CN113134088B

CN113134088B - Composition containing biological polysaccharide and application thereof

Info

Publication number: CN113134088B
Application number: CN202110064679.0A
Authority: CN
Inventors: 郭宏亮; 庄秀园; 郭晓宇; 朱斌念; 叶榛; 吴佳迪
Original assignee: Perman Zhejiang Biotechnology Co ltd
Current assignee: Perman Zhejiang Biotechnology Co ltd
Priority date: 2020-01-17
Filing date: 2021-01-18
Publication date: 2024-03-12
Anticipated expiration: 2041-01-18
Also published as: CN113134087A; CN113134089A; CN113134088A; CN113134089B; CN113134087B

Abstract

The invention provides a composition containing biological polysaccharide and application thereof. Specifically, the composition comprises: component (a): beta-glucan; and component (b): chemical stripping agents; component (c): no or skin penetrating agent; and (d) a pharmaceutically or cosmetically acceptable carrier; the weight ratio of the component (a) to the component (b) is 1:1-40. The composition of the present invention can prevent and/or treat acne.

Description

Composition containing biological polysaccharide and application thereof

Technical Field

The invention relates to the technical field of biology, in particular to a composition containing biological polysaccharide and application thereof.

Background

With the development of society, people increasingly aim at their own external image, and the health conditions of skin and hair directly influence the confidence of people. However, skin diseases such as acne are very common due to genetic hormone levels, lifestyle and environmental changes and the like during the growth phase.

Acne is a chronic inflammatory disease involving the pilosebaceous glands, often leading to skin lesions. Common acne treatment medicines such as antibiotics, retinoic acid, benzoyl peroxide, plant bactericidal and bacteriostatic components and the like can inhibit Propionibacterium acnes and the like, but have the problems of drug resistance, large irritation, dependence and the like, and seriously influence the treatment effect of acne. In addition, such antiseptic products tend to disrupt the ecological balance of the flora on the skin surface, thereby causing more serious skin problems. The effective components for treating acne in the current market are generally bactericides, and only have a simple bactericidal effect, but have limited anti-inflammatory effect and no effect on repairing skin.

Accordingly, there is a need in the art to develop a composition that is effective in preventing and treating acne and/or improving skin health.

Disclosure of Invention

It is an object of the present invention to provide a composition which can prevent and/or treat acne and/or improve skin health.

In a first aspect of the invention there is provided the use of a composition for the preparation of a composition or formulation for the prevention and/or treatment of acne;

wherein the composition comprises:

component (a): beta-glucan; and

component (b): chemical stripping agents;

component (c): no or skin penetrating agent; and

(d) A pharmaceutically or cosmetically acceptable carrier;

wherein the chemical stripping agent is a compound selected from the group consisting of: fruit acid, lactic acid, citric acid, glycolic acid, tartaric acid, salicylic acid, acetic acid, trichloroacetic acid, retinoic acid, phenol, resorcinol, or combinations thereof;

the weight ratio of the component (a) to the component (b) is 1:1-40;

and the pH of the composition is 2.0-9.0, preferably 3.0-8.5, preferably 4.0-8.0, preferably 4.5-7.5.

In another preferred embodiment, the salt comprises a pharmaceutically acceptable salt or a cosmetically acceptable salt.

In another preferred embodiment, the composition or formulation is in the form of a transdermal dosage form, a subcutaneous dosage form, preferably selected from the group consisting of: microneedles (e.g., microneedle arrays), nanoemulsions.

In a second aspect of the present invention, there is provided a composition comprising:

component (a): beta-glucan; and

component (b): chemical stripping agents;

component (c): no or skin penetrating agent; and

(d) A pharmaceutically or cosmetically acceptable carrier;

the weight ratio of the component (a) to the component (b) is 1:1-40.

In another preferred embodiment, the pH of the composition is from 2.0 to 9.0, preferably from 3.0 to 8.5, preferably from 4.0 to 8.0, preferably from 4.5 to 7.5, such as 5, 5.5, 6.0 or 6.5.

In another preferred embodiment, the weight ratio of component (a) to component (b) in the composition is from 1:1 to 20, preferably from 1:1 to 10, more preferably from 1:1 to 5, such as 1:2, 1:3 or 1:4.

In another preferred embodiment, the chemical exfoliating agent is selected from the group consisting of: sodium L-lactate, lactic acid, salicylic acid, or a combination thereof; preferably, L-sodium lactate.

In another preferred embodiment, the weight ratio of component (a) to component (c) is from 1:0 to 1:30, preferably from 1:0.05 to 1:15.

In another preferred embodiment, the pH of the composition is from 5 to 6.5, preferably from 5.5 to 6.5.

In another preferred embodiment, the weight ratio of component (a) to component (b) is from 1:2 to 30, more preferably from 1:3 to 20, still more preferably from 1:3 to 10.

In another preferred embodiment, the ingredients (a) and (b) comprise from 0.01 to 40wt%, preferably from 0.05 to 20wt%, more preferably from 0.1 to 5wt%, such as 0.3wt%, 0.5wt%, 0.8wt%, 1wt% or 2wt% of the total weight of the composition.

In another preferred embodiment, the component (a) comprises 0.001 to 5wt%, preferably 0.01 to 2wt%, more preferably 0.02 to 1wt%, more preferably 0.05 to 0.5wt%, such as 0.01wt%, 0.02wt%, 0.03wt%, 0.05wt%, 0.08wt%, 0.1wt%, 0.2wt%, 0.3wt% or 0.4wt% of the total weight of the composition.

