WO2022073484A1 - Skin composition and use thereof - Google Patents

Abstract

Provided are a skin composition and the use thereof. In particular, provided is the use of a composition, the composition being used for preparing: (a) a cosmetic for acne removal, or (b) a drug for treating and/or preventing acne; and the composition comprising: (a) a first active ingredient: azelaic acid; and (b) a second active ingredient: a biological polysaccharide. It is firstly discovered that the azelaic acid and biological polysaccharide have a synergistic effect on the treatment of acne, the combination of the two can significantly reduce side effects, such as stinging and/or pruritus, caused by the azelaic acid, and same are very suitable for preparing drugs or acne-removing cosmetics for treating acne.

Description

Dermal compositions and their uses technical field

The present invention relates to the field of skin care. In particular, the present invention relates to an anti-acne and/or anti-acne composition for skin.

Background technique

Acne, also known as pimples, pimples, pimples or folliculitis, is one of the most common skin diseases in cosmetic dermatology caused by the blockage and inflammation of hair follicles and sebaceous glands. Occurs on the face, neck, chest, back, shoulders and upper arms. More common in puberty, endocrine changes during puberty, increased androgen secretion, strong sebaceous gland secretion, causing hair follicle blockage, and inflammation caused by bacteria easily multiplying in hair follicles. Therefore, it is generally believed that acne is related to endocrine, sebum and microorganisms. Repeated attacks can leave uneven scars, bluish-black calcified nodules and hyperpigmentation on the face, which have a profound impact on adolescents' psychology and social interaction. If not treated in time or properly prevented, it will leave scars that will not heal for a lifetime.

For acne, anti-acne drugs are mainly used in the market at present. Mainly include anti-androgens, antibiotics, retinoids and so on. Hormone drugs such as anti-androgens can easily cause endocrine disorders, affect sexual function, and also affect bone development, which has a huge impact on adolescent patients. If antibiotics are used for a long time, bacteria will develop drug resistance, the treatment effect will decrease day by day, and it will also lead to dysbiosis. Retinoic acid drugs have been verified by animal experiments and have strong teratogenicity. Topical application of retinoic acid on the skin has clear embryotoxicity and teratogenicity to mice, rats, hamsters, and rabbits in the embryo sensitive period. It can cause maternal system toxicity, and retinoic acid can also cause liver damage. The safety of clinical medication still needs to be carefully evaluated.

However, the long-term application of these drugs makes acne prone to recurrence during the treatment process, and it is easy to cause bacteria to develop drug resistance, aggravate endocrine disorders, and even induce other skin diseases. The long-term toxic side effects bring great physical and mental pain to patients.

Therefore, there is an urgent need to provide an acne-removing composition that is safe, has less toxic and side effects, and has more significant effects.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide a safe, less toxic and side effect, quick-acting composition and its use in anti-acne and/or anti-acne.

In the first aspect of the present invention, there is provided the use of a composition for preparing: (a) a cosmetic for removing acne; or (b) a medicament for treating and/or preventing acne;

Wherein, the composition includes:

(a) a first active ingredient: azelaic acid; and

(b) Second active ingredient: β-glucan.

In another preferred embodiment, the β-glucan is β-D-glucan.

In another preferred embodiment, the β-glucan is β-1,3-glucan, preferably, β-1,3-glucan with β-1,6-branch.

In another preferred embodiment, the β-glucan includes n repeating units shown in formula I,

Wherein, a is an integer ≥ 0, preferably 0-50, preferably 0-10, more preferably 0-3, more preferably 1-2, more preferably 1; b is an integer ≥ 0, more preferably It is preferably 0-19, preferably 0-4, more preferably 0-1, more preferably 0. Formula I is a basic repeating unit, which can be repeated in a large number to form macromolecular β-glucan, the repeating number n is an integer of ≥ 3, preferably 30-60000, more preferably 100-10000, such as 200, 1000 , 2000, 5000, 8000 or 20000.

In another preferred example, the branching degree (DB) of the β-glucan is 0.02-0.8, preferably 0.1-0.5, preferably 0.2-0.4.

In another preferred embodiment, the β-glucan includes a β-glucan having a triple helix three-dimensional structure.

In another preferred example, the β-1,3-main chain of the β-glucan is the main body of the triple helix three-dimensional structure.

In another preferred example, the β-1,6-branch of the β-glucan is located outside the triple helix three-dimensional structure.

In another preferred embodiment, the molecular weight of the β-glucan is ≥2kD, preferably 2kD-40000kD, more preferably 20kD-20000kD.

In another preferred example, the molecular weight of the β-glucan can be 5kD-35000kD; 10kD-30000kD; 50kD-25000kD; 100kD-20000kD; 200kD-18000kD; 400kD-16000kD; 2000kD-4000kD; 3000kD-5000kD; 4000kD-6000kD; 5000kD-7000kD; 6000kD-8000kD; 7000kD-9000kD;

In another preferred embodiment, the β-glucan is selected from the group consisting of: Schizophyllum β-glucan, Lentinus edodes β-glucan, Sclerotinia β-glucan, Grifola frondosa β-glucan Glycan, Pleurotus, mushroom beta-glucan, yeast beta-glucan, oat beta-glucan, or a combination thereof.

In another preferred embodiment, the β-glucan is Schizophyllum β-glucan.

In another preferred embodiment, the mushroom β-glucan has 5 β-1,3- main chains with 2 β-1,6- branches, and each branch has 1 glucose residue based β-glucan.

In another preferred embodiment, the purity of the β-glucan is ≥70%, preferably ≥90%, more preferably ≥95%, more preferably ≥99%.

In another preferred embodiment, the β-glucan has good stability.

In another preferred embodiment, the beta-glucan is in a solid form or a liquid form, such as beta-glucan solid particles or powder, or beta-glucan aqueous solution.

In another preferred example, the particle size of the β-glucan particles or powder is ≤20 mm, preferably 0.001-10 mm, more preferably 0.01-5 mm, more preferably 0.1-2 mm.

