HK1178443A - Use of 2,3-dihydroxypropyl dodecanoate for treating seborrhea - Google Patents

Description

Use of 2, 3-dihydroxypropyl dodecanoate for treating seborrheic dermatitis

Technical Field

The present invention relates to 2, 3-dihydroxypropyl dodecanoate for its use in the treatment of seborrheic dermatitis. The seborrheic dermatitis may be associated with the skin or scalp.

The invention also relates to a cosmetic composition comprising 2, 3-dihydroxypropyl dodecanoate for the treatment of seborrheic dermatitis.

Background

Sebum is the secretion of the skin, the sebaceous glands of the lipid membrane, which helps to protect the skin and, in combination with perspiration, protects the skin from dryness.

Sebum enables the skin to be waterproofed and plays a role in the development of epidermal structures.

It protects the skin from microorganisms by acidification (presence of lactic and fatty acids) and provides a degree of water repellency. It is capable of making the skin soft and plays a role in epidermal growth.

It is also found on body hair and hair.

Sebum is produced by the sebaceous glands.

In general, humans have 2,000,000 sebaceous glands attached to 6,000,000 body hairs and hair.

Sebaceous glands are unevenly distributed. The density of the sebaceous glands on the face and scalp reaches 300 to 900 sebaceous glands/cm²And the density is about 100 sebaceous glands/cm in the upper chest and back²。

Sebaceous glands have a secretory pattern of whole plasma secretion, i.e. complete cellular clearance. The secretory part is alveolar sound.

Seborrheic dermatitis consists of an overproduction of sebum by the sebaceous glands.

Seborrheic dermatitis may have various causes:

the nervous system: emotional stress and nervous tension which worsen the sebum secretion function,

the fatigue of the human body is caused,

an unbalanced diet is one in which the weight of the individual,

certain drugs (psychotropic drugs),

"deprives" the skin and/or scalp, and causes an inappropriate cosmetic treatment of reactive seborrheic dermatitis,

the main causes are hormonal: sebaceous glands are hormone-dependent and their activity is affected by androgens. Androgens are active only under the influence of 5-alpha reductaseThe 5-alpha reductase metabolizes androgen in the sebaceous gland, inducing cortical production. Hyperactivation of 5-alpha reductase causes seborrheic dermatitis.

Signs of seborrheic dermatitis can be found in the central regions of the face (forehead, nose, chin), where the sebaceous glands are the most abundant and largest. Seborrheic dermatitis also occurs on the scalp where it is primarily in the frontal, frontotemporal areas, and the crown of the head.

Seborrheic dermatitis causes aesthetic problems. In the case of skin, the skin shows a shiny appearance, a dull complexion and an enlarged opening of the hair follicle. Moreover, makeup does not allow a good control of this so-called greasy skin type.

In the case of seborrheic dermatitis of the scalp, the hair appears greasy and dull and difficult to style. In the case of severe seborrheic dermatitis, it is referred to as oily, moist, and may be associated with a rancid odor.

Disclosure of Invention

In order to treat seborrheic dermatitis and remedy the aesthetic problems associated with seborrheic dermatitis, it has surprisingly been demonstrated that the use of 2, 3-dihydroxypropyl dodecanoate makes it possible to inhibit 5-alpha reductase activity and thus reduce sebum secretion.

1)2, 3-dihydroxypropyl dodecanoate:

2, 3-dihydroxypropyl dodecanoate (formula 1), also glycerol laurate or glycerol monolaurate, which is formed from lauric acid and glycerol and has the chemical formula C ₁₅H₃₀O₄An ester of (a). It is commonly used as an emulsifier as for example in household cleaning products, as well as in some food products.

Formula 1: 2, 3-dihydroxypropyl dodecanoate

2) 5-alpha reductase

There are two isozymes of5-alpha reductase: 5-alpha reductase 1 and 5-alpha reductase 2. Type 1 is expressed essentially in The skin, located in The sebaceous glands and dermal papillae and is active at pH 7, whereas type 2 is expressed in The prostate and is active at pH 5 (Luu-The et al, Characterisation, Expression and immunological localization of5-alpha reproduction in human skin, The Journal of investigative Dermatology, p221-226,1994).

