WO2019223699A1 - 预防和治疗痤疮和激素依赖性皮炎的生物多糖及其应用 - Google Patents

预防和治疗痤疮和激素依赖性皮炎的生物多糖及其应用 Download PDF

Info

Publication number
WO2019223699A1
WO2019223699A1 PCT/CN2019/087845 CN2019087845W WO2019223699A1 WO 2019223699 A1 WO2019223699 A1 WO 2019223699A1 CN 2019087845 W CN2019087845 W CN 2019087845W WO 2019223699 A1 WO2019223699 A1 WO 2019223699A1
Authority
WO
WIPO (PCT)
Prior art keywords
glucan
acne
hormone
skin
beta
Prior art date
Application number
PCT/CN2019/087845
Other languages
English (en)
French (fr)
Inventor
郭宏亮
庄秀园
叶榛
吴佳迪
朱勤健
王轩
Original Assignee
浙江立恩生物科技有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 浙江立恩生物科技有限公司 filed Critical 浙江立恩生物科技有限公司
Priority to CN201980002828.1A priority Critical patent/CN110769836B/zh
Priority to US17/057,749 priority patent/US20220000902A1/en
Publication of WO2019223699A1 publication Critical patent/WO2019223699A1/zh

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/008—Preparations for oily skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof

Definitions

  • the invention relates to the field of biotechnology, in particular to a biological polysaccharide for preventing and treating acne and hormone-dependent dermatitis, and application thereof.
  • Acne is a chronic inflammatory disease involving the sebaceous glands of the hair follicle, which often causes skin lesions.
  • the main causes of acne include endocrine disorders, abnormal keratinization of the hair follicles, and subsequently blockage of pores, creating opportunities for P. acnes infection and causing skin inflammation.
  • the treatment of acne generally includes controlling sebum secretion, improving keratosis, antibacterial infection, and anti-inflammatory.
  • Common acne treatment drugs such as antibiotics, vitamin A acid, benzoyl peroxide, and plant bactericidal and bacteriostatic ingredients can achieve the effects of inhibiting Propionibacterium acnes, but they have problems such as resistance, irritation and dependence.
  • Treatment of acne can be used to achieve the effects of inhibiting Propionibacterium acnes, but they have problems such as resistance, irritation and dependence.
  • the effective ingredients for treating acne on the market are generally bactericides. These ingredients can only play a bactericidal effect, while the anti-inflammatory effect is limited, and it has no effect on skin repair.
  • Hormone-dependent dermatitis is caused by long-term incorrect use of topical drugs or cosmetics containing glucocorticoids. In recent years, the incidence of morbidity has increased significantly, and it is difficult to cure. At present, the commonly used treatments stay on the moisturizing, anti-inflammatory, anti-allergic and anti-infection treatments, with long treatment cycles and poor results.
  • the object of the present invention is to provide a medicament which can effectively treat acne and / or hormone-dependent dermatitis.
  • Another object of the present invention is to provide a biological polysaccharide having the effect of preventing and treating acne and / or hormone-dependent dermatitis and its application.
  • ⁇ -glucan for preparing a preparation or composition for preventing and / or treating acne and / or hormone-dependent dermatitis.
  • the ⁇ -glucan is ⁇ -D-glucan.
  • the ⁇ -glucan is ⁇ -1,3-glucan, and preferably, ⁇ -1,3-glucan having a ⁇ -1,6-branch.
  • l is an integer ⁇ 0, preferably 0-50, preferably 0-10, more preferably 0-3, more preferably 1-2, more preferably 1;
  • m is an integer ⁇ 0, more It is preferably 0-19, preferably 0-4, more preferably 0-1, more preferably 0;
  • n is an integer of ⁇ 3, preferably 30-60000, more preferably 100-10000 .
  • the ⁇ -glucan has a degree of branching (DB) of 0.02-0.8, preferably 0.1-0.5, and preferably 0.2-0.4.
  • the ⁇ -glucan includes a ⁇ -glucan having a triple helix structure.
  • the ⁇ -glucan content of the triple helix structure is 80%, 90%, 95%, based on the total molar amount of ⁇ -glucan.
  • the ⁇ -1,3- backbone of the ⁇ -glucan is the main body of the triple helix three-dimensional structure.
  • the ⁇ -1,6-branches of the ⁇ -glucan are located on the outside of the triple helix three-dimensional structure.
  • the molecular weight of the ⁇ -glucan is ⁇ 2kD, preferably 2kD-40000kD, more preferably 20kD-20000kD.
  • the molecular weight of the ⁇ -glucan may be 5kD-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.
  • the ⁇ -glucan is selected from the group consisting of Schizophyllum ⁇ -glucan, Lentinus edodes ⁇ -glucan, Micronucleus ⁇ -glucan, Grifola frondosa ⁇ -glucan Glycan, pleurum polysaccharide, mushroom beta-glucan, yeast beta-glucan, oat beta-glucan, or a combination thereof.
  • the beta-glucan is Schizophyllum beta-glucan.
  • the mushroom ⁇ -glucan is a main chain of every 5 ⁇ -1,3-, with 2 branches of ⁇ -1,6-, and each branch has 1 glucose residue. ⁇ -glucan.
  • the purity of the ⁇ -glucan is ⁇ 70%, preferably ⁇ 90%, more preferably ⁇ 95%, more preferably ⁇ 99%.
  • the ⁇ -glucan has good stability.
  • the ⁇ -glucan is in a solid form or a liquid form, such as a solid particle or powder of ⁇ -glucan, or an aqueous ⁇ -glucan solution.
  • the particle size of the ⁇ -glucan particles or powder is ⁇ 20mm, preferably 0.001-10mm, more preferably 0.01-5mm, and even more preferably 0.1-2mm.
  • the ⁇ -glucan is a completely water-soluble ⁇ -glucan.
  • the ⁇ -glucan (particle or powder) has good water solubility and / or natural solubility.
  • the solubility of the ⁇ -glucan (granule or powder) in water (100 g) at 25 ° C is greater than or equal to 0.0001 g, preferably 0.01 to 50 g, and more preferably 0.1 to 10 g.
  • the solubility of the ⁇ -glucan (granule or powder) in water (100 g) at 25 ° C may be 0.1-100 g; 0.2-90 g; 0.5-80 g; 1-50 g; or, 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; or 1-3g; 2- 4g; 3-5g; 4-6g; 5-7g; 6-8g; 7-9g; 8-10g.
  • the ⁇ -glucan solution is a solution of ⁇ -glucan in water, that is, an aqueous ⁇ -glucan solution.
  • the ⁇ -glucan (water) solution has a large viscosity; preferably, a 0.5% ⁇ -glucan aqueous solution (at 25 ° C) has a viscosity of ⁇ 40 mPa ⁇ s, and more preferably 100-10000mPa ⁇ s, more preferably 500-2000mPa ⁇ s.
  • the viscosity of the 0.5-% ⁇ -glucan aqueous solution may be 50-10000 mPa ⁇ s; 100-9000 mPa ⁇ s; 200-8000 mPa ⁇ s; 300-7000 mPa ⁇ s; 400-6000mPa ⁇ s; 450-5000mPa ⁇ s; 500-5000mPa ⁇ s; 550-4000mPa ⁇ s; 600-3000mPa ⁇ s; 650-2000mPa ⁇ s; 700-1500mPa ⁇ s.
  • the ⁇ -glucan aqueous solution with a mass concentration of 1% has high clarity or high light transmittance, and the light transmittance of the ⁇ -glucan aqueous solution with a mass concentration of 1% ⁇ 50%, preferably ⁇ 80%, preferably ⁇ 85%, more preferably ⁇ 95%;
  • the ⁇ -glucan solution has good stability.
  • the prevention and / or treatment of acne includes: preventing the generation of acne, improving or relieving the symptoms of acne, accelerating acne regression or healing, improving acne scars (acne marks), or accelerating acne scars (acne marks) Subside.
  • the "acne” refers to a chronic inflammatory skin disease of the sebaceous gland units of the hair follicles, which mainly occurs in adolescents, and the clinical manifestations are acne, pimples, pustules, nodules, etc. Shaped skin lesions are also known as acne.
  • the acne includes severe acne and mild acne.
  • the acne is selected from the group consisting of whiteheads, blackheads, pimples, pustular acne, cystic acne, nodular acne, or a combination thereof.
  • the prevention and / or treatment of hormone-dependent dermatitis includes: preventing the generation of hormone-dependent dermatitis, improving or relieving symptoms of hormone-dependent dermatitis, accelerating the regression or healing of hormone-dependent dermatitis, and improving hormone dependence Dermatitis-scarred scars or accelerated resolution of hormone-dependent dermatitis scars.
  • hormone-dependent dermatitis refers to dermatitis caused by long-term repeated improper external use of hormones (clinical manifestations include: thinning of the epidermis and dermis, hypopigmentation, exposure of blood vessels, rosacea, acne Dermatitis, folliculitis, characterized by hormone dependence and rebound phenomenon, also known as hormone face).
  • the symptoms of hormone-dependent dermatitis are selected from the group consisting of pruritus, burning, pain, dryness, desquamation, tightness, facial flushing, erythema, papules, and skin atrophy. Capillary dilatation, acne, rosacea-like changes, pigmentation or loss, facial skin atrophy, hair follicle inflammatory pustules, etc.
  • the preparation or composition contains (a) ⁇ -glucan; and optionally (b) a pharmaceutically, cosmetically, or device-acceptable carrier or excipient.
  • the formulation or composition contains (a) Schizophyllum beta-glucan; and optionally (b) a pharmaceutically, cosmetically, or device-acceptable carrier or excipient. Agent.
  • the formulation or composition contains 0.0001 to 99 wt%, preferably 0.001 to 90 wt%, more preferably 0.01 to 50 wt%, and more preferably 0.05 to 10 wt% ⁇ -glucan.
  • the total weight of the formulation or composition 0.0001 to 99 wt%, preferably 0.001 to 90 wt%, more preferably 0.01 to 50 wt%, and more preferably 0.05 to 10 wt% ⁇ -glucan.
  • the mass concentration of the ⁇ -glucan in the preparation or composition is ⁇ 1 ⁇ g / mL, and specifically, it can be 1 ⁇ g / mL-200 mg / mL, or 1 ⁇ g / mL-5 mg / mL , Or 1 ⁇ g / mL-1mg / mL.
  • the preparation or composition is also used to enhance skin immunity or active defense function.
  • the preparation or composition is also used to prevent and / or treat skin mucosal inflammation or other skin inflammatory diseases.
  • the preparation or composition is further used for preventing and / or treating a skin problem selected from the group consisting of dryness, redness, allergies, inflammation, fine lines, stains, oily, or a combination thereof .
  • the dosage form of the composition or preparation is a solid dosage form, a semi-solid dosage form, or a liquid dosage form, such as a solution, a gel, a cream, an emulsion, or the like.
  • the composition is a pharmaceutical composition or a cosmetic composition, preferably an external pharmaceutical dosage form.
  • the preparation is an external preparation or a transdermal preparation (such as an external solution, an ointment, a patch, etc.).
  • the preparation or composition includes a cosmetic, a food, a medical device or a medicine, and the specific cosmetic may be a functional cosmetic.
  • a preparation comprising ⁇ -glucan.
  • the ⁇ -glucan is selected from the group consisting of Schizophyllum ⁇ -glucan, Lentinus edodes ⁇ -glucan, Micronucleus ⁇ -glucan, Grifola frondosa ⁇ -glucan Glycan, pleurum polysaccharide, mushroom beta-glucan, yeast beta-glucan, oat beta-glucan, or a combination thereof.
  • the beta-glucan is Schizophyllum beta-glucan.
  • the ⁇ -glucan is a completely water-soluble ⁇ -glucan.
  • the preparation is Schizophyllum beta-glucan, and the beta-glucan has good water solubility, natural solubility and / or resolubility.
  • the ⁇ -glucan in the preparation is in a solid form or a liquid form.
  • the preparation contains an aqueous ⁇ -glucan solution, and the mass concentration of the ⁇ -glucan is 0.0001-50 wt%, preferably 0.02-10 wt%, more preferably 0.05-5 wt% , Based on the total weight of the ⁇ -glucan aqueous solution.
  • the content of the ⁇ -glucan aqueous solution in the preparation is 80% by weight, preferably 90% by weight, more preferably 95% by weight, more preferably 99% by weight, and 99.5% by weight. % Based on the total weight of the formulation.
  • the ⁇ -glucan in the preparation has one or more characteristics selected from the group consisting of:
  • the purity of the ⁇ -glucan is ⁇ 70%, preferably ⁇ 90%, more preferably ⁇ 95%, more preferably ⁇ 99%;
  • the ⁇ -glucan has good water solubility, re-solubility and / or natural solubility
  • the ⁇ -glucan aqueous solution has high clarity or high light transmittance; preferably, the ⁇ -glucan aqueous solution having a mass concentration of 1% has a light transmittance of ⁇ 50%, preferably ⁇ 80%, preferably ⁇ 85%, more preferably ⁇ 95%;
  • the ⁇ -glucan solution has a large viscosity; preferably, the 0.5-% ⁇ -glucan aqueous solution (at 25 ° C) has a viscosity of ⁇ 40 mPa ⁇ s, more preferably 100-10000, and more preferably 600-2000mPa ⁇ s;
  • the ⁇ -glucan aqueous solution has good stability; and / or
  • the molecular weight of the ⁇ -glucan is ⁇ 2kD, preferably 2kD-40000kD, and more preferably 20kD-20000kD.
  • the preparation contains (a) ⁇ -glucan; and (b) a pharmaceutically, cosmetically, or device-acceptable carrier or excipient.
  • the preparation contains 0.0001 to 99% by weight, preferably 0.001 to 90% by weight, more preferably 0.01 to 50% by weight, and more preferably 0.05 to 10% by weight ⁇ -glucan. By weight.
  • the preparation further contains (c) a second active ingredient, which is an active ingredient different from the ⁇ -glucan for treating acne and / or hormone-dependent dermatitis, Or active ingredients for treating skin mucosal inflammation or other skin diseases.
  • a second active ingredient which is an active ingredient different from the ⁇ -glucan for treating acne and / or hormone-dependent dermatitis, Or active ingredients for treating skin mucosal inflammation or other skin diseases.
  • the active ingredient for treating acne is selected from the group consisting of antibiotics, bacteriostats, vitamin A acids, ⁇ -hydroxy acids, plant bacteriostatic components, glucocorticoids, estrogen, Progestins, or a combination thereof; specifically, for example, erythromycin, benzoyl peroxide, isotretinoin, adapalene, azelaic acid, nicotinamide, sulfur, razolicin, salicylic acid, or a combination thereof .
  • the active ingredient for treating hormone-dependent dermatitis is selected from the group consisting of a humectant, a skin barrier repair ingredient, a non-hormonal immunosuppressant for external use, an antihistamine, an antiallergic drug, an antibacterial agent, and Antibiotics and the like, specifically, for example, glycerin, allantoin, hyaluronic acid, polyglutamic acid, aloe vera gel, silicone oil, horse oil, sheep oil, ceramide, epidermal growth factor, tacrolimus, pimecrolimus, Loratadine, ebastine, boric acid, benzalkonium chloride, erythromycin, etc., or a combination thereof.
  • a humectant e.glycerin, allantoin, hyaluronic acid, polyglutamic acid, aloe vera gel, silicone oil, horse oil, sheep oil, ceramide, epidermal growth factor, tacrolimus, pimecrolimus, Loratad
  • the active ingredient for treating acne and / or hormone-dependent dermatitis is selected from the group consisting of traditional Chinese medicine and its extracts: clearing heat and dissolving epidermis, clearing heat, dampening and detoxifying, clearing heat, cooling blood and detoxifying, promoting blood circulation and removing blood stasis Sanjie, Harmony and Chongren, Qufeng dehumidifier, or a combination thereof; specifically, for example, Atractylodes macrocephala, Pinellia ternata, Bupleurum, Chenpi, Red peony, Rhubarb, Dihuang, Poria, Licorice, Guizhi, Coptis chinensis, Cotinus coggygria, product Snowgrass, turmeric, honeysuckle, forsythia, peony root / bark, burdock, coriander leaves, dandelion, ginseng, mulberry bark, yam, raw hawthorn, ebony, wild chrysant
  • the active ingredient for treating skin mucosal inflammation or other skin diseases is selected from the group consisting of antihistamines, antibiotics, antifungals, hormones, immunosuppressants, vitamins, and vitamin A acids.
  • the preparation is used for preventing and / or treating acne and / or hormone-dependent dermatitis.
  • composition product includes:
  • a first pharmaceutical composition containing (a) a first active ingredient, the first active ingredient being ⁇ -glucan; and (b) pharmaceutically, cosmetically, or Device-acceptable carriers or excipients; and
  • a second pharmaceutical composition which is an acne treatment drug, a hormone-dependent dermatitis treatment drug, or a skin and mucous membrane inflammation or other skin disease treatment drug.
  • the first pharmaceutical composition contains 0.0001-99 wt%, preferably 0.001-90 wt%, more preferably 0.01-50 wt%, more preferably 0.05-10 wt% ⁇ -glucan, Based on the total weight of the first pharmaceutical composition.
  • the ⁇ -glucan is selected from the group consisting of Schizophyllum ⁇ -glucan, Lentinus edodes ⁇ -glucan, Micronucleus ⁇ -glucan, Grifola frondosa ⁇ -glucan Glycan, pleurum polysaccharide, mushroom beta-glucan, yeast beta-glucan, oat beta-glucan, or a combination thereof.
  • the ⁇ -glucan is a ⁇ -glucan of Schizophyllum.
  • the acne treatment drug contains (a) a second active ingredient, which is an active ingredient for treating acne different from the ⁇ -glucan; and (b) pharmaceutically, Cosmetically or device-acceptable carriers or excipients.
  • the hormone-dependent dermatitis treatment drug contains (a) a second active ingredient, which is an active ingredient different from the ⁇ -glucan for treating hormone-dependent dermatitis; and (b) Pharmaceutically, cosmetically, or device-acceptable carriers or excipients.
  • the acne treatment drug is selected from the group consisting of antibiotics, bacteriostats, vitamin A acids, ⁇ -hydroxy acids, plant bactericidal antibacterial ingredients, glucocorticoids, estrogen, pregnancy Hormones, or a combination thereof; specifically, for example, erythromycin, benzoyl peroxide, isotretinoin, adapalene, azelaic acid, nicotinamide, sulfur, razorcin, salicylic acid, or a combination thereof.
  • the active ingredient for treating hormone-dependent dermatitis is selected from the group consisting of a humectant, a skin barrier repair ingredient, a non-hormonal immunosuppressant for external use, an antihistamine, an antiallergic drug, an antibacterial agent, and Antibiotics and the like, specifically, for example, glycerin, allantoin, hyaluronic acid, polyglutamic acid, aloe vera gel, silicone oil, horse oil, sheep oil, ceramide, epidermal growth factor, tacrolimus, pimecrolimus, Loratadine, ebastine, boric acid, benzalkonium chloride, erythromycin, etc., or a combination thereof.
  • a humectant e.glycerin, allantoin, hyaluronic acid, polyglutamic acid, aloe vera gel, silicone oil, horse oil, sheep oil, ceramide, epidermal growth factor, tacrolimus, pimecrolimus, Loratad
  • the acne and / or hormone-dependent dermatitis treatment drug is selected from the group consisting of traditional Chinese medicine and its extracts: clearing heat and dissolving epidermis, clearing heat, dampening and detoxifying, clearing heat, cooling blood, detoxifying, and promoting blood circulation and removing blood stasis.
  • Knotting, reconciliation, Qufeng dehumidification, or a combination thereof specifically, for example, Atractylodes macrocephala, Pinellia ternata, Bupleurum chinensis, Chenpi, Chiba, Rhubarb, Dihuang, Poria, Licorice, Guizhi, Coptis chinensis, Cotinus coggygria, Snow Grass, turmeric, honeysuckle, forsythia, peony root / bark, burdock, coriander leaves, dandelion, ginseng, mulberry peel, yam, raw hawthorn, ebony, wild chrysanthemum, raw barley, charcoal, cilantro, bamboo Ru, Jihuo, Duhuo, Fengfeng, Qinji, Weilingxian, Wujiapi, or a combination thereof.
  • the medicine for treating skin mucosal inflammation or other skin diseases is selected from the group consisting of antihistamines, antibiotics, antifungals, hormones, immunosuppressants, vitamins, and vitamin A acids. , Cleaners, protectants, antipruritics, keratin enhancers, exfoliants, astringents, caustics, antibacterials, antifungals, antivirals, insecticides, sunscreens, decolorants, or combinations thereof; specifically Places, such as chlorpheniramine, loratadine, astemizole, ranitidine, dexamethasone, methylprednisolone, nystatin, ketoconazole, clotrimazole, 5-fluorocytosine , Adapalene, triptolide, chloroquine, iodocho, calamine lotion, or a combination thereof.
  • Cleaners protectants, antipruritics, keratin enhancers, exfoliants, astringents, caustics, antibacterials
  • first pharmaceutical composition and the second pharmaceutical composition are independent or combined into one.
  • composition product is used for treating and / or preventing acne and / or hormone-dependent dermatitis.
  • the composition product is a cosmetic or a medicament.
  • a method for preventing and / or treating acne and / or hormone-dependent dermatitis comprising the steps of: (a) administering ⁇ -glucan to a subject in need.
  • the ⁇ -glucan is selected from the group consisting of Schizophyllum ⁇ -glucan, Lentinus edodes ⁇ -glucan, Micronucleus ⁇ -glucan, Grifola frondosa ⁇ -glucan Glycan, pleurum polysaccharide, mushroom beta-glucan, yeast beta-glucan, oat beta-glucan, or a combination thereof.