In another preferred embodiment, the β-glucan is completely water-soluble β-glucan.

In another preferred embodiment, the β-glucan (granule or powder) has good water solubility and/or natural solubility.

In another preferred example, the solubility of the β-glucan (granule or powder) in water (100 g) at 25° C. is ≥0.0001 g, preferably 0.01-50 g, more preferably 0.1-10 g.

In another preferred example, the solubility of the beta-glucan (granule or powder) in water (100g) at 25°C may be 0.1-100g; 0.2-90g; 0.5-80g; 1-50g; The solubility can be 0.1-0.3g; 0.2-0.4g; 0.3-0.5g; 0.4-0.6g; 0.5-0.7g; 0.6-0.8g; 0.7-0.9g; 0.8-1g; 4g; 3-5g; 4-6g; 5-7g; 6-8g; 7-9g; 8-10g.

In another preferred embodiment, the beta-glucan solution is a solution of beta-glucan in water, that is, an aqueous beta-glucan solution.

In another preferred example, the β-glucan (water) solution has a high viscosity; preferably, the viscosity of the β-glucan aqueous solution (at 30°C) with a mass concentration of 0.5% is ≥40 mPa·s, more preferably 100-10000 mPa·s, more preferably 500-2000 mPa·s.

In another preferred example, the viscosity of the β-glucan aqueous solution (30°C) with a mass concentration of 0.5% may be 50-10000mPa·s; 100-9000mPa·s; 200-8000mPa·s; 300-7000mPa·s s; 400-6000mPa·s; 450-5000mPa·s; 500-5000mPa·s; 550-4000mPa·s; 600-3000mPa·s; 650-2000mPa·s; 700-1500mPa·s.

In another preferred example, the aqueous solution of β-glucan with a mass concentration of 1% has high clarity or high light transmittance, and the light transmittance of the β-glucan aqueous solution with a mass concentration of 1% ≥50%, preferably ≥80%, preferably ≥85%, more preferably ≥95%;

In another preferred embodiment, the β-glucan solution has good stability.

In another preferred example, the weight ratio of the first active ingredient to the second active ingredient is 20:0.01-5.

In another preferred example, the weight ratio of the first active ingredient to the second active ingredient is 20:0.02-2.5; 20:0.05, 20:0.1, 20:0.2, 20:0.3, 20:0.4, 20:0.5, 20:0.6, 20:0.7, 20:0.8.

In another preferred embodiment, the acne (pimple) includes one or more symptoms selected from the group consisting of whiteheads, blackheads, inflammatory papules, pustules, nodules, and cysts.

In another preferred example, the acne (pimples) is broken skin type acne and/or closed type acne.

In another preferred embodiment, the cosmetic or drug is a cosmetic or drug with reduced side effects.

In another preferred embodiment, the side effects are those caused by azelaic acid.

In another preferred embodiment, the side effects are selected from the group consisting of tingling, itching, or a combination thereof.

In another preferred embodiment, the acne treatment further includes reducing the formation and/or the degree of acne scars.

In another preferred embodiment, the acne marks include pigmentation, nodules and scars.

In another preferred embodiment, the composition includes:

Azelaic acid 5-30 wt%; and

Beta-glucan 0.01-5 wt%; and

A cosmetically or pharmaceutically acceptable carrier or excipient.

In another preferred embodiment, the azelaic acid accounts for 6-29wt% of the total weight of the composition, preferably 10-25wt%, preferably 10-20wt%, such as 12-25wt% or 15-22wt%.

In another preferred example, β-glucan accounts for 0.01-3wt%, preferably 0.02-2wt%, preferably 0.025-1wt%, more preferably 0.05-0.5wt% or 0.1-0.3wt%.

In another preferred embodiment, the β-glucan is Schizophyllum β-glucan.

In another preferred example, the viscosity of the aqueous solution with a mass concentration of 0.5% Schizophyllum β-glucan (30°C, rotor 3, 30rpm) is ≥400mPa·s, preferably 500-2000mPa·s, more Best place, 1000-1600mPa.s.

In another preferred embodiment, the molecular weight of the Schizophyllum β-glucan is 200kD-20000kD, preferably 400kD-10000kD, more preferably 450kD-8000kD, and most preferably 1000kD-5000kD.

In another preferred embodiment, the carrier or excipient is selected from the group consisting of moisturizing agents, skin conditioning agents, thickening agents, emollients, emulsifiers, antioxidants, preservatives, anti-ultraviolet agents, film-forming agents, Oil-soluble gelling agents, organically modified clay minerals, resins, antibacterial agents, fragrances, salts, pH adjusters, conditioners, chelating agents, cooling agents, anti-inflammatory agents, skin beautifying ingredients, vitamins, amino acids, nucleic acids , an inclusion compound, a solvent (eg, water), or a combination thereof.

In another preferred embodiment, the composition includes 1-25wt% of skin conditioning agent, preferably 2-20wt%, more preferably 5-15wt%.

In another preferred embodiment, the skin conditioning agent is selected from the group consisting of bisabolol, allantoin, witch hazel extract, purslane extract, astragalus extract, gentian anti-irritant factor, glycyrrhizic acid Dipotassium, octanoylglycine, Centella asiatica extract, zinc pyrrolidone carboxylate, copper pyrrolidone carboxylate, cannabidiol, venom-like tripeptide, palmitoyl tripeptide, acetyl dipeptide, acetyl hexapeptide, or a combination thereof .

In another preferred embodiment, the skin conditioning agent includes witch hazel extract, preferably, the composition includes 1-12wt% witch hazel extract, preferably 2-10wt%, more preferably Ground, 4-8 wt%.

In another preferred embodiment, the carrier or excipient includes the following group: humectant, thickener, emollient, emulsifier, antioxidant, preservative and deionized water.