5-alpha reductase is an enzyme involved in steroid metabolism (Luu-The et al, mutation and immunological localization of5-alpha reductase inhuman skin, The Journal of investigative Dermatology, p221-226,1994).

More specifically, the enzyme reduces the Δ 4,5 linkage of testosterone (formula 2) to produce dihydrotestosterone (androsarone) (DHT) (formula 3), which is also an androgen.

The sebaceous glands are hormone-dependent and their function is related to testosterone. Testosterone is produced by the testes, ovaries (androstenedione) and adrenal glands (dehydroepiandrosterone). In the target cell, testosterone is converted to active DHT by 5-alpha reductase. Upon binding to cytoplasmic matrix receptors, DHT binds to nuclear receptors and induces the synthesis of proteins responsible for sebum production.

Seborrheic dermatitis is associated with hyperactivity of 5-alpha reductase, which is associated with an increase in the number of cytoplasmic mesenchymal receptors.

Thus, inhibition of the activity of 5-alpha reductase makes it possible to reduce androgen metabolism and thus sebum production.

3) Biological results: inhibition of 5-alpha reductase activity of 2, 3-dihydroxypropyl dodecanoate:

the scheme is as follows:

biological model:

cell type: normal Human Dermal Fibroblasts (NHDF).

The culture conditions are as follows: 37 ℃ and 5% CO₂。

Culture medium: DMEM supplemented with 2mM L-glutamine, 50U/ml penicillin, 50. mu.g/ml streptomycin, 10% fetal bovine serum.

Test medium: DMEM supplemented with 2mM L-glutamine, 50U/ml penicillin, 50. mu.g/ml streptomycin and 1% fetal bovine serum.

Radioisotope-labeled testosterone: [4-14C ]]Testosterone (Amersham). The radioisotope-labeled testosterone was dissolved in ethanol and diluted in the test medium.

Test compounds:

test compounds: 2, 3-dihydroxypropyl dodecanoate.

Positive control: finasteride.

Finasteride is well known and is used to inhibit the activity of 5-alpha reductase and thereby prevent the metabolism of testosterone into DHT.

Comparison: ethanol, which does not have 5-alpha reductase inhibitory activity.

Cell culture and treatment:

the fibroblasts were cultured to confluence (confluency). The medium was then removed and replaced with test medium with or without test compound, positive control or control, and the cells were preincubated for 24 hours. After incubation, cells were treated with test compound or negative control and radioisotope-labeled testosterone was added. The cells were then incubated for 24 hours. All experiments were performed 3 times.

Extraction and analysis:

the steroid was extracted from the supernatant with two volumes of chloroform/methanol and dried. The various molecular entities (testosterone metabolites) were separated by thin layer chromatography on silica gel plates (reversed phase/silica gel, Whatman) in a solvent mixture containing dichloromethane, ethyl acetate and methanol.

The silica gel plates were autoradiographed and testosterone metabolites were quantified using a phosphorescent imager (phorimageer), a beta radiation detector and special software (packardinscription).

A decrease in the amount of radioisotope-labeled DHT detected is indicative of 5-alpha reductase activity.

Data processing:

using Microsoft The software analyzes the raw data.

Viability ═ optical density of sample/optical density of control x 100

The results are shown in FIG. 1, which additionally illustrates the effect of 2, 3-dihydroxypropyl dodecanoate on DHT production by human fibroblasts.

The ethanol control was observed to have no effect on testosterone metabolism and thus did not inhibit 5-alpha reductase activity.

The positive control (finasteride) tested at 10 μ M significantly reduced testosterone metabolism to DHT, thus inhibiting the activity of 5- α reductase.

In the case of 2, 3-dihydroxypropyl dodecanoate, inhibition of 5-alpha reductase activity was also observed. Furthermore, a dose effect of this inhibition was observed: for 75 μ M2, 3-dihydroxypropyl dodecanoate, the activity of 5- α reductase was reduced to 66%.

These results demonstrate that 2, 3-dihydroxypropyldodecanoate does inhibit the activity of 5-alpha reductase.

