la forme d’un sérum comprenant, relatif au poids total de la composition (D) : de 0,2 à 10,0 % en poids de L-cystéamine ou l’un de ses sels pharmaceutiquement acceptables, de 1 ,0 à 20,0 % en poids d’acide ascorbique, de préférence de 2,0 à 20,0 % en poids d’acide ascorbique et de 0,1 à 5,0 % en poids d’acide phytique, dans laquelle le pH de ladite composition est inférieur à 5,0. The present invention relates to a depigmentation composition [composition (D), hereinafter] in the form of a serum comprising, relative to the total weight of the composition (D): from 0.2 to 10.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts, from 1.0 to 20.0% by weight of ascorbic acid, preferably from 2.0 to 20.0% by weight of ascorbic acid and from 0.0% by weight of ascorbic acid, 1 to 5.0% by weight of phytic acid, wherein the pH of said composition is less than 5.0.
La L-cystéamine et l’acide ascorbique sont généralement connus pour leurs propriétés dépigmentantes. Cependant, ces deux molécules actives sont instables en solution aqueuse, ce qui empêche jusqu’à présent leur utilisation combinée dans des formulations cosmétiques. Les inventeurs ont trouvé de manière surprenante que, dans la composition (D) telle que décrite ci-dessus, la L-cystéamine et l’acide ascorbique sont tous deux stables pendant la durée du stockage dans des conditions de commerce. Ceci permet à la composition (D) de présenter une odeur agréable et
une coloration claire sur une période étendue, et par ailleurs de développer une action dépigmentante supérieure à celle de l’étalon-or en la matière qu’est l’hydroquinone. L-cysteamine and ascorbic acid are generally known for their depigmenting properties. However, these two active molecules are unstable in aqueous solution, which until now prevents their combined use in cosmetic formulations. The inventors have surprisingly found that, in composition (D) as described above, L-cysteamine and ascorbic acid are both stable during storage under commercial conditions. This allows composition (D) to have a pleasant odor and clear coloring over an extended period, and also to develop a depigmenting action superior to that of the gold standard in the matter which is hydroquinone.
Il apparait en effet que, lorsque l’acide ascorbique et la cystéamine sont stabilisées dans la composition (D), se développe une synergie entre leurs activités dépigmentantes. It appears in fact that, when ascorbic acid and cysteamine are stabilized in composition (D), a synergy develops between their depigmenting activities.
Comme décrit ci-dessus, la composition (D) comprend, relatif au poids total de la composition (D), de 0,2 à 10,0% en poids de L-cystéamine ou l’un de ses sels pharmaceutiquement acceptables. As described above, composition (D) comprises, relative to the total weight of composition (D), from 0.2 to 10.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts.
Dans le contexte de la présente invention les termes « cystéamine » et « L- cystéamine » sont utilisés de manière interchangeable pour faire référence au composé qui peut être synthétisé par les mammifères par dégradation du Coenzyme A, de formule générale C2N7NS et aussi connu sous la dénomination beta- mercaptoethylamine. In the context of the present invention the terms "cysteamine" and "L-cysteamine" are used interchangeably to refer to the compound which can be synthesized by mammals by degradation of Coenzyme A, of general formula C2N7NS and also known as name beta-mercaptoethylamine.
Dans le contexte de la présente invention, le terme « sel pharmaceutiquement acceptable » fait référence aux sels d’acide inorganiques ou organiques relativement non-toxiques de la cystéamine. Ces sels peuvent être préparés in situ durant la préparation ou l’isolation de la cystéamine, ou en faisant réagir séparément la cystéamine purifiée avec un acide organique ou inorganique adapté, et en isolant le sel ainsi formé. Des exemples de sels pharmaceutiquement acceptables comprennent les sels hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, valerate, oxalate, benzoate, lactate, phosphate, tosylate, citrate, fumarate, tartrate, succinate. De préférence, le sel pharmaceutiquement acceptable de la cystéamine est la cystéamine hydrochloride. In the context of the present invention, the term "pharmaceutically acceptable salt" refers to the relatively non-toxic inorganic or organic acid salts of cysteamine. These salts can be prepared in situ during the preparation or isolation of the cysteamine, or by separately reacting the purified cysteamine with a suitable organic or inorganic acid, and isolating the salt thus formed. Examples of pharmaceutically acceptable salts include hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, valerate, oxalate, benzoate, lactate, phosphate, tosylate, citrate, fumarate, tartrate, succinate. Preferably, the pharmaceutically acceptable salt of cysteamine is cysteamine hydrochloride.
De préférence, ladite composition (D) comprend, relatif au poids total de la composition (D), au moins 0,5% en poids, préférentiellement au moins 1 ,0% en poids, encore plus préférentiellement au moins 2,0% en poids, de manière préférée au moins 3,0% en poids de L-cystéamine ou l’un de ses sels pharmaceutiquement acceptables. Preferably, said composition (D) comprises, relative to the total weight of the composition (D), at least 0.5% by weight, preferably at least 1.0% by weight, even more preferably at least 2.0% by weight. weight, preferably at least 3.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts.
De préférence, ladite composition (D) comprend, relatif au poids total de la composition (D), au plus 9,0% en poids, préférentiellement au plus 8,0% en poids, encore plus préférentiellement au plus 7,0% en poids, de manière préférée au plus 6,0% en poids de L-cystéamine ou l’un de ses sels pharmaceutiquement acceptables. Preferably, said composition (D) comprises, relative to the total weight of the composition (D), at most 9.0% by weight, preferably at most 8.0% by weight, even more preferably at most 7.0% by weight. weight, preferably at most 6.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts.
Selon une variante préférée de la présente invention, ladite composition (D) comprend, relatif au poids total de la composition (D), au moins 0,5% en poids et au plus 9,0% en poids, préférentiellement au moins 1 ,0% en poids et au plus 8,0% en poids, encore plus préférentiellement au moins 2,0% en poids et au plus 7,0% en
poids, de manière préférée au moins 3,0% en poids et au plus 6,0% en poids de L- cystéamine ou l’un de ses sels pharmaceutiquement acceptables. According to a preferred variant of the present invention, said composition (D) comprises, relative to the total weight of the composition (D), at least 0.5% by weight and at most 9.0% by weight, preferably at least 1, 0% by weight and at most 8.0% by weight, even more preferably at least 2.0% by weight and at most 7.0% by weight weight, preferably at least 3.0% by weight and at most 6.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts.
Selon l’invention, ladite composition (D) comprend, relatif au poids total de la composition (D), de 2,0 à 20,0% en poids d’acide ascorbique. According to the invention, said composition (D) comprises, relative to the total weight of the composition (D), from 2.0 to 20.0% by weight of ascorbic acid.
Dans le contexte de la présente invention le terme « acide ascorbique » fait référence au composé organique de formule générale CeHsOe aussi connu sous la dénomination acide hexuronique. L’acide ascorbique existe sous deux forme énantiomériques (L et D). De préférence, l’acide ascorbique est l’énantiomère L de l’acide ascorbique. In the context of the present invention the term “ascorbic acid” refers to the organic compound of general formula CeHsOe also known under the name hexuronic acid. Ascorbic acid exists in two enantiomeric forms (L and D). Preferably, ascorbic acid is the L-enantiomer of ascorbic acid.
De préférence, ladite composition (D) comprend, relatif au poids total de la composition (D), au moins 3,0% en poids, préférentiellement au moins 4,0% en poids, encore plus préférentiellement au moins 5,0% en poids, de manière préférée au moins 6,0% en poids de d’acide ascorbique. Preferably, said composition (D) comprises, relative to the total weight of the composition (D), at least 3.0% by weight, preferably at least 4.0% by weight, even more preferably at least 5.0% by weight. weight, preferably at least 6.0% by weight of ascorbic acid.