In another preferred embodiment, based on the total weight of the composition, the composition comprises:

Thickener 0.1-5wt%,

Humectant 2-20wt%,

Emollient 0-15wt%,

0-5 wt% emulsifier, and

Antioxidant 0-5wt%.

In another preferred embodiment, the composition includes 0.5-2 wt% thickener.

In another preferred embodiment, the composition includes 5-15 wt % of a moisturizing agent.

In another preferred embodiment, the composition includes 0-10wt% of emollient, preferably 1-10wt%.

In another preferred embodiment, the composition includes 0.2-2wt% emulsifier, preferably 0.8-1.5wt%.

In another preferred embodiment, the composition includes 0.2-2wt% antioxidant, preferably 0.5-1wt%.

In another preferred embodiment, the composition further includes a preservative.

In another preferred embodiment, the composition includes 20-80 wt% deionized water.

In another preferred embodiment, the composition dosage form is selected from the following group: liquid dosage form, semi-solid or solid dosage form, preferably ointment, cream, emulsion, oil, powder, solution, gel, spray formulations, foams, suspensions, lotions, sticks.

In another preferred embodiment, the composition does not contain one or more components selected from the group consisting of antibiotics, bacteriostatic agents, retinoic acid, and hormones.

In another preferred example, the aqueous solution of the Schizophyllum β-glucan has a high viscosity; preferably, the viscosity of the aqueous solution with a mass concentration of 0.5% (30° C., rotor 3, 30 rpm) is ≥ ≥ 400 mPa·s, and more Good ground 500-2000mPa·s.

In another preferred embodiment, the light transmittance of the aqueous solution with the mass concentration of Schizophyllum β-glucan of 0.5% is ≥ 80%, preferably ≥ 85%, more preferably ≥ ≥ 90%;

In another preferred embodiment, the thickener is selected from the group consisting of fatty alcohols, fatty acids, alkanolamides, ethers, esters, amine oxides, celluloses, polyacrylic acids, natural gums type, polymeric thickeners, or a combination thereof.

In another preferred embodiment, the moisturizing agent is selected from the group consisting of polyols, natural moisturizing factors, amino acids, macromolecular biochemical molecules, or a combination thereof.

In another preferred example, the emollient is selected from the group consisting of isononyl isononanoate, pentaerythritol tetra(ethylhexanoate), cetearyl alcohol ethylhexanoate, caprylic acid triglyceride, capric acid Acid triglycerides, triglycerides (ethylhexanoate), cocoa butter substitute, grapeseed oil, shea butter, isooctyl palmitate, jojoba oil, PEG-6 caprylic/capric glycerides, Macadamia Oil, Squalane, Camellia Oil, Grape Seed Oil, Emu Oil, Hydrogenated Polydecene, Isohexadecane, PEG/PPG-17/6 Copolymer, Cetylstearyl Alcohol, C12-15 Silicone oils such as alkanol benzoate, PEG-12/dimethicone, or a combination thereof.

In another preferred embodiment, the emulsifier is selected from the group consisting of polysorbate-80, PEG-60 hydrogenated castor oil, PEG-40 hydrogenated castor oil, hydrogenated lecithin, beeswax, polyol ester, fatty alcohol polyol Macromolecular emulsifiers such as oxyethylene ether, hydroxyethyl acrylate/sodium acryloyl dimethyl taurate copolymer, or combinations thereof.

In another preferred embodiment, the antioxidant is selected from the group consisting of vitamin A, vitamin E, cysteine, ascorbic acid, superoxide dismutase, glutathione peroxidase, coenzyme Q10, tocopheryl acetate ester, ergothioneine, or a combination thereof.

In another preferred embodiment, the preservative is selected from the group consisting of phenols, acids, parabens, isothiazolinones, urea formaldehyde releasers, bacteriostatic agents, and not in the list of preservatives But no added preservatives (such as hexylene glycol, pentylene glycol, ethylhexylglycerol, p-hydroxyacetophenone, capryloyl hydroxamic acid, etc.) that can play a preservative effect, or a combination thereof.

In another preferred embodiment, the composition comprises, % based on the total weight of the composition:

Element	wt%
Azelaic acid	8-22
Schizophyllum β-glucan	0.02-0.6
witch hazel extract	4-6
Caprylic/Capric Triglycerides	4-6
1,3-Butanediol	2-5
Polyglyceryl ether-26	2.5-3.5
1,3-Propanediol	1-3.5
glycerin	0-5
trehalose	0.8-1.2
Ammonium acryloyl dimethyl taurate/vp copolymer	0.6-1.2

Purslane Extract	0-2.5
Cannabidiol	0-0.1
gentian anti-irritant	0-1
bisabolol	0.1-1
1,2-Pentanediol	0-1
PEG-60 Hydrogenated Castor Oil	0.4-0.6
Allantoin	0.1-0.3
preservative	Moderate
water	margin

.

A second aspect of the present invention, a method of treating and/or preventing acne, comprising the steps of: administering to a subject in need thereof an effective amount of the composition,

Wherein, the composition includes:

(a) a first active ingredient: azelaic acid; and

(b) Second active ingredient: β-glucan.

In another preferred embodiment, the β-glucan is Schizophyllum β-glucan.

In another preferred embodiment, the application is to apply the composition of the present invention to the affected area of acne.

In another preferred embodiment, the subject is a mammal, such as a human, a rat, or a mouse.

In another preferred example, the subject is a pregnant woman or a person with sensitive skin.

It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described in the following (eg, the embodiments) can be combined with each other to constitute new or preferred technical solutions. Due to space limitations, we will not repeat them here.

Description of drawings

Figure 1: Comparison of acne before and after male volunteer A tried formula III cream.

Figure 2: Comparison of acne before and after male volunteer A tried formula IV cream.

Figure 3: Comparison of acne before and after male volunteer B tried formula V cream.

Figure 4: Comparison of acne before and after the male volunteer C tried formula VI cream.

Figure 5: Comparison of acne conditions before and after male volunteer D tried formula VI cream.