  • the beta-glucan is Schizophyllum beta-glucan.
  • the subject includes a patient with acne, a patient with hormone-dependent dermatitis, or a normal population.
  • FIG. 1 shows a Fourier transform infrared spectrum of Schizophyllum beta-glucan prepared in Example 1.
  • Figure 2 shows a comparison of ⁇ -glucan stability.
  • the left bottle is a commercially available 1.0% oat ⁇ -glucan solution
  • the right bottle is a 1.0% Schizophyllum ⁇ -glucan prepared by the present invention.
  • Figure 3 shows the effect of Schizophyllum beta-glucan on the skin.
  • a and B are photos of a patient with severe acne in Example 2 before and after 1 month of trial of the Schizophyllum beta-glucan product.
  • C and D are photographs of another patient with mild acne and red blood cells in Example 2 before and after trial of a Schizophyllum beta-glucan product, respectively.
  • Figure 4 shows a comparison of the effects of Patient A in Example 4 before and after the trial of the Schizophyllum beta-glucan product.
  • FIG. 5 shows the comparison of the effects of Patient B in Example 4 before and after the trial of the Schizophyllum beta-glucan product.
  • FIG. 6 shows a comparison of the effects of Patient C in Example 4 before and after the trial of the Schizophyllum beta-glucan product.
  • Figure 7 shows the comparison of the effect of Patient D in Example 4 before and after the trial of the Schizophyllum beta-glucan product.
  • FIG. 8 shows the change of facial acne after patient F in Example 13 tried a mask containing Schizophyllum beta-glucan as the main active ingredient.
  • FIG. 9 shows a comparison of the effects of Patient H in Example 14 before and after the trial of the Schizophyllum beta-glucan product.
  • Figure 10 shows a comparison of the effects of Patient I in Example 14 before and after the trial of the Schizophyllum beta-glucan product.
  • ⁇ -glucan especially ⁇ -glucan (such as Schizophyllum beta-glucan), which has natural solubility, high molecular weight, and high viscosity
  • Schizophyllum beta-glucan significantly relieves and improves acne and / or hormone-dependent dermatitis, effectively controls the occurrence of acne and / or hormone-dependent dermatitis, and accelerates the healing of acne and / or hormone-dependent dermatitis and / Or faded effect.
  • Schizophyllum beta-glucan can also enhance the skin's active defense function, activate the skin's natural immunity, antibacterial, anti-inflammatory, and repair the skin, treat or prevent skin mucosal inflammation or other skin inflammatory diseases, and improve dry skin or red blood cells in patients Relieve skin irritation, fine lines, stains, or oil from patients. Based on this, the present invention has been completed.
  • the term “about” means that the value can vary from the recited value by no more than 1%.
  • the expression “about 100” includes all values between 99 and 101 and (eg, 99.1, 99.2, 99.3, 99.4, etc.).
  • the terms "containing” or “including (comprising)” may be open, semi-closed, and closed. In other words, the term also includes “consisting essentially of” or “consisting of”.
  • the term "fully water-soluble” refers to said solid form of ⁇ -glucan that can be completely dissolved in water to form an aqueous solution of ⁇ -glucan, that is, the solubility of ⁇ -glucan in 100 g of water at 25 ° C ⁇ 0.0001 g , Preferably 0.01-50 g, more preferably 0.1 g-10 g.
  • the term "naturally soluble” refers to the property of ⁇ -glucan in its natural state, which completely dissolves in water to form an aqueous solution.
  • the "native ⁇ -glucan” refers to ⁇ -glucan produced by natural methods (such as biological fermentation), and the ⁇ -glucan has not undergone any chemical modification and has not undergone any chemical modification. Physical and / or chemical and / or biological methods interrupt their long chain molecules and reduce their molecular mass.
  • the ⁇ -glucan of the present invention is a ⁇ -glucan in a natural state.
  • acne types include: pimple acne, pustular acne, nodular acne, cystic acne. specifically,
  • Papular acne inflammatory or non-inflammatory small particles of acne, ⁇ 5mm in diameter, can be dispersed or dense and will appear in tablets.
  • Pustular acne Acne with small pustules and inflammatory pimples, ⁇ 5mm in diameter.
  • the pustule contains a large amount of pus and is relatively viscous.
  • Nodular acne On the basis of pustular acne, a large amount of keratin, sebum and pus cells in the hair follicle sebum accumulates, causing the structure of the hair follicle sebum to be destroyed, forming a red or light color that is high on the skin surface or under the skin. Nodules, the invading part is deep, the touch is hard, and some of them are painful.
  • Cystic acne mainly cystic masses of different sizes, no sharp, severe inflammation, contains a large amount of tissue fluid, strong pressure pain, often ulceration and pus. It is often accompanied by pimples, nodules, pustules, and abscesses.
  • hormone-dependent dermatitis refers to dermatitis caused by long-term repeated improper use of external hormones.
  • the clinical manifestations are thinning of the epidermis and dermis, hypopigmentation, vascular exposure, rosacea-like, acne-like dermatitis, folliculitis, having It is characterized by hormone dependence and rebound phenomenon, also known as hormone face. specifically,
  • Epidermis and dermis thinning Local long-term topical hormones can cause the formation of stratum corneum particles to become thinner and thinner.
  • the elastic changes in dermal glycoproteins and proteoglycans weaken the adhesion between collagen fibrils, and collagen synthesis decreases and becomes thinner. .
  • hypopigmentation and hyperpigmentation As the number of layers of the stratum corneum decreases, melanin migrated to the keratinocytes decreases, causing hypopigmentation. And pigmentation may be related to glucocorticoid-activated melanocyte regeneration pigment.
  • the weakening of the adhesion between collagen fibers in the blood vessel wall can cause blood vessels to widen, and the disappearance of dermal collagen causes the blood vessels on the surface to be exposed.
  • Rosacea-like and acne-like dermatitis In hormone-induced rosacea-like skin lesions, the density of Demodex mites in hair follicles is significantly increased. Demodex mites close the outlet of the sebaceous glands of the hair follicles, causing inflammatory or allergic reactions. Hyperplasia of sebaceous glands, leading to a characteristic rosacea-like rash. Hormones can degenerate and degenerate the hair follicle epithelium, cause the outlet to be blocked, and cause acne-like rashes or aggravate the original acne.
  • Folliculitis Due to the immunosuppressive effects of hormones, local hair follicles can become infected and primary folliculitis can worsen.
  • Hormone dependence and rebound phenomenon The anti-inflammatory properties of hormones can inhibit the development of pimples and reduce itching, vasoconstriction, and erythema disappear. However, hormones can not eliminate the cause of the disease, and often cause exacerbation of the original disease after being stopped. Bounces such as inflammatory edema, redness, burning, discomfort and acute impetigo. This phenomenon often occurs 2 to 10 days after stopping the hormone and lasts for a few days or about 3 weeks. Due to the rebound phenomenon, patients continue to use hormones, resulting in hormone dependence.
  • the primary skin disease has been cured, and obvious erythema has repeatedly appeared, and dermatitis manifestations such as pimples, pustules, disappearance of skin lines, and desquamation.
  • Symptoms such as hyperpigmentation (decreased), atrophic lines, telangiectasias, hairiness, pustules, etc., accompanied by tingling and burning sensation after long-term use.
  • ⁇ -glucan is a natural polysaccharide. In the natural environment, many types of ⁇ -glucan can be found. It usually exists in the cell walls of special types of bacteria, yeasts, fungi (ganoderma), and can also exist in the cell wall. Coating of higher plant seeds. There are two main methods for producing ⁇ -glucan. One is to directly extract from oat and other grains or mushrooms and other fruiting body fungi; the other is to use liquid fermentation of fungi or bacteria to extract and process the fermentation broth to ⁇ -glucan was obtained.
  • the ⁇ -glucan of the present invention and “the biological polysaccharide of the present invention” are used interchangeably, and mainly refer to the ⁇ -glucan according to the first aspect of the present invention.
  • Schizophyllum beta-glucan from the lower group: Schizophyllum beta-glucan, Shiitake mushroom beta-glucan, Micronucleus beta-glucan, Grifola frondosa beta-glucan, Pleurotus ostreatus, mushroom beta-glucan, yeast beta -Glucan, oat beta-glucan, or a combination thereof; preferably Schizophyllum beta-glucan.
  • Schizophyllum beta-glucan refers to beta-glucan derived from Schizophyllum.
  • the structure of the ⁇ -glucan is shown in Formula I.
  • the molecular weight of the ⁇ -glucan is ⁇ 2kD, preferably 2kD-40000kD, more preferably 20kD-20000kD.
  • the molecular weight of the ⁇ -glucan may be 5kD-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.
  • the purity of the ⁇ -glucan is ⁇ 70%, preferably ⁇ 90%, more preferably ⁇ 95%, more preferably ⁇ 99%.
  • the ⁇ -glucan has good stability.
  • the ⁇ -glucan is in a solid form or a liquid form, such as a solid particle or powder of ⁇ -glucan, or an aqueous ⁇ -glucan solution.
  • the particle size of the ⁇ -glucan particles or powder is ⁇ 20mm, preferably 0.001-10mm, more preferably 0.01-5mm, and even more preferably 0.1-2mm.
  • the ⁇ -glucan (particle or powder) has good water solubility and / or natural solubility.
  • the solubility of the ⁇ -glucan (granule or powder) in water (100 g) at 25 ° C is greater than or equal to 0.0001 g, preferably 0.01 to 50 g, and more preferably 0.1 to 10 g.
  • the solubility of the ⁇ -glucan (granule or powder) in water (100 g) at 25 ° C may be 0.1-100 g; 0.2-90 g; 0.5-80 g; 1-50 g; or, 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; or 1-3g; 2- 4g; 3-5g; 4-6g; 5-7g; 6-8g; 7-9g; 8-10g.
  • the ⁇ -glucan solution is a solution of ⁇ -glucan in water, that is, an aqueous ⁇ -glucan solution.
  • the ⁇ -glucan (water) solution has a large viscosity; preferably, a 0.5% ⁇ -glucan aqueous solution (at 25 ° C) has a viscosity of ⁇ 40 mPa ⁇ s, and more preferably 100-10000mPa ⁇ s, more preferably 500-2000mPa ⁇ s.
  • the viscosity of the 0.5-% ⁇ -glucan aqueous solution may be 50-10000 mPa ⁇ s; 100-9000 mPa ⁇ s; 200-8000 mPa ⁇ s; 300-7000 mPa ⁇ s; 400-6000mPa ⁇ s; 450-5000mPa ⁇ s; 500-5000mPa ⁇ s; 550-4000mPa ⁇ s; 600-3000mPa ⁇ s; 650-2000mPa ⁇ s; 700-1500mPa ⁇ s.
  • the ⁇ -glucan aqueous solution with a mass concentration of 1% has high clarity or high light transmittance, and the light transmittance of the ⁇ -glucan aqueous solution with a mass concentration of 1% ⁇ 50%, preferably ⁇ 80%, preferably ⁇ 85%, more preferably ⁇ 95%;
  • the ⁇ -glucan solution has good stability.
  • the ⁇ -glucan is derived from higher plants or various bacteria and fungi.
  • the embodiment of the present invention specifically takes the fermentation product of Schizophyllum as an example, but is not limited thereto.
  • the beta-glucan of the present invention is a functional component for preventing and treating acne and / or hormone-dependent dermatitis.
  • the beta-glucan enhances the resistance of normal skin, thereby effectively preventing the infection of external pathogenic microorganisms;
  • ⁇ -glucan can prevent damage caused by excessive inflammation, and can also promote the repair of damaged skin.
  • the ⁇ -glucan of the invention also enhances the active defense function of the skin, stimulates the basic immune function of the cell, and prevents excessive inflammation, and has a two-way immune regulation function, which will not harm the patient's skin or make it resistant.
  • the present invention provides a preparation or composition for preventing and / or treating acne and / or hormone-dependent dermatitis, said preparation or composition comprising (a) ⁇ -glucan; and optionally (b) a pharmaceutical Or cosmetically acceptable carrier or excipient.
  • the formulation or composition contains (a) Schizophyllum beta-glucan; and optionally (b) a pharmaceutically, cosmetically, or device-acceptable carrier or excipient. Agent.
  • the formulation or composition contains 0.0001-99 wt%, preferably 0.001-90 wt%, more preferably 0.01-50 wt%, more preferably 0.05-10 wt% ⁇ -glucan (preferably Schizochytrium beta-glucan), based on the total weight of the formulation or composition.
  • ⁇ -glucan preferably Schizochytrium beta-glucan
  • the mass concentration of the ⁇ -glucan in the preparation or composition is ⁇ 1 ⁇ g / mL, and specifically, it can be 1 ⁇ g / mL-200 mg / mlL, or 1 ⁇ g / mL-5 mg / mL , Or 1 ⁇ g / mL-1mg / mL.
  • the preparation contains a Schizophyllum beta-glucan aqueous solution
  • the content of the Schizophyllum beta-glucan aqueous solution in the preparation is ⁇ 80% by weight, preferably ⁇ 90% by weight, more preferably ⁇ 95% by weight, more preferably ⁇ 99% by weight, more preferably ⁇ 99.5% by weight, based on the total weight of the formulation.
  • the mass concentration of Schizophyllum beta-glucan in the Schizophyllum beta-glucan aqueous solution is 0.0001-50 wt%, preferably 0.02-10 wt%, more preferably 0.05-5wt% based on the total weight of the Schizophyllum beta-glucan aqueous solution.
  • the present invention provides a preparation for preventing and / or treating acne and / or hormone-dependent dermatitis, the preparation comprising: ⁇ -glucan, 1,3-butanediol , 1,3-propanediol, polyethylene glycol 400, glycerin, hyaluronic acid, deionized water.
  • the "active ingredient (first active ingredient)" in the preparation or composition according to the present invention refers to the ⁇ -glucan (preferably Schizophyllum ⁇ -glucan) according to the present invention.
  • the "active ingredient (first active ingredient)", preparation and / or composition according to the present invention can be used for preventing and / or treating acne and / or hormone-dependent dermatitis.
  • the "active ingredient (first active ingredient)" the preparation and / or the composition are further used for preventing and / or treating skin mucosal inflammation or other skin inflammatory diseases.
  • the "active ingredient (first active ingredient)" are further used for preventing and / or treating a skin problem selected from the group consisting of dryness, redness, allergies, inflammation , Fine lines, stains, oil, or a combination thereof.
  • the "second active ingredient” refers to an active ingredient different from the ⁇ -glucan used in the present invention for treating acne and / or hormone-dependent dermatitis, or an active ingredient for treating skin mucosal inflammation or other skin diseases.
  • a "safe and effective amount” means that the amount of the active ingredient is sufficient to significantly improve the condition or symptoms without causing serious side effects.
  • the pharmaceutical composition contains 1-2000 mg of active ingredient / dose, and more preferably 10-200 mg of active ingredient / dose.
  • the "one dose” is a tablet or an injection.
  • “Pharmaceutically acceptable carrier” refers to one or more compatible solid or liquid fillers or gel substances that are suitable for human use and must have sufficient purity and low enough toxicity.
  • composition here means that each component in the composition can blend with the active ingredient of the present invention and each other without significantly reducing the medicinal effect of the active ingredient.
  • Examples of pharmaceutically acceptable carriers are cellulose and its derivatives (such as sodium carboxymethyl cellulose, sodium ethyl cellulose, cellulose acetate, etc.), gelatin, talc, and solid lubricants (such as stearic acid). , Magnesium stearate), calcium sulfate, vegetable oils (such as soybean oil, sesame oil, peanut oil, olive oil, etc.), polyols (such as propylene glycol, glycerin, mannitol, sorbitol, etc.), emulsifiers Wetting agents (such as sodium lauryl sulfate), colorants, flavoring agents, stabilizers, antioxidants, preservatives, pyrogen-free water, etc.
  • cellulose and its derivatives such as sodium carboxymethyl cellulose, sodium ethyl cellulose, cellulose acetate, etc.
  • gelatin such as sodium carboxymethyl cellulose, sodium ethyl cellulose, cellulose acetate, etc.
  • the ⁇ -glucan of the present invention can form a complex with a macromolecular compound or a polymer through non-bonding.
  • the ⁇ -glucan of the present invention can be connected to a macromolecular compound or a polymer through a chemical bond.
  • the macromolecular compound may be a biological macromolecule such as an oligosaccharide, a protein, a nucleic acid, a polypeptide, or the like.
  • the administration method of the active ingredient or the pharmaceutical composition of the present invention is not particularly limited, and representative administration methods include, but are not limited to, external application, oral administration, intratumoral, rectal, parenteral (intravenous, intramuscular, or subcutaneous) and the like.
  • Solid dosage forms include capsules, tablets, pills, powders and granules.
  • the active ingredient is mixed with at least one conventional inert excipient or carrier, such as sodium citrate or dicalcium phosphate, or one or more of the following ingredients:
  • fillers or compatibilizers such as starch, lactose, sucrose, glucose, mannitol and silicic acid;
  • Binders such as hydroxymethyl cellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and acacia;
  • humectants such as glycerin
  • disintegrants such as agar, calcium carbonate, potato starch or tapioca starch, alginic acid, certain complex silicates, and sodium carbonate;
  • absorption accelerators such as quaternary amine compounds
  • an adsorbent such as kaolin; and / or
  • Lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate, or mixtures thereof.
  • the dosage form may also comprise buffering agents.
  • the solid dosage forms can also be prepared using coatings and shell materials, such as casings and other materials known in the art. They may contain opaque agents, and the release of the active ingredient in such a composition may be released in a certain part of the digestive tract in a delayed manner.
  • coatings and shell materials such as casings and other materials known in the art. They may contain opaque agents, and the release of the active ingredient in such a composition may be released in a certain part of the digestive tract in a delayed manner.
  • embedding components that can be used are polymeric substances and waxes.
  • Liquid dosage forms include pharmaceutically acceptable emulsions, solutions, suspensions, syrups or elixirs.
  • liquid dosage forms may contain inert diluents such as water or other solvents, solubilizers, and emulsifiers commonly used in the art, for example, ethanol, isopropanol, ethyl carbonate, ethyl acetate, propylene glycol, 1, 3-butanediol, dimethylformamide, and oils, especially cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil, and sesame oil, or mixtures thereof.
  • the composition may also contain adjuvants such as wetting agents, emulsifying and suspending agents, sweeteners, flavoring agents, and perfumes.
  • the suspension may contain suspending agents such as, for example, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methoxide and agar, or mixtures of these and the like.
  • suspending agents such as, for example, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methoxide and agar, or mixtures of these and the like.
  • the composition may comprise physiologically acceptable sterile aqueous or anhydrous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into a sterile injectable solution or dispersion.
  • Suitable aqueous and non-aqueous vehicles, diluents, solvents or excipients include water, ethanol, polyols and suitable mixtures thereof.
  • a safe and effective amount of the composition of the present invention is administered to a mammal (such as a human) in need of treatment, wherein the dosage when administered is a pharmaceutically considered effective administered dose, and for a 60 kg body weight,
  • the daily dose is usually 1 to 10,000 mg, preferably 10 to 2000 mg, and more preferably 20 to 1000 mg.
  • the specific dosage should also consider factors such as the route of administration, the patient's health, and other factors, which are all within the skill of a skilled physician.
  • composition product which comprises:
  • a first pharmaceutical composition containing (a) a first active ingredient, the first active ingredient being ⁇ -glucan; and (b) pharmaceutically, cosmetically, or Device-acceptable carriers or excipients; and
  • a second pharmaceutical composition which is different from the first pharmaceutical composition for treating acne and / or hormone-dependent dermatitis, or for treating skin mucous membrane inflammation or other skin diseases.
  • composition of the present invention can be administered alone or in combination with other therapeutic drugs (such as formulated in the same pharmaceutical composition).
  • the pharmaceutical composition of the present invention can also be used in combination with other drugs known to treat or ameliorate similar conditions.
  • the combination is administered, the original drug is administered in the same manner and dose, while the pharmaceutical composition of the present invention is used simultaneously or subsequently.
  • Drug combinations also include the use of a pharmaceutical composition of the invention with one or more other known drugs over overlapping periods of time.
  • the dose of the pharmaceutical composition or the known drug of the present invention may be lower than that when they are used alone.
  • the ⁇ -glucan (such as Schizophyllum ⁇ -glucan) of the present invention is very effective in preventing and / or treating acne and / or hormone-dependent dermatitis.
  • the ⁇ -glucan of the present invention can not only be used to prevent and / or treat acne and / or hormone-dependent dermatitis, but also enhance the active defense function of the skin, stimulate the basic immune function of the cell, and prevent excessive inflammation, and have two-way immunity Regulating functions, it can antibacterial, anti-inflammatory and repair skin, prevent and / or treat skin mucosal inflammation or other skin inflammatory diseases, dryness, red bloodshot, allergies, inflammation, fine lines, stains, oily, etc.
  • the beta-glucan of the present invention (preferably Schizophyllum beta-glucan) is a biological polysaccharide of pure natural origin, has complete solubility or natural solubility, and has not undergone any chemical and / or physical modification or Modification.
  • the ⁇ -glucan of the present invention completely retains the three-dimensional conformation of the triple helix, and has better activity for preventing and / or treating acne and / or hormone-dependent dermatitis.
  • the ⁇ -glucan of the present invention has excellent stability, can coexist with most substances and maintain its activity, so it has a wide range of applications, and can be combined with other acne and / or hormone-dependent dermatitis treatment drugs or skin care products Use to improve skin quality while preventing and treating acne and / or hormone-dependent dermatitis.
  • the ⁇ -glucan obtained by Schizophyllum fermentation is taken as an example, but it is not limited thereto.
  • the fermentation broth in the following examples was passed through the fermentation of Schizophyllum species (Schizophyllum ses Fr-1003, product catalog: Purchased from the American Type Strain Collection Center [ATCC]), as follows:
  • Schizophyllum species activation 200g / L of potato, 30g / L of glucose, 10g / L of sodium chloride, 20g / L of agar are made into a plate culture medium, and the Schizophyllum strain is inoculated on the plate medium , And cultured in a constant temperature incubator at 25 ° C for 7 days to obtain a flat mycelium;
  • Seed activation 100 g / L of potato starch, 40 g / L of glucose, 2 g / L of yeast extract, 2 g / L of yeast extract, and water-containing liquid culture medium are filled into a shake flask with a liquid content of 1/3 Taking the plate mycelium obtained in step 1 to inoculate the shake flask, shaking culture at 160 rpm in a constant temperature shaker at 25 ° C. for 7 days, as a seed liquid;
  • Fermentation culture 50g / L of glucose, 50g / L of sucrose, 5g / L of soybean powder (Shandong Zhaoyuan Thermometer Food Co., Ltd.), 2g / L of yeast extract, 0.5g / L of potassium dihydrogen phosphate, 7 Fermentation medium made of hydrated magnesium sulfate 0.5g / L, ammonium sulfate 0.5g / L, potassium nitrate 6g / L and water was added to a fermentor and sterilized at 121 ° C for 15 minutes.
  • the seed solution obtained in step 2 was inoculated with the above fermentation In a tank, agitated at 4 Lpm for aeration and fermentation for 8 days at a constant temperature of 300 rpm at 25 ° C. to obtain a Schizophyllum fermentation broth.
  • step (2) Centrifuge the immersion solution obtained in step (1) at 4,000 rpm for 5 minutes, and take the supernatant; filter the supernatant with a 300-mesh filter cloth under negative pressure, and take the filtered supernatant for use. liquid;
  • step (3) Heat the leaching solution after the filtration in step (2) to 50 ° C, and simultaneously add 200 mesh wood activated carbon and 8-16 mesh coconut shell activated carbon, and the added volume of each activated carbon is the volume of the immersion serum volume. 1%. Continue to stir at 50 ° C and 350rpm for 4h, cool it and wait until it is used to obtain the infusion solution mixed with activated carbon; then use the 300 mesh filter cloth and SCP-321 # filter plate ( The pore size is about 1.5 ⁇ m).
  • step (4) Quickly mix the filtered solution from step (4) with 95% edible ethanol (volume ratio of 1: 3) and stir until a precipitate is obtained; then re-dissolve the precipitate to the original volume and then quickly Mix with 95% edible ethanol (volume ratio of 1: 3) and stir until a precipitate is obtained;
  • step (5) The precipitate obtained in step (5) is placed in a perforated tray and dried using an electric oven at 40 ° C until constant weight to obtain a dried product;
  • the 0.5-% ⁇ -glucan solution has a light transmittance of 90% at a wavelength of 600 nm (detected by a spectrophotometer), and a viscosity of 600 mPa ⁇ s or more at 40 ° C.
  • the functional group positions are basically consistent. As shown in Figure 1, the main functional group positions are:
  • step (7) in the second part of Example 1 0.3%, 0.5%, 0.8%, 1.0% (mass-volume ratio) ⁇ -glucan aqueous solution was prepared, and the dynamic viscosity was measured at 25 ° C. The results are shown in Table 3. As the ⁇ -glucan content increased, the viscosity of each sample also increased, which was 472, 740, 2150, and 3100 mPa ⁇ s.
  • step (7) in the second part of Example 1 0.3%, 0.5%, 0.8%, 1.0% (mass-volume ratio) ⁇ -glucan aqueous solution was prepared, and the light transmittance of the solution was measured at a wavelength of 600 nm. As shown in Table 3, the transmittance of each sample was 96.5%, 93.1%, 87.5%, and 81.1%, respectively.
  • the method for measuring the light transmittance is as follows:
  • step (7) in the second part of Example 1 0.5%, 0.8%, 1.0% (mass-volume ratio) ⁇ -glucan aqueous solution was prepared, and after adding a preservative, 24 samples were placed at room temperature (not protected from light). The stability of the solution was observed, and the dynamic viscosity and light transmittance of the solution were measured. As a result, the above three solution states are all very stable, and their viscosity and light transmittance do not change much, among which the light transmittance has even improved (see Figure 2, Table 3).
  • a is commercially available dispersible yeast ⁇ -glucan particles (insoluble in water), and b is commercially available soluble yeast ⁇ -glucan powder.
  • the ⁇ -glucan solution prepared in Example 1 at a concentration of 5 mg / mL was diluted to 1 mg / mL with a commercially available lotion, and after cleansing, it was directly applied to the facial skin.
  • the use period is 2 months.
  • Example 1 the inventors unexpectedly discovered for the first time that the ⁇ -glucan solution prepared in Example 1 had the effect of preventing and treating acne.
  • Figures 3A and B are a comparison of photos of a severe acne patient before (Figure 3A) and after ( Figure 3B) trials of ⁇ -glucan products, trial for 1 month Later, the patient had less acne and the newly developed ones subsided quickly (Figure 3B).
  • Figures 3C and D show the comparison of the effect of another patient with mild acne before and after the trial ( Figure 3C) and after the trial ( Figure 3D). After 1 month of trial, the patient has reduced acne, greatly reduced the degree of redness on the face, and the skin. become bright and clean.
  • the ⁇ -glucan prepared in the method of Example 1 has significant effects on the prevention and treatment of acne and the improvement of red blood cells, and also has excellent effects on dry skin, peeling, allergies, fine lines, stains, and oil production. effect.
  • the ⁇ -glucan solution prepared in Example 1 at a concentration of 5 mg / mL was diluted to 1 mg / mL with pure water, and an appropriate amount of a preservative was added. After the patient cleansed his face, apply it directly to the facial skin. On average, it was used twice a day for 8 weeks, and the trial effect was evaluated at 3 days, 1 week, 2 weeks, 4 weeks, and 8 weeks.
  • the evaluation indicators after the trial are as follows:
  • Example 2 According to the trial effect in Example 2, the prevention and improvement effects of ⁇ -glucan products on acne are mainly investigated. Targeted selection of patients with different degrees of acne for investigation, not limited to men and women. The results are shown in Figures 4-7.
  • FIG. 6 A case of male mild acne patient C before and after using the ⁇ -glucan product prepared in Example 1 is shown in FIG. 6. During the use of this product, it was found that it has obvious effects on removing acne and has a preventive effect on acne. After using it for a period of time, the acne on the face was controlled and the acne marks gradually subsided.
  • FIG. 7 A case of adolescent male severe acne patient D before and after the trial of the ⁇ -glucan product prepared in Example 1 is shown in FIG. 7.
  • This patient had severe facial and systemic acne due to a strong puberty hormone secretion.
  • the 1-mg / mL ⁇ -glucan (aqueous solution) product has a significant inhibitory effect on acne that has already formed. As shown in Figure 7, this product will accelerate acne healing and inhibit inflammation caused by infection. .
  • the commercially available Schizophyllum beta-glucan was diluted with pure water to 1 mg / mL, and an appropriate amount of a preservative was added. After cleansing, apply it directly to the facial skin. After 12 months of trial of 12 patients with different degrees of acne, 4 patients found that the commercially available Schizophyllum beta-glucan can alleviate acne, the original acne partially subsided, and occasionally new acne occurred, and the rate of regression accelerated . Another 8 patients reported that the test product had no therapeutic effect on acne, but the effect of hydrating and moisturizing was better. The above trial results show that the lower viscosity Schizophyllum beta-glucan has a certain therapeutic effect on acne, but the effect is not as good as the high viscosity and high molecular weight Schizophyllum beta-glucan prepared in Example 1.
  • Example 7 Anti-acne effect of commercially available dispersive yeast ⁇ -glucan
  • a commercially available dispersible (water-insoluble) yeast ⁇ -glucan particle was purchased, and it was dispersed to 1 mg / mL using pure water, and an appropriate amount of a preservative was added. After the patient cleansed his face, shake the test article evenly and apply it directly to the facial skin. Five patients with different degrees of acne tested for 2 weeks, reflecting that the test product had no effect on acne, but showed signs of exacerbation. Two normal skin volunteers experienced pimples-like acne on the face after a 1-week trial. The freshly configured yeast ⁇ -glucan particle dispersion was stopped and the ⁇ -glucan solution prepared in Example 2 was used for 2 days.
  • a commercially available soluble yeast ⁇ -glucan powder was purchased, and a 1 mg / mL yeast ⁇ -glucan solution was prepared with pure water.
  • the Schizophyllum beta-glucan solution prepared in Example 1 was diluted with pure water to 1mg / mL.
  • the two solutions were mixed at a ratio of 1: 1, and an appropriate amount of a preservative was added to prepare two kinds of composite solutions with a content of 0.5 mg / mL of ⁇ -glucan.
  • the original acne partially or basically subsided, of which 5 completely subsided; 4 patients reported The acne had redness and aggravation before the trial period, but after the trial period, acne subsided quickly; 3 patients reported that the ⁇ -glucan complex solution had a significant relief effect on acne. After 2 months of trial, 9 of the 20 patients were cured and 11 were basically cured.
  • the above trial results show that the combination of commercially available soluble yeast ⁇ -glucan and Schizophyllum beta-glucan has a significant therapeutic effect on acne, and the effect is better than when two ⁇ -glucans are used alone.
  • a commercially available 1% (ie, 10 mg / mL) oat ⁇ -glucan solution was purchased, diluted to 1 mg / mL with pure water, and applied directly to the facial skin after cleansing.
  • the above trial results show that commercially available oat ⁇ -glucan has no therapeutic effect on acne.
  • Example 10 Anti-acne effect of acne treatment drugs combined with ⁇ -glucan
  • a 12-year-old adolescent girl developed a papular acne with a large inflammatory pustule on her forehead, which spread to the cheeks and nose. It is clinically recommended to use retinoic acid cream and fusidic acid cream in combination to treat acne.
  • a combination of adapalene gel and metronidazole cream has also been suggested. After using the above combination, it was found that the above combination has an effect on larger particles of inflammatory pustules, but it is not effective on sheeting pimples, and dandruff appears after use, and there is peeling.
  • Example 1 While continuing to use the above-mentioned vitamin A acid cream and fusidic acid cream, the ⁇ -glucan prepared in Example 1 was used for treatment. Dilute it to 1mg / mL with pure water and add an appropriate amount of preservative. After cleansing, apply directly to the facial skin. After 3 days of use, the original large-scale papules gradually subsided, and the peeling phenomenon was effectively alleviated. Later, due to the acne appearing in the physiological cycle, it can also be effectively controlled, the number of acne is reduced, the volume of a single acne becomes smaller, and it quickly subsides, showing the effect of preventing acne.
  • the course of acne ranges from 2 months to 18 years.
  • the degree of acne skin lesions was different, including 32 pimples, 16 pustular acne, and 10 cystic acne.
  • the ⁇ -glucan solution prepared in Example 1 at a concentration of 5 mg / mL was diluted to 1 mg / mL with pure water and an appropriate amount of a preservative was added. After cleansing, it was directly applied to the facial skin, and it was used twice a day on average.
  • the different types of patients described above were randomly divided into the continuous use group and the discontinued group.
  • the patients in the continued use group continued to use the ⁇ -glucan solution prepared in Example 1 at 1 mg / mL for 8 weeks, and the patients in the disabled group were no longer provided with test products.
  • the patient used the 1-mg / mL ⁇ -glucan solution prepared in Example 1 for more than 18 months or more.
  • the acne recurrence situation is shown in Table 6.
  • the acne recurrence rate of 58 patients was 100%, and the acne remission time exceeded 7 days.
  • the recurrence score is as high as 181 points (the average score after half-grouping is 90.5 points).
  • the acne recurrence rate of patients in the withdrawal group was 55%, which was significantly lower than that before the use of ⁇ -glucan solution (100%). And the recurrence is very slight, the number of new acne is small, the area is small, no inflammation, usually completely subsided in 2-3 days, leaving no acne marks. According to the scoring rules, the relapse score of the disabled group was only 25 points.
  • the acne recurrence rate was significantly lower than that in the disabled group (24%), and the recurrence was more mild.
  • the number of new acne is less, the area is small, no inflammation, and it usually completely subsides within 1-2 days. Leave acne marks.
  • the scoring rule the relapse score of the continued use group was only 9 points.
  • Patient A and Patient C had effective control of acne in the first round of trial, and basically recovered. Within 8 weeks of continued use, no new acne formed. After the second round was discontinued after 8 weeks, no recurrence was seen within six months. At the end of the first round of trial in Patient D, acne was effectively relieved; acne was also effectively controlled after switching to oral Chinese medicine combined with other anti-acne drugs for external use. However, acne still recurred after the drug was discontinued, and the degree did not decrease significantly.
  • Patient B and another patient E used the ⁇ -glucan solution prepared in Example 1 for a long time and diluted to 1 mg / mL with pure water.
  • Patient B has been used for 18 months.
  • her skin is in good condition, acne is effectively prevented, and no recurrence occurs.
  • the acne marks have basically subsided, her skin is healthy, smooth and plump, and there are no adverse side effects.
  • Patient E a 38-year-old female, was used for 30 months. Except that acne was effectively prevented from recurring, acne marks and acne scars all subsided. The original fine lines are gradually reduced, the skin is healthy, smooth and plump, and there are no adverse side effects.
  • This embodiment provides 7 kinds of skin care products such as anti-acne essence, and the formula of the anti-acne skin care products is shown in Table 7.
  • Example 13 Ameliorating effect of facial mask prepared with ⁇ -glucan as main active ingredient on acne
  • a 47-year-old female patient, G used hormone-containing cosmetics for a long time, causing hormone-dependent dermatitis, redness and swelling of the face, and infection. After 1 year of dermatology treatment at the top three hospitals, and using the cosmetics recommended by the hospital to repair the barrier, the infection status was controlled, but the facial redness and swelling were not effectively treated. Using the skin care essence prepared in Formula 1 of Example 12 for one month, the feedback of swelling and ulceration was controlled, leaving only scars caused by long-term skin lesions.
  • the present invention finds for the first time that ⁇ -glucan has significant effects in treating and preventing acne, especially the high-viscosity, high-molecular-weight Schizophyllum beta-glucan prepared in Example 1 of the present invention.
  • the present invention finds for the first time that ⁇ -glucan has significant efficacy in treating hormone-dependent dermatitis, especially the high-viscosity, high-molecular-weight Schizophyllum beta-glucan prepared in Example 1 of the present invention.
  • the present invention finds that the activity of ⁇ -glucan for treating and preventing acne and / or hormone-dependent dermatitis is related to the degree of branching, the amount of glucose in the side chain, the three-dimensional structure, and the molecular weight. Unbranched biopolysaccharides have no activity or are less effective in treating and preventing acne and / or hormone-dependent dermatitis.
  • the degree of branching of yeast dextran is indefinite, and the side chain consisting of ⁇ -1,6-glycosidic bonds is randomly extended on the main chain.
  • the amount of glucose in the side chain is large and uncertain, and as many as hundreds.
  • Granular yeast glucan has a long side chain and is easy to form a tight network structure. Soluble yeast ⁇ -glucan has undergone structural modification and its original activity has been greatly affected. It is acne and / or hormone dependent Dermatitis is not as effective in treatment and prevention as Schizophyllum beta-glucan.
  • Schizophyllum beta-glucan has a moderate degree of branching, only one glucose residue in the side chain, and a high molecular weight. It has a large and long three-dimensional triple helix structure, which has a good treatment and prevention of acne and / or hormone-dependent dermatitis. active.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Birds (AREA)
  • Polymers & Plastics (AREA)
  • Biochemistry (AREA)
  • Materials Engineering (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cosmetics (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