De préférence, ladite composition (D) comprend, relatif au poids total de la composition (D), au plus 15,0% en poids, préférentiellement au plus 12,0% en poids, encore plus préférentiellement au plus 10,0% en poids, de manière préférée au plus 8,0% en poids d’acide ascorbique. Preferably, said composition (D) comprises, relative to the total weight of the composition (D), at most 15.0% by weight, preferably at most 12.0% by weight, even more preferably at most 10.0% by weight. weight, preferably at most 8.0% by weight of ascorbic acid.
Selon une variante préférée de la présente invention, ladite composition (D) comprend, relatif au poids total de la composition (D), au moins 3,0% en poids et au plus 15,0% en poids, préférentiellement au moins 4,0% en poids et au plus 12,0% en poids, encore plus préférentiellement au moins 5,0% en poids et au plus 10,0% en poids, de manière préférée au moins 6,0% en poids et au plus 8,0% en poids d’acide ascorbique. According to a preferred variant of the present invention, said composition (D) comprises, relative to the total weight of the composition (D), at least 3.0% by weight and at most 15.0% by weight, preferably at least 4, 0% by weight and at most 12.0% by weight, even more preferably at least 5.0% by weight and at most 10.0% by weight, preferably at least 6.0% by weight and at most 8 .0% by weight of ascorbic acid.
Selon l’invention, ladite composition (D) comprend, relatif au poids total de la composition (D), de 0,1 à 5,0% en poids d’acide phytique. According to the invention, said composition (D) comprises, relative to the total weight of the composition (D), from 0.1 to 5.0% by weight of phytic acid.
Dans le contexte de la présente invention le terme « acide phytique » fait référence à l’hexaphosphate d’inositol (IP6). Cependant, étant donné que l’IP6 n’existe généralement pas sous forme pure, le terme englobe également les phosphates d'inositol qui sont des catabolites de l'I P6, y compris le pentaphosphate d'inositol (IP5), le tétraphosphate d'inositol (IP4), le triphosphate d'inositol (IP3), le diphosphate d'inositol (IP2) et le monophosphate d'inositol (IP1), leurs sels et leurs mélanges. Le terme "acide phytique" ne fait pas référence à l'inositol, le produit entièrement hydrolysé de l'acide phytique (IP0). Ainsi, le terme "acide phytique" englobe les catabolites, les produits d'hydrolyse, les sels et les analogues (par exemple, les esters et les sels). Tels qu'ils sont utilisés ici, les termes IP6, IP5, IP4, IP3, IP2, IP1 , et leurs sels, font référence à tout isomère de ce phosphate d'inositol particulier.
Par ailleurs, alors que les IP6, IP5, IP4, IP3, IP2 et IP1 sous forme de sel sont typiquement appelés "phytates", le terme "acide phytique" utilisé ici inclut également ces phytates. Un exemple de contre-ion du phytate est le sodium (tel que le phytate de sodium). Toutefois, le contre-ion peut être, par exemple, du calcium, du magnésium, du fer, du cuivre ou du zinc. In the context of the present invention the term "phytic acid" refers to inositol hexaphosphate (IP6). However, because IP6 does not generally exist in pure form, the term also encompasses inositol phosphates that are catabolites of I P6, including inositol pentaphosphate (IP5), inositol tetraphosphate inositol (IP4), inositol triphosphate (IP3), inositol diphosphate (IP2) and inositol monophosphate (IP1), their salts and their mixtures. The term "phytic acid" does not refer to inositol, the fully hydrolyzed product of phytic acid (IP0). Thus, the term "phytic acid" encompasses catabolites, hydrolysis products, salts, and analogs (e.g., esters and salts). As used herein, the terms IP6, IP5, IP4, IP3, IP2, IP1, and salts thereof, refer to any isomer of that particular inositol phosphate. Furthermore, while IP6, IP5, IP4, IP3, IP2 and IP1 in salt form are typically called "phytates", the term "phytic acid" used herein also includes these phytates. An example of a counterion to phytate is sodium (such as sodium phytate). However, the counterion can be, for example, calcium, magnesium, iron, copper or zinc.
Par conséquent, le terme "acide phytique" tel qu'il est utilisé ici comprend la forme acide et la forme sel de l'acide phytique. Dans certains modes de réalisation, l'acide phytique est la forme acide ou des combinaisons de formes acides. Dans certains cas, l'acide phytique est la forme sel ou des combinaisons de formes sel. Dans certains cas, l'acide phytique est une combinaison de la forme acide (ou de combinaisons de formes acides) et de la forme sel (ou de combinaisons de formes sel). Therefore, the term "phytic acid" as used herein includes both the acid form and the salt form of phytic acid. In some embodiments, the phytic acid is the acidic form or combinations of acidic forms. In some cases, phytic acid is the salt form or combinations of salt forms. In some cases, phytic acid is a combination of the acid form (or combinations of acid forms) and the salt form (or combinations of salt forms).
De préférence, ladite composition (D) comprend, relatif au poids total de la composition (D), au moins 0,2% en poids, préférentiellement au moins 0,3% en poids, encore plus préférentiellement au moins 0,4% en poids, de manière préférée au moins 0,5% en poids de d’acide phytique. Preferably, said composition (D) comprises, relative to the total weight of the composition (D), at least 0.2% by weight, preferably at least 0.3% by weight, even more preferably at least 0.4% by weight. weight, preferably at least 0.5% by weight of phytic acid.
De préférence, ladite composition (D) comprend, relatif au poids total de la composition (D), au plus 4,0% en poids, préférentiellement au plus 3,0% en poids, encore plus préférentiellement au plus 2,0% en poids, de manière préférée au plus 1 ,5% en poids d’acide phytique. Preferably, said composition (D) comprises, relative to the total weight of the composition (D), at most 4.0% by weight, preferably at most 3.0% by weight, even more preferably at most 2.0% by weight. weight, preferably at most 1.5% by weight of phytic acid.
Selon une variante préférée de la présente invention, ladite composition (D) comprend, relatif au poids total de la composition (D), au moins 0,2% en poids et au plus 4,0% en poids, préférentiellement au moins 0,3% en poids et au plus 3,0% en poids, encore plus préférentiellement au moins 0,4% en poids et au plus 2,0% en poids, de manière préférée au moins 0,5% en poids et au plus 1 ,5% en poids d’acide phytique. According to a preferred variant of the present invention, said composition (D) comprises, relative to the total weight of the composition (D), at least 0.2% by weight and at most 4.0% by weight, preferably at least 0. 3% by weight and at most 3.0% by weight, even more preferably at least 0.4% by weight and at most 2.0% by weight, preferably at least 0.5% by weight and at most 1 .5% by weight of phytic acid.
Selon l’invention, ladite composition (D) présente un pH inférieur à 5,0. According to the invention, said composition (D) has a pH less than 5.0.
Les inventeurs ont découvert de manière surprenante que la présence d’acide phytique en combinaison avec un pH inférieur à 5,0 permet de stabiliser à la fois la cystéamine et l’acide ascorbique dans une composition, et produire ainsi une composition de dépigmentation ayant une activité puissante, rapide et sélective sur les mélanocytes, tout en ne présentant pas d’effet secondaires néfaste, n’ayant pas l’odeur désagréable caractéristique de la cystéamine et ayant une durée de conservation acceptable. The inventors have surprisingly discovered that the presence of phytic acid in combination with a pH less than 5.0 makes it possible to stabilize both cysteamine and ascorbic acid in a composition, and thus produce a depigmentation composition having a powerful, rapid and selective activity on melanocytes, while not presenting harmful side effects, not having the unpleasant odor characteristic of cysteamine and having an acceptable shelf life.
De préférence, le pH de la composition (D) est au plus de 4,5, préférentiellement au plus de 4,0.
De préférence, le pH de la composition (D) est au moins de 3,0, préférentiellement au moins de 3,2. Preferably, the pH of composition (D) is at most 4.5, preferably at most 4.0. Preferably, the pH of composition (D) is at least 3.0, preferably at least 3.2.