Figure 6: Comparison of acne conditions before and after male volunteer D tried formula VIII cream.

Figure 7: Comparison of acne conditions before and after female volunteer E tried formula VII cream.

Detailed ways

After extensive and in-depth research, the present inventors have provided an anti-acne composition through a large number of screenings and tests. The inventors unexpectedly found that azelaic acid and β-glucan (especially Schizophyllum β-glucan) have a synergistic effect in the treatment of acne, and only a very small amount of β-glucan can be added. Significantly enhances acne treatment and reduces side effects such as stinging and/or itching caused by azelaic acid. The present invention has been completed on this basis.

the term

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

As used herein, when used in reference to a specifically recited value, the term "about" means that the value may vary by no more than 1% from the recited value. For example, as used herein, the expression "about 100" includes all values between 99 and 101 and (eg, 99.1, 99.2, 99.3, 99.4, etc.).

As used herein, the terms "containing" or "including (including)" can be open, semi-closed, and closed. In other words, the term also includes "consisting essentially of," or "consisting of."

As used herein, the term "room temperature" refers to a temperature of 4-40°C, preferably, 25±5°C.

Active ingredient

The invention provides the use of azelaic acid and beta-glucan as active ingredients, which are used in combination in treating acne.

In another preferred embodiment, the β-glucan is Schizophyllum β-glucan.

As used herein, the term "azelaic acid", commonly known as azelaic acid, refers to a

structural compounds.

As used herein, the term "Schizophyllum beta-glucan" refers to beta-glucan produced by Schizophyllum commune Fr. It can usually be extracted from Schizophyllum fruiting bodies, fermentation broth and/or mycelium.

Preferably, the molecular weight of the Schizophyllum β-glucan is 200kD-20000kD, preferably 400kD-10000kD, more preferably 450kD-8000kD, and most preferably 1000kD-5000kD.

In another preferred example, the aqueous solution of the Schizophyllum β-glucan has a high viscosity; preferably, the viscosity of the aqueous solution with a mass concentration of 0.5% (30° C., rotor 3, 30 rpm) is greater than or equal to 400 mPa·s, preferably 500-2000 mPa·s, more preferably, 1000-1600 mPa·s. Viscosity can reflect the molecular weight of beta-glucan.

In the active ingredient combination, the first active ingredient and the second active ingredient may be independent of each other, or may be combined together to form an active ingredient composition.

Preferably, the weight ratio of the first active ingredient to the second active ingredient is 20:0.01-5.

acne

As used herein, the terms "acne," "pox," and "pimples" are used interchangeably to refer to acne. Usually, it is called "acne" or "pimple" in the cosmetic field, and "acne" in medicine.

As used herein, acne types mainly include: papular acne, pustular acne, nodular acne, cystic acne.

Papular acne: inflammatory or non-inflammatory small granular acne, diameter ≤ 5mm, can be scattered or dense and appear in pieces.

Pustular acne: mainly small pustules, accompanied by inflammatory papules, the diameter is less than or equal to 5mm, and the pustules contain a large amount of pus, which is relatively viscous.

Nodular acne: On the basis of pustular acne, a large number of keratin, sebum and pus cells accumulate in the sebum of the hair follicle, which destroys the sebum structure of the hair follicle and forms a red or light color above or under the skin Nodules, the invasion site is deep, the touch is hard, and some are painful when pressed.

Cystic acne: mainly cystic masses of different sizes, without cusps, with severe inflammation, containing a large amount of tissue fluid, strong pain when pressing, often bursting and overflowing with pus. Often accompanied by papules, nodules, pustules, abscesses and so on.

Composition and use

The composition of the present invention includes:

(a) a first active ingredient: azelaic acid; and

(b) Second active ingredient: β-glucan.

Typically, the first active ingredient and the second active ingredient are prepared together with a cosmetically or pharmaceutically acceptable carrier or excipient to form a composition suitable for administration.

The first active ingredient and the second active ingredient of the present invention have a synergistic effect in treating acne, and surprisingly, β-glucan (especially Schizophyllum β-glucan) can reduce the azelaic acid-induced Side effects (such as stinging, itching, etc.), the combination or composition of the above-mentioned active ingredients is particularly suitable for preparing a cosmetic for acne treatment; or a medicament for treating and/or preventing acne.

As used herein, the terms "cosmetic acceptable" or "pharmaceutically acceptable" ingredients refer to ingredients that are suitable for use in humans and/or animals without undue adverse side effects (eg, toxicity, irritation, and allergy), i.e., reasonable the benefit/risk ratio of the substance.

As used herein, the term "effective dose" refers to any amount of a cosmetic or drug, as described below, which, when used alone or in combination with another therapeutic agent, promotes regression of disease, which manifests itself as disease The severity of symptoms decreased and the frequency and duration of disease-free periods increased. A "therapeutically effective dose" of a drug of the present invention also includes a "prophylactically effective dose", which is any amount of the drug as described below, when the amount of the drug is administered alone or in combination with another therapeutic agent In a subject at risk of developing the disease or suffering from relapse of the disease, the occurrence or relapse of the disease can be inhibited.

"Prevention" and "treatment" as used in the present invention include delaying and stopping the progression of the disease, or eliminating the disease, and do not require 100% inhibition, elimination and reversal. In some embodiments, the composition or pharmaceutical composition of the present invention prevents, alleviates, inhibits and/or reverses acne as compared to levels observed in the absence of the composition or pharmaceutical composition of the present invention, for example At least about 10%, at least about 30%, at least about 50%, or at least about 80%.

Preferably, the carrier or excipient is selected from the group consisting of humectants, skin conditioners, thickeners, emollients, emulsifiers, antioxidants, preservatives, anti-ultraviolet agents, film formers, oil-soluble gels Chemical agents, organically modified clay minerals, resins, fragrances, salts, pH adjusters, conditioners, antibacterial agents, chelating agents, cooling agents, anti-inflammatory agents, skin beautifying ingredients, vitamins, amino acids, nucleic acids, inclusion compounds , a solvent (eg, water), or a combination thereof.