一种具有预防和治疗痤疮和/或激素依赖性皮炎功效的生物多糖及其应用。具体地提供了β-葡聚糖的用途，用于制备一种制剂或组合物，所述制剂或组合物用于预防和/或治疗痤疮和/或激素依赖性皮炎。所述β-葡聚糖有明显缓解和改善痤疮和/或激素依赖性皮炎，有效控制痤疮和/或激素依赖性皮炎的发生，加速痤疮和/或激素依赖性皮炎愈合和/或消退的作用。

Description

预防和治疗痤疮和激素依赖性皮炎的生物多糖及其应用 技术领域
本发明涉及生物技术领域，尤其涉及一种用于预防和治疗痤疮和激素依赖性皮炎的生物多糖及其应用。
背景技术
痤疮是一种累及毛囊皮脂腺的慢性炎症性疾病，常引起皮损。痤疮发病的主要原因，包括内分泌失调，毛囊角化异常，继而引起毛孔堵塞，为痤疮丙酸杆菌的感染创造机会，引起皮肤炎症。当前，针对痤疮的治疗，一般为控制皮脂分泌、改善角化异常、抗细菌感染，以及消炎等。常见的痤疮治疗药物如抗生素、维生素A酸、过氧化苯甲酰、以及植物杀菌抑菌成分等，虽能达到抑制痤疮丙酸杆菌等作用，但存在耐药、刺激性大和依赖性等问题，严重影响了痤疮的治疗效果。此外，这类杀菌产品容易破坏皮肤表面菌群生态平衡，从而造成更严重的皮肤问题。目前市场上治疗痤疮的功效成分一般都是杀菌剂，这些成分只能单纯的起到杀菌作用，而消炎效果有限，对皮肤的修复更是没有效果。
激素依赖性皮炎是由于长期不正确使用含糖皮质激素的外用药物或者化妆品导致的，近年来发病上升趋势明显，且顽固难以治愈。目前常用的治疗手段停留在保湿、抗炎抗过敏和抗感染治疗上，治疗周期长，效果差。
因此，本领域迫切需要开发一种能有效预防和治疗上述皮肤问题的药物。
发明内容
本发明的目的是提供一种能有效治疗痤疮和/或激素依赖性皮炎的药物。
本发明的另一目的是提供一种具有预防和治疗痤疮和/或激素依赖性皮炎功效的生物多糖及其应用。
本发明的第一方面，提供了一种β-葡聚糖的用途，用于制备一制剂或组合物，所述制剂或组合物用于预防和/或治疗痤疮和/或激素依赖性皮炎。
在另一优选例中，所述β-葡聚糖为β-D-葡聚糖。
在另一优选例中，所述β-葡聚糖为β-1,3-葡聚糖，优选地，具有β-1,6-分支的β-1,3-葡聚糖。
在另一优选例中，所述β-葡聚糖的结构如式I所示，
Figure PCTCN2019087845-appb-000001
其中，l为≥0的整数，较佳地0-50，较佳地0-10，更佳地0-3，更佳地1-2，更佳地1；m为≥0的整数，较佳地为0-19，较佳地为0-4，更佳地为0-1，更佳地为0；n为≥3的整数，较佳地为30-60000，更佳地100-10000。
在另一优选例中，所述β-葡聚糖的分支度(DB)为0.02-0.8，较佳地0.1-0.5，较佳地0.2-0.4。
在另一优选例中，所述β-葡聚糖包括具有三螺旋立体结构的β-葡聚糖。
在另一优选例中，所述三螺旋立体结构的β-葡聚糖的含量为80％，90％，95％，按β-葡聚糖的总摩尔量计。
在另一优选例中，所述β-葡聚糖的β-1,3-主链为三螺旋立体结构的主体。
在另一优选例中，所述β-葡聚糖的β-1,6-分支位于三螺旋立体结构的外侧。
在另一优选例中，所述β-葡聚糖的分子量≥2kD，较佳地2kD-40000kD，更佳地20kD-20000kD。
在另一优选例中，所述β-葡聚糖的分子量可以为5kD-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；或者8000kD-10000kD。
在另一优选例中，所述β-葡聚糖选自下组：裂褶菌β-葡聚糖、香菇β-葡聚糖、小核菌β-葡聚糖、灰树花β-葡聚糖、侧耳多糖、蘑菇β-葡聚糖、酵母β-葡聚糖、燕麦β-葡聚糖、或其组合。
在另一优选例中，所述β-葡聚糖为裂褶菌β-葡聚糖。
在另一优选例中，所述香菇β-葡聚糖为每5个β-1,3-的主链，带有2个β-1,6-的分支，且每个分支1个葡萄糖残基的β-葡聚糖。
在另一优选例中，所述β-葡聚糖的纯度≥70％，较佳地≥90％，更佳地≥95％，更佳地≥99％。
在另一优选例中，所述β-葡聚糖具有良好的稳定性。
在另一优选例中，所述β-葡聚糖呈固态形式或液态形式，如β-葡聚糖固体颗粒或粉末、或β-葡聚糖水溶液。
在另一优选例中，所述β-葡聚糖颗粒或粉末的粒径≤20mm，较佳地0.001-10mm，更佳地0.01-5mm，更佳地0.1-2mm。
在另一优选例中，所述β-葡聚糖为完全水溶的β-葡聚糖。
在另一优选例中，所述β-葡聚糖(颗粒或粉末)具有良好的水溶性和/或天然可溶性。
在另一优选例中，所述β-葡聚糖(颗粒或粉末)在25℃水(100g)中的溶解度≥0.0001g，较佳地0.01-50g，更佳地0.1-10g。
在另一优选例中，所述β-葡聚糖(颗粒或粉末)在25℃水(100g)中的溶解度可以为0.1-100g；0.2-90g；0.5-80g；1-50g；或者，所述溶解度可以为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；或者1-3g；2-4g；3-5g；4-6g；5-7g；6-8g；7-9g；8-10g。
在另一优选例中，所述β-葡聚糖溶液为β-葡聚糖在水中的溶液，即β-葡聚糖水溶液。
在另一优选例中，所述β-葡聚糖(水)溶液粘度大；较佳地，质量浓度为0.5％的β-葡聚 糖水溶液(25℃时)粘度≥40mPa·s，更佳地100-10000mPa·s，更佳地500-2000mPa·s。
在另一优选例中，所述质量浓度为0.5％的β-葡聚糖水溶液(25℃)粘度可以为50-10000mPa·s；100-9000mPa·s；200-8000mPa·s；300-7000mPa·s；400-6000mPa·s；450-5000mPa·s；500-5000mPa·s；550-4000mPa·s；600-3000mPa·s；650-2000mPa·s；700-1500mPa·s。
在另一优选例中，所述质量浓度为1％的β-葡聚糖的水溶液具有高澄清度或高透光率，所述质量浓度为1％的β-葡聚糖水溶液的透光率≥50％，较佳地≥80％，较佳地≥85％，更佳地≥95％；
在另一优选例中，所述β-葡聚糖溶液具有良好的稳定性。
在另一优选例中，所述预防和/或治疗痤疮包括：预防痤疮的生成、改善或缓解痤疮症状、加快痤疮消退或愈合、改善痤疮疤痕(痘印)、或加快痤疮疤痕(痘印)消退。
在另一优选例中，所述“痤疮”指毛囊皮脂腺单位的一种慢性炎症性皮肤病，主要好发于青少年，临床表现以好发于面部的粉刺、丘疹、脓疱、结节等多形性皮损为特点，又称青春痘。
在另一优选例中，所述痤疮包括严重痤疮和轻度痤疮。
在另一优选例中，所述痤疮选自下组：白头粉刺、黑头粉刺、丘疹性痤疮、脓包性痤疮、囊肿性痤疮、结节性痤疮、或其组合。
在另一优选例中，所述预防和/或治疗激素依赖性皮炎包括：预防激素依赖性皮炎的生成、改善或缓解激素依赖性皮炎症状、加快激素依赖性皮炎消退或愈合、改善激素依赖性皮炎残留的疤痕、或加快激素依赖性皮炎疤痕的消退。
在另一优选例中，所述“激素依赖性皮炎”指因长期反复不当的外用激素引起的皮炎(临床表现包括：表皮和真皮变薄、色素减退沉着、血管显露、酒渣样、痤疮样皮炎、毛囊炎、具有激素依赖和反跳现象为特点，又称激素脸)。
在另一优选例中，所述激素依赖性皮炎症状选自下组：皮肤瘙痒、灼热、疼痛、干燥、脱屑、紧绷感，面部皮肤出现潮红，反复发生红斑、丘疹、皮肤萎缩变薄、毛细血管扩张，痤疮泛发，酒渣鼻样改变，色素沉着或脱失，面部皮肤出现萎缩纹、毛囊炎性脓包等。
在另一优选例中，所述制剂或组合物含有(a)β-葡聚糖；以及任选的(b)药学上、化妆品学上、或器械类可接受的载体或赋形剂。
在另一优选例中，所述制剂或组合物含有(a)裂褶菌β-葡聚糖；以及任选的(b)药学上、化妆品学上、或器械类可接受的载体或赋形剂。
在另一优选例中，所述制剂或组合物含有0.0001-99wt％，较佳地0.001-90wt％，更佳地0.01-50wt％，更佳地0.05-10wt％的β-葡聚糖，按制剂或组合物的总重量计。
在另一优选例中，所述β-葡聚糖在所述制剂或组合物中的质量浓度为≥1μg/mL，具体可以为1μg/mL-200mg/mL，或者1μg/mL-5mg/mL，或者1μg/mL-1mg/mL。
在另一优选例中，所述制剂或组合物还用于增强皮肤免疫力或主动防御功能。
在另一优选例中，所述制剂或组合物还用于预防和/或治疗皮肤黏膜炎症或其他皮肤炎性疾病。
在另一优选例中，所述制剂或组合物还用于预防和/或治疗选自下组的皮肤问题：干 燥、红血丝、过敏、炎症、细纹、色斑、出油、或其组合。
在另一优选例中，所述组合物或制剂的剂型为固体剂型、半固体剂型、或液体剂型，如溶液、凝胶、膏霜、乳液等。
在另一优选例中，所述组合物为药物组合物或化妆品组合物，较佳地为外用药物剂型。
在另一优选例中，所述制剂为外用制剂或透皮制剂(如外用溶液剂、软膏剂、贴剂等)。
在另一优选例中，所述制剂或组合物包括化妆品、食品、医疗器械或药品，具体化妆品可以为功效型化妆品。
本发明的第二方面，提供了一种制剂，所述制剂包含β-葡聚糖。
在另一优选例中，所述β-葡聚糖选自下组：裂褶菌β-葡聚糖、香菇β-葡聚糖、小核菌β-葡聚糖、灰树花β-葡聚糖、侧耳多糖、蘑菇β-葡聚糖、酵母β-葡聚糖、燕麦β-葡聚糖、或其组合。
在另一优选例中，所述β-葡聚糖为裂褶菌β-葡聚糖。
在另一优选例中，所述β-葡聚糖为完全水溶的β-葡聚糖。
在另一优选例中，所述制剂为裂褶菌β-葡聚糖，且所述β-葡聚糖具有良好的水溶性、天然可溶性和/或复溶性。
在另一优选例中，所述制剂中的β-葡聚糖呈固态形式或液体形式。
在另一优选例中，所述制剂中包含β-葡聚糖水溶液，所述β-葡聚糖的质量浓度为0.0001-50wt％，较佳地0.02-10wt％，更佳地0.05-5wt％，按β-葡聚糖水溶液的总重量计。
在另一优选例中，所述制剂中β-葡聚糖水溶液的含量≥80wt％，较佳地≥90wt％，更佳地≥95wt％，更佳地≥99wt％，更佳地≥99.5wt％，按制剂的总重量计。
在另一优选例中，所述制剂中的β-葡聚糖具有选自下组一个或多个特征：
(1)所述β-葡聚糖的纯度≥70％，较佳地≥90％，更佳地≥95％，更佳地≥99％；
(2)所述β-葡聚糖具有良好的水溶性、复溶性和/或天然可溶性；
(3)所述β-葡聚糖(固体颗粒或粉末)在25℃水中的溶解度≥0.0001g/100g水，较佳地0.01-50g/100g水，更佳地0.1g-10g/100g水；
(4)所述β-葡聚糖的水溶液具有高澄清度或高透光率；优选地，所述质量浓度为1％的β-葡聚糖水溶液的透光率≥50％，较佳地≥80％，较佳地≥85％，更佳地≥95％；
(5)所述β-葡聚糖溶液粘度大；优选地，质量浓度为0.5％的β-葡聚糖水溶液(25℃时)粘度≥40mPa·s，更佳地100-10000，更佳地600-2000mPa·s；
(6)所述β-葡聚糖的水溶液具有良好的稳定性；和/或
(7)所述β-葡聚糖的分子量≥2kD，较佳地2kD-40000kD，更佳地20kD-20000kD。
在另一优选例中，所述制剂含有(a)β-葡聚糖；以及(b)药学上、化妆品学上、或器械类可接受的载体或赋形剂。
在另一优选例中，所述制剂含有0.0001-99wt％，较佳地0.001-90wt％，更佳地0.01-50wt％，更佳地0.05-10wt％的β-葡聚糖，按制剂的总重量计。
在另一优选例中，所述制剂还含有(c)第二活性成分，所述第二活性成分为不同于所述β-葡聚糖的治疗痤疮和/或激素依赖性皮炎的活性成分，或治疗皮肤黏膜炎症或其他皮 肤疾病的活性成分。
在另一优选例中，所述治疗痤疮活性成分选自下组：抗生素类、抑菌剂类、维生素A酸类、α-羟酸类、植物杀菌抑菌成分、糖皮质激素、雌激素、孕激素、或其组合；具体地，例如红霉素、过氧化苯甲酰、异维A酸、阿达帕林、壬二酸、烟酰胺、硫磺、雷琐辛、水杨酸、或其组合。
在另一优选例中，所述治疗激素依赖性皮炎的活性成分选自下组：保湿剂、皮肤屏障修复成分、外用非激素类免疫抑制剂、抗组胺药、抗过敏药、抗菌剂以及抗生素等，具体地，例如甘油、尿囊素、透明质酸、聚谷氨酸、芦荟胶、硅油、马油、绵羊油、神经酰胺、表皮生长因子、他克莫司、吡美莫司、氯雷他定、依巴斯汀、硼酸、苯扎氯铵、红霉素等，或其组合。
在另一优选例中，所述治疗痤疮和/或激素依赖性皮炎活性成分选自下组中药及其提取物：清热解表类、清热利湿解毒类、清热凉血解毒类、活血化瘀散结类、调和冲任类、祛风除湿、或其组合；具体地，例如白术、半夏、柴胡、陈皮、赤芍、大黄、地黄、茯苓、甘草、桂枝、黄连、黄芩、积雪草、姜黄、金银花、连翘、牡丹根/皮、牛蒡子、枇杷叶、蒲公英、人参、桑白皮、山药、生山楂、乌梅、野菊花、生薏苡仁、焦栀子、枳实、竹茹、羌活、独活、防风、秦艽、威灵仙、五加皮或其组合。
在另一优选例中，所述治疗皮肤黏膜炎症或其他皮肤疾病的活性成分选自下组：抗组胺类、抗生素类、抗真菌药、激素类、免疫抑制剂、维生素类、维生素A酸类、清洁剂、保护剂、止痒剂、角质促成剂、角质剥脱剂、收敛剂、腐蚀剂、抗菌剂、抗真菌剂、抗病毒剂、杀虫剂、遮光剂、脱色剂、或其组合；具体地，例如氯苯那敏、氯雷他定、阿司咪唑、雷尼替丁、地塞米松、甲基泼尼松龙、制霉菌素、酮康唑、克霉唑、5-氟胞嘧啶、阿达帕林、雷公藤多甙、氯喹、碘町、炉甘石洗剂、或其组合。
在另一优选例中，所述制剂用于预防和/或治疗痤疮和/或激素依赖性皮炎。
本发明的第三方面，提供了一种组合物产品，所述组合物产品包括：
(1)第一药物组合物，所述第一药物组合物含有(a)第一活性成分，所述第一活性成分为β-葡聚糖；和(b)药学上、化妆品学上、或器械类可接受的载体或赋形剂；以及
(2)第二药物组合物，所述第二药物组合物为痤疮治疗药物、激素依赖性皮炎治疗药物或皮肤黏膜炎症或其他皮肤疾病的治疗药物。
在另一优选例中，所述第一药物组合物含有0.0001-99wt％，较佳地0.001-90wt％，更佳地0.01-50wt％，更佳地0.05-10wt％的β-葡聚糖，按第一药物组合物的总重量计。
在另一优选例中，所述β-葡聚糖选自下组：裂褶菌β-葡聚糖、香菇β-葡聚糖、小核菌β-葡聚糖、灰树花β-葡聚糖、侧耳多糖、蘑菇β-葡聚糖、酵母β-葡聚糖、燕麦β-葡聚糖、或其组合。
在另一优选例中，所述β-葡聚糖为裂褶菌的β-葡聚糖。
在另一优选例中，所述痤疮治疗药物含有(a)第二活性成分，所述第二活性成分为不同于所述β-葡聚糖的治疗痤疮活性成分；和(b)药学上、化妆品学上、或器械类可接受的载体或赋形剂。
在另一优选例中，所述激素依赖性皮炎治疗药物含有(a)第二活性成分，所述第二活 性成分为不同于所述β-葡聚糖的治疗激素依赖性皮炎活性成分；和(b)药学上、化妆品学上、或器械类可接受的载体或赋形剂。
在另一优选例中，所述痤疮治疗药物选自下组：抗生素类、抑菌剂类、维生素A酸类、α-羟酸类、植物杀菌抑菌成分、糖皮质激素、雌激素、孕激素、或其组合；具体地，例如红霉素、过氧化苯甲酰、异维A酸、阿达帕林、壬二酸、烟酰胺、硫磺、雷琐辛、水杨酸、或其组合。
在另一优选例中，所述治疗激素依赖性皮炎的活性成分选自下组：保湿剂、皮肤屏障修复成分、外用非激素类免疫抑制剂、抗组胺药、抗过敏药、抗菌剂以及抗生素等，具体地，例如甘油、尿囊素、透明质酸、聚谷氨酸、芦荟胶、硅油、马油、绵羊油、神经酰胺、表皮生长因子、他克莫司、吡美莫司、氯雷他定、依巴斯汀、硼酸、苯扎氯铵、红霉素等，或其组合。
在另一优选例中，所述痤疮和/或激素依赖性皮炎治疗药物选自下组中药及其提取物：清热解表类、清热利湿解毒类、清热凉血解毒类、活血化瘀散结类、调和冲任类、祛风除湿、或其组合；具体地，例如白术、半夏、柴胡、陈皮、赤芍、大黄、地黄、茯苓、甘草、桂枝、黄连、黄芩、积雪草、姜黄、金银花、连翘、牡丹根/皮、牛蒡子、枇杷叶、蒲公英、人参、桑白皮、山药、生山楂、乌梅、野菊花、生薏苡仁、焦栀子、枳实、竹茹、羌活、独活、防风、秦艽、威灵仙、五加皮或其组合。