Selon une variante préféré de l’invention, le pH de la composition (D) est d’au moins 3,2 et d’au plus 4,0. Avantageusement, le pH de la composition (D) est d’environ 3,8. According to a preferred variant of the invention, the pH of composition (D) is at least 3.2 and at most 4.0. Advantageously, the pH of composition (D) is approximately 3.8.
Selon une variante préférée de l’invention la composition (D) est tamponnée à l’aide d’un acide faible présent dans la composition (D). Avantageusement, l’acide faible comprend l’acide citrique. According to a preferred variant of the invention, composition (D) is buffered using a weak acid present in composition (D). Advantageously, the weak acid comprises citric acid.
Les inventeurs ont découvert de manière surprenante que la présence d’un tampon permet de maintenir le pH de la composition (D) selon l’invention à des valeurs acceptables, et ce même après son application sur la zone à traiter chez le sujet. Ainsi, la composition (D) maintient son odeur agréable plusieurs heures après application. A contrario, les compositions de l’art antérieur ne sont pas tamponnées et doivent être lavées de la zone traitée rapidement (applications dites « fugaces ») après application afin d’éviter le développement de l’odeur désagréable caractéristique de la dégradation de la L-cystéamine. La composition (D) selon l’invention présente donc une grande stabilité après application sur le zone à traiter, en particulier une grande stabilité cutanée. The inventors have surprisingly discovered that the presence of a buffer makes it possible to maintain the pH of the composition (D) according to the invention at acceptable values, even after its application to the area to be treated on the subject. Thus, composition (D) maintains its pleasant odor several hours after application. Conversely, the compositions of the prior art are not buffered and must be washed from the treated area quickly (so-called “fleeting” applications) after application in order to avoid the development of the unpleasant odor characteristic of the degradation of the L -cysteamine. The composition (D) according to the invention therefore has great stability after application to the area to be treated, in particular great skin stability.
Selon l’invention, ladite composition (D) est sous la forme d’un sérum. Dans le contexte de la présente invention, le terme « sérum » fait référence à une composition essentiellement liquide ayant la capacité d’être facilement absorbée par la peau. Typiquement, les sérums sont commercialisés sous la forme de bouteilles munies d’un compte-gouttes. According to the invention, said composition (D) is in the form of a serum. In the context of the present invention, the term "serum" refers to an essentially liquid composition having the ability to be easily absorbed by the skin. Typically, serums are marketed in the form of bottles fitted with a dropper.
Contrairement aux crèmes ou aux onguents, les sérums permettent une meilleure pénétration cutanée des principes actifs. Unlike creams or ointments, serums allow better skin penetration of active ingredients.
Selon une variante préférée de l’invention, ladite composition (D) sous la forme d’un sérum comprend, relatif au poids total de ladite composition (D) : de 3,0 à 6,0 % en poids de L-cystéamine ou l’un de ses sels pharmaceutiquement acceptables, de 6,0 à 8,0 % en poids d’acide ascorbique, et de 0,5 à 1 ,5 % en poids d’acide phytique, dans laquelle le pH de ladite composition est compris entre 3,2 et 4,0.According to a preferred variant of the invention, said composition (D) in the form of a serum comprises, relative to the total weight of said composition (D): from 3.0 to 6.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts, from 6.0 to 8.0% by weight of ascorbic acid, and from 0.5 to 1.5% by weight of phytic acid, in which the pH of said composition is between 3.2 and 4.0.
De manière avantageuse, ladite composition (D) comprend en outre, relatif au poids total de ladite composition (D), de 1 ,0 à 20,0 % en poids d’un extrait de feuilles de Ginkgo biloba. Advantageously, said composition (D) further comprises, relative to the total weight of said composition (D), from 1.0 to 20.0% by weight of an extract of Ginkgo biloba leaves.
Dans le contexte de la présente invention, le terme « extrait de feuilles de Ginkgo biloba » correspond à sa signification usuelle conne dans l’état de la
technique. En général, un extrait de feuilles de Ginkgo biloba peut être obtenu par extraction à l’aide d’un solvent organique (comme le propylène glycol et/ou l’éthanol) à partir de feuilles de Ginkgo biloba. Le processus d’extraction peut également contenir des étapes additionnelles. Généralement, les extraits de feuilles de Ginkgo biloba sont riches en flavones glycosides et en terpènes lactones, et contiennent des bilobalides, des Ginkgolides (A, B et C) de la quercétine et du kaempférol. In the context of the present invention, the term “Ginkgo biloba leaf extract” corresponds to its usual meaning known in the state of the technical. In general, Ginkgo biloba leaf extract can be obtained by extraction using an organic solvent (such as propylene glycol and/or ethanol) from Ginkgo biloba leaves. The extraction process may also contain additional steps. Generally, Ginkgo biloba leaf extracts are rich in flavone glycosides and terpene lactones, and contain bilobalides, Ginkgolides (A, B and C), quercetin and kaempferol.
Les extraits sont généralement obtenus par extraction à l’aide d’un solvent et sont ensuite concentrés et/ou séchés. Donc, dans le contexte de la présente invention, le terme « extrait » comprend à la fois les extraits solides et liquides. De préférence, I’ extrait de feuilles de Ginkgo biloba est un extrait liquide. Extracts are generally obtained by solvent extraction and are then concentrated and/or dried. Therefore, in the context of the present invention, the term "extract" includes both solid and liquid extracts. Preferably, the Ginkgo biloba leaf extract is a liquid extract.
Avantageusement, ladite composition (D) comprend, relatif au poids total de la composition (D), au moins 2,0 % en poids, de manière encore plus avantageuse au moins 4,0 % en poids, encore plus avantageusement au moins 5,0 % en poids d’un extrait de feuilles de Ginkgo biloba. Advantageously, said composition (D) comprises, relative to the total weight of the composition (D), at least 2.0% by weight, even more advantageously at least 4.0% by weight, even more advantageously at least 5, 0% by weight of Ginkgo biloba leaf extract.
Avantageusement, ladite composition (D) comprend, relatif au poids total de la composition (D), au plus 15,0 % en poids, de manière encore plus avantageuse au plus 12,0 % en poids, encore plus avantageusement au plus 10,0 % en poids d’un extrait de feuilles de Ginkgo biloba. Advantageously, said composition (D) comprises, relative to the total weight of the composition (D), at most 15.0% by weight, even more advantageously at most 12.0% by weight, even more advantageously at most 10, 0% by weight of Ginkgo biloba leaf extract.
Selon une variante préférée de l’invention, ladite composition (D) comprend, relatif au poids total de ladite composition (D), de 5,0 à 10,0 % en poids d’un extrait de feuilles de Ginkgo biloba. According to a preferred variant of the invention, said composition (D) comprises, relative to the total weight of said composition (D), from 5.0 to 10.0% by weight of an extract of Ginkgo biloba leaves.
Selon une variante préférée de l’invention, ladite composition (D) sous la forme d’un sérum comprend, relatif au poids total de ladite composition (D) : de 3,0 à 6,0 % en poids de L-cystéamine ou l’un de ses sels pharmaceutiquement acceptables, de 6,0 à 8,0 % en poids d’acide ascorbique, de 0,5 à 1 ,5 % en poids d’acide phytique, et de 5,0 à 10,0 % en poids d’un extrait de feuilles de Ginkgo biloba, dans laquelle le pH de ladite composition est compris entre 3,2 et 4,0.According to a preferred variant of the invention, said composition (D) in the form of a serum comprises, relative to the total weight of said composition (D): from 3.0 to 6.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts, from 6.0 to 8.0% by weight of ascorbic acid, from 0.5 to 1.5% by weight of phytic acid, and from 5.0 to 10.0 % by weight of an extract of Ginkgo biloba leaves, in which the pH of said composition is between 3.2 and 4.0.