The thickeners include fatty alcohols or fatty acids such as lauryl alcohol, fatty acids; alkanolamides such as cocamide; ethers such as cetyl polyoxyethylene (3) ether; esters such as PEG-150 distearate ; amine oxides such as cocamidopropyl amine oxide; cellulose such as carboxymethyl cellulose; polyacrylic acid such as carbomer; natural gum and its modifications such as sodium alginate, xanthan gum; and new One or more than two kinds of polymer thickeners such as polyvinylpyrrolidone, acryloyldimethyl ammonium tauronate/vp copolymer, etc.

The moisturizing agent refers to polyols, natural moisturizing factors, amino acids, macromolecular biochemical molecule moisturizing agents, and combinations thereof, specifically glycerol, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, caprylyl glycol, sorbitan Alcohol, Xylitol, Polyethylene Glycol, PCA-Na, Sodium Lactate, Urea, Hydrolyzed Protein, Soy Protein, Collagen, Chondroitin Sulfate, Ceramide, Betaine, Trehalose, Chitosamine, Polyglyceryl Ether- 26. One of sodium hyaluronate and D-panthenol or two or more in any proportion.

Described emollient refers to various synthetic esters and natural oils such as isononyl isononanoate, pentaerythritol tetra(ethylhexanoate), cetearyl alcohol ethylhexanoate, caprylic/capric triglyceride , Triglyceride (ethylhexanoate), Cocoa Butter Replacement, Grapeseed Oil, Shea Butter, Isooctyl Palmitate, Jojoba Oil, PEG-6 Caprylic/Capric Glycerides, Macadamia Oil, Squalane, Camellia Seed Oil, Grape Seed Oil, Emu Oil, Hydrogenated Polydecene, Isohexadecane, PEG/PPG-17/6 Copolymer, Cettostearyl Alcohol, C12-15 Alkanol Benzyl One or more of two or more of acid esters, silicone oils such as PEG-12/polydimethylsiloxane, etc., in any ratio.

The skin conditioning agent refers to raw materials with functions such as anti-inflammatory, anti-allergic, soothing, anti-oxidation and oil control, such as bisabolol, allantoin, witch hazel extract, purslane extract, astragalus extract, gentian Anti-irritant, Dipotassium Glycyrrhizinate, Caprylyl Glycine, Centella Asiatica Extract, Zinc Pyrrolidone Carboxylate, Copper Pyrrolidone Carboxylate, Cannabidiol, Venom-like Tripeptide, Palmitoyl Tripeptide, Acetyl Dipeptide, Acetyl One of the hexapeptides or the like or two or more in any ratio. The extract or extract can be a commercially available product commonly used in the art, for example, the witch hazel extract is the natural extract of witch hazel, which can be purchased commercially.

The emulsifier is polysorbate-80, PEG-60 hydrogenated castor oil, PEG-40 hydrogenated castor oil, hydrogenated lecithin, beeswax, polyol ester, fatty alcohol polyoxyethylene ether, hydroxyethyl acrylate/acryloyl One kind or two or more kinds of polymer emulsifiers, such as sodium dimethyl taurate copolymer, etc., in an arbitrary ratio.

The antioxidant is one of vitamin A, vitamin E, cysteine, ascorbic acid, superoxide dismutase, glutathione peroxidase, coenzyme Q10, tocopheryl acetate, ergothioneine, etc. Any ratio of two or more.

The preservatives are methylparaben, ethylparaben, propylparaben, butylparaben and other paraben esters; methylisothiazolinone, methylchloroisothiazolinone, etc. Isothiazolinones; DMDM hydantoin, imidazolidinyl urea, bis(hydroxymethyl) imidazolidinyl urea and other formaldehyde releasers; pentanediol, hexanediol, caprylyl glycol, phenethyl alcohol, phenylpropanol , ethylhexylglycerin, glycerol caprate, capric acid, glycerol caprylate, sorbitan caprylate, glyceryl undecylenate, p-hydroxyacetophenone, levulinic acid, anisic acid, capryloylhydroxime One or more than two kinds of antiseptic system without preservative system such as acid.

The composition of the present invention is suitable for external use on the skin. They may be in liquid, semi-solid or solid dosage forms, more preferably ointments, creams, emulsions, oils, powders, solutions, gels, sprays, foams, suspensions, lotions or patches sticks. They can also be in the form of suspensions of microspheres or nanospheres, or in the form of lipid or polymeric carriers, or in the form of polymeric patches, and in the form of controlled release hydrogels. These compositions for topical application may be in the form of anhydrous, aqueous or emulsion formulations.

The main advantages of the present invention include:

1. The combination of β-glucan and azelaic acid not only shows a synergistic effect in treating acne, but also can significantly reduce side effects such as stinging and/or itching caused by azelaic acid, which is very suitable for For the preparation of medicines for treating acne or cosmetic products for treating acne.

2. The composition of the present invention is convenient to use, safe, non-teratogenic, non-toxic and non-toxic.

3. The composition of the present invention may not contain hormone components, and will not affect the endocrine and the growth and development of adolescents.

4. The composition of the present invention can be free of antibiotics and will not cause drug resistance problems.

5. The composition of the present invention does not have teratogenic components, and also does not cause serious consequences such as liver damage, and even pregnant women can use it with confidence.

6. The composition of the present invention has high efficacy and quick effect on acne of various degrees.

The present invention will be further described below in conjunction with specific implementation. It should be understood that these examples are only used to illustrate the present invention and not to limit the scope of the present invention. In the following examples, the experimental methods without specific conditions are usually in accordance with conventional conditions, or in accordance with the conditions suggested by the manufacturer. Percentages and parts are by weight unless otherwise indicated.