在另一优选例中，所述皮肤黏膜炎症或其他皮肤疾病的治疗药物选自下组：抗组胺类、抗生素类、抗真菌药、激素类、免疫抑制剂、维生素类、维生素A酸类、清洁剂、保护剂、止痒剂、角质促成剂、角质剥脱剂、收敛剂、腐蚀剂、抗菌剂、抗真菌剂、抗病毒剂、杀虫剂、遮光剂、脱色剂、或其组合；具体地，例如氯苯那敏、氯雷他定、阿司咪唑、雷尼替丁、地塞米松、甲基泼尼松龙、制霉菌素、酮康唑、克霉唑、5-氟胞嘧啶、阿达帕林、雷公藤多甙、氯喹、碘町、炉甘石洗剂、或其组合。
在另一优选例中，所述第一药物组合物和第二药物组合物为各自独立的、或合二为一的。
在另一优选例中，所述组合物产品用于治疗和/或预防痤疮和/或激素依赖性皮炎。
在另一优选例中，所述组合物产品为化妆品或药物。
本发明的第四方面，提供了一种预防和/或治疗痤疮和/或激素依赖性皮炎的方法，包括步骤：(a)给需要的对象施用β-葡聚糖。
在另一优选例中，所述β-葡聚糖选自下组：裂褶菌β-葡聚糖、香菇β-葡聚糖、小核菌β-葡聚糖、灰树花β-葡聚糖、侧耳多糖、蘑菇β-葡聚糖、酵母β-葡聚糖、燕麦β-葡聚糖、或其组合。
在另一优选例中，所述β-葡聚糖为裂褶菌β-葡聚糖。
在另一优选例中，所述的对象包括痤疮患者、激素依赖性皮炎患者、或正常人群。
应理解，在本发明范围内中，本发明的上述各技术特征和在下文(如实施例)中具体描述的各技术特征之间都可以互相组合，从而构成新的或优选的技术方案。限于篇幅，在此不再一一累述。
附图说明
图1显示了实施例1中制备的裂褶菌β-葡聚糖的傅里叶变换红外光谱图。
图2显示了β-葡聚糖稳定性对比，左边一瓶为市售1.0％燕麦β-葡聚糖溶液，右边一瓶为本发明制备的1.0％裂褶菌β-葡聚糖。
图3显示了裂褶菌β-葡聚糖对皮肤的影响。A和B分别为实施例2中一位严重痤疮患者试用裂褶菌β-葡聚糖制品前和试用1个月后的照片。C和D分别为实施例2中另一位轻度痤疮和红血丝患者试用裂褶菌β-葡聚糖制品前和试用1个月后的照片。
图4显示了实施例4中患者A在试用裂褶菌β-葡聚糖制品前后的效果比对。
图5显示了实施例4中患者B在试用裂褶菌β-葡聚糖制品前后的效果比对。
图6显示了实施例4中患者C在试用裂褶菌β-葡聚糖制品前后的效果比对。
图7显示了实施例4中患者D在试用裂褶菌β-葡聚糖制品前后的效果比对。
图8显示了实施例13中患者F试用以裂褶菌β-葡聚糖为主要活性成分的面膜后，面部痤疮的变化情况。
图9显示了实施例14中患者H在试用裂褶菌β-葡聚糖制品前后的效果比对。
图10显示了实施例14中患者I在试用裂褶菌β-葡聚糖制品前后的效果比对。
具体实施方式
本发明人经过广泛而深入的研究，首次意外地发现，β-葡聚糖，尤其是具有天然可溶性、高分子量、高粘度的β-葡聚糖(如裂褶菌β-葡聚糖)，能够非常有效地预防和/或治疗痤疮、激素依赖性皮炎。实验表明，裂褶菌β-葡聚糖有明显缓解和改善痤疮和/或激素依赖性皮炎，有效控制痤疮和/或激素依赖性皮炎的发生，加速痤疮和/或激素依赖性皮炎愈合和/或消退的作用。同时裂褶菌β-葡聚糖还能增强皮肤主动防御功能，激活皮肤天然免疫，抗菌、消炎和修复皮肤，治疗或预防皮肤黏膜炎症或其他皮肤炎性疾病，改善患者皮肤干燥或皮肤红血丝，缓解患者皮肤过敏、细纹、色斑或出油。在此基础上，完成了本发明。
术语说明
除非另外定义，否则本文中所用的全部技术与科学术语均具有如本发明所属领域的普通技术人员通常理解的相同含义。
如本文所用，在提到具体列举的数值中使用时，术语“约”意指该值可以从列举的值变动不多于1％。例如，如本文所用，表述“约100”包括99和101和之间的全部值(例如，99.1、99.2、99.3、99.4等)。
如本文所用，术语“含有”或“包括(包含)”可以是开放式、半封闭式和封闭式的。换言之，所述术语也包括“基本上由…构成”、或“由…构成”。
如本文所用，术语“完全水溶”指所述固态形式的β-葡聚糖，可以在水中完全溶解成为β-葡聚糖水溶液，即在25℃100g水中β-葡聚糖的溶解度≥0.0001g，较佳地0.01-50g，更佳地0.1g-10g。
如本文所用，术语“天然可溶性”指天然状态的β-葡聚糖本身所具有的、在水中完全溶解形成水溶液的性质。所述“天然状态的β-葡聚糖”，是指使用天然方法生产得到(如生物 发酵)的β-葡聚糖，所述β-葡聚糖没有经过任何化学改性、并且没有经过任何物理的和/或化学的和/或生物的方法将其长链分子打断而降低其分子质量。在另一优选例中，本发明β-葡聚糖为天然状态的β-葡聚糖。
如本文所用，痤疮类型包括：丘疹性痤疮、脓疱性痤疮、结节性痤疮、囊肿性痤疮。具体地，
丘疹性痤疮：炎性或非炎性的小颗粒痤疮，直径≤5mm，可分散或密集会成片出现。
脓疱性痤疮：以小脓疱为主，伴有炎性丘疹的痤疮，直径≤5mm，脓包内含有大量脓液，比较粘稠。
结节性痤疮：在脓疱性痤疮的基础上，毛囊皮脂内大量的角化物、皮脂和脓细胞堆积，使毛囊皮脂结构被破坏而形成高出于皮肤表面或在皮肤下的红色或浅色结节，侵犯部位较深，触感较硬，压之有的有痛感。
囊肿性痤疮：以大小不一的囊肿性包块为主，无尖，炎症较重，内含大量组织液，按压痛感强，常破溃溢脓。常伴有丘疹、结节、脓疱、脓肿等。
激素依赖性皮炎
所述“激素依赖性皮炎”，是指因长期反复不当的外用激素引起的皮炎，临床表现以表皮和真皮变薄、色素减退沉着、血管显露、酒渣样、痤疮样皮炎、毛囊炎、具有激素依赖和反跳现象为特点，又称激素脸。具体地，
表皮与真皮变薄：局部长期外用激素，可导致角质层颗粒形成减少而变薄，真皮的糖蛋白和蛋白聚糖的弹性变化使胶原的原纤维间粘附力减弱，胶原合成减少而变薄。
色素减退、沉着：由于角质层的层数减少，迁移到角质形成细胞的黑素减少，引起色素减退。而色素沉着可能与糖皮质激素激活黑素细胞再生色素有关。
血管显露：由于血管壁的胶原纤维间粘附力减弱可导致血管变宽，真皮胶原的消失而导致表面的血管显露。
酒渣样、痤疮样皮炎：在激素诱导的酒渣鼻样皮损中，毛囊蠕形螨的密度显著增高，蠕形螨封闭毛囊皮脂腺出口，引起炎症反应或变态反应，强效激素还可使皮脂腺增生，导致特有的酒渣鼻样皮疹。激素能使毛囊上皮退化变性，导致出口被堵塞，出现痤疮样皮疹或使原有的痤疮加重。
毛囊炎：因激素的免疫抑制作用，可使局部毛囊发生感染和原发毛囊炎加重。
激素依赖和反跳现象：激素的抗炎特性，可抑制丘疹的发展和减轻瘙痒，血管收缩，红斑消失，然而激素不能消除疾病的病因，停用后常可引起原有疾病加重，可表现为炎性水肿，发红，烧灼感，不适感和急性的脓疱疹等反跳现象。该现象常常发生在停用激素后2～10天，并持续几天或3周左右。因反跳现象导致患者继续外用激素，而造成激素依赖。
激素依赖性皮炎的一般诊断方法有：
1.长期反复外用糖皮质激素>1月，用时可好，停药又发的现象。
2.原发性皮肤病已治愈，又反复出现明显的红斑，丘疹、脓疱、皮纹消失、脱屑等皮炎表现。
3.多发于面部、外阴、皱褶部等皮肤薄嫩处。
4.长期用药后留下色素沉着(减退)、萎缩纹、毛细血管扩张、多毛、脓疱等症状， 伴有刺痛、烧灼感。
β-葡聚糖
β-葡聚糖是一种天然多糖，在自然环境中可以找到相当多种类的β-葡聚糖，通常存在于特殊种类的细菌、酵母菌、真菌(灵芝)的细胞壁中，也可存在于高等植物种子的包被中。β-葡聚糖的生产方法主要有两种，其一是从燕麦等谷物或蘑菇等子实体真菌中直接提取；其二是通过真菌或细菌的液体发酵，经由对发酵液进行提取加工，以获得β-葡聚糖。
如本文所用，“本发明β-葡聚糖”、“本发明生物多糖”可互换使用，主要是指本发明第一方面所述的β-葡聚糖，所述β-葡聚糖选自下组：裂褶菌β-葡聚糖、香菇β-葡聚糖、小核菌β-葡聚糖、灰树花β-葡聚糖、侧耳多糖、蘑菇β-葡聚糖、酵母β-葡聚糖、燕麦β-葡聚糖、或其组合；优选地裂褶菌β-葡聚糖。
如本文所用，“裂褶菌β-葡聚糖”指来源于裂褶菌的β-葡聚糖。
在另一优选例中，所述β-葡聚糖的结构如式I所示。
在另一优选例中，所述β-葡聚糖的分子量≥2kD，较佳地2kD-40000kD，更佳地20kD-20000kD。
在另一优选例中，所述β-葡聚糖的分子量可以为5kD-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；或者8000kD-10000kD。
在另一优选例中，所述β-葡聚糖的纯度≥70％，较佳地≥90％，更佳地≥95％，更佳地≥99％。
在另一优选例中，所述β-葡聚糖具有良好的稳定性。
在另一优选例中，所述β-葡聚糖呈固态形式或液态形式，如β-葡聚糖固体颗粒或粉末、或β-葡聚糖水溶液。
在另一优选例中，所述β-葡聚糖颗粒或粉末的粒径≤20mm，较佳地0.001-10mm，更佳地0.01-5mm，更佳地0.1-2mm。
在另一优选例中，所述β-葡聚糖(颗粒或粉末)具有良好的水溶性和/或天然可溶性。
在另一优选例中，所述β-葡聚糖(颗粒或粉末)在25℃水(100g)中的溶解度≥0.0001g，较佳地0.01-50g，更佳地0.1-10g。
在另一优选例中，所述β-葡聚糖(颗粒或粉末)在25℃水(100g)中的溶解度可以为0.1-100g；0.2-90g；0.5-80g；1-50g；或者，所述溶解度可以为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；或者1-3g；2-4g；3-5g；4-6g；5-7g；6-8g；7-9g；8-10g。
在另一优选例中，所述β-葡聚糖溶液为β-葡聚糖在水中的溶液，即β-葡聚糖水溶液。
在另一优选例中，所述β-葡聚糖(水)溶液粘度大；较佳地，质量浓度为0.5％的β-葡聚糖水溶液(25℃时)粘度≥40mPa·s，更佳地100-10000mPa·s，更佳地500-2000mPa·s。
在另一优选例中，所述质量浓度为0.5％的β-葡聚糖水溶液(25℃)粘度可以为50-10000mPa·s；100-9000mPa·s；200-8000mPa·s；300-7000mPa·s；400-6000mPa·s；450-5000mPa·s；500-5000mPa·s；550-4000mPa·s；600-3000mPa·s；650-2000mPa·s； 700-1500mPa·s。
在另一优选例中，所述质量浓度为1％的β-葡聚糖的水溶液具有高澄清度或高透光率，所述质量浓度为1％的β-葡聚糖水溶液的透光率≥50％，较佳地≥80％，较佳地≥85％，更佳地≥95％；
在另一优选例中，所述β-葡聚糖溶液具有良好的稳定性。
在另一优选例中，所述β-葡聚糖来源于高等植物或者各种细菌、真菌。
本发明的实施例具体以裂褶菌的发酵产物为例，但不限于此。
本发明β-葡聚糖是一种预防和治疗痤疮和/或激素依赖性皮炎的功效成分，一方面是β-葡聚糖增强正常皮肤的抵御能力，从而有效预防外界病原微生物的侵染；另一方面，对于细菌感染等造成的皮肤炎症，β-葡聚糖可防止炎症过度而造成损伤，同时还能促进受损皮肤的修复。本发明β-葡聚糖还增强皮肤主动防御功能，激发细胞基础免疫功能，同时预防过度炎症，具有双向免疫调节功能，不会伤害患者皮肤或使其产生耐药性。
制剂或组合物
本发明提供一种用于预防和/或治疗痤疮和/或激素依赖性皮炎的制剂或组合物，所述制剂或组合物含有(a)β-葡聚糖；以及任选的(b)药学上、化妆品学上、或器械类可接受的载体或赋形剂。
在另一优选例中，所述制剂或组合物含有(a)裂褶菌β-葡聚糖；以及任选的(b)药学上、化妆品学上、或器械类可接受的载体或赋形剂。
在另一优选例中，所述制剂或组合物含有0.0001-99wt％，较佳地0.001-90wt％，更佳地0.01-50wt％，更佳地0.05-10wt％的β-葡聚糖(优选地裂褶菌β-葡聚糖)，按制剂或组合物的总重量计。
在另一优选例中，所述β-葡聚糖在所述制剂或组合物中的质量浓度为≥1μg/mL，具体可以为1μg/mL-200mg/mlL，或者1μg/mL-5mg/mL，或者1μg/mL-1mg/mL。
在另一优选例中，所述制剂含有裂褶菌β-葡聚糖水溶液，所述制剂中裂褶菌β-葡聚糖水溶液的含量≥80wt％，较佳地≥90wt％，更佳地≥95wt％，更佳地≥99wt％，更佳地≥99.5wt％，按制剂的总重量计。
在另一优选例中，所述制剂中，裂褶菌β-葡聚糖水溶液中的裂褶菌β-葡聚糖的质量浓度为0.0001-50wt％，较佳地0.02-10wt％，更佳地0.05-5wt％，按裂褶菌β-葡聚糖水溶液的总重量计。
在一个优选的实施方式中，本发明提供了一种用于预防和/或治疗痤疮和/或激素依赖性皮炎的制剂，所述制剂包括：β-葡聚糖、1,3-丁二醇、1,3-丙二醇、聚乙二醇400、甘油、透明质酸、去离子水。
在另一优选例中，所述制剂的组分如表1所示：
表1 具有预防和/或治疗痤疮和/或激素依赖性皮炎功效的制剂
Figure PCTCN2019087845-appb-000002
Figure PCTCN2019087845-appb-000003
本发明所述制剂或组合物中的“活性成分(第一活性成分)”是指本发明所述的β-葡聚糖(优选地裂褶菌β-葡聚糖)。
本发明所述的“活性成分(第一活性成分)”、制剂和/或组合物可用于预防和/或治疗痤疮和/或激素依赖性皮炎。
在另一优选例中，所述“活性成分(第一活性成分)”、制剂和/或组合物还用于预防和/或治疗皮肤黏膜炎症或其他皮肤炎性疾病。
在另一优选例中，所述“活性成分(第一活性成分)”、制剂和/或组合物还用于预防和/或治疗选自下组的皮肤问题：干燥、红血丝、过敏、炎症、细纹、色斑、出油、或其组合。
“第二活性成分”是指本发明中不同于所述β-葡聚糖的治疗痤疮和/或激素依赖性皮炎的活性成分，或治疗皮肤黏膜炎症或其他皮肤疾病的活性成分。
“安全有效量”指的是：活性成分的量足以明显改善病情或症状，而不至于产生严重的副作用。
通常，药物组合物含有1-2000mg活性成分/剂，更佳地，含有10-200mg活性成分/剂。较佳地，所述的“一剂”为一个药片或一支注射针剂。
“药学上可接受的载体”指的是：一种或多种相容性固体或液体填料或凝胶物质，它们适合于人使用，而且必须有足够的纯度和足够低的毒性。
“相容性”在此指的是组合物中各组份能和本发明的活性成分以及它们之间相互掺和，而不明显降低活性成分的药效。
药学上可以接受的载体部分例子有纤维素及其衍生物(如羧甲基纤维素钠、乙基纤维素钠、纤维素乙酸酯等)、明胶、滑石、固体润滑剂(如硬脂酸、硬脂酸镁)、硫酸钙、植物油(如豆油、芝麻油、花生油、橄榄油等)、多元醇(如丙二醇、甘油、甘露醇、山梨醇等)、乳化剂
Figure PCTCN2019087845-appb-000004
润湿剂(如十二烷基硫酸钠)、着色剂、调味剂、稳定剂、抗氧化剂、防腐剂、无热原水等。
在另一优选例中，本发明β-葡聚糖可与大分子化合物或高分子通过非键合作用形成复合物。
在另一优选例中，本发明β-葡聚糖可通过化学键与大分子化合物或高分子相连接。所述大分子化合物可以是生物大分子如高聚糖、蛋白、核酸、多肽等。
本发明的活性成分或药物组合物的施用方式没有特别限制，代表性的施用方式包括但不限于：外敷、口服、瘤内、直肠、肠胃外(静脉内、肌肉内或皮下)等。
固体剂型包括胶囊剂、片剂、丸剂、散剂和颗粒剂。
在这些固体剂型中，活性成分与至少一种常规惰性赋形剂或载体混合，如柠檬酸钠或 磷酸二钙，或与下述成分一种或多种混合：
(a)填料或增容剂，例如，淀粉、乳糖、蔗糖、葡萄糖、甘露醇和硅酸；
(b)粘合剂，例如，羟甲基纤维素、藻酸盐、明胶、聚乙烯基吡咯烷酮、蔗糖和阿拉伯胶；
(c)保湿剂，例如，甘油；
(d)崩解剂，例如，琼脂、碳酸钙、马铃薯淀粉或木薯淀粉、藻酸、某些复合硅酸盐、和碳酸钠；
(e)缓溶剂，例如石蜡；
(f)吸收加速剂，例如，季胺化合物；
(g)润湿剂，例如鲸蜡醇和单硬脂酸甘油酯；
(h)吸附剂，例如，高岭土；和/或
(i)润滑剂，例如，滑石、硬脂酸钙、硬脂酸镁、固体聚乙二醇、十二烷基硫酸钠，或其混合物。