In another preferred embodiment, the component (b) comprises 0.01 to 35wt%, preferably 0.05 to 25wt%, more preferably 0.1 to 10wt%, more preferably 0.2 to 3wt%, more preferably 0.5 to 2wt%, such as 0.3wt%, 0.6wt%, 0.8wt%, 1.0wt%, 1.2wt%, 1.5wt% or 1.8wt% of the total weight of the composition.

In another preferred embodiment, the composition is used to improve stretch marks.

In another preferred embodiment, the skin penetrating agent is selected from the group consisting of: water, azones, sulfoxides, pyrrolidinones, fatty acids and esters thereof, amino acids and esters thereof, alcohols, polyols, terpenes, cyclodextrins, phospholipids, surfactants, or combinations thereof.

In another preferred embodiment, the skin penetrating agent is present in an amount of 0 to 10wt%, preferably 0.1 to 5wt%, more preferably 0.2 to 2wt%, such as 0.4wt%, 0.5wt%, 0.6wt%, 0.8wt%, 1.0wt%, based on the total weight of the composition.

In another preferred embodiment, the skin penetrating agent is selected from the group consisting of: azone, menthol, lauryl alcohol, or a combination thereof, preferably azone.

In another preferred embodiment, the composition further comprises a substance selected from the group consisting of: moisturizers, anti-inflammatory agents, preservatives, pH modifiers, chelating agents, water, fragrances, or combinations thereof.

In another preferred embodiment, the composition further comprises a humectant.

In another preferred embodiment, the humectant is selected from the group consisting of: d-panthenol, allantoin, xanthan gum, hyaluronic acid, 1, 3-butanediol, octylglycol, glycerol, polyglutamic acid, aloe vera gel, silicone oil, horse oil, sheep oil, ceramide, chitosan amine, sodium pyrrolidone carboxylate, or a combination thereof.

In another preferred embodiment, the humectant is present in an amount of from 0 to 15wt%, preferably from 2 to 12wt%, more preferably from 5 to 10wt%, such as 3wt%, 4wt%, 5wt%, 6wt%, 7wt%, 8wt% based on the total weight of the composition.

In another preferred embodiment, the composition further comprises an anti-inflammatory agent.

In another preferred embodiment, the anti-inflammatory agent is selected from the group consisting of: antibiotics, bacteriostats, benzoyl peroxide, plant bactericidal and bacteriostatic components, glucocorticoids, azelaic acid, nicotinamide, sulfur, resorcinol, swertiamarin, or combinations thereof, preferably swertiamarin, or combinations thereof.

In another preferred embodiment, the anti-inflammatory agent is present in an amount of 0 to 10wt%, preferably 0.1 to 8wt%, more preferably 0.2 to 5wt%, such as 0.0001wt%, 0.0003wt%, 0.0005wt%, 0.01wt%, 0.5wt%, 1wt%, 2wt%, 3wt%, or 5wt%, based on the total weight of the composition.

In another preferred embodiment, the composition further comprises a substance selected from the group consisting of: chitosan, lecithin, or a combination thereof.

In another preferred embodiment, the composition further comprises a liposome/nanoparticle forming agent, such as a phospholipid, lecithin, cholesterol, glycerol monooleate, or a combination thereof.

In another preferred embodiment, the composition further comprises an active ingredient having an acne treatment efficacy selected from the group consisting of: chemically synthesized drugs, natural drugs, traditional Chinese medicines and extracts thereof, natural products and extracts thereof, or combinations thereof.

In another preferred embodiment, the active ingredient having an efficacy for treating acne is selected from the group consisting of: antibiotics, bacteriostats, retinoids, alpha-hydroxy acids, beta-hydroxy acids, plant bactericidal and bacteriostatic components, glucocorticoids, estrogens, progestins, or combinations thereof; specifically, for example, erythromycin, benzoyl peroxide, isotretinoin, adapalene, azelaic acid, nicotinamide, sulfur, resorcinol, salicylic acid, or a combination thereof.

In another preferred embodiment, the traditional Chinese medicine for treating acne and the extract thereof are selected from the group consisting of: clearing heat and relieving exterior syndrome, clearing heat and promoting diuresis and removing toxic substances, clearing heat and cooling blood and removing toxic substances, activating blood and dissolving stasis and resolving hard mass, harmonizing chong and ren meridians, dispelling wind and removing dampness, or a combination thereof; specifically, for example, atractylodis rhizoma, rhizoma Pinelliae, bupleuri radix, pericarpium Citri Tangerinae, radix Paeoniae Rubra, radix et rhizoma Rhei, rehmanniae radix, radix Sophorae Flavescentis, saviae Miltiorrhizae radix, poria, glycyrrhrizae radix, ramulus Cinnamomi, coptidis rhizoma, scutellariae radix, herba Centellae, curcuma rhizome, flos Lonicerae, fructus forsythiae, radix moutan root/bark, burdock, folium Eriobotryae, herba Taraxaci, herba Hedyotidis Diffusae, ginseng radix, cortex Mori, rhizoma Dioscoreae, fructus crataegi, mume fructus, flos Chrysanthemi Indici, coicis semen, fructus Gardeniae Preparata, fructus Aurantii Immaturus, caulis Bambusae in Taenia, notopterygii rhizoma, radix Angelicae Pubescentis, radix Saposhnikoviae, radix Gentianae Marcrophyllae, radix Clematidis, cortex Acanthopanacis or combinations thereof.

In another preferred embodiment, the natural product for treating acne and its extract are selected from the group consisting of: chamomile, grape seed, melaleuca alternifolia, camellia oleifera, witch hazel, jojoba, tilia, parsley, aloe, purslane, rose, rice, wheat, kelp, silk, or a combination thereof.