Schizophyllum β-glucan (Schizophyllum communeFr.), purchased from Zhejiang Lien Biotechnology Co., Ltd. (β-glucan molecular weight≥2000kD, 0.5wt% aqueous solution viscosity>1000mPa s (30℃, rotor 3, 30rpm), generally 1000-1600mPa·s (30°C, rotor 3, 30rpm), and the rest of the substances are common components in the market.

Example 1. Preparation of anti-acne cream

1. Prepare anti-acne cream according to the formula in Table 1, % by total weight

Table 1 Anti-acne cream formula

2. The preparation method is as follows:

1. Take the calculated amount of water, add azelaic acid, β-glucan, 1,3-butanediol, 1,3-propanediol, polyglyceryl ether-26, glycerin, trehalose, 1,2 -Pentylene glycol, allantoin and other high-temperature-resistant water-soluble or hot-water-soluble substances, mix well, and place in a water bath above 90°C until all substances are dissolved.

2. Take the required amount of thickener, such as ammonium acryloyl dimethyl taurate/vp copolymer or other thickeners, and add it to the oil phase such as caprylic acid/capric triglyceride for dispersion (the thickener may not be used. Disperse, add to the water phase when homogenizing), also placed in the above water bath, so that the two phases reach the same temperature.

3. Mix the two phases, at the same time add emulsifiers such as PEG-60 hydrogenated castor oil (it can also be added to any one of the two phases before mixing), homogenize (homogenization refers to high-speed stirring, such as using mechanical equipment to make The mixture is highly homogenized to achieve emulsification), so that the ingredients are mixed well and a homogeneous cream is obtained.

4. Continuously homogenize, add witch hazel extract, snake venom tripeptide-1, purslane extract, cannabidiol, gentian anti-irritant factor, bisabolol and other activities when the temperature drops to 40-45 ℃ Substances or raw materials that are not resistant to high temperatures.

5. Add spices, preservatives and volatile substances and mix well.

Example 2. Test evaluation of anti-acne cream on broken skin type acne volunteers

60 volunteers suffering from broken skin acne were divided into 6 groups, 10 people in each group, respectively used the anti-acne creams of formulas I, II, III, IV, IX, X in the above-mentioned embodiment 1, in the morning and evening on the acne affected area. Each small area is smeared once and used for 3 days for evaluation. While evaluating the therapeutic effect, the adverse reactions were evaluated.

Treatment effect standard: (regression rate = number of acnes subsided/number of initial acnes)

(1) Cure: acne all subsided, no recurrence within three months;

(2) Significantly effective: the acne subsidence rate is above 60%;

(3) Effective: acne subsidence rate is 20%-60%;

(4) Invalid: acne subsidence rate is less than 20% or no obvious change from before treatment.

For broken skin acne, the effect of removing acne after volunteer test is shown in Table 2:

Table 2 Therapeutic effects and adverse reactions in patients with broken skin acne

As can be seen from Table 2, the formula I of 20% azelaic acid (Schizophyllum β-glucan) is treated for 3 days for broken skin type acne, and its effective rate is as high as 80%, and the cure rate is 20%. And the formula II of 0.1% Schizophyllum β-glucan (without azelaic acid) has an effective rate of 90% and a cure rate of 20%. When the two are used in combination, such as formula III (10% azelaic acid combined with 0.05% Schizophyllum β-glucan), the effective rate is 100%, and the cure rate is 40%, which is significantly higher than the single use of azelaic acid. Acid or Schizophyllum β-glucan (100% increase in cure rate), it can be seen that azelaic acid and Schizophyllum β-glucan have a synergistic effect in the treatment of acne.

And the anti-acne cream formulas III and IV of the present invention, which are used in combination with azelaic acid and Schizophyllum β-glucan, can reach 100% effectiveness in treating broken skin type acne, and the average cure rate is 45%. With IV, the cure rate reached 50% within 3 days, and the average time to effect was only 0.90 days.

However, yeast β-glucan and oat β-glucan did not significantly promote the efficacy of the formula.

Broken skin acne refers to obvious damage to the skin at the acne site. The composition can avoid the skin barrier function and enter directly by topical application. The adverse reactions of azelaic acid at the broken skin are mainly stinging and itching, but due to The tingling sensation can mask minor sensations such as itching, so stinging is mainly recorded here. Except for formula II, which has no adverse reactions, the other formulas containing azelaic acid have adverse reactions of varying degrees.

The stinging reaction mainly occurs 1-5 minutes after smearing. Among them, formulas I, IX, and X last for a long time, about 9.8 minutes on average, while formulas III and IV last for a short time, with an average of 4.8 minutes, and then disappear on their own. Follow-up adverse effects, the volunteers told that the adverse reactions were acceptable. According to the statistical data of adverse reactions, Schizophyllum β-glucan has a significant improvement effect on adverse reactions, and the stinging duration of formula III and IV is far less than that of formulas I and IX without Schizophyllum β-glucan. and X. In addition, the improvement effect of Schizophyllum β-glucan on adverse reactions was dose-dependent, and the adverse reactions gradually decreased with the increase of the addition amount.

Some adverse reactions such as tingling and itching exhibited by the anti-acne cream are caused by azelaic acid, but they can disappear in a short time. Between 1 and 9, the lower the value is, the lower it represents about safety), which is a very safe raw material, and there is no need to worry about the above-mentioned adverse reactions that will bring other safety issues.

Example 3. Anti-acne cream closed-type acne volunteer test evaluation

60 volunteers suffering from closed acne were divided into 6 groups with 10 people in each group, respectively using the anti-acne creams of formulas I, II, III, IV, IX, X in the above-mentioned embodiment 1, respectively, in the morning and evening on the acne affected area. Apply once on a small area, and use it for 1 week for evaluation. While evaluating the therapeutic effect, the adverse reactions were evaluated.