胶囊剂、片剂和丸剂中，剂型也可包含缓冲剂。
所述的固体剂型还可采用包衣和壳材制备，如肠衣和其它本领域公知的材料。它们可包含不透明剂，并且，这种组合物中活性成分的释放可以延迟的方式在消化道内的某一部分中释放。可采用的包埋组分的实例是聚合物质和蜡类物质。
液体剂型包括药学上可接受的乳液、溶液、悬浮液、糖浆或酊剂。除了活性成分外，液体剂型可包含本领域中常规采用的惰性稀释剂，如水或其它溶剂，增溶剂和乳化剂，例如，乙醇、异丙醇、碳酸乙酯、乙酸乙酯、丙二醇、1,3-丁二醇、二甲基甲酰胺以及油，特别是棉籽油、花生油、玉米胚油、橄榄油、蓖麻油和芝麻油或这些物质的混合物等。除了这些惰性稀释剂外，组合物也可包含助剂，如润湿剂、乳化剂和悬浮剂、甜味剂、矫味剂和香料。
除了活性成分外，悬浮液可包含悬浮剂，例如，乙氧基化异十八烷醇、聚氧乙烯山梨醇和脱水山梨醇酯、微晶纤维素、甲醇铝和琼脂或这些物质的混合物等。
组合物可包含生理上可接受的无菌含水或无水溶液、分散液、悬浮液或乳液，和用于重新溶解成无菌的可注射溶液或分散液的无菌粉末。适宜的含水和非水载体、稀释剂、溶剂或赋形剂包括水、乙醇、多元醇及其适宜的混合物。
使用药物组合物时，是将安全有效量的本发明组合物施用于需要治疗的哺乳动物(如人)，其中施用时剂量为药学上认为的有效给药剂量，对于60kg体重的人而言，日给药剂量通常为1～10000mg，较佳地10～2000mg，更佳地20～1000mg。当然，具体剂量还应考虑给药途径、病人健康状况等因素，这些都是熟练医师技能范围之内的。
本发明还提供了一种组合物产品，所述组合物产品包括：
(1)第一药物组合物，所述第一药物组合物含有(a)第一活性成分，所述第一活性成分为β-葡聚糖；和(b)药学上、化妆品学上、或器械类可接受的载体或赋形剂；以及
(2)第二药物组合物，所述第二药物组合物为不同于第一药物组合物的痤疮和/或激素依赖性皮炎治疗药物、或皮肤黏膜炎症或其他皮肤疾病的治疗药物。
本发明组合物可以单独给药，或者与其他治疗药物联合给药(如配制在同一药物组合物中)。
本发明药物组合物也可以与已知的治疗或改进相似病状的其它药物联用。联合给药时，原来药物的给药方式和剂量保持不变，而同时或随后使用本发明药物组合物。药物联用也包括在重叠的时间段使用本发明药物组合物与其它一种或几种已知药物。当本发明药物组合物与其它一种或几种药物进行药物联用时，本发明药物组合物或已知药物的剂量可能比它们单独用药时的剂量较低。
本发明的主要优点包括：
(a)本发明β-葡聚糖(如裂褶菌β-葡聚糖)能够非常有效地预防和/或治疗痤疮和/或激素依赖性皮炎。
(b)本发明β-葡聚糖治疗痤疮和/或激素依赖性皮炎的副作用非常低，不破坏皮肤表面菌群生态平衡，不会伤害患者皮肤或使其产生耐药性。
(c)本发明β-葡聚糖不仅可以用于预防和/或治疗痤疮和/或激素依赖性皮炎，还可增强皮肤主动防御功能，激发细胞基础免疫功能，同时预防过度炎症，具有双向免疫调节功能，可以抗菌、消炎和修复皮肤，预防和/或治疗皮肤黏膜炎症或其他皮肤炎性疾病、干燥、红血丝、过敏、炎症、细纹、色斑、出油等。
(d)本发明β-葡聚糖与其他治疗痤疮和/或激素依赖性皮炎药物结合，可以进一步增强预防和/或治疗效果，具有协同作用。
(e)本发明β-葡聚糖(优选地裂褶菌β-葡聚糖)为纯天然来源的生物多糖，具有完全可溶性或天然可溶性，并且未经过任何化学和/或物理的改性或修饰。
(f)本发明β-葡聚糖完整保留了三螺旋的三维构象，具有更好的预防和/或治疗痤疮和/或激素依赖性皮炎活性。
(g)本发明β-葡聚糖具有极佳的稳定性，能够与大多数物质共存而保持其活性，因而应用领域广泛，可与其他痤疮和/或激素依赖性皮炎治疗药物或者护肤品结合使用，在预防和治疗痤疮和/或激素依赖性皮炎的同时，改善肤质。
下面结合具体实施例，进一步阐述本发明。应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方法，通常按照常规条件，例如Sambrook等人，分子克隆：实验室手册(New York:Cold Spring Harbor Laboratory Press,1989)中所述的条件，或按照制造厂商所建议的条件。除非另外说明，否则百分比和份数是重量百分比和重量份数。
下述实施例中所使用的实验方法如无特殊说明，均为常规方法。
下述实施例中所用的材料、试剂、设备等，如无特殊说明，均可从商业途径得到。
实施例1、β-葡聚糖的获得以及测定
本实施例仅以裂褶菌发酵获得的β-葡聚糖为例，但不限于此。
一、裂褶菌菌种发酵液的获得
下述实施例中的发酵液通过发酵裂褶菌菌种(裂褶菌Schizophyllum commune Fr—1003，产品目录：
Figure PCTCN2019087845-appb-000005
购于美国模式菌种收集中心[ATCC])，具体如下：
1、裂褶菌菌种活化：将马铃薯200g/L、葡萄糖30g/L、氯化钠10g/L、琼脂20g/L制成 平板培养基，把裂褶菌菌种接种到该平板培养基上，于25℃恒温培养箱内培养7天得到平板菌丝体；
2、种子活化：将马铃薯淀粉100g/L、葡萄糖40g/L、酵母浸膏2g/L、酵母浸粉2g/L、水制成的液体培养基装入摇瓶，装液量为1/3，取步骤1所得的平板菌丝体接种该摇瓶，于25℃恒温摇床内160rpm震荡培养培养7天，作为种子液；
3、发酵培养：将葡萄糖50g/L、蔗糖50g/L、黄豆粉(山东招远市温计食品有限公司)5g/L、酵母浸粉2g/L、磷酸二氢钾0.5g/L、七水合硫酸镁0.5g/L、硫酸铵0.5g/L、硝酸钾6g/L和水制成的发酵培养基加入发酵罐中121℃灭菌15分钟，再将步骤2所得的种子液接种上述发酵罐中，25℃恒温300rpm搅拌4Lpm通气发酵培养8天，得到裂褶菌发酵液。
二、β-葡聚糖的分离纯化及β-葡聚糖溶液的制备
(1)将上述第一部分得到的裂褶菌发酵液与4倍体积的蒸馏水混合，60℃下浸煮8h，得到浸煮液；
(2)将步骤(1)得到的浸煮液在4,000rpm离心5min，取上清液；将上清液用300目的滤布负压过滤，取滤出清液待用，即为浸煮清液；
(3)将步骤(2)过滤后的浸煮清液加热至50℃，向其中同时加入200目的木质活性炭及8～16目的椰壳活性炭，每种活性炭的添加体积为浸煮清液体积的1％。于50℃，350rpm条件下持续搅拌4h，冷却后待用，得到混合有活性炭的浸煮清液；再将混合有活性炭的浸煮清液依次使用300目滤布及SCP-321#滤板(孔径大小约1.5μm)进行负压抽滤，取过滤后的清液待用；
(4)将Solarbio脂肪酶(L8070，酶活力100～400U/mg)溶于生理磷酸盐缓冲液中，按10U/mL的酶用量，将脂肪酶溶液加入步骤(3)制备的滤液中，搅拌均匀后40℃酶解2h；再将Solarbio中性蛋白酶(Z8030，酶活力>60U/mg)溶于生理磷酸盐缓冲液中，按60U/mL的酶用量，将中性蛋白酶溶液加入上述酶解液中，搅拌均匀后，40℃酶解2h。酶解结束后90℃水浴加热30min，以灭酶活，再以SCP-321#滤板(孔径大小约1.5μm)进行负压抽滤，取过滤后的清液待用；
(5)将步骤(4)过滤后的清液快速与95％浓度的食用乙醇混合(体积比为1：3)，搅拌，直至得到析出物；再将析出物重新溶解至原体积，后快速与95％浓度的食用乙醇混合(体积比为1：3)，搅拌，直至得到析出物；
(6)将步骤(5)得到的析出物置于带孔托盘中，使用电热烘箱40℃烘干，直至恒重，得干燥产物；
(7)将上述步骤(6)得到的β-葡聚糖干燥物粉碎，称取粉碎物5g，溶解于1,000mL超纯水中，维持600rpm搅拌2h，直至β-葡聚糖充分溶解，得到β-葡聚糖溶液；将上述β-葡聚糖溶液使用5μm滤膜进行负压抽滤，并添加适量化妆品用防腐剂后，即可得到浓度为0.5％的高粘度、高透光率的β-葡聚糖溶液。
该质量浓度为0.5％的β-葡聚糖溶液在600nm波长(以分光光度计检测)下的透光率可以达到90％，40℃时粘度可达600mPa·s以上。
三、β-葡聚糖的鉴定与检测
1、β-葡聚糖的红外光谱鉴定
对上述0.5％的β-葡聚糖溶液进行鉴定，具体按照《中华人民共和国药典》(2010版)二部附录IV中方法C使用红外光谱法，将105℃烘干后的样品，使用傅里叶变换红外光谱仪进行全波长扫描。结果上述实施例1第二部分步骤(7)得到的0.5％溶液为β-葡聚糖溶液。
与酵母β-葡聚糖行业标准QBT 4572-2013中酵母β-葡聚糖的红外光谱图对比，官能团位置基本吻合。如图1所示，主要的官能团位置为：
1)3301cm -1附近有较强，较宽的吸收峰(糖类O-H键伸缩振动吸收峰)
2)2921cm -1附近有较弱的吸收峰(糖类C-H键伸缩振动吸收峰)
3)886cm -1附近有较弱的吸收峰(糖类β构型特征振动吸收峰)
4)1076cm -1附近有较强的吸收峰(糖类C-OH，C-O-C伸缩振动吸收峰)
傅里叶变换红外光谱测试结果表明，本实施例得到的产物为β-葡聚糖。
2、β-葡聚糖的含量检测
对上述实施例1第二部分步骤(6)得到的干燥产物进行β-葡聚糖定量检测，具体按照酵母β-葡聚糖行业标准QBT 4572-2013中酵母β-葡聚糖含量测定方法，将得到的β-葡聚糖干燥物样品研磨至直径1.0mm左右后进行。结果产物中β-葡聚糖含量为99.23％。
3、β-葡聚糖溶液的激素检测
对上述0.5％的β-葡聚糖溶液进行48项激素测定，具体按照《化妆品安全技术规范》(2015年版)第四章2.4雌三醇等7种组分第一法高压液相色谱-二极管阵列检测器法和GB/T24800.2-2009化妆品中四十一种糖皮质激素的测定液相色谱/串联质谱法和薄层层析法进行。结果上述实施例1第二部分步骤(7)得到的0.5％β-葡聚糖溶液中，未检出上述激素(结果见表2)。
表2 48项激素测定
Figure PCTCN2019087845-appb-000006
Figure PCTCN2019087845-appb-000007
4、β-葡聚糖溶液的粘度测定
按照实施例1第二部分步骤(7)的方法，配制0.3％、0.5％、0.8％、1.0％(质量体积比)的β-葡聚糖水溶液，于25℃时分别检测动力粘度。结果详见表3，随着β-葡聚糖含量的提高，各样品的粘度也递增，分别为472、740、2150和3100mPa·s。
取市售分散性(不溶于水)酵母β-葡聚糖颗粒(购自Wellmune公司)，准确称取2g，加入去离子水混合，并定容至200mL，得到质量体积比为1.0％的酵母β-葡聚糖混悬液，于25℃时检测动力粘度。结果该1.0％的酵母β-葡聚糖混悬液的动力粘度为0mPa·s(见表3)。
取市售可溶性酵母β-葡聚糖粉末(购自Wellmune公司)，准确称取2g，加入去离子水溶解，并定容至200mL，得到质量体积比为1.0％的酵母β-葡聚糖水溶液，于25℃时检测动力粘度。结果该1.0％的酵母β-葡聚糖水溶液的动力粘度为0mPa·s(见表3)。
上述动力粘度的测定方法如下：
(1)取200mL上述溶液样品，置于250mL烧杯中；
(2)将盛有上述溶液/混合液样品的烧杯置于水浴锅中，25℃保温1h；
(3)使用旋转粘度计，检测25℃下各样品的动力粘度。
5、β-葡聚糖溶液的透光率测定
按照实施例1第二部分步骤(7)的方法，配制0.3％、0.5％、0.8％、1.0％(质量体积比)的β-葡聚糖水溶液，于600nm波长处测定溶液透光率，结果如见表3所示，各样品的透光率分别为96.5％、93.1％、87.5％和81.1％。
取市售1.0％的燕麦β-葡聚糖溶液(购自Symrise公司)，于600nm波长处测定溶液透光率，结果透光率为59.7％(见表3)。
取市售分散性酵母β-葡聚糖颗粒，准确称取2g，加入去离子水混合，并定容至200mL，得到质量体积比为1.0％的酵母β-葡聚糖混悬液，于600nm波长处测定混悬液透光率，结果透光率仅为1.3％(见表3)。
取市售可溶性酵母β-葡聚糖粉末，准确称取2g，加入去离子水溶解，并定容至200mL，得到质量体积比为1.0％的酵母β-葡聚糖水溶液，于600nm波长处测定溶液透光率，结果透光率为68.4％(见表3)。
上述透光率的测定方法如下：
(1)取10mL上述溶液样品置于离心管中；
(2)1000rpm低速离心1min，以去除气泡(两种酵母β-葡聚糖溶液/悬液无气泡，未经离心处理)；
(3)小心取3mL至1cm玻璃比色皿内，避免气泡；
(4)使用分光光度计，以去离子水作为空白参照(去离子水的透光率为100％计)，于600nm波长处测定样品透光率。
6、β-葡聚糖溶液的稳定性测定
按照实施例1第二部分步骤(7)的方法，配制0.5％、0.8％、1.0％(质量体积比)的β-葡聚糖水溶液，加入防腐剂后，室温(未避光)放置24个月，观察溶液稳定性，并检测溶液动力粘度和透光率。结果，上述三种溶液状态均十分稳定，其粘度和透光率变化不大，其中透光率甚至有所提高(见图2、表3)。
取市售1.0％的燕麦β-葡聚糖溶液，室温(未避光)放置24个月，观察溶液稳定性，并检 测溶液动力粘度和透光率。结果，该1.0％的燕麦β-葡聚糖溶液状态十分不稳定，室温放置3个月后就有固形物析出，导致其粘度和透光率无法检测(见图2、表3)。
表3 各种β-葡聚糖溶液动力粘度数据
Figure PCTCN2019087845-appb-000008
注：a为市售分散性酵母β-葡聚糖颗粒(不溶于水)，b为市售可溶性酵母β-葡聚糖粉末。
实施例2、β-葡聚糖对皮肤作用评估
1、观察对象
征集20名志愿者，年龄21-50周岁，对皮肤问题未进行严格规定，凡认为皮肤状况需要改善的，都可以自愿加入。
2、使用方法
将5mg/mL浓度的实施例1中制备的β-葡聚糖溶液，用市售化妆水稀释至1mg/mL，洁面后，直接涂抹于面部皮肤。使用周期为2个月。
3、结果及分析
1)痤疮
通过此次试用，本发明人首次意外地发现，实施例1中制备的β-葡聚糖溶液具有预防和治疗痤疮的功效。
在20名志愿者中，有8名志愿者患有不同程度的痤疮：有严重囊肿性痤疮，也有偶尔才发作的丘疹性痤疮。但在试用结果上，都基本相似，即所有患者都反映，试用2周后，痤疮发的少，消得快。试用2个月后，β-葡聚糖溶液对痤疮的有效率达到100％。
痤疮与红血丝等皮肤问题的改善如图3所示，图3A和B为一位严重痤疮患者试用β-葡聚糖制品前(图3A)后(图3B)的照片对比，试用1个月后，患者痤疮减少，新长出来的也能很快消退(图3B)。图3C、D为另一位轻度痤疮和红血丝患者试用前(图3C)后(图3D)的效果对比，试用1个月后，该患者痤疮发生减少，面部泛红程度大大减轻，皮肤变光洁。
2)除痤疮外其他皮肤问题
实施例1方法制备的β-葡聚糖除了具有显著的预防和治疗痤疮、改善红血丝的效果外，对皮肤干燥、脱皮、过敏、细纹、色斑以及出油等问题，也具有优良的效果。
表4 β-葡聚糖试用品对除痤疮外其他皮肤问题的改善作用
皮肤问题 干燥 脱皮 过敏 细纹 色斑 出油 红血丝
问题人数 8 2 3 3 2 3 1
正反馈人数 8 2 3 2 1 2 1
从表4可知，除痤疮外，正反馈最多的是皮肤干燥问题，有8人表示有效。其次是过敏，有3人有效。脱皮、细纹和控油各有2人有效，而色斑和红血丝各有1人有效。
实施例3、普通痤疮患者试用β-葡聚糖效果统计
1、观察对象
征集寻常痤疮患者25名，年龄10-36岁，其中男性患者8例，女性17例。痤疮病程从2个月至16年不等。患者痤疮皮损程度各异，有丘疹性痤疮、脓包性痤疮、囊肿性痤疮、结节性痤疮等，未加以区别对待。
2、使用方法
将5mg/mL浓度的实施例1中制备的β-葡聚糖溶液，用纯水稀释至1mg/mL，并添加适量防腐剂。患者洁面后，直接将其涂抹于面部皮肤。平均每天使用2次，连续使用8周，在使用3天、1周、2周、4周以及8周时评价试用效果。
3、评价指标
试用后的评价指标如下：
1)痊愈：原有痤疮完全消退，且不再有新的痤疮发生；