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

In another preferred embodiment, the beta-glucan is beta-1, 3-glucan, preferably beta-1, 3-glucan having beta-1, 6-branches.

In another preferred embodiment, the beta-glucan has a structure as shown in formula I,

wherein l is an integer of 0 or more, preferably 1 to 100, 0 to 50, 0 to 10, more preferably 0 to 3, still more preferably 1 to 2, still more preferably 1; m is an integer of 0 or more, preferably 0 to 19, more preferably 0 to 4, still more preferably 0 to 1, still more preferably 0; n is an integer of 3 or more, preferably 30 to 60000, more preferably 100 to 10000.

In another preferred embodiment, the beta-glucan has a branching Degree (DB) of 0.02-0.8, preferably 0.1-0.5, preferably 0.25-0.4, more preferably 0.2-0.4.

In another preferred embodiment, the beta-glucan comprises beta-glucan having a triple helix stereo structure.

In another preferred embodiment, the content of beta-glucan of the triple helix stereo structure is 80%,90%,95% based on the total molar amount of beta-glucan.

In another preferred embodiment, the beta-1, 3-backbone of the beta-glucan is the main body of a triple helix stereo structure.

In another preferred embodiment, the beta-1, 6-branch of the beta-glucan is located outside the triple helix stereo structure.

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

In another preferred example, the molecular weight of the beta-glucan may be 5kD to 35000kD;10kD-30000kD;50kD-25000kD;100kD-20000kD;200kD-18000kD;400kD-16000kD;500kD-14000kD;1000kD-12000kD;2000kD-4000kD;3000kD-5000kD;4000kD-6000kD;5000kD-7000kD;6000kD-8000kD;7000kD-9000kD; or 8000kD-10000kD.

In another preferred embodiment, the β -glucan is selected from the group consisting of: schizophyllum commune beta-glucan, lentinus edodes beta-glucan, sclerotium beta-glucan, grifola frondosa beta-glucan, pleurotus ostreatus polysaccharide, mushroom beta-glucan, yeast beta-glucan, or a combination thereof.

In another preferred embodiment, the beta glucan is schizophyllan beta glucan.

In another preferred embodiment, the lentinula edodes beta-glucan is a beta-glucan with 2 beta-1, 6-branches per 5 beta-1, 3-backbones, and 1 glucose residue per branch.

In another preferred embodiment, the beta glucan (or active ingredient) is not or does not contain oat beta glucan.

In another preferred embodiment, the beta-glucan has a purity of not less than 70%, preferably not less than 90%, more preferably not less than 95%, still more preferably not less than 99%.

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

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

In another preferred embodiment, the solubility of the beta-glucan (particles or powder) in water (100 g) at 25 ℃ is ≡0.0001g, preferably 0.01-50g, more preferably 0.1-10g.

In another preferred example, the solubility of the beta-glucan (particles or powder) in water (100 g) at 25 ℃ may be 0.1-100g;0.2-90g;0.5-80g;1-50g; alternatively, the solubility may 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; or 1-3g;2-4g;3-5g;4-6g;5-7g;6-8g;7-9g; or 8-10g.

In another preferred embodiment, the β -glucan (water) solution is of high viscosity; preferably, the aqueous beta-glucan solution (at 25 ℃) having a mass concentration of 0.5% has a viscosity of not less than 40 mPas, more preferably 100-10000 mPas, still more preferably 500-2000 mPas.

In another preferred example, the aqueous beta-glucan solution (25 ℃) having a mass concentration of 0.5% may have a viscosity of 50 to 10000 mPa-s; 100-9000 mPa.s; 200-8000 mPa.s; 300-7000 mPas; 400-6000 mPa.s; 450-5000 mPa.s; 500-5000 mPa.s; 550-4000 mPa.s; 600-3000 mPa.s; 650-2000 mPa.s; or 700-1500 mPas.

In another preferred embodiment, the aqueous solution of beta-glucan having a mass concentration of 1% has a high clarity or high light transmittance, and the aqueous solution of beta-glucan having a mass concentration of 1% has a light transmittance of 50% or more, preferably 80% or more, preferably 85% or more, more preferably 95% or more.

In another preferred embodiment, the composition is in a dosage form selected from the group consisting of: transdermal dosage forms, subcutaneous dosage forms, preferably selected from the group consisting of: microneedles (e.g., microneedle arrays), nanoemulsions.

In another preferred embodiment, the dosage form of the composition is selected from the group consisting of: solutions, gels, creams, emulsions, liposomes, microemulsions, nanoemulsions, nanoparticles, nanospheres, liquid crystal spheres, vehicles, alcohol liposomes, vesicles, microneedles (e.g., microneedle arrays), patches (transdermal patches), or combinations thereof.

In another preferred embodiment, the dosage form of the composition may be selected from the group consisting of (but not limited to): solid, semi-solid, or liquid dosage forms, such as solutions, gels, creams, emulsions, essences, nanomicrospheres, microneedles (e.g., microneedle arrays), transdermal patches, and the like.

In another preferred embodiment, the composition comprises:

0.01-2 parts by weight of component (a);

0.1 to 5 parts by weight of component (b);

0-4 parts by weight of a skin penetrating agent;

0-15 parts by weight of a humectant;

0-10 parts by weight of an anti-inflammatory agent;

0-0.5 parts by weight of a preservative;

wherein the weight ratio of the component (a) to the component (b) is 1:1-40.

In another preferred embodiment, the composition comprises:

0.01-2wt% of component (a);

0.1-5wt% of component (b);

0-4wt% skin penetration agent;

0-15wt% of a humectant;

0-10wt% of an anti-inflammatory agent;

0-0.5wt% preservative;

the balance being water, wherein the weight ratio of the component (a) to the component (b) is 1:1-40.