De manière avantageuse, ladite composition (D) comprend en outre, relatif au poids total de ladite composition (D), de 0,1 à 5,0 % en poids, plus avantageusement de 0,3 à 3,0 % en poids, encore plus avantageusement de 0,5 % à 2,0 % en poids d’un peptide dépigmentant. Avantageusement, ledit peptide dépigmentant est l’acétyl glycyl beta-alanine. Advantageously, said composition (D) further comprises, relative to the total weight of said composition (D), from 0.1 to 5.0% by weight, more advantageously from 0.3 to 3.0% by weight, even more advantageously from 0.5% to 2.0% by weight of a depigmenting peptide. Advantageously, said depigmenting peptide is acetyl glycyl beta-alanine.
De manière avantageuse, ladite composition (D) comprend en outre, relatif au poids total de ladite composition (D), de 10,0 à 60,0 % en poids, plus avantageusement de 20,0 à 50,0 % en poids, encore plus avantageusement de 30,0
% à 40,0 % en poids d’un épaississant. Avantageusement, ledit épaississant est le propylène glycol et/ou un éther de polyéthylèneglycol de glycéine. Advantageously, said composition (D) further comprises, relative to the total weight of said composition (D), from 10.0 to 60.0% by weight, more advantageously from 20.0 to 50.0% by weight, even more advantageously 30.0 % to 40.0% by weight of a thickener. Advantageously, said thickener is propylene glycol and/or a polyethylene glycol glycein ether.
De manière avantageuse, ladite composition (D) comprend en outre, relatif au poids total de ladite composition (D), de 5,0 à 30,0 % en poids, plus avantageusement de 10,0 à 20,0 % en poids, encore plus avantageusement de 12,0 % à 18,0 % en poids d’eau. Advantageously, said composition (D) further comprises, relative to the total weight of said composition (D), from 5.0 to 30.0% by weight, more advantageously from 10.0 to 20.0% by weight, even more advantageously from 12.0% to 18.0% by weight of water.
De manière avantageuse, ladite composition (D) comprend en outre, relatif au poids total de ladite composition (D), de 10,0 à 40,0 % en poids, plus avantageusement de 12,0 à 30,0 % en poids, encore plus avantageusement de 15,0 % à 25,0 % en poids d’un solvant organique miscible dans l’eau. Avantageusement, ledit solvant organique miscible dans l’eau est l’isopentyldiol et/ou l’ethoxydiglycol. Advantageously, said composition (D) further comprises, relative to the total weight of said composition (D), from 10.0 to 40.0% by weight, more advantageously from 12.0 to 30.0% by weight, even more preferably from 15.0% to 25.0% by weight of an organic solvent miscible in water. Advantageously, said water-miscible organic solvent is isopentyldiol and/or ethoxydiglycol.
De manière avantageuse, ladite composition (D) comprend en outre, relatif au poids total de ladite composition (D), de 0,1 à 50 % en poids, plus avantageusement de 0,2 à 3,0 % en poids, encore plus avantageusement de 0,5 % à 2,0 % en poids d’un agent émolliant siliconé. Avantageusement, ledit agent émolliant siliconé est le PEG-8 dimethicone. Advantageously, said composition (D) further comprises, relative to the total weight of said composition (D), from 0.1 to 50% by weight, more advantageously from 0.2 to 3.0% by weight, even more advantageously from 0.5% to 2.0% by weight of a silicone emollient agent. Advantageously, said silicone emollient agent is PEG-8 dimethicone.
De manière avantageuse, ladite composition (D) comprend en outre, relatif au poids total de ladite composition (D), de 0,1 à 50 % en poids, plus avantageusement de 0,2 à 3,0 % en poids, encore plus avantageusement de 0,5 % à 2,0 % en poids d’une alkanolamine. Avantageusement, ladite alkanolamine est l’aminomethyl propanol. Advantageously, said composition (D) further comprises, relative to the total weight of said composition (D), from 0.1 to 50% by weight, more advantageously from 0.2 to 3.0% by weight, even more advantageously from 0.5% to 2.0% by weight of an alkanolamine. Advantageously, said alkanolamine is aminomethyl propanol.
Selon un variante préférée de l’invention, la composition (D) selon l’invention est destinée à une administration topique, de préférence sur la peau et/ou les cheveux. According to a preferred variant of the invention, the composition (D) according to the invention is intended for topical administration, preferably on the skin and/or hair.
Dans un autre aspect, la présente invention concerne la composition (D) selon l’invention pour utilisation comme médicament. In another aspect, the present invention relates to the composition (D) according to the invention for use as a medicine.
L’ensemble des définitions, préférences et aspects préférés décrits ci-dessus pour la composition (D) selon l’invention s’appliquent également mutatis mutandis pour son utilisation comme médicament. All of the definitions, preferences and preferred aspects described above for composition (D) according to the invention also apply mutatis mutandis for its use as a medicine.
De manière avantageuse, la composition (D) selon l’invention est utilisée dans le traitement et/ou la prévention d’au moins un trouble de la pigmentation cutanée, de préférence un trouble de la pigmentation cutanée lié à une production excessive de mélanine et/ou un nombre anormalement élevé de mélanocytes. Advantageously, the composition (D) according to the invention is used in the treatment and/or prevention of at least one skin pigmentation disorder, preferably a skin pigmentation disorder linked to excessive production of melanin and /or an abnormally high number of melanocytes.
Ainsi, la présente invention porte donc sur la composition (D) selon l’invention pour utilisation dans le traitement et/ou la prévention d’au moins un trouble de la pigmentation. En particulier, le trouble de la pigmentation, tel que les affections,
lésions ou dommages non-cosmétiques, sont liés à une production excessive de mélanine ou un nombre anormalement élevé de mélanocytes. Thus, the present invention therefore relates to the composition (D) according to the invention for use in the treatment and/or prevention of at least one pigmentation disorder. In particular, pigmentation disorder, such as conditions, non-cosmetic lesions or damage, are linked to excessive production of melanin or an abnormally high number of melanocytes.
Selon un autre aspect, la présente invention concerne également une méthode pour réduire et/ou prévenir au moins un trouble de la pigmentation, comprenant l’administration topique de la composition de dépigmentation (D), à un sujet en ayant besoin. According to another aspect, the present invention also relates to a method for reducing and/or preventing at least one pigmentation disorder, comprising the topical administration of the depigmentation composition (D), to a subject in need thereof.
Un grand nombre de troubles de la pigmentation de la peau sont caractérisés par une production et/ou une accumulation accrue de mélanine. La lumière ultraviolette, les hormones, les inflammations chroniques, les frottements, ainsi que la production anormale de l’alpha melanoctye stimulating hormone (alpha-MSH) sont des éléments déclencheurs de tels troubles. Many skin pigmentation disorders are characterized by increased production and/or accumulation of melanin. Ultraviolet light, hormones, chronic inflammation, friction, as well as abnormal production of alpha melanoctye stimulating hormone (alpha-MSH) are triggers for such disorders.
Des exemples non-limitatifs de tels troubles de la pigmentation comprennent notamment l’hyperpigmentation, le mélasma, les hyperpigmentations postinflammatoires, les radiodermites, le lentigo solaire ou sénile, l’hyperpigmentation induite par la lumière, et l’hyperpigmentation induite par une exposition chimique. Non-limiting examples of such pigmentation disorders include hyperpigmentation, melasma, postinflammatory hyperpigmentations, radiodermatitis, solar or senile lentigo, hyperpigmentation induced by light, and hyperpigmentation induced by chemical exposure. .
Les inventeurs ont découvert de manière surprenante que de tels troubles de la pigmentation peuvent être traitées de manière efficace par le complexe ou la composition selon l’invention, et ce avec une activité supérieure à celle de l’étalon-or en la matière qu’est l’hydroquinone. The inventors have surprisingly discovered that such pigmentation disorders can be treated effectively by the complex or composition according to the invention, and this with an activity greater than that of the gold standard in the matter that is hydroquinone.
Dans un autre aspect, la présente invention concerne l’utilisation non- thérapeutique, cosmétique, de la composition (D) selon l’invention pour réduire la pigmentation normale de la peau et/ou des cheveux. In another aspect, the present invention relates to the non-therapeutic, cosmetic use of the composition (D) according to the invention to reduce normal pigmentation of the skin and/or hair.