The standard of therapeutic effect is the same as in Example 2, and for closed acne, the effect of removing acne after the volunteer test is as shown in Table 3:

Table 3 Therapeutic effects and adverse reactions in patients with closed acne

As can be seen from Table 3, the formula I containing 20% azelaic acid (Schizophyllum azela beta-glucan) was treated for 1 week for closed acne, and its effective rate was as high as 90%, and the cure rate was 30%. The formula II containing 0.1% Schizophyllum β-glucan (without azelaic acid) had an effective rate of 80% and a cure rate of 10%. When the two are used in combination, such as formula III (10% azelaic acid combined with 0.05% Schizophyllum β-glucan), the effective rate is 100%, and the cure rate is 50%, which is significantly higher than that of azelaic acid alone. Acid or Schizophyllum β-glucan, it can be seen that azelaic acid and Schizophyllum β-glucan have a synergistic effect in the treatment of acne.

The anti-acne cream formulas III and IV used in combination with azelaic acid and Schizophyllum β-glucan of the present invention have an average effectiveness of treating closed acne of 100% and an average cure rate of 55%, of which formula IV The cure rate is 60% after 1 week of use.

The adverse reactions of closed acne were mainly tingling and itching, and some volunteers had both. Except that formula II has no adverse reaction, all other formulas containing azelaic acid have adverse reactions of varying degrees.

The stinging reaction mainly occurred 1-5 minutes after application, and the incidence rate of formula I, IX, X was 53.3%, and the duration was longer, with an average of 9.93 minutes, while the incidence rate of formula III and IV was 35%, and the duration was longer. Short, an average of 4.2 minutes. The itching reaction was similar to stinging, and the azelaic acid formulation without Schizophyllum β-glucan had a high incidence of pruritus reaction (73.3%) and lasted for more than 20 minutes, while the Combined use (formula III, IV), the incidence of itching reaction decreased to 40%, and the duration decreased to less than 8 minutes, with an average of 5.8 minutes. Subsequently, the above-mentioned adverse reactions such as tingling and itching disappeared on their own without subsequent adverse effects, and the volunteers reported that the adverse reactions were acceptable.

According to the statistics of adverse reactions, Schizophyllum β-glucan can significantly improve adverse reactions, and the incidence and duration of stinging and itching of formula III and IV are much less than those without Schizophyllum β-glucan. Formulations I, IX and X. In addition, the improvement effect of Schizophyllum β-glucan on adverse reactions was dose-dependent, and the adverse reactions gradually decreased with the increase of the addition amount.

Example 4. Analysis of volunteer trial cases

According to the test results in Examples 2 and 3, focus on the improvement effect of the product of the present invention on acne.

Patients with different degrees of acne were selected for investigation, male or female. The results are shown in Figures 1-7.

Figure 1 shows a male volunteer A, 29 years old, with long-term acne on the right face and uneven skin. The formula III cream was tried, and the results showed that after 1 day of trial, the skin on the slightly raised acne site gradually flattened or scabbed, and after 2 days of trial, there was basically no raised inflammatory acne on the skin.

Figure 2 shows a male volunteer A, 29 years old, with long-term acne on the right face and uneven skin. Try formula IV cream when acne recurs. After 1 day of trial use, the inflammatory acne that was originally protruding and red was completely healed and scabbed. After 3 days, the scabs fell off, and there were no obvious new acne marks.

Figure 3 shows a case of male volunteer B, 28 years old, with long-term recurrent acne on the mandibular margin, and a large number of outbreaks at the same time, lighter in summer and heavier in winter. In summer, I tried Formula V Cream, and after 1 day of trial, the acne area scabs, and after 2 days, the scabs fall off. After 2 weeks of trial, there was no recurrence and no severe acne breakouts in winter.

Figure 4 shows a case of male volunteer C, 34 years old, with occasional acne, and the forehead acne has broken skin. Tried formula VI cream for 1 day, and the acne area was calmed and scabbed. On the 2nd day of trial, the scab basically fell off, leaving only slight acne marks. The volunteer was accompanied by tingling and itching when using the cream, the stinging lasted about 2 minutes, and the itching lasted about 5 minutes.

Figure 5 shows a case of male volunteer D, 14 years old, with acne outbreaks on the back for about 1 year, and the skin lesions are large. Trial formula VI cream was effective for 1 day, and by the 4th day, most of the acnes subsided, inflammation and redness subsided.

Figure 6 shows a male volunteer D, 14 years old, with acne outbreaks on the back for about 1 year. After trying formula VI cream for improvement, it relapsed after discontinuation for a period of time, and many acne marks were produced. Tried formula VIII cream for 10 days, and the original large-sized acne got better, especially the acne marks were obviously faded.

Figure 7 shows a case of female volunteer E, 40 years old, who used skin care products containing Schizophyllum β-glucan for a long time, and had occasional acne. In the picture, an inflamed pustule-type small acne occurred under the nose. After 0.5 days of trial of formula VII cream, the pustule fell off by itself, and after 2 days of trial, there was basically no acne marks.

Example 5. Influence of Schizophyllum β-glucan on formula effect and irritation

Formula I and Formula IV in Example 1 are selected for comparison. The difference between the two is that Formula IV has added 0.1% Schizophyllum β-glucan, Formula I has not added Schizophyllum β-glucan, and the therapeutic effect standard Same as Example 2.

Tingling and itching are divided into grades I, II, III, and IV respectively: the scores corresponding to each grade (the higher the score, the more serious the adverse reaction) are as follows:

I. No stinging/no itching; count as 0 points;

II. Slight tingling/slight itching; 1 point;

III. Moderate tingling, tolerable/moderate itching, tolerable; 2 points;

IV. Severe tingling, unbearable/severe itching, unbearable; 3 points.

30 volunteers with acne on both cheeks randomly applied the formula I and formula IV creams in Example 1 on the left and right faces of the acne affected area in small areas in the morning and evening respectively. After the first application, the left and right faces were subsequently applied. The sample is fixed. Apply for 7 days. While evaluating the therapeutic effect, the adverse reactions were evaluated.