In a third aspect of the present invention, there is provided a patch comprising:

a substrate having disposed thereon an array of microneedles having tips, wherein the microneedles comprise a composition according to the second aspect of the invention.

In another preferred embodiment, the microneedle further comprises a water-soluble polymer.

In another preferred embodiment, the water-soluble polymer is selected from the group consisting of: dextran, polyethylene glycol, polyvinylpyrrolidone, dextran, dextrin, hydroxyethyl starch, cellulose derivatives, polyvinyl alcohol, or combinations thereof.

In another preferred embodiment, the microneedles may have a length of 0.2-5mm, preferably 0.5-2.5mm, below the stratum corneum.

In a fourth aspect of the present invention, there is provided a method for preventing and/or treating acne, comprising the steps of:

the composition of the second aspect of the invention is administered to a subject in need thereof.

In another preferred embodiment, the method of administration is selected from the group consisting of: transdermal, subcutaneous and/or transdermal absorption.

In another preferred embodiment, the composition may be applied by a method selected from the group consisting of: painting, massaging, physical sanding, injection, electroporation, thermal perforation, ultrasound introduction, microneedle array introduction, nanoplate introduction, laser introduction, ion introduction, magnetic introduction, electrode scanning system introduction, transdermal application, or combinations thereof.

In another preferred embodiment, the subject is a mammal.

In another preferred embodiment, the subject is selected from the group consisting of: human, murine, cat or dog.

In a fifth aspect of the invention, there is provided a method of administering a β -glucan comprising the steps of: the beta-glucan or a composition containing the beta-glucan is introduced into the skin by subcutaneous administration and/or transdermal absorption.

In another preferred embodiment, the method of administration is for the use of the beta-glucan for the prevention and/or treatment of acne.

In another preferred embodiment, the method is selected from the group consisting of: physical transdermal techniques, chemical transdermal techniques, biological transdermal techniques, transdermal iontophoresis techniques, or combinations thereof.

It is understood that within the scope of the present invention, the above-described technical features of the present invention and technical features specifically described below (e.g., in the examples) may be combined with each other to constitute new or preferred technical solutions. And are limited to a space, and are not described in detail herein.

Drawings

Figure 1 shows an example of the change in facial acne in volunteers following use of formulation ix composition in example 2.

FIG. 2 shows an example of acne changes in sensitive skin volunteers following the use of the composition of formula X in example 2.

Figure 3 shows an example of acne change in closed-acne volunteers following use of the composition of formula x in example 2.

Figure 4 shows an example of acne change in closed-acne volunteers following use of formulation ix composition in example 3.

Figure 5 shows an example of a closed-mouth acne volunteer change after use of the formulation vii composition in combination with microneedles in example 3.

Detailed Description

The present inventors have made extensive and intensive studies and, as a result, have provided a composition containing beta-glucan through a large number of screening and testing. The composition of the invention can significantly improve the use effect of the beta-glucan by combining the (a) beta-glucan and the (b) chemical stripping agent, for example, the prevention and/or treatment of acne is significantly accelerated, and the effect is enhanced. And the composition is prepared into a form suitable for transdermal or subcutaneous administration, so that the beta-glucan enters the skin, the acne treatment effect can be further improved, and the onset time is shortened. The present invention has been completed on the basis of this finding.

Studies have shown that little prevention and/or treatment of acne is observed with either the chemical exfoliant alone, the moisturizer alone, or the skin penetrating agent alone. In addition, when component (a) is used alone, some of the β -glucan species (e.g., oat β -glucan) hardly shows an effect of preventing and/or treating acne, while some of the β -glucan species (e.g., schizophyllum beta-glucan) has a certain improvement effect, but tends to be slow in effect, requiring a very long time (e.g., about 1 to 4 weeks or more).

The inventors have unexpectedly found that when a specific ratio is used, components (a) and (b) can act synergistically to significantly prevent and/or treat acne. Experiments show that the composition of the invention can not only remarkably improve the acne treatment effect (prevent the generation of acne, improve or relieve acne symptoms, quicken the resolution or healing of acne, improve acne scars (acne marks), quicken the resolution of acne scars (acne marks), or a combination thereof), but also reduce the skin sensibility and reduce the recurrence of acne, especially for closed acnes (such as white comedones) with poor beta-glucan effect of schizophyllum commune alone, the acne treatment effect can be obviously changed (2-3 days). In addition, the two components are matched for long-term use, and the skin barrier function is not weakened as the single use of the exfoliating agent, so that the effect of preventing acne recurrence can be achieved. The two are matched for use, so that the Chinese medicinal composition is efficient and safe, and is suitable for people with sensitive skin acne.

When given in a particular transdermal dosage form such as microneedles (e.g., with the addition of a skin promoter), it is unexpected that the compositions of the present invention can exert a significant effect on some patients suffering from acne for a prolonged period of time within 0.5-2 days without causing a reduction in skin barrier function. This suggests that the composition containing components (a) and (b) of the present invention, through reasonable compounding of the active ingredients, on the one hand significantly accelerates the progress of acne healing, and on the other hand enables the skin health to be radically reversed, thereby achieving the effect of preventing acne recurrence, and the effect of treating acne, which would otherwise take 1-4 weeks to achieve with component (a) alone, is produced in as little as 0.5 days.

Terminology

Unless defined otherwise, 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 can vary no more than 1% from the recited value. For example, as used herein, the expression "about 100" includes 99 and 101 and all values therebetween (e.g., 99.1, 99.2, 99.3, 99.4, etc.).