Dans le contexte de la présente invention, l’expression « pigmentation normale de la peau et/ou des cheveux » fait référence à une peau saine et/ou des cheveux sains, ne présentant pas de trouble de la pigmentation. In the context of the present invention, the expression “normal pigmentation of the skin and/or hair” refers to healthy skin and/or healthy hair, not presenting a pigmentation disorder.
Les inventeurs on en effet découvert de manière surprenante que l’apparence générale d’un sujet peut être améliorée suite à l’utilisation de la composition (D) selon l’invention. The inventors have in fact surprisingly discovered that the general appearance of a subject can be improved following the use of composition (D) according to the invention.
La composition (D) selon l’invention peut être utilisée pour rendre les cheveux plus clairs comparé à la couleur naturelle des cheveux. Par exemple, elle peut rendre les cheveux bruns, roux ou blonds comparé à la couleur naturelle des cheveux. The composition (D) according to the invention can be used to make hair lighter compared to the natural color of the hair. For example, it can make hair brown, red or blonde compared to the natural hair color.
Ladite composition (D) selon l’invention peut être utilisée pour réduire la pigmentation normale de la peau et/ou des cheveux, de préférence la peau et/ou les cheveux du visage. Said composition (D) according to the invention can be used to reduce the normal pigmentation of the skin and/or hair, preferably the skin and/or hair of the face.
Ladite composition (D) selon l’invention peut être utilisée pour traiter et/ou prévenir les cernes.
Selon un autre aspect, la présente invention concerne également une méthode pour réduire la pigmentation normale de la peau et/ou des cheveux, comprenant l’administration topique de la composition de dépigmentation (D), à un sujet en ayant besoin. Said composition (D) according to the invention can be used to treat and/or prevent dark circles. According to another aspect, the present invention also relates to a method for reducing normal pigmentation of the skin and/or hair, comprising the topical administration of the depigmentation composition (D), to a subject in need thereof.
L’ensemble des définitions, préférences et aspects préférés décrits ci-dessus pour la composition (D) selon l’invention s’appliquent également mutatis mutandis pour leur utilisation non-thérapeutique dans la réduction de la pigmentation naturelle de la peau et/ou des cheveux. All of the definitions, preferences and preferred aspects described above for composition (D) according to the invention also apply mutatis mutandis for their non-therapeutic use in the reduction of the natural pigmentation of the skin and/or hair.
La présente invention porte en outre sur une méthode de production de ladite composition (D) selon l’invention, ladite méthode comprenant les étapes de : contacter de 1 ,0 à 20,0 % en poids d’acide ascorbique, de préférence de 2,0 à 20,0 % en poids d’acide ascorbique ; et de 0,5 à 2,0 % en poids d’acide phytique, relatif au poids total de ladite composition, de manière à obtenir un premier mélange, et contacter ledit premier mélange avec de 0,2 à 20,0 % en poids de L- cystéamine ou l’un de ses sels pharmaceutiquement acceptables. The present invention further relates to a method for producing said composition (D) according to the invention, said method comprising the steps of: contacting from 1.0 to 20.0% by weight of ascorbic acid, preferably 2 0 to 20.0% by weight of ascorbic acid; and from 0.5 to 2.0% by weight of phytic acid, relative to the total weight of said composition, so as to obtain a first mixture, and contact said first mixture with from 0.2 to 20.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts.
L’ensemble des définitions, préférences et aspects préférés décrits ci-dessus pour la composition (D) selon l’invention s’appliquent également mutatis mutandis pour la méthode de production de ladite composition. All of the definitions, preferences and preferred aspects described above for composition (D) according to the invention also apply mutatis mutandis for the method of producing said composition.
L’invention va à présent être décrite plus en détail en se référant aux exemples suivants, qui détaillent des illustrations non-limitatives de différents aspects de l’invention.
Préparation d’une composition de dépigmentation (D) selon invention. The invention will now be described in more detail with reference to the following examples, which detail non-limiting illustrations of different aspects of the invention. Preparation of a depigmentation composition (D) according to the invention.
Une composition de dépigmentation (D) selon l’invention a été préparée en mélangeant les différents ingrédients repris dans le Tableau 1 , ci-dessous. La formulation de la composition est détaillée ci-dessous et se présente sous la forme d’un sérum.
Tableau 1
A depigmentation composition (D) according to the invention was prepared by mixing the different ingredients listed in Table 1, below. The formulation of the composition is detailed below and comes in the form of a serum. Table 1
Le tampon citrate est constitué d’un mélange d’acide citrique 0,7 M et de citrate trisodique 0,7 M. Le pH de la composition (D) est mesuré à 3,8. The citrate buffer consists of a mixture of 0.7 M citric acid and 0.7 M trisodium citrate. The pH of composition (D) is measured at 3.8.
L’extrait de feuilles de Ginkgo biloba se présente sous la forme d’un liquide brunâtre composé à 75,0 % de propylène glycol et à 25,0 % d’un extrait sec de feuilles de Ginkgo biloba. Les spécifications dudit extrait sec de feuilles de Ginkgo biloba sont reprises dans le Tableau 2, ci-dessous. Ginkgo biloba leaf extract comes in the form of a brownish liquid composed of 75.0% propylene glycol and 25.0% dry extract of Ginkgo biloba leaves. The specifications of said dry extract of Ginkgo biloba leaves are given in Table 2, below.
Tableau 2
Table 2
La cystéamine est un composé très malodorant qui donne une odeur d’œuf pourri aux formulations cosmétiques qui en contiennent. Bien que certaines formulations contenant de la cystéamine ayant une odeur réduite existent, celles-ci présentent malgré tout une certaine odeur qui est incommodante pour les utilisateurs. En revanche, la composition (D) ci-dessus ne produit aucune odeur, ce qui est un avantage indéniable vis-à-vis des autres formulations topiques contenant de la cystéamine. Cysteamine is a very smelly compound that gives a rotten egg smell to cosmetic formulations that contain it. Although some formulations containing cysteamine with reduced odor exist, they still have a certain odor which is bothersome to users. On the other hand, composition (D) above does not produce any odor, which is an undeniable advantage over other topical formulations containing cysteamine.
Exemple 2: Evaluation de la stabilité de la composition (D) selon l’invention. Example 2: Evaluation of the stability of composition (D) according to the invention.
La stabilité de la composition (D) décrite à l’Exemple 1 est évaluée sur une période de 6 mois. The stability of the composition (D) described in Example 1 is evaluated over a period of 6 months.
Une courbe de calibration a été réalisée en dissolvant de la cystéamine chlorydrate dans de l’eau milliQ à des concentrations de 0,1 , 0,2, 1 ,0 et 2,0 mg/mL. La courbe de calibration a été réalisée à partir de ces quatre points en rapportant les aires sous les pics mesurés en HPLC à 215 nm en fonction de la masse de cystéamine injectée sur la colonne HPLC et des concentrations des standards respectivement. Chaque solution standard a été analysée trois fois en HPLC afin de réaliser une moyenne sur les intégrations de l’aire sous le signal correspondant à la cystéamine. A calibration curve was produced by dissolving cysteamine hydrochloride in milliQ water at concentrations of 0.1, 0.2, 1.0 and 2.0 mg/mL. The calibration curve was produced from these four points by reporting the areas under the peaks measured in HPLC at 215 nm as a function of the mass of cysteamine injected onto the HPLC column and the concentrations of the standards respectively. Each standard solution was analyzed three times by HPLC in order to average the integrations of the area under the signal corresponding to cysteamine.
Une échantillon de la composition (D) de 136,9 mg a été pesé dans un ballon de 10 mL et ensuite dilué dans 5 mL d’eau milliQ. La solution aqueuse obtenue est transférée dans une ampoule à décanter et la phase aqueuse est lavée deux fois avec 2 mL d”éther diéthylique. La phase aqueuse est récupérée et centrifugée 10
minutes à 4,500 rpm. Finalement, 1 mL de la solution centrifugée est placée dans un pilulier pour analyse HPLC. A sample of composition (D) of 136.9 mg was weighed into a 10 mL flask and then diluted in 5 mL of milliQ water. The aqueous solution obtained is transferred to a separatory funnel and the aqueous phase is washed twice with 2 mL of diethyl ether. The aqueous phase is recovered and centrifuged 10 minutes at 4,500 rpm. Finally, 1 mL of the centrifuged solution is placed in a pillbox for HPLC analysis.