It is therefore an object of the present invention to use 2, 3-dihydroxypropyl dodecanoate for the treatment of seborrheic dermatitis, preferably of the skin or scalp. The invention relates to the use of 2, 3-dihydroxypropyl dodecanoate as a sebum oil control cosmetic.

Seborrheic dermatitis is often associated with androgenic alopecia. Alopecia is defined as partial or total hair loss. The life of hair is limited by a cycle called the hair cycle (cycle pilaire), which comprises three successive phases. The growth phase is a period of active and sustained growth that is associated with strong metabolic activity at the root level. During the catastrophe phase, mitotic activity slows down. The hair undergoes a decline, the development of the hair follicle is hindered and its dermal implantation occurs at an increasingly higher level. The final phase is a resting phase consisting of the resting phase of the hair follicle, and the hair is eventually pushed by the newly growing hair, shedding. The hair cycle is complete and another hair cycle can begin. The human hair roots each have a life of about 20 to 25 cycles. During aging, the hair becomes fine and its life cycle becomes shorter.

Thus, hereditary androgenetic alopecia (formerly known as seborrheic dermatitis alopecia) is the most common form of alopecia and affects approximately 70% of men. Hair with a shorter life cycle is a major feature of androgenetic alopecia. All other symptoms are simply the result of this shorter life cycle. Initially, the problems caused by this form of hair loss stem from the fact that androgens accelerate the growth phase, force the hair to move very rapidly to the resting phase, and do not allow sufficient time for the hair follicles to produce high quality keratin. Then a vicious circle appears: the faster the hair is produced, the faster it falls off and the faster it passes each other during the week, each time producing weaker and shorter hair than the previous time. Eventually, the inventory of the renewal cycle is exhausted, and the capsule no longer produces anything and dies. This form of alopecia due to excess androgen also affects women during menopause or receiving androgen therapy. It begins at the temple and vertex.

Thus, reducing the activity of 5-alpha reductase would inhibit seborrheic dermatitis and thus slow hair loss.

4) Composition comprising a metal oxide and a metal oxide

The invention also relates to a cosmetic composition comprising 2, 3-dihydroxypropyl dodecanoate for the treatment of seborrheic dermatitis. In particular, the present invention relates to a cosmetic composition comprising 2, 3-dihydroxypropyl dodecanoate for treating seborrheic dermatitis of the skin or scalp. The subject of the present invention also consists of a method for the cosmetic treatment of seborrheic dermatitis comprising the application to the skin or scalp of a cosmetic composition according to the invention. In particular, it may consist of a method for the cosmetic treatment of seborrheic dermatitis of the skin or scalp.

According to the invention, the cosmetic composition may comprise from 0.01 to 20% by weight, preferably from 0.5 to 10% by weight, more particularly from 1 to 5% by weight, of 2, 3-dihydroxypropyl dodecanoate, relative to the total weight of the composition.

According to another embodiment of the invention, the cosmetic composition is of the type further comprising rippan thermal spring (l 'eau thermal d' avene).

The ripping hot spring water composition is as follows:

yayang hot spring water composition	mg/ml
		Chloride compound	5.4
Bicarbonate salt	226.7
		Sulfates of sulfuric acid	13.1
Silicon dioxide	14
		Calcium carbonate	42.7
Magnesium alloy	21.2
		Sodium salt	4.8
Potassium salt	0.8
		Iron	0.005
Selenium	0.005
		Zinc	0.02
Copper (Cu)	0.005
		Drying the residue	207
Mineralization of	Is low in

pH	7.5
		Permeability of	Hypotonic condition

Another embodiment according to the present invention is a cosmetic composition wherein 2, 3-dihydroxypropyl dodecanoate is the only active substance.

According to the invention, the cosmetic composition is a composition comprising 2, 3-dihydroxypropyl dodecanoate, ripping hot spring water and a cosmetically acceptable base.

The term "cosmetically acceptable base" refers to any adjuvant or vehicle suitable for the manufacture, storage, or application of the cosmetic composition.