The results of use and adverse reactions are shown in Table 4:

As can be seen from Table 4, itching as an adverse reaction was more severe and lasted longer than stinging. Adding 0.1% Schizophyllum β-glucan to the treatment of acne with azelaic acid and adverse reactions were improved. The total scores for stinging and itching of Schizophyllum-free β-glucan Formula I were 118 and 177, respectively, and the durations were approximately 9.5 minutes and 22.1 minutes, respectively, at 1 week of use, a slight improvement over the first day of use but not the same. Significant; total scores for stinging and pruritus of formula IV containing 0.1% Schizophyllum β-glucan were 91 and 113, respectively, and the durations were approximately 4.3 minutes and 6.4 minutes, respectively, when used for 1 week, which was significantly lower than when used on the first day. Significant improvement.

Compared with formula I without Schizophyllum β-glucan, formula IV containing 0.1% Schizophyllum β-glucan has greater improvement in both adverse reactions, and the improvement in itching is more obvious.

Example 6. Comparison with the formula effect described in the CN110522761A patent

Twenty-five common acne patients, aged 10-36 years, were selected. The formula V cream from Example 1 was selected and used twice a day. 8 weeks of continuous use. Trial effects were evaluated at 1 day, 2 days, 3 days, 1 week, 2 weeks, 4 weeks, and 8 weeks of use. If the volunteer's acne healed during this 8-week test, the cream was discontinued until the end of the test period.

The evaluation indicators are as follows:

1) Recovery: the original acne completely subsided, and no new acne occurs;

2) Basic recovery: the original acne completely subsided, and occasionally new acne occurs, but they are very small and can be quickly subsided;

3) Relief: Part of the original acne subsides, and occasionally new acne occurs, and the subsidence speed is accelerated;

4) Ineffective: the original acne basically did not subside, and the new acne was not controlled;

5) Aggravation: The original acne is aggravated, and new acne is continuously generated.

The statistics of the results are shown in Table 5:

Table 5 Effect statistics of trial formula V cream in patients with common acne

As can be seen from Table 5, compared with the formula described in CN110522761A, the time required for the product of the present invention to play an effect is greatly shortened, and more than half of the people can produce an effect in about 2 days, and basically recover from illness in about 1 week.

Azelaic acid is a known active ingredient for acne, but its side effects, such as tingling and itching, can seriously affect the patient's experience. Through the combined use of azelaic acid and beta-glucan, the composition of the present invention not only makes the product more effective in treating acne, but also significantly reduces adverse reactions (such as reduced itching and stinging, and shortened duration), and can Improve patient or consumer comfort and compliance.

All documents mentioned herein are incorporated by reference in this application as if each document were individually incorporated by reference. In addition, it should be understood that after reading the above teaching content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Claims (15)

1. Use of a composition, characterized in that it is used to prepare: (a) a cosmetic for acne treatment; or (b) a medicament for treating and/or preventing acne;

   Wherein, the composition includes:

   (a) a first active ingredient: azelaic acid; and

   (b) Second active ingredient: β-glucan.
2. The use according to claim 1, wherein the beta-glucan comprises n repeating units represented by formula I,

   

   Wherein, a is an integer ≥ 0, preferably 0-50, preferably 0-10, more preferably 0-3, more preferably 1-2, more preferably 1; b is an integer ≥ 0, more preferably Preferably 0-19, preferably 0-4, more preferably 0-1, more preferably 0; n is an integer ≥ 3, preferably 30-60000, more preferably 100-10000 .
3. The use according to claim 1, wherein the degree of branching of the beta-glucan is 0.02-0.8, preferably 0.1-0.5, preferably 0.2-0.4.
4. The use according to claim 1, wherein the molecular weight of the β-glucan is ≥2kD, preferably 2kD-40000kD, more preferably 20kD-20000kD.
5. The use according to claim 1, wherein the β-glucan is selected from the group consisting of: Schizophyllum β-glucan, Lentinus edodes β-glucan, Sclerotinia β-glucan, Grifola beta-glucan, Pleurotus polysaccharide, mushroom beta-glucan, yeast beta-glucan, oat beta-glucan, or a combination thereof.
6. The use according to claim 1, wherein the weight ratio of the first active ingredient to the second active ingredient is 20:0.01-5.
7. The use according to claim 1, characterized in that the acne (pimples) is broken skin acne and/or closed acne.
8. The use of claim 1, wherein the acne (pimple) comprises one or more symptoms selected from the group consisting of whiteheads, blackheads, inflammatory papules, pustules, nodules, cysts .
9. The use according to claim 1, wherein the cosmetic or drug is a cosmetic or drug with reduced side effects; and the side effect is a side effect caused by azelaic acid.
10. The use of claim 9, wherein the side effect is selected from the group consisting of stinging, itching, or a combination thereof.
11. The use of claim 1, wherein the composition comprises:

    Azelaic acid 5-30wt%;

    Beta-glucan 0.01-5 wt%; and

    A cosmetically or pharmaceutically acceptable carrier or excipient.
12. The use of claim 1, wherein the azelaic acid comprises 10-25 wt%, more preferably 10-20 wt%, such as 12-25 wt% or 15-22 wt%, based on the total weight of the composition.
13. The use according to any one of claims 1-12, wherein the β-glucan is Schizophyllum β-glucan.
14. The use of claim 1, wherein the carrier or excipient is selected from the group consisting of moisturizing agents, skin conditioning agents, thickening agents, emollients, emulsifiers, antioxidants, preservatives, anti-ultraviolet rays Agents, film-forming agents, oil-soluble gelling agents, organomodified clay minerals, resins, antibacterial agents, fragrances, salts, pH adjusters, conditioners, chelating agents, cooling agents, anti-inflammatory agents, skin beautifying ingredients , vitamins, amino acids, nucleic acids, inclusion compounds, solvents (eg, water), or combinations thereof.
15. A method for treating and/or preventing acne, comprising the steps of: administering an effective amount of a composition to a subject in need, wherein the composition comprises: (a) a first active ingredient: azelaic acid; and (b) a second active ingredient: beta-glucan.

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