2)基本痊愈：原有痤疮完全消退，偶尔有新的痤疮发生，但都很小，且能够很快消退；
3)缓解：原有痤疮部分消退，偶尔有新的痤疮发生，消退速度加快；
4)无效：原有痤疮基本没有消退，新痤疮也不受控制；
5)加重：原有痤疮程度加重，新痤疮不断生成。
4、结果分析
试用结果统计见表5。
1)使用3天：3位患者的症状得到缓解；1位患者有加重症状，在我们事先告知的情况下，该患者继续使用；有效率为12％；
2)使用1周：使用3天症状加重的1位患者得到有效缓解；另有4位患者出现症状加重的现象，上述患者也继续坚持使用；有效率为16％；
3)使用2周：2位患者基本痊愈；使用1周症状加重的4位患者得到有效缓解，另有17位患者也反映症状得到缓解，共计21位患者的症状得到有效缓解；有效率为92％；
4)使用4周：2位患者痊愈，12位患者基本痊愈；10位患者得到缓解；有效率为96％；
5)使用8周：7位患者痊愈，16位患者基本痊愈；2位患者得到缓解；有效率为100％。
表5 普通痤疮患者试用实施例1方法制备的β-葡聚糖的效果统计
Figure PCTCN2019087845-appb-000009
Figure PCTCN2019087845-appb-000010
实施例4、痤疮患者试用β-葡聚糖效果个例分析
根据实施例2中的试用效果，重点考察β-葡聚糖产品对痤疮的预防和改善效果。有目的地选择不同程度痤疮患者进行考察，男女不限。结果如图4-图7所示。
1)一例青春期男性轻度痤疮患者A的试用结果如图4所示。使用含1mg/mL的实施例1中制备的β-葡聚糖(水溶液)产品3天后，该患者由于上夜班导致的皮肤痤疮以及粗糙等问题得到有效改善。此外，发现该患者使用β-葡聚糖产品2周，痤疮的再次形成得到有效控制，其部分痘印也逐渐消除，显示有预防痤疮的作用。
2)一例女性中度痤疮患者B，27岁，油性皮肤。右脸从19岁开始长痤疮，每次例假之前1周的时间痤疮比较严重，例假开始即好转，具有周期性。鼻翼两侧皮肤出油量大，不定时长痤疮，且长痤疮之前该部位将发红，有疼痛感，有较严重炎症，且持续时间较长，一般10天左右才能逐步消退。
试用前该患者右脸有六七处痤疮处于炎症状态，其余为痘印。使用1mg/mL的实施例1中制备的β-葡聚糖(水溶液)产品1周左右，右脸痤疮区域发红，再坚持使用2天后，红色消退，呈现为普通痘印。此后该患者坚持使用β-葡聚糖产品，右脸不再出现严重痤疮，偶尔出现丘疹型小痤疮，1-2天后也会消退，不再发展成为程度严重的痤疮，显示有预防痤疮的作用；半年之后，原有的痘印也得到部分消退。
试用前该患者下巴发生较大面积痤疮，且痤疮处皮肤下发硬、红肿，有疼痛感，详见图5。使用1mg/mL实施例1中制备的β-葡聚糖(水溶液)产品9天后，痤疮区域的发硬红肿得到明显的控制，单个痤疮面积逐渐缩小，至12天时红肿消退。
3)一例男性轻度痤疮患者C试用实施例1中制备的β-葡聚糖产品的前后效果如图6所示。使用过程中发现该产品对祛痘有明显的效果，而且对痤疮有预防作用。坚持使用一段时间后，脸上的痤疮得到控制，并且痘印也在慢慢消退。
4)一例青春期男性严重痤疮患者D试用实施例1中制备的β-葡聚糖产品的前后效果对比如图7所示。该患者由于青春期激素分泌旺盛而导致严重的面部及全身性痤疮。对于该患者，1mg/mL的β-葡聚糖(水溶液)产品，针对已经形成的痤疮，有明显的抑制作用，如图7所示，该产品会加速痤疮愈合，抑制由于感染而造成的炎症。
实施例5、市售裂褶菌β-葡聚糖的抗痤疮作用
购买市售裂褶菌β-葡聚糖，用于痤疮患者的治疗。经检测，该市售1％(即10mg/mL)裂褶菌β-葡聚糖在25℃时动力粘度为120mPa·s，透光率为99.9％。
将上述市售裂褶菌β-葡聚糖用纯水稀释至1mg/mL并添加适量防腐剂，洁面后，直接涂抹于面部皮肤。12位不同程度痤疮患者试用2个月后，有4位患者发现该市售裂褶菌β-葡聚糖对痤疮有缓解作用，原有痤疮部分消退，偶尔有新的痤疮发生，消退速度加快。另外8位患者反映该试用品对痤疮没有治疗效果，但补水保湿效果较好。上述试用结果表明， 较低粘度裂褶菌β-葡聚糖对痤疮有一定的治疗效果，但效果不如实施例1中制备的具有高粘度和高分子量裂褶菌β-葡聚糖。
实施例6、市售可溶性酵母β-葡聚糖的抗痤疮作用
购买市售可溶性酵母β-葡聚糖粉末，用纯水配制成1mg/mL的β-葡聚糖溶液并添加适量防腐剂，洁面后直接涂抹于面部皮肤。20位不同程度痤疮患者试用2个月后，7位患者发现该市售可溶性酵母β-葡聚糖对痤疮有缓解作用，原有痤疮部分消退，偶尔有新的痤疮发生，消退速度加快。8位患者反馈，该市售可溶性酵母β-葡聚糖对痤疮有轻微的舒缓作用，但对新痤疮的再次发生无明显作用。另外5位患者反映该试用品对痤疮没有治疗效果。上述试用结果表明，市售可溶性酵母β-葡聚糖对痤疮有一定的治疗效果，但效果不如实施例1中制备的具有高粘度和高分子量裂褶菌β-葡聚糖。
实施例7、市售分散性酵母β-葡聚糖的抗痤疮作用
购买市售分散性(不溶于水)酵母β-葡聚糖颗粒，使用纯水将其分散至1mg/mL，并添加适量防腐剂。患者洁面后，将试用品摇匀，并直接涂抹于面部皮肤。5位不同程度痤疮患者试用2个周后，反映该试用品对痤疮没有治疗效果，反而有加重迹象。2位正常皮肤志愿者试用1周后，面部出现丘疹样痤疮；停用该新鲜配置的酵母β-葡聚糖颗粒分散液，使用实施例2中制备的β-葡聚糖溶液2天后，丘疹样痤疮消退；之后再次试用新鲜配置的酵母β-葡聚糖颗粒分散液3天，面部重新出现丘疹样痤疮。上述试用结果表明，市售分散性酵母β-葡聚糖，对皮肤具有刺激作用，不适合直接使用于皮肤。
实施例8、市售可溶性酵母β-葡聚糖与裂褶菌β-葡聚糖联用的抗痤疮作用
购买市售可溶性酵母β-葡聚糖粉末，用纯水配制成1mg/mL的酵母β-葡聚糖溶液，将实施例1中制备的裂褶菌β-葡聚糖溶液用纯水稀释至1mg/mL。以1:1的比例，将上述两种溶液混合，并补充适量防腐剂，制成两种β-葡聚糖含量均为0.5mg/mL的复合液。患者洁面后，将β-葡聚糖复合液试用品摇匀并直接涂抹于面部皮肤。20位不同程度痤疮患者试用1个月后，13位患者发现该β-葡聚糖复合液对痤疮具有显著的治疗作用，原有痤疮部分或基本消退，其中5位完全消退；4位患者反馈，试用前期痤疮有发红加重现象，但坚持试用后，痤疮迅速消退；3位患者反馈β-葡聚糖复合液对痤疮具有明显缓解作用。试用2个月后，20位患者中，9位痊愈，11位基本痊愈。上述试用结果表明，市售可溶性酵母β-葡聚糖与裂褶菌β-葡聚糖联用，对痤疮具有明显的治疗效果，且效果优于两种β-葡聚糖单独使用时。
实施例9、市售燕麦β-葡聚糖的抗痤疮作用
购买市售1％(即10mg/mL)燕麦β-葡聚糖溶液，用纯水稀释成1mg/mL，洁面后直接涂抹于面部皮肤。15位不同程度痤疮患者试用2个月后，均反映该试用品对痤疮没有治疗效果。上述试用结果表明，市售燕麦β-葡聚糖对痤疮没有治疗效果。
实施例10、痤疮治疗药物与β-葡聚糖联用的抗痤疮作用
1例12岁青春期女孩，额头爆发成片丘疹性痤疮伴较大炎性脓包，并波及脸颊、鼻翼部位。临床建议使用维A酸乳膏以及夫西地酸乳膏联合治疗痤疮。也有建议阿达帕林凝胶、甲硝唑乳膏联合治疗。使用上述组合后发现，上述组合对于较大颗粒炎性脓包有作用，但对于成片的丘疹无效，且用后出现皮屑，有脱皮现象。
在继续使用上述维A酸乳膏和夫西地酸乳膏的同时，使用实施例1中制备的β-葡聚糖进行治疗。用纯水将其稀释至1mg/mL并添加适量防腐剂，洁面后，直接涂抹于面部皮肤。使用3天后，原有大面积丘疹逐渐消退，脱皮现象也得到有效缓解。之后，由于生理周期出现的痤疮，也能够得到有效控制，痤疮数量减少，单个痤疮体积变小，且很快消退，显示有预防痤疮的作用。
实施例11、β-葡聚糖对痤疮复发的预防作用
1、观察对象
为考察实施例1方法制备的β-葡聚糖对痤疮再次复发的预防作用：
1)征集周期性复发的痤疮患者58名，年龄12-38岁，皆为女性患者。痤疮病程从2个月至18年不等。患者痤疮皮损程度各异，有丘疹性痤疮32名、脓包性痤疮16名、囊肿性痤疮10名。
2)跟踪调查上述实施例4中的1位女性患者及3位男性痤疮患者。
2、使用方法
将5mg/mL浓度的实施例1中制备的β-葡聚糖溶液，用纯水稀释至1mg/mL并添加适量防腐剂，洁面后，直接涂抹于面部皮肤，平均每天使用2次。
1)短期跟踪调查
连续使用8周后，将上述不同类型的患者随机对半分为继续使用组和停用组。其中继续使用组患者继续使用1mg/mL的实施例1中制备的β-葡聚糖溶液8周，停用组患者不再提供试用品。于再次使用或者停用的第8周，对患者进行跟踪调查。
2)长期跟踪调查
患者使用实施例1中制备的1mg/mL的β-葡聚糖溶液时间超过18个月或更长。
3、评价指标
根据每月新发生痤疮的数量、直径以及消退时间，对复发情况进行评分，分值越低，复发情况越轻微，分值越高，复发情况越严重。
1)0分：不再有新的痤疮发生；
2)1分：微量复发，每月新痤疮数≤1个，直径≤2mm，且在2天内消退；
3)2分：少量复发，每月新痤疮数2-5个，直径≤2mm，且在2天内消退；
4)3分：中等复发，每月新痤疮数5-10个，直径≤5mm，且在3-7天内消退；
4)4分：可控性复发，每月新痤疮数≥10个，直径≤5mm，7-10天内消退；
4)5分：爆发，每月新痤疮数≥10个，直径≥5mm，消退时间≥10天；
4、试用结果
1)对女性痤疮生理周期性复发的预防作用
由于生理周期的原因，女性患者存在痤疮复发的现象。使用实施例1中制备的β-葡聚 糖溶液8周后，58位女性患者的分为继续使用组和停用组以跟踪痤疮复发情况。调查结果如表6所示。
表6 女性痤疮的生理周期性复发效果比较
Figure PCTCN2019087845-appb-000011
患者使用实施例1中制备的β-葡聚糖溶液前，其痤疮复发情况如表6所示，58位患者痤疮复发率为100％，痤疮消退时间都超过7天。按照评分规则计算，复发分值高达181分(对半分组后平均分值为90.5分)。
停用组患者的痤疮复发率为55％，比使用β-葡聚糖溶液前(100％)明显降低。且复发 情况极轻微，新长的痤疮个数少、面积小、无炎症、一般2-3天完全消退，不留痘印。按照评分规则，停用组复发分值仅为25分。
继续使用组患者，其痤疮复发率比停用组明显降低(24％)，且复发情况更加轻微，新长的痤疮个数少、面积小、无炎症、一般在1-2天内完全消退，不留痘印。按照评分规则，继续使用组复发分值仅为9分。
本对比试验结果表明，实施例1中制备的β-葡聚糖溶液，对患者痤疮复发具有极明显的预防作用，且随着使用时间的延长，预防效果更为明显。
2)男性痤疮周期性复发
对实施例4中3名男性患者进行跟踪调查，其中患者A和患者C在第一轮试用结束后，继续使用8周，而患者D在第一轮试用结束后停用本发明制备的β-葡聚糖，改为口服中药与外用其他抗痤疮药物的联合疗法。
患者A和患者C在第一轮试用时，痤疮已经得到有效控制，达到基本痊愈的效果。在继续使用的8周时间内，不再形成新的痤疮。第二轮8周后停用，半年内未见复发。患者D在第一轮试用结束时，痤疮得到有效缓解；在改为口服中药与外用其他抗痤疮药物联合疗法后，痤疮也得到了有效控制。但停药后痤疮仍复发，且程度没有明显减轻。
3)长期使用患者预防情况
患者B与另一位患者E长期使用实施例1中制备、并以纯水稀释至1mg/mL的β-葡聚糖溶液。患者B使用时间为18个月，目前皮肤状况良好，痤疮得到有效预防，不再复发，痘印已经基本消退，皮肤健康光洁饱满，无不良副作用。
患者E，女性38岁，使用时间为30个月，除痤疮得到有效预防不再复发外，痘印以及痘疤全部消退。原有细纹逐渐减少，皮肤健康光洁饱满，无不良副作用。
实施例12、抗痤疮护肤品
本实施例提供了7种抗痤疮精华液等护肤品，所述抗痤疮护肤品的配方如表7所示。
表7 以β-葡聚糖为主要功效成分的抗痤疮护肤品配方
Figure PCTCN2019087845-appb-000012
Figure PCTCN2019087845-appb-000013
将按照表7配制成的抗痤疮精华液等护肤品，于早晚洁面后直接涂抹于面部皮肤。平均每天使用2次，连续使用8周，并评价试用效果。结果表明，上述抗痤疮护肤品均可显著治疗痤疮，加快痤疮消退，消除痘印，并有效控制痤疮的再次发生，具有预防痤疮的作用。
实施例13以β-葡聚糖为主要活性成分制备的面膜对痤疮的改善作用
按照表8的配方，制备面膜。一例25岁女性长期痤疮患者F(病程3年，期间不停治疗，但均无效果)每日使用一贴，其面部痤疮改善变化如图8所示。在使用第3-4天时，痤疮有发红加重现象，但坚持试用，到第7天时，已有明显改善。至第13天，痤疮基本消退，仅剩痘印。
表8 具有预防和/或治疗痤疮功效的制剂
Figure PCTCN2019087845-appb-000014
实施例14、β-葡聚糖对激素依赖性皮炎的作用
几例激素依赖性皮炎患者试用β-葡聚糖，也取得了意想不到的效果。
1)一例47岁女性患者G，长期使用含有激素的化妆品，造成激素依赖性皮炎，面部红肿破溃，并伴有感染。经三甲医院皮肤科治疗1年，并使用医院推荐的修复屏障的化妆 品，感染状况得到控制，但面部红肿破溃未得到有效治疗。使用实施例12配方1制备的护肤精华液1个月，反馈红肿破溃得到控制，仅剩由于长期皮损造成的疤痕。
2)一例48岁女性患者H，长期使用含有激素的化妆品，造成激素依赖性皮炎，面部皮肤红肿，瘙痒，不能再使用其他任何护肤品。使用实施例1方法制备的5mg/mL裂褶菌β-葡聚糖，用于洁肤和护肤(5mg/mL裂褶菌β-葡聚糖，用水稀释20倍后用于清洁皮肤；5mg/mL裂褶菌β-葡聚糖，用水稀释5倍后用于日常护肤)。试用11天后，面部消肿，无瘙痒症状，且肤色恢复正常(图9)
3)1例10岁女孩患者I，严重依赖润唇膏，在连续每天多次(6-8次)使用润唇膏6个月后，由于家长未及时购买，自我感觉唇部灼热疼痛，再次使用唇膏后，上述症状消退。之后家长让其停用，1天后发现唇部红肿，上下唇均有丘疹样疙瘩，左下唇角有脓性丘疹(图10左)。使用按照实施例1方法制备的5mg/mL无菌裂褶菌β-葡聚糖(无防腐剂)，直接涂抹于唇部。为防止裂褶菌β-葡聚糖染菌，每天使用一支(25mL)。使用36h后，嘴唇红肿消退，同时唇上及嘴角丘疹消失(图10右)。半个月后，由于感觉唇部干燥及没有意识到问题的严重性，再次使用润唇膏2天，在家长要求下停用后，唇部再次红肿、干裂。使用5mg/mL无菌裂褶菌β-葡聚糖和绵羊油后2日，唇部出现蜕皮现象。之后停用绵羊油，仅每日多次外涂5mg/mL无菌裂褶菌β-葡聚糖，2日后红肿消退。之后巩固使用裂褶菌β-葡聚糖1个月，未再次复发。
讨论
本发明首次发现，β-葡聚糖具有显著的治疗和预防痤疮的功效，尤其是本发明实施例1中制备的高粘度、高分子质量的裂褶菌β-葡聚糖。
本发明首次发现，β-葡聚糖具有显著的治疗激素依赖性皮炎的功效，尤其是本发明实施例1中制备的高粘度、高分子质量的裂褶菌β-葡聚糖。
本发明发现β-葡聚糖的治疗和预防痤疮和/或激素依赖性皮炎活性与其分支度高低、侧链的葡萄糖数量、立体结构、分子量均有关系。无分支度的生物多糖没有治疗和预防痤疮和/或激素依赖性皮炎的活性，或效果较差。
酵母葡聚糖的分支度不定，主链上随机延伸出由β-1,6-糖苷键构成的侧链，侧链的葡萄糖数量较大且不定，多的可高达上百个。颗粒性酵母葡聚糖侧链长度长，容易形成严密的网状结构，而可溶性酵母β-葡聚糖经历了结构的改性，原有活性受到了极大影响，对痤疮和/或激素依赖性皮炎的治疗和预防效果不如裂褶菌β-葡聚糖。
裂褶菌β-葡聚糖分支度适中，侧链仅一个葡萄糖残基，同时分子质量高，具有较大较长的立体三螺旋结构，具有很好的治疗和预防痤疮和/或激素依赖性皮炎活性。
在本发明提及的所有文献都在本申请中引用作为参考，就如同每一篇文献被单独引用作为参考那样。此外应理解，在阅读了本发明的上述讲授内容之后，本领域技术人员可以对本发明作各种改动或修改，这些等价形式同样落于本申请所附权利要求书所限定的范围。