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

As used herein, "preventing" and "treating" include delaying and stopping the progression of a disease, or eliminating a disease, and do not require 100% inhibition, elimination, and reversal. In some embodiments, the composition or formulation of the invention prevents, reduces, inhibits, and/or reverses, for example, at least about 10%, at least about 30%, at least about 50%, or at least about 80% of a related disease, symptom, as compared to the level observed in the absence of the composition or formulation of the invention.

Beta-glucan

Beta-glucan is a natural polysaccharide, and a considerable variety of beta-glucan can be found in natural environments, usually in cell walls of special species of bacteria, yeasts, fungi (ganoderma lucidum) and also in the coating of higher plant seeds. The production method of the beta-glucan mainly comprises two methods, one is directly extracted from grains such as oat or fruiting body fungi such as mushrooms; and secondly, the beta-glucan is obtained by liquid fermentation of fungi or bacteria and extraction processing of fermentation liquor.

As used herein, "beta-glucan of the invention", "biopolysaccharide of the invention" are used interchangeably and refer primarily to the beta-glucan of the first aspect of the invention, which is selected from the group consisting of: schizophyllum commune beta-glucan, lentinus edodes beta-glucan, sclerotium beta-glucan, grifola frondosa beta-glucan, pleurotus ostreatus polysaccharide, mushroom beta-glucan, yeast beta-glucan, or a combination thereof; preferably schizophyllum beta-glucan.

As used herein, "schizophyllum beta-glucan" refers to beta-glucan derived from schizophyllum. Typically, the schizophyllum beta-glucan of the present invention is derived from the fermentation product of schizophyllum.

In another preferred embodiment, the structure of the beta-glucan is shown in formula I.

In another preferred embodiment, the beta glucan has good stability.

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

In another preferred example, the beta-glucan solution is a solution of beta-glucan in water, i.e., an aqueous beta-glucan solution.

In another preferred embodiment, the aqueous solution of 1% by mass of beta-glucan has a high clarity or high light transmittance, and the light transmittance of the 1% by mass of the aqueous solution of beta-glucan is greater than or equal to 50%, preferably greater than or equal to 80%, preferably greater than or equal to 85%, more preferably greater than or equal to 95%;

in another preferred embodiment, the beta-glucan solution has good stability.

In another preferred embodiment, the β -glucan is derived from higher plants or various bacteria, fungi.

Acne treatment

Acne is a chronic inflammatory disease involving the pilosebaceous glands, often leading to skin lesions. The main causes of acne pathogenesis include endocrine dyscrasia, abnormal follicular keratinization, which in turn causes pore blockage, creates opportunities for propionibacterium acnes infection, and causes skin inflammation. Currently, treatments for acne are generally directed to controlling sebum secretion, ameliorating keratinization abnormalities, combating bacterial infections, and diminishing inflammation, among others. Common acne treatment medicines such as antibiotics, retinoic acid, benzoyl peroxide, plant bactericidal and bacteriostatic components and the like can inhibit Propionibacterium acnes and the like, but have the problems of drug resistance, large irritation, dependence and the like, and seriously influence the treatment effect of acne. In addition, such antiseptic products tend to disrupt the ecological balance of the flora on the skin surface, thereby causing more serious skin problems. The effective components for treating acne in the current market are generally bactericides, and only have a simple bactericidal effect, but have limited anti-inflammatory effect and no effect on repairing skin.

As used herein, acne types include: papular acne, pustular acne, nodular acne, and cystic acne. In particular, the method comprises the steps of,

Papular acne: inflammatory or non-inflammatory small particle acne with diameter less than or equal to 5mm can be scattered or densely formed into pieces.

Pustular acne: the acne with pimple is mainly small pustules, the diameter is less than or equal to 5mm, and the pustules contain a large amount of pus and are sticky.

Nodular acne: on the basis of pustular acne, a large amount of keratoses, sebum and pus cells accumulate in the pilo-sebum, so that the pilo-sebum structure is destroyed to form red or light-colored nodules which are higher than the surface of the skin or under the skin, the invasion part is darker, the touch feeling is harder, and the skin is pressed to have pain.

Cystic acne: the cyst type bag blocks with different sizes are mainly used, the cyst type bag blocks have no tip, are heavy in inflammation, contain a large amount of tissue fluid, are strong in pressing pain and are often broken and overflowed. Often accompanied by papules, nodules, pustules, abscesses, and the like.

Wherein, the papular acne is divided into closed comedones and open comedones according to the communication condition with the outside.

Acne with white head: the pilo-sebaceous gland orifice is blocked by keratinocytes, and the keratin and sebum are filled therein, not in communication with the outside, forming closed comedones, which appear as slightly protruding whiteheads. Because the medicine is not communicated with the outside, active substances or medicines are difficult to enter the acne, so that the treatment of closed white comedones is very difficult.

Comedo: the pilo-sebaceous glands are blocked by the keratins and sebum, and the openings are communicated with the outside to form open comedones, and the surface looks like larger or smaller black spots.

Composition and method for producing the same

The present invention provides a composition comprising: component (a): beta-glucan; and component (b): chemical stripping agents.

The chemical exfoliating agent exfoliates the epidermis of the skin to some extent, replacing the new epidermis, and thus providing a better condition to the epidermis.

In the present invention, the kind of the chemical stripping agent is not particularly limited, and chemical stripping agents commonly used in the art, such as α -hydroxy acid, β -hydroxy acid, etc., may be used.

Preferably, the chemical stripping agent is a compound selected from the group consisting of: fruit acid, lactic acid, citric acid, glycolic acid, tartaric acid, salicylic acid, acetic acid, trichloroacetic acid, retinoic acid, phenol, resorcinol, or combinations thereof.