The composition according to the invention may be in any form conventionally used for topical application, in particular in the form of a hydroalcoholic, in the form of an oil-in-water or water-in-oil or multiple emulsion, an oily gel, or a liquid, pasty or solid anhydrous product, or in the form of a dispersion in which small spheres are present. These compositions are prepared using conventional methods.

The composition may be in any suitable dosage form. The composition may be in the form of: aqueous, alcoholic, hydroalcoholic or oily solutions, lotions or serological dispersions, suspensions, microcapsules or microparticles; ionic and/or nonionic vesicle dispersions, aqueous, oily washes or in the form of serum; foaming agents, solid formulations such as sticks; also comprises a pressurized propellant, an aerosol composition, a gel or in the form of a patch.

The composition may have variable fluidity and have the appearance of a white or coloured cream, ointment, milk or paste. Optionally, it may be applied to the skin or hair in the form of an aerosol.

The compositions according to the invention may be in the form of hair care compositions, in particular shampoos, hair-waving agents, setting agents, creams or gels, dyeing compositions or anti-alopecia gels.

It may also be in the form of a facial or body cleansing, protecting or caring composition (for example day cream, night cream, makeup remover, body lotion for protection or treatment, skin care lotion, gel or foam), cosmetic composition such as foundation.

If the composition is an emulsion, the proportion of the fatty phase may vary from 5% to 80% by weight, preferably from 5% to 50% by weight, relative to the total weight of the composition. The oils, waxes, emulsifiers and co-emulsifiers used in the composition in the form of an emulsion are selected from those conventionally used in the cosmetic field.

-a fatty phase:

the term fatty phase refers to lipophilic compounds such as oils, gums, pastes and waxes.

The oil is preferably selected from the group consisting of vegetable oils, animal oils, mineral oils, synthetic oils, silicone oils, liquid fatty acid esters, liquid fatty acids, and liquid fatty amides.

Examples of vegetable oils include in particular sweet almond oil, avocado oil, castor oil, olive oil, jojoba liquid wax, sunflower oil, wheat germ oil, sesame oil, peanut oil, grapeseed oil, soybean oil, rapeseed oil, safflower oil, coconut oil, corn oil, hazelnut oil, almond oil and malus calophyllum oil (l' hue de calophylum).

In particular, perhydrosqualene can be cited as an example of animal oil.

Examples of synthetic oils include in particular squalene, poly (. alpha. -olefins) such as isododecane or isohexadecane, transesterified vegetable oils and fluorinated oils.

Examples of the silicone oil include cyclic polydimethylsiloxane (INCI name: cyclomethicone) such as decamethylpentasiloxane and linear polymethylsiloxane of low viscosity.

Waxes suitable for use in the present invention are, for example, waxes of animal, vegetable, mineral or synthetic origin, such as beeswax, spermaceti, fluorinated or perfluorinated waxes, lanolin wax, candelilla (candelilla) wax, Ouricury (Ouricury) wax, Carnauba (carnuba) wax, japan wax, cocoa butter wax, cork fibre or sugar cane wax, rice bran wax, pine wax, cotton wax; microcrystalline waxes, paraffins, petroleum oils, vaseline, ozokerite, montan waxes, hydrogenated oils having a temperature above 40 ℃ such as hydrogenated jojoba oil, polyethylene waxes and waxes obtained by Fischer-Tropsch synthesis (synth se fischer-Tropsch).

The wax may also be selected from waxy fatty alcohols and waxy fatty esters.

Waxy fatty acid esters are fatty acid esters, i.e., carboxylic acid esters containing at least 10 carbon atoms and a monohydric or polyhydric alcohol. The waxy fatty acid esters suitable for use in the composition according to the invention may be mono-, di-or triesters. Examples of waxy esters include myristyl myristate and stearyl stearate.

Waxy fatty acids suitable for use in the composition according to the invention preferably contain from 12 to 24 carbon atoms and may be saturated or unsaturated, optionally branched, and contain one or more hydroxyl functional groups. Examples include lauric acid, stearic acid, palmitic acid and behenic acid.

Examples of waxy amides include ceramides such as n-oleylsphinganine.