Les conditions de l’analyse sont les suivantes : The conditions of the analysis are as follows:
- Appareillage : HPLC Agilent 1100 series connectée à un détecteur DAD Colonne : Agilent Eclipse Plus C18 (3,5 pm) - 4,6 x 100 mm Flux : 1 ,0 mL/min Volume d’injection : 2 pL - Apparatus: HPLC Agilent 1100 series connected to a DAD detector Column: Agilent Eclipse Plus C18 (3.5 pm) - 4.6 x 100 mm Flow: 1.0 mL/min Injection volume: 2 pL
Eluant : H2O/CH3CN - 85/15 (v/v). La phase mobile est une solution aqueuse (4mM) de 1 -heptanesulfonate de sodium contenant 0,1% en poids de HCOOH Eluent: H2O/CH3CN - 85/15 (v/v). The mobile phase is an aqueous solution (4mM) of sodium 1-heptanesulfonate containing 0.1% by weight of HCOOH
Température colonne : 40°C Column temperature: 40°C
Longueurs d’onde sélectionnées : 215 nm et 254 nm Selected wavelengths: 215 nm and 254 nm
La teneur en cystéamine dans la composition (D) a été évaluée sur une période de 6 mois. A cet effet, la quantité de cystéamine a été dosée à intervalles réguliers. La stabilité a été évaluée dans des conditions de conservation normales (25°C et 60% d’humidité relative). The cysteamine content in composition (D) was evaluated over a period of 6 months. For this purpose, the quantity of cysteamine was measured at regular intervals. Stability was evaluated under normal storage conditions (25°C and 60% relative humidity).
Les résultats de ces expériences sont présentés dans le Tableau 3, ci-dessous. The results of these experiments are presented in Table 3, below.
Tableau 3
Table 3
Les résultats obtenus démontrent que la composition (D) selon l’invention présente une quantité de cystéamine conforme (> 90%) sur l’ensemble de la durée de l’étude de stabilité, soit 6 mois dans des conditions de commerce. Par ailleurs, sur l’ensemble de la durée du test aucune altération de la coloration ni de l’odeur de la composition (D) n’a pu être observée. Ces observations sont surprenantes étant donné que la
cystéamine et l’acide ascorbique sont généralement oxydés en quelques heures dans des formulations cosmétiques de ce type. The results obtained demonstrate that the composition (D) according to the invention presents a consistent quantity of cysteamine (> 90%) over the entire duration of the stability study, i.e. 6 months under commercial conditions. Furthermore, over the entire duration of the test no alteration in the coloring or odor of composition (D) could be observed. These observations are surprising given that the Cysteamine and ascorbic acid are generally oxidized within a few hours in cosmetic formulations of this type.
Evaluation clinique de activité de dépigmentation de la composition (D) selon l’invention sur les mélasma en comparaison avec un sérum dosé à 4% en hydroquinone. Clinical evaluation of the depigmentation activity of composition (D) according to the invention on melasma in comparison with a serum dosed at 4% hydroquinone.
Le traitement de choix (« étalon-or ») pour les troubles de la pigmentation cutanée est l’hydroquinone, généralement dosée à 4%. Ces expériences visent à comparer l’efficacité de la composition (D) avec un sérum dosé à 4% en hydroquinone dans un groupe clinique avec une application hémifaciale randomisée en double-aveugle. The treatment of choice (“gold standard”) for skin pigmentation disorders is hydroquinone, generally dosed at 4%. These experiments aim to compare the effectiveness of composition (D) with a serum dosed at 4% hydroquinone in a clinical group with a randomized, double-blind hemifacial application.
Cet essai clinique hémifacial est réalisé chez des sujets âgés de 20 à 70 ans, phototypes II, III ou IV et complété par des sujets de phototypes V et VI. La composition (D) est appliqué sur le côté droit du visage et le sérum dosé à 4% en hydroquinone sur le côté gauche du patient. Les résultats sont évalués 3 fois chez un praticien aux jours 0, 60 et 120 avec des photographies standard, des photographies à la lampe Wood, et la colorimétrie pour les indices mMasi et MELASqol. L’échelle d’amélioration esthétique globale est également utilisée pour évaluer la différence d’aspect de la peau à l’aide de photographies standardisées. Cette étude est menée dans l’hémisphère Nord. This hemifacial clinical trial is carried out in subjects aged 20 to 70 years, phototypes II, III or IV and completed by subjects of phototypes V and VI. Composition (D) is applied to the right side of the face and the serum dosed at 4% hydroquinone to the left side of the patient. The results are evaluated 3 times by a practitioner on days 0, 60 and 120 with standard photographs, Wood lamp photographs, and colorimetry for the mMasi and MELASqol indices. The Global Aesthetic Improvement Scale is also used to assess the difference in skin appearance using standardized photographs. This study is being conducted in the Northern Hemisphere.
Les critères d’exclusion sont la grossesse, la sensibilité à certains des ingrédients actifs, des affections cutanées du visage (infections de la peau, eczéma, psoriasis, rosacée, herpès, etc.) ou les allergies sévères. Exclusion criteria are pregnancy, sensitivity to some of the active ingredients, facial skin conditions (skin infections, eczema, psoriasis, rosacea, herpes, etc.) or severe allergies.
Les produits sont appliqués une fois par jour, le soir, sur la zone spécifiée. La zone traitée n’est pas lavée après application. 20 patients sont enrôlés dans l’étude, pour une durée de 4 mois. The products are applied once a day, in the evening, to the specified area. The treated area is not washed after application. 20 patients are enrolled in the study, for a period of 4 months.
Chaque opérateur reçoit deux lots de vingt traitements chacun pour vingt patients étiquetés « Produit côté droit » et « Produit côté gauche ». Il remet au patient une fiche d’évaluation ainsi qu’une trousse de traitement. Il remplit lui-même la fiche d’observation du praticien. Each operator receives two batches of twenty treatments each for twenty patients labeled “Right side product” and “Left side product”. He gives the patient an evaluation sheet as well as a treatment kit. He fills out the practitioner observation form himself.
Le praticien prend une photo de la face et effectue une évaluation colorimétrique des visites, le jour du début (marquage T0), après 2 mois (marquage T60) et une photo finale après 4 mois d’intervention (marquage T120). Les photographies sont à la fois
standard et sous lumière Wood pour classer le mélasme entre superficiel, moyen, et dermique. The practitioner takes a photo of the face and carries out a colorimetric evaluation of the visits, on the day of the start (T0 marking), after 2 months (T60 marking) and a final photo after 4 months of intervention (T120 marking). The photographs are both standard and under Wood light to classify melasma between superficial, medium, and dermal.
Une préparation hydratante sans parfum appelée est fournie à chaque patient et un écran solaire 50+ SPF est utilisé chaque matin. A fragrance-free moisturizing preparation called is provided to each patient and a 50+ SPF sunscreen is used each morning.
L’ensemble des données récoltées démontrent que le traitement avec la composition (D) diminue l’hyperpigmentation (indices mMasi et MELASqol) de la peau de façon homogène et sans effet secondaire, et ce avec une performance supérieure au traitement référence à l’hydroquinone ainsi qu’aux autres alternatives contenant de la cystéamine. Par ailleurs, l’odeur du produit reste acceptable sur la durée de l’étude, malgré le fait que la composition (D) ne soit pas lavée après application sur la zone traitée.