Preferably, the weight ratio of component (a) to component (b) is from 1:1 to 40, preferably from 1:2 to 30, more preferably from 1:3 to 20, more preferably from 1:3 to 10.

In another preferred embodiment, the components (a) and (b) comprise from 0.01 to 40wt%, preferably from 0.05 to 20wt%, more preferably from 0.1 to 5wt% of the total weight of the composition.

In the present invention, the ingredient (a) and the ingredient (b) may better exert a synergistic effect when the composition is at a specific pH (2.0 to 9.0), preferably pH of 2.0 to 9.0, preferably 3.0 to 8.5, preferably 4.0 to 8.0, preferably 4.5 to 7.5.

Preferably, the composition of the present invention further comprises ingredient (c): skin penetration agents (also known as penetration enhancers). The skin penetration agent may enhance or accelerate penetration of component (a) and/or component (b) through the skin.

In the present invention, the type of the skin penetrating agent is not particularly limited, and skin penetrating agents commonly used in the art can be used.

Preferably, the skin penetration agent is selected from the group consisting of: water, azones, sulfoxides, pyrrolidinones, fatty acids and esters thereof, amino acids and esters thereof, alcohols, polyols, terpenes, cyclodextrins, phospholipids, surfactants, or combinations thereof.

In another preferred embodiment, the composition further comprises a humectant.

In the invention, D-panthenol, allantoin, sodium pyrrolidone carboxylate, polyalcohol and the like are mainly used as moisturizers, and are helpful for further promoting the beta-glucan to play a role.

Preferably, the humectant is selected from the group consisting of: d-panthenol, allantoin, xanthan gum, hyaluronic acid, 1, 3-butanediol, octylglycol, glycerol, polyglutamic acid, aloe vera gel, silicone oil, horse oil, sheep oil, ceramide, chitosan amine, sodium pyrrolidone carboxylate, or a combination thereof.

In another preferred embodiment, the humectant is present in an amount of from 0 to 15wt%, preferably from 2 to 12wt%, more preferably from 5 to 10wt% based on the total weight of the composition.

The composition of the present invention may further comprise (d) a pharmaceutically or cosmetically acceptable carrier. The composition of the present invention may be suitably selected according to the formulation and use.

Typically, the cosmetically acceptable carrier is selected from the group consisting of: moisturizers, antioxidants, anti-uv agents, preservatives, film formers, oil-soluble gelling agents, organically modified clay minerals, resins, antimicrobial agents, fragrances, salts, pH adjusters, conditioners, thickeners, chelating agents, cooling agents, anti-inflammatory agents, skin beautifying ingredients, vitamins, amino acids, nucleic acids, hormones, inclusion compounds, solvents (such as water), or combinations thereof.

In another preferred embodiment, the anti-inflammatory agent is selected from the group consisting of: antibiotics, bacteriostats, plant bactericidal components, glucocorticoids, benzoyl peroxide, azelaic acid, nicotinamide, sulfur, resorcinol, swertiamarin, witch hazel extract, zinc pyrrolidone carboxylate, or combinations thereof.

In another preferred embodiment, the active ingredient having an efficacy for treating acne is selected from the group consisting of: antibiotics, bacteriostats, retinoids, alpha-hydroxy acids, beta-hydroxy acids, plant bactericidal and bacteriostatic components, glucocorticoids, estrogens, progestins, or combinations thereof; specifically, for example, erythromycin, nystatin, ketoconazole, clotrimazole, chlorpheniramine, loratadine, astemizole, ranitidine, dexamethasone, methylprednisolone, 5-fluorocytosine, benzoyl peroxide, isotretinoin, adapalene, azelaic acid, nicotinamide, sulfur, resorcinol, salicylic acid, triptolide, chloroquine, iodoting, calamine lotion, boric acid, benzalkonium chloride, vitamin C, or combinations thereof.

In another preferred embodiment, the composition further comprises a liposome and a nanoparticle forming agent, such as a phospholipid, lecithin, cholesterol, glycerol monooleate, or a combination thereof.

Dosage form

In the present invention, the composition has no particular requirement on the dosage form, and can be prepared into dosage forms commonly used in the art.

In the present invention, when a specific transdermal administration form such as a microneedle is used, the composition can exert a remarkable therapeutic effect on some patients suffering from acne for a long period of time within 0.5 to 2 days.

Thus, the composition of the present invention is preferably in a dosage form selected from the group consisting of: transdermal administration forms, percutaneous administration forms, subcutaneous administration forms.

Preferably, the dosage form of the composition is selected from the group consisting of (but not limited to): solutions, gels, creams, emulsions, liposomes, microemulsions, nanoemulsions, nanoparticles, nanospheres, liquid crystal spheres, vehicles, alcohol liposomes, vesicles, microneedle arrays, patches (transdermal patches), or combinations thereof.

For example, dosage forms in the form of microneedle arrays can be prepared by combining the compositions of the present invention with suitable carriers (e.g., water-soluble polymers, etc.) using methods commonly practiced in the art for microneedle preparation. The microneedle array delivers the active ingredient in the composition of the present invention to a specific site or a specific skin sub-layer (sublayer) of the skin, particularly a site or sub-layer where hair follicles are located, through micro-tunnels formed in the skin such as the stratum corneum, thereby exerting the effect of preventing and/or treating acne by the ingredients (a) and (b). Or the composition of the invention may be administered in conjunction with a device having a microneedle array (e.g., nanocrystalline).