-an emulsifier:

the emulsifier makes it easier to disperse the two immiscible phases. The emulsifiers and co-emulsifiers are present in the composition in a proportion ranging from 0.3% to 30%, preferably from 0.5 to 20%, most preferably from 0.5 to 10% by weight, relative to the total weight of the composition.

The emulsifying system may in particular comprise one or more compounds selected from the group consisting of ethoxylated fatty alcohols, fatty acids and PEG esters, ethoxylated partial fatty acid glycerides, polyglycerol fatty acid triglycerides and ethoxylated derivatives thereof.

Ethoxylated fatty acid alcohols according to the present invention include ethylene oxide addition products with behenyl alcohol, particularly those containing 6 to 12 oxyethylenated groups (e.g., behenyl polyether-9 or behenyl polyether-10); ethylene oxide addition products with stearyl alcohol, especially those containing 6 to 12 oxyethylenated groups (e.g. steareth-9); ethylene oxide addition products with isostearyl alcohols, for example those containing 6 to 12 oxyethylenated groups (isosteareth-9), and mixtures thereof.

Nonionic surfactants also include the different oxyethylenated fatty alcohols described above, i.e. the ethylene oxide addition products of lauryl alcohol (laureth-9 to laureth-50); with cetearyl alcohol or ethylene oxide addition products of cetearyl alcohol (ceteareth-9 to ceteareth-30), with ethylene oxide addition products of cetyl alcohol (ceteth-9 to ceteth-30); and mixtures thereof.

Additional surfactants may also be included in the composition. These additional surfactants may be salts of fatty acids having from 8 to 30 carbon atoms such as palmitates, stearates, behenates, glyceryl fatty acid esters such as glyceryl stearate; fatty acid salts containing 2 to 8 ethylene oxide groups and oxyethylenated derivatives of fatty acid glycerides and mixtures thereof, and any emulsifiers and regulators known to the person skilled in the art.

-preservatives:

the preservatives are present in the composition in a proportion ranging from 0.1% to 5%, preferably from 0.1% to 1% by weight relative to the total weight of the composition.

The composition may further comprise an antibacterial agent such as a preservative or antifungal agent selected from alcohols suitable to contain one or more aromatic substituents, for example phenoxyethanol alcohols such as 2-phenoxyethanol, 1-phenoxy-2-propanol, benzyl alcohol, 2-hydroxybiphenyl, parabens (parab's) such as methyl paraben, ethyl paraben, propyl paraben, butyl paraben, isobutyl paraben, sodium methyl paraben, sodium ethyl paraben, sodium propyl paraben, sodium isobutyl paraben, sodium butyl paraben or sodium isobutyl paraben, imidazolidinyl urea, diazolidinyl urea, sodium hydroxymethylglycinate, halogenated derivatives such as iodopropynyl butylcarbamate, 2-bromo-2-nitropropane-1, 3-diol, 2,4,4 '-trichloro-2' -hydroxydiphenyl ether (triclosan), 3,4,4 '-trichlorocarbanilide (triclocarban), chlorobiunulum, 2, 4-dichlorobenzyl alcohol, N- (4-chlorophenyl-N' - (3, 4-dichlorophenylurea, 1, 2-dibromo-2, 4-dicyanobutane, chloroxylenol, ketoconazole, oxiconazole, butoconazole, clotrimazole, econazole, eniconazole, fenticonazole, miconazole, sulconazole, tioconazole, fluconazole, itraconazole, terconazole, active substances containing one or more cationic nitrogens such as cetyltrimethylammonium chloride, cetylpyridinium chloride, benzethonium chloride, diisobutylethylethyl-dimethylbenzylammonium chloride, diisobutyl-phenoxy-ethoxyethyl-dimethylbenzylammonium chloride, N-alkyl-N, N-dimethyl-benzylammonium chloride, bromide, saccharinate, trimethylammonium chloride, sodium aluminum chlorohydroxyacetate, trihexadecylmethylammonium chloride, diaminoalkylamide, organic acids and salts thereof such as citric acid, unsaturated antibacterial agents such as farnesol, terbinafine or naftifine, heterocyclic aromatic agents such as bifonazole, cloconazole, isoconazole, any other antibacterial or antifungal agent known to those skilled in the art; and mixtures thereof.