Essais comparatifs de compositions selon l’invention avec les compositions décrites dans le document CH706226B1. a) Les compositions suivantes ont été comparées en termes de stabilité au cours du temps : All the data collected demonstrate that treatment with composition (D) reduces hyperpigmentation (mMasi and MELASqol indices) of the skin in a homogeneous manner and without side effects, with superior performance to the hydroquinone treatment. as well as other alternatives containing cysteamine. Furthermore, the odor of the product remains acceptable over the duration of the study, despite the fact that composition (D) is not washed after application to the treated area. Comparative tests of compositions according to the invention with the compositions described in document CH706226B1. a) The following compositions were compared in terms of stability over time:
Formulation selon l’exemple 1 du document CH706226B1 : 3% de L- cystéamine + 1 % sodium ascorbyl phosphate + 0.5% acide citrique + 95,5% d’eau ; Formulation according to example 1 of document CH706226B1: 3% L-cysteamine + 1% sodium ascorbyl phosphate + 0.5% citric acid + 95.5% water;
Formulation selon l’invention : 3% de L-cystéamine + 1 % d’acide ascorbique + 0.5% d’acide phytique + 95,5% d’eau. Formulation according to the invention: 3% L-cysteamine + 1% ascorbic acid + 0.5% phytic acid + 95.5% water.
Une analyse HPLC a été réalisée au départ de 1 mL de chacune des formulations avec un même appareillage et selon les mêmes paramètres que ceux décrits à l’exemple 2. Les résultats obtenus sont présentés au tableau 4 ci-dessous.
Tableau 4
An HPLC analysis was carried out starting from 1 mL of each of the formulations with the same equipment and according to the same parameters as those described in Example 2. The results obtained are presented in Table 4 below. Table 4
Comme on peut le constater, une formulation (composition) selon l’invention présente une stabilité augmentée par rapport à celle déterminée pour une formulation selon l’exemple 1 du document CH706226B1. As can be seen, a formulation (composition) according to the invention has increased stability compared to that determined for a formulation according to Example 1 of document CH706226B1.
Notons que pour la formulation selon l’exemple 1 document CH706226B1 le produit de dégradation de la cystéamine, à savoir la cystamine, a été détecté systématiquement. Au contraire, pour la formulation selon l’invention, aucune trace de cystamine n’a été détectée, ce qui confirme bien la stabilité d’une formulation (composition) selon l’invention par rapport à celles décrites dans l’état de la technique. b) Les compositions suivantes ont été comparées en termes de stabilité au cours du temps : Note that for the formulation according to Example 1 document CH706226B1 the degradation product of cysteamine, namely cystamine, was systematically detected. On the contrary, for the formulation according to the invention, no trace of cystamine was detected, which clearly confirms the stability of a formulation (composition) according to the invention compared to those described in the state of the art. . b) The following compositions were compared in terms of stability over time:
Formulation selon l’exemple 2 du document CH706226B1 : 4,8% de L- cystéamine + 0,5% sodium ascorbyl phosphate + 0,5% ascorbyl palmilate + 0,2% acide glycolique + 94% d’eau; Formulation according to example 2 of document CH706226B1: 4.8% L-cysteamine + 0.5% sodium ascorbyl phosphate + 0.5% ascorbyl palmilate + 0.2% glycolic acid + 94% water;
Formulation selon l’invention : 4,8% de L-cystéamine + 1 % d’acide ascorbique + 0,2% d’acide phytique + 94% d’eau. Formulation according to the invention: 4.8% L-cysteamine + 1% ascorbic acid + 0.2% phytic acid + 94% water.
Une analyse HPLC a été réalisée au départ de 1 mL de chacune des formulations avec un même appareillage et selon les mêmes paramètres que ceux décrits à l’exemple 2. Les résultats obtenus sont présentés au tableau 5 ci-dessous.
Tableau 5
An HPLC analysis was carried out starting from 1 mL of each of the formulations with the same equipment and according to the same parameters as those described in Example 2. The results obtained are presented in Table 5 below. Table 5
Comme on peut le constater, une formulation (composition) selon l’invention présente une stabilité augmentée par rapport à celle déterminée pour une formulation selon l’exemple 2 du document CH706226B1. As can be seen, a formulation (composition) according to the invention has increased stability compared to that determined for a formulation according to Example 2 of document CH706226B1.
Notons que pour la formulation selon l’exemple 2 document CH706226B1 le produit de dégradation de la cystéamine, à savoir la cystamine, a été détecté systématiquement. Au contraire, pour la formulation selon l’invention, aucune trace de cystamine n’a été détectée, ce qui confirme bien la stabilité d’une formulation (composition) selon l’invention par rapport à celles décrites dans l’état de la technique. c) Les compositions suivantes ont été comparées en termes de stabilité au cours du temps : Note that for the formulation according to example 2 document CH706226B1 the degradation product of cysteamine, namely cystamine, was systematically detected. On the contrary, for the formulation according to the invention, no trace of cystamine was detected, which clearly confirms the stability of a formulation (composition) according to the invention compared to those described in the state of the art. . c) The following compositions were compared in terms of stability over time:
Formulation selon l’exemple 3 du document CH706226B1 : 8% de L- cystéamine + 1% sodium ascorbyl phosphate + 1 ,5% ascorbyl palmilate + 0,5% acide lactique + 89% d’eau; Formulation according to example 3 of document CH706226B1: 8% L-cysteamine + 1% sodium ascorbyl phosphate + 1.5% ascorbyl palmilate + 0.5% lactic acid + 89% water;
Formulation selon l’invention : 8% de L-cystéamine + 2,5 % d’acide ascorbique + 0.5% d’acide phytique + 89% d’eau. Formulation according to the invention: 8% L-cysteamine + 2.5% ascorbic acid + 0.5% phytic acid + 89% water.
Une analyse HPLC a été réalisée au départ de 1 mL de chacune des formulations avec un même appareillage et selon les mêmes paramètres que ceux décrits à l’exemple 2. Les résultats obtenus sont présentés au tableau 6 ci-dessous.
Tableau 6
An HPLC analysis was carried out starting from 1 mL of each of the formulations with the same equipment and according to the same parameters as those described in Example 2. The results obtained are presented in Table 6 below. Table 6
Comme on peut le constater, une formulation (composition) selon l’invention présente une stabilité augmentée par rapport à celle déterminée pour une formulation selon l’exemple 3 du document CH706226B1 . As can be seen, a formulation (composition) according to the invention has increased stability compared to that determined for a formulation according to Example 3 of document CH706226B1.
Notons que pour la formulation selon l’exemple 3 document CH706226B1 le produit de dégradation de la cystéamine, à savoir la cystamine, a été détecté systématiquement. Au contraire, pour la formulation selon l’invention, aucune trace de cystamine n’a été détectée, ce qui confirme bien la stabilité d’une formulation (composition) selon l’invention par rapport à celles décrites dans l’état de la technique.
Note that for the formulation according to example 3 document CH706226B1 the degradation product of cysteamine, namely cystamine, was systematically detected. On the contrary, for the formulation according to the invention, no trace of cystamine was detected, which clearly confirms the stability of a formulation (composition) according to the invention compared to those described in the state of the art. .
Claims
1. Composition de dépigmentation [composition (D), ci-après] sous la forme d’un sérum comprenant, relatif au poids total de la composition (D) : 1. Depigmentation composition [composition (D), hereinafter] in the form of a serum comprising, relative to the total weight of composition (D):
- de 0,2 à 10,0 % en poids de L-cystéamine ou l’un de ses sels pharmaceutiquement acceptables ; - from 0.2 to 10.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts;
- de 1,0 à 20,0 % en poids d’acide ascorbique, de préférence de 2,0 à 20,0 % en poids d’acide ascorbique; - from 1.0 to 20.0% by weight of ascorbic acid, preferably from 2.0 to 20.0% by weight of ascorbic acid;
- de 0,1 à 5,0 % en poids d’acide phytique ; et dans laquelle le pH de ladite composition (D) est inférieur à 5,0. - from 0.1 to 5.0% by weight of phytic acid; and wherein the pH of said composition (D) is less than 5.0.