The compositions of the present invention may facilitate absorption by methods commonly used in the art, such as physical transdermal techniques, chemical transdermal techniques, biological transdermal techniques, transdermal iontophoresis techniques, or combinations thereof.

Typically, the composition is applied by a method selected from the group consisting of: painting, massaging, physical sanding, injection, electroporation, thermal perforation, ultrasound introduction, microneedle (e.g., microneedle array) introduction, nanoplate introduction, laser introduction, ion introduction, magnetic introduction, electrode scanning system introduction, transdermal patch application, or combinations thereof.

An electrode scanning system (electrode scanning system, ESS), such as a Novosis ESS patch, has an electric field generated only within the patch, thereby avoiding adverse effects such as burning and irritation caused by iontophoresis current passing through the skin.

Preferably, the dosage form of the composition may be selected from the group consisting of (but not limited to): solid, semi-solid, or liquid dosage forms, such as solutions, gels, creams, emulsions, essences, nanomicrospheres, microneedles (e.g., microneedle arrays), transdermal patches, and the like.

The compositions of the present invention may be applied in combination with other methods commonly used in the art: such as massage, physical sanding, laser surgery, etc. The administration may be simultaneous or sequential.

Use of the same

The present invention provides the use of the composition of the invention for the preparation of a composition for the prevention and/or treatment of acne (e.g., face, back, chest);

the present inventors have unexpectedly found that when component (a) is used in combination with component (b), both have a significant synergistic effect, which effect is significantly improved over the use of component (a) or component (b) alone, e.g., the rate of recovery of acne is significantly increased.

In another preferred embodiment, the acne comprises closed comedones, open comedones, papules, pustules, and/or nodules, or a combination thereof.

In another preferred embodiment, the preventing and/or treating acne comprises: preventing acne formation, improving or alleviating acne symptoms, accelerating acne regression or healing, improving acne scars (blemishes), or accelerating acne scar (blemishes), or a combination thereof.

In another preferred embodiment, the acne comprises severe acne and mild acne.

In the present invention, the use and method of the present invention are non-diagnostic and non-therapeutic methods.

The main advantages of the invention include:

(1) In the composition, the beta-glucan and the chemical stripping agent have obvious synergistic effect, and the effect and the acting speed of the beta-glucan can be obviously improved.

(2) The composition of the present invention has remarkable effects in preventing and treating acne.

(3) Compared with the prior art that beta-glucan is prepared into external preparations such as cream and the like, the inventor discovers that the effect of the beta-glucan is better through transdermal and subcutaneous administration, so that the composition has more obvious effect when the composition is in a transdermal, subcutaneous and other administration dosage form.

(4) The invention provides a patch containing the composition and provided with a microneedle array capable of penetrating skin, which can achieve excellent effects without the aid of other expensive equipment, and is low in cost and convenient to use.

(5) The composition has obvious protective effect on skin injury (such as allergy, stinging, itching, erythema and the like) caused by chemical substances.

(6) The composition has obvious protective effect on damage caused by physical injury transdermal administration modes (such as laser, micro-needle, injection, perforation, nano-wafer and the like), can prevent and/or improve side effects such as allergy, stinging, itching, erythema and the like, and can prevent and/or treat acne and accelerate skin healing.

The invention is further described below in conjunction with the specific embodiments. It is to be understood that these examples are illustrative of the present invention and are not intended to limit the scope of the present invention. The experimental methods, in which specific conditions are not noted in the following examples, are generally conducted under conventional conditions or under conditions recommended by the manufacturer. Percentages and parts are by weight unless otherwise indicated.

The experimental methods used in the following examples are conventional methods unless otherwise specified.

Materials, reagents, equipment and the like used in the examples described below are commercially available unless otherwise specified.

The schizophyllum beta-glucan used in the examples of the present invention was identical to the schizophyllum beta-glucan described in CN110090168A example 1.

Example 1

Preparation of essence

According to Table 1, compositions I-XII (unit wt%, based on the total weight of the concentrate) were formulated:

table 1 composition formulation table

Example 2

Comparing the effect of formulas IX and X on preventing and treating acne

The 40 volunteers (with varying degrees of facial acne) were collected and divided equally into two groups of 20, the first group using formulation IX composition and the second group using formulation X composition, with trial time of 14 days as a cycle and each volunteer trial composition no less than 1 cycle. At the same time, the volunteers who were required to be tested had been suspended from using other anti-acne products 14 days in advance. During the trial period, after the face is cleaned in the morning and evening every day, a proper amount of the composition product is evenly coated on the face and gently massaged until the composition product is absorbed. During the process, a product evaluation record table is used for recording daily changes, data are collected after trial is finished, and acne removal effect is counted.

Table 2 comparison of the acne treatment effects of formulas IX and X

As a result, the first group of volunteers who used the composition of formula ix had significantly improved facial acne on average for 6-8 days with an effective rate of 100% and a cure rate of 75% (table 2, fig. 1); wherein figure 1 is an example of a volunteer of this group whose right cheek had long suffered from acne. After 1 day of application of the formulation IX composition, the acne area was reddened and after 4 days of application, the remaining areas were significantly improved except for the two more refractory acnes, by day 7 of application, and the treatment was substantially healed.

The second group of volunteers who used the composition of formula X had significantly improved facial acne on average for 1-3 days with an effective rate of 100% and a cure rate of 90% (Table 2, FIG. 2). In fig. 2, an example of a sensitive skin acne volunteer of this group, the daily face was prone to reddening and large grain acne was frequently present on the forehead and upper cheeks. After 1 day of formula X, a) facial redness improved, b) the original inflammatory mature acne was effectively converged, c) the original slightly prominent small acne appeared as a white purulent spot. After 2 days of use, a) the original inflammatory acne is smoothed, b) the white pus spots of the small acne are collected, c) the acne and the redness of the face are improved as a whole. After 4 days of trial, acne was substantially healed. The volunteer fed back that the skin state was stable during use and the skin sensitivity was improved.