-a thickener:

the thickening agent is present in the composition in a proportion ranging from 0.1% to 20% by weight, preferably from 0.1% to 10% by weight, relative to the total weight of the composition.

The composition may also contain thickeners or rheology modifiers such as, for example, hydrophobically modified ethoxylated nonionic urethanes, thickening polycarboxylic acids such as acrylate/steareth-20 methacrylate copolymers, carbomers, acrylate copolymers and acrylate/C10-C30 alkyl acrylate crosspolymers; natural gums and clays, modified clays such as bentonite, fatty acid metal salts such as aluminum stearate and hydrophobic silica; and mixtures thereof.

-a pH adjusting agent:

the composition may also comprise acids and bases for adjusting the pH range of the composition. The base may be mineral (sodium hydroxide, potassium carbonate, ammonium) or organic such as mono-, di-or triethanolamine, aminomethyl propylene glycol, N-methyl-glucamine, basic amino acids such as arginine and lysine; and mixtures thereof.

The composition may further comprise one or more other ingredients such as pH buffers, vitamins, fragrances and any other useful compounds known to those skilled in the art.

Detailed Description

The following examples provide non-limiting illustrations of the invention.

Example 1: composition for application to skin

Example 2: composition for hair

2, 3-dihydroxypropyl dodecanoate	1%
		Sodium lauryl Ether sulfate	9%
Lauryl betaine	2%
		Sodium magnesium alkyl ether sulfate	1%
PEG-18 glyceryl oleate/Cocoacid esters	1%
		Polyquaternary ammonium salt 22	0.5%
NaCl	Proper amount to viscosity
		Citric acid	To a proper amount of pH
Water (W)	Proper amount to 100g

Example 3: composition for hair

2, 3-dihydroxypropyl dodecanoate

0.5%

Sodium lauryl Ether sulfate	9%
		Cetroronium chloride	0.3%
Tween 20	5%
		Na2EDTA	0.2%
Thickening agent	4%
		NaCl	Proper amount to viscosity
Citric acid	To a proper amount of pH
		Water (W)	Proper amount to 100g

Claims (12)

1. Use of 2, 3-dihydroxypropyl dodecanoate for the treatment of seborrheic dermatitis.
2. 2. Use according to claim 1, characterized in that the seborrheic dermatitis is associated with the skin.
3. 3. Use according to claim 1, characterized in that the seborrheic dermatitis is associated with the scalp.
4. 4. Use according to claim 3 for slowing down hair loss.
5. 5. An anti-seborrheic dermatitis composition comprising 2, 3-dihydroxypropyl dodecanoate for treating seborrheic dermatitis.
6. 6. The composition for the treatment of seborrheic dermatitis according to claim 5, wherein the seborrheic dermatitis is related to the skin.
7. 7. The composition for the treatment of seborrheic dermatitis according to claim 5, wherein the seborrheic dermatitis is associated with the scalp.
8. 8. The anti-seborrheic dermatitis composition according to any of claims 5 to 7, characterized in that it comprises from 0.01 to 20% by weight, preferably from 0.5 to 10% by weight, more particularly from 1 to 5% by weight, of 2, 3-dihydroxypropyl dodecanoate, relative to the total weight of the composition.
9. 9. The anti-seborrheic dermatitis composition according to any of claims 5 to 8, characterized in that it comprises 2, 3-dihydroxypropyl dodecanoate as the sole active ingredient.
10. 10. The anti-seborrheic dermatitis composition according to any one of claims 5 to 8, characterized in that it comprises creutton hot spring water.
11. 11. The anti-seborrheic dermatitis composition according to any of claims 5 to 10, characterized in that it comprises 2, 3-dihydroxypropyl dodecanoate, yavenon spa water and a cosmetically acceptable base.
12. 12. A method for the cosmetic treatment of seborrheic dermatitis comprising applying a cosmetic composition as defined in at least any one of claims 5 to 11 to the skin or scalp.