2. La composition de dépigmentation selon la revendication 1 , comprenant de 2,0 à 8,0 % en poids de L-cystéamine ou de l’un de ses sels pharmaceutiquement acceptables, relatif au poids total de la composition (D). 2. The depigmentation composition according to claim 1, comprising from 2.0 to 8.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts, relative to the total weight of the composition (D).
3. La composition de dépigmentation selon l’une quelconque des revendications précédentes, comprenant de 5,0 à 10,0 % en poids d’acide ascorbique, relatif au poids total de la composition (D). 3. The depigmentation composition according to any one of the preceding claims, comprising from 5.0 to 10.0% by weight of ascorbic acid, relative to the total weight of the composition (D).
4. La composition de dépigmentation selon l’une quelconque des revendications précédentes, comprenant de 0,4 à 2,0 % en poids d’acide phytique, relatif au poids total de la composition (D). 4. The depigmentation composition according to any one of the preceding claims, comprising from 0.4 to 2.0% by weight of phytic acid, relative to the total weight of the composition (D).
5. La composition de dépigmentation selon l’une quelconque des revendications précédentes, dans laquelle le pH de ladite composition est compris entre 3,2 et 4,0. 5. The depigmentation composition according to any one of the preceding claims, in which the pH of said composition is between 3.2 and 4.0.
6. La composition de dépigmentation selon l’une quelconque des revendications précédentes, comprenant relatif au poids total de la composition (D) : 6. The depigmentation composition according to any one of the preceding claims, comprising relative to the total weight of the composition (D):
- de 2,0 à 8,0 % en poids de L-cystéamine ; - from 2.0 to 8.0% by weight of L-cysteamine;
- de 5,0 à 10,0 % en poids d’acide ascorbique ; - from 5.0 to 10.0% by weight of ascorbic acid;
- de 0,4 à 2,0 % en poids d’acide phytique ; et dans laquelle le pH de ladite composition est compris entre 3,2 et 4,0.
- from 0.4 to 2.0% by weight of phytic acid; and wherein the pH of said composition is between 3.2 and 4.0.
7. La composition de dépigmentation selon l’une quelconque des revendications précédentes, comprenant en outre de 1,0 à 20,0 % en poids d’un extrait de feuilles de Ginkgo biloba. 7. The depigmentation composition according to any one of the preceding claims, further comprising from 1.0 to 20.0% by weight of an extract of Ginkgo biloba leaves.
8. La composition de dépigmentation selon l’une quelconque des revendications précédentes, ladite composition étant destinée à une administration topique, de préférence sur la peau et/ou sur les cheveux. 8. The depigmentation composition according to any one of the preceding claims, said composition being intended for topical administration, preferably on the skin and/or on the hair.
9. Composition de dépigmentation selon l’une quelconque des revendications précédentes, pour utilisation comme médicament. 9. Depigmentation composition according to any one of the preceding claims, for use as a medicine.
10. La composition de dépigmentation pour utilisation selon la revendication 9, pour utilisation dans le traitement ou la prévention d’au moins un trouble de la pigmentation cutanée. 10. The depigmentation composition for use according to claim 9, for use in the treatment or prevention of at least one skin pigmentation disorder.
11. La composition de dépigmentation pour utilisation selon la revendication 9 ou 10, dans laquelle le trouble de la pigmentation cutanée est sélectionné parmi le groupe constitué de l’hyperpigmentation, le mélasma et le lentigo solaire ou sénile. 11. The depigmentation composition for use according to claim 9 or 10, wherein the skin pigmentation disorder is selected from the group consisting of hyperpigmentation, melasma and solar or senile lentigo.
12. Utilisation cosmétique non-thérapeutique d’une composition de dépigmentation (D) selon l’une quelconque des revendications 1 à 8 pour réduire la pigmentation naturelle de la peau et/ou des cheveux. 12. Non-therapeutic cosmetic use of a depigmentation composition (D) according to any one of claims 1 to 8 to reduce the natural pigmentation of the skin and/or hair.
13. Méthode pour la production de la composition de dépigmentation (D) selon l’une quelconque des revendications 1 à 8, ladite méthode comprenant les étapes de : 13. Method for the production of the depigmentation composition (D) according to any one of claims 1 to 8, said method comprising the steps of:
(i) contacter de 1,0 à 20,0 % en poids d’acide ascorbique, de préférence de 2,0 à 20,0 % en poids d’acide ascorbique, et de 0,5 à 2,0 % en poids d’acide phytique, relatif au poids total de ladite composition, de manière à obtenir un premier mélange, et (i) contacting 1.0 to 20.0% by weight of ascorbic acid, preferably 2.0 to 20.0% by weight of ascorbic acid, and 0.5 to 2.0% by weight of phytic acid, relative to the total weight of said composition, so as to obtain a first mixture, and
(ii) contacter ledit premier mélange avec de 0,2 à 20,0 % en poids de L- cystéamine ou l’un de ses sels pharmaceutiquement acceptables.
(ii) contacting said first mixture with 0.2 to 20.0% by weight of L-cysteamine or one of its pharmaceutically acceptable salts.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BE20225872A BE1030501B1 (en) | 2022-10-26 | 2022-10-26 | Depigmentation composition |
| BEBE2022/5872 | 2022-10-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2024089078A1 true WO2024089078A1 (en) | 2024-05-02 |
Family
ID=84329420
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2023/079731 WO2024089078A1 (en) | 2022-10-26 | 2023-10-25 | Depigmentation composition comprising l-cysteamine, ascorbic acid and phytic acid |
Country Status (2)
| Country | Link |
|---|---|
| BE (1) | BE1030501B1 (en) |
| WO (1) | WO2024089078A1 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005041820A (en) * | 2003-07-23 | 2005-02-17 | Hoyu Co Ltd | Hair dyeing composition |
| CH706226B1 (en) | 2012-03-06 | 2016-03-31 | Behrooz Kasraee | Preparation for skin lightening. |
-
2022
- 2022-10-26 BE BE20225872A patent/BE1030501B1/en active IP Right Grant
-
2023
- 2023-10-25 WO PCT/EP2023/079731 patent/WO2024089078A1/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005041820A (en) * | 2003-07-23 | 2005-02-17 | Hoyu Co Ltd | Hair dyeing composition |
| CH706226B1 (en) | 2012-03-06 | 2016-03-31 | Behrooz Kasraee | Preparation for skin lightening. |
Non-Patent Citations (5)
| Title |
|---|
| ATALLAH, C. ET AL.: "Challenges forcysteamine stabilization, quantification, and biological effects improvement.", JOURNAL OF PHARMACEUTICAL ANALYSIS., vol. 10, 2020, pages 499 - 516 |
| AUSTIN AU ET AL: "Topical treatments for melasma: a systematic review of randomized controlled trials", JOURNAL OF DRUGS IN DERMATOLOGY, STRATEGIC COMMUNICATION IN DERMATOLOGY, NEW YORK, NY, US, vol. 18, no. 11, 1 November 2019 (2019-11-01), pages 1156 - 1171, XP009542278, ISSN: 1545-9616 * |
| BOO Y.C.: "Ascorbic Acid (Vitamin C) as a Cosmeceutical to Increase Dermal Collagen for Skin Antiaging Purposes : Emerging Combination Therapies.", ANTIOXIDANTS., vol. 11, 2022, pages 1663 |
| CHAOWATTANAPANIT SUTEERAPORN ET AL: "Postinflammatory hyperpigmentation: A comprehensive overview Treatment options and prevention", JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, vol. 77, no. 4, 31 October 2017 (2017-10-31), pages 607 - 621, XP085202024, ISSN: 0190-9622, DOI: 10.1016/J.JAAD.2017.01.036 * |
| LIMA P.B. ET AL., A COMPARATIVE STUDY OF TOPICAL 5% CYSTÉAMINE VERSUS 4% HYDROQUINONE IN THE TREATMENT OF FACIAL MELASMA IN WOMEN |
Also Published As
| Publication number | Publication date |
|---|---|
| BE1030501B1 (en) | 2023-11-29 |
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