Notably, the second group used formulation x composition had significantly improved efficacy against closed acne over formulation ix composition. In this experiment, 5 volunteers belonged to closed-mouth acne, wherein 3 of the first group had very weak closed-mouth acne improvement effect, and the preliminary improvement effect could be found only about 10 days or more, but the second group had a significant improvement effect in 2.5 days for another 2 closed-mouth acne volunteers of formula X composition, which was 75% shorter in time than the first group. Fig. 3 shows one example of a trial change in a volunteer with closed acne, whose skin was originally rough and felt to have a small graininess, and after application of the composition of formula x, the skin was gradually fine and smooth, and after 2.5 days, the skin had no graininess.

In addition, after 2 months of trial, the skin of two groups of volunteers is gradually bright and clean and fine, and the skin adverse reaction caused by using chemical exfoliants such as redness, dryness and the like is avoided. Can be used for long term to effectively prevent acne recurrence.

Formulas IX and X differ mainly in that formula X also contains a skin penetration enhancer. The beta-glucan is combined with the chemical stripping agent and the penetration enhancer at the same time, so that the product can be effectively assisted to be absorbed by skin better, and the effect of the product can be exerted more rapidly and remarkably.

Example 3

Comparing the effect of the formula VII, the formula IX and the microneedle array patch

30 closed acne volunteers were collected and divided equally into three groups of 10. The first group uses the composition IX of the formula only, and after cleansing the face in the morning and evening, a proper amount of the composition product is taken and evenly coated on the face, and is gently massaged until being absorbed. In the second group of 10 volunteers, after cleaning the face in the morning and evening by using the composition of the formula VII alone, a proper amount of the composition is uniformly coated on the face and gently massaged until the composition is absorbed. A third group of 10 volunteers used the composition of formula VII simultaneously with the second group, beginning every third day with the product in the form of a microneedle array patch (formula VII). The trial time was one cycle of 14 days, with each volunteer trial product no less than 1 cycle. At the same time, the volunteers who were required to be tested had been suspended from using other anti-acne products 14 days in advance. During the process, a product evaluation record table is used for recording daily changes, data are collected after trial is finished, and acne removal effect is counted.

Table 3 comparison of formulas IX and VII and microneedle array patch treatment effect on closed acne

Results the average 8-10 days of facial acne feedback was significantly improved in the first group of volunteers with an effective rate of 90% and a cure rate of 60% (table 3, fig. 4). Wherein fig. 4 is a volunteer with closed comedones mixed with comedones and papular acne. The composition of formula IX is effective in controlling blackheads and pimples 3-4 days, and closed comedones are changed by 8 days until 10 days.

The second group of volunteers fed back, and the average facial acne of 2-3 days was significantly improved, the effective rate was 100% and the cure rate was 70% (Table 3). The third group of volunteers fed back, the average of 1.5-3 days (0.5-2 days after the first use of the microneedle array patch) of facial acne was significantly improved, the effective rate was 100%, and the cure rate was 90% (table 3, fig. 5). Wherein fig. 5 is an example of a volunteer with closed comedones mixed with papular acne. When the composition of the formula VII is used for 1 day, pimple acne redness is effectively controlled, and closed acnes start to protrude out of the skin surface; after the VII+microneedle array patch is used for 1 day, pimples are effectively converged, and closed acne is reduced; at 5 days of use, acne is effectively controlled, the skin area is flat, and only acne marks remain.

The results suggest that the efficacy of the beta-glucan-containing product can be more effectively exerted by the physical introduction method and the chemical stripping method.

All documents mentioned in this application are incorporated by reference as if each were individually incorporated by reference. Further, it will be appreciated that various changes and modifications may be made by those skilled in the art after reading the above teachings, and such equivalents are intended to fall within the scope of the claims appended hereto.

Claims

1. Use of a composition for the preparation of a formulation for the prevention and/or treatment of acne, wherein the composition consists of: schizophyllum beta-glucan, L-sodium lactate, D-panthenol, allantoin, xanthan gum, hyaluronic acid, 1, 3-butanediol, glycerol, sodium pyrrolidone carboxylate, azone, preservative, deionized water, and adjusting the final pH to 6.2;

wherein, the schizophyllum commune beta-glucan is 0.1wt%, L-sodium lactate is 0.3wt%, D-panthenol is 0.2wt%, allantoin is 0.2wt%, xanthan gum is 0.1wt%, hyaluronic acid is 0.1wt%, 1, 3-butanediol is 5wt%, glycerin is 2wt%, sodium pyrrolidone carboxylate is 0.1wt%, and azone is 0.5wt%;

And the molecular weight of the schizophyllum commune beta-glucan is 3000kD-5000kD.

2. The use according to claim 1, wherein the formulation is in the form of a transdermal or subcutaneous dosage form.

3. The use according to claim 1, wherein the formulation is in the form of a microneedle or nanoemulsion.

4. A composition, characterized in that it consists of: schizophyllum beta-glucan, L-sodium lactate, D-panthenol, allantoin, xanthan gum, hyaluronic acid, 1, 3-butanediol, glycerol, sodium pyrrolidone carboxylate, azone, preservative, deionized water, and adjusting the final pH to 6.2;

5. The composition of claim 4, wherein the composition is in a transdermal or subcutaneous dosage form.

6. The composition of claim 4, wherein the composition is in the form of a microneedle or nanoemulsion.