Claims (15)

  1. 一种β-葡聚糖的用途，其特征在于，用于制备一制剂或组合物，所述制剂或组合物用于预防和/或治疗痤疮和/或激素依赖性皮炎。
  2. 如权利要求1所述的用途，其特征在于，所述β-葡聚糖为β-1,3-葡聚糖。
  3. 如权利要求1所述的用途，其特征在于，所述β-葡聚糖为具有β-1,6-分支的β-1,3-葡聚糖。
  4. 如权利要求1所述的用途，其特征在于，所述β-葡聚糖的结构如式I所示，
    Figure PCTCN2019087845-appb-100001
    其中，l为≥0的整数，较佳地0-50，较佳地0-10，更佳地0-3，更佳地1-2，更佳地1；m为≥0的整数，较佳地为0-19，较佳地为0-4，更佳地为0-1，更佳地为0；n为≥3的整数，较佳地为30-60000，更佳地100-10000。
  5. 如权利要求1所述的用途，其特征在于，所述β-葡聚糖的分支度为0.02-0.8，较佳地0.1-0.5，较佳地0.2-0.4。
  6. 如权利要求1所述的用途，其特征在于，所述β-葡聚糖的分子量≥2kD，较佳地2kD-40000kD，更佳地20kD-20000kD。
  7. 如权利要求1所述的用途，其特征在于，所述β-葡聚糖选自下组：裂褶菌β-葡聚糖、香菇β-葡聚糖、小核菌β-葡聚糖、灰树花β-葡聚糖、侧耳多糖、蘑菇β-葡聚糖、酵母β-葡聚糖、燕麦β-葡聚糖、或其组合。
  8. 如权利要求1所述的用途，其特征在于，所述预防和/或治疗痤疮包括：预防痤疮的生成、改善或缓解痤疮症状、或加快痤疮消退或愈合、或改善痤疮疤痕(痘印)、或加快痤疮疤痕(痘印)消退。
  9. 如权利要求1所述的用途，其特征在于，所述预防和/或治疗激素依赖性皮炎包括：预防激素依赖性皮炎的生成、改善或缓解激素依赖性皮炎症状、或加快激素依赖性皮炎消退或愈合、或改善激素依赖性皮炎造成的疤痕、或加快激素依赖性皮炎造成疤痕的消退。
  10. 如权利要求1所述的用途，其特征在于，所述制剂或组合物还用于预防和/或治疗皮肤黏膜炎症或其他皮肤炎性疾病。
  11. 如权利要求1所述的用途，其特征在于，所述制剂或组合物含有(a)β-葡聚糖；以及任选的(b)药学上、化妆品学上、或器械类可接受的载体或赋形剂。
  12. 一种制剂，其特征在于，所述制剂含有(a)β-葡聚糖；以及(b)药学上、化妆品学 上、或器械类可接受的载体或赋形剂。
  13. 如权利要求12所述的制剂，其特征在于，所述制剂还含有(c)第二活性成分，所述第二活性成分为不同于所述β-葡聚糖的治疗痤疮和/或激素依赖性皮炎的活性成分，或治疗皮肤黏膜炎症或其他皮肤疾病的活性成分。
  14. 如权利要求12所述的制剂，其特征在于，所述制剂用于预防和/或治疗痤疮和/或激素依赖性皮炎。
  15. 一种组合物产品，其特征在于，所述组合物产品包括：
    (1)第一药物组合物，所述第一药物组合物含有(a)第一活性成分，所述第一活性成分为β-葡聚糖；和(b)药学上可接受的载体；以及
    (2)第二药物组合物，所述第二药物组合物为痤疮和/或激素依赖性皮炎治疗药物、或皮肤黏膜炎症或其他皮肤疾病的治疗药物。
PCT/CN2019/087845 2018-05-23 2019-05-21 预防和治疗痤疮和激素依赖性皮炎的生物多糖及其应用 WO2019223699A1 (zh)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN201980002828.1A CN110769836B (zh) 2018-05-23 2019-05-21 预防和治疗痤疮和激素依赖性皮炎的生物多糖及其应用
US17/057,749 US20220000902A1 (en) 2018-05-23 2019-05-21 Biological polysaccharide for preventing and treating acne and steroid-dependent dermatitis and use thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201810503734.X 2018-05-23
CN201810503734.XA CN110522761B (zh) 2018-05-23 2018-05-23 一种具有预防和治疗痤疮功效的生物多糖及其应用

Publications (1)

Publication Number Publication Date
WO2019223699A1 true WO2019223699A1 (zh) 2019-11-28

Family

ID=68617189

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/087845 WO2019223699A1 (zh) 2018-05-23 2019-05-21 预防和治疗痤疮和激素依赖性皮炎的生物多糖及其应用

Country Status (3)

Country Link
US (1) US20220000902A1 (zh)
CN (2) CN110522761B (zh)
WO (1) WO2019223699A1 (zh)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111973620B (zh) * 2019-05-21 2024-04-16 浙江立恩生物科技有限公司 用于预防和治疗激素依赖性皮炎的生物多糖及其应用
CN110974722B (zh) * 2019-12-24 2023-05-09 浙江立恩生物科技有限公司 一种生物多糖在洗护产品中的应用
CN113134088B (zh) * 2020-01-17 2024-03-12 铂曼(浙江)生物科技有限公司 一种含有生物多糖的组合物及其应用
CN113749998A (zh) * 2020-06-06 2021-12-07 伍新维 一种复合祛痘霜及其制备方法
CN114306106B (zh) * 2020-10-09 2023-03-31 铂曼(浙江)生物科技有限公司 皮肤用组合物及其用途
CN114306107B (zh) * 2020-10-09 2023-09-01 铂曼(浙江)生物科技有限公司 功效型皮肤用产品及其制备方法
CN112826977B (zh) * 2020-12-31 2022-09-27 山东纳美德生物科技有限公司 一种液体敷料、皮肤外用组合物及其制备方法及应用
US11572420B1 (en) 2021-07-30 2023-02-07 Tissue repair ltd Isolated biological polysaccharide compound, methods of use and methods of manufacture thereof
US11384160B1 (en) 2021-07-30 2022-07-12 Tissue repair ltd Method of making a beta glucan compound

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060247205A1 (en) * 1998-09-25 2006-11-02 Patchen Myra L Very high molecular weight beta-glucans
US20080095731A1 (en) * 2005-06-21 2008-04-24 Shekhar Mitra Personal Care Compositions Comprising Alpha-Glucans and/or Beta-Glucans
CN102600494A (zh) * 2012-03-30 2012-07-25 武汉华纳联合药业有限公司 一种多糖组合物及其制备方法和用途
CN103981201A (zh) * 2014-05-30 2014-08-13 武汉大学 一种β-葡聚糖基因载体及其制备方法和应用

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6369216B1 (en) * 1998-09-25 2002-04-09 Biopolymer Engineering Pharmaceutical, Inc. Very high molecular weight β-glucans
KR102275267B1 (ko) * 2014-01-25 2021-07-09 주식회사 엘지생활건강 피부 개선용 조성물
CN106075120B (zh) * 2016-07-01 2019-09-20 宁波希诺亚海洋生物科技有限公司 一种湿疹乳膏剂
CN106075399A (zh) * 2016-07-22 2016-11-09 简婷婷 用于激素性皮炎的组合物，制剂及制备方法和应用

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060247205A1 (en) * 1998-09-25 2006-11-02 Patchen Myra L Very high molecular weight beta-glucans
US20080095731A1 (en) * 2005-06-21 2008-04-24 Shekhar Mitra Personal Care Compositions Comprising Alpha-Glucans and/or Beta-Glucans
CN102600494A (zh) * 2012-03-30 2012-07-25 武汉华纳联合药业有限公司 一种多糖组合物及其制备方法和用途
CN103981201A (zh) * 2014-05-30 2014-08-13 武汉大学 一种β-葡聚糖基因载体及其制备方法和应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JESENAK, M. ET AL.: "3-Glucan-Based Cream (Containing Pleuran Isolated from Pleurotus Ostreatus) in Supportive Treatment of Mild-to-Moderate Atopic Dermatitis", JOURNAL OF DERMATOLOGICAL TREATMENT, vol. 27, no. 4, 9 December 2015 (2015-12-09), pages 351 - 354, ISSN: 0954-6634 *

Also Published As

Publication number Publication date
CN110522761B (zh) 2022-03-25
CN110769836A (zh) 2020-02-07
CN110769836B (zh) 2022-12-23
CN110522761A (zh) 2019-12-03
US20220000902A1 (en) 2022-01-06

Similar Documents

Publication Publication Date Title
WO2019223699A1 (zh) 预防和治疗痤疮和激素依赖性皮炎的生物多糖及其应用
KR102494228B1 (ko) 효모 추출물의 신규 화장품용 및/또는 기능식품용 또는 피부과용 용도
KR100847104B1 (ko) 아토피 피부염 개선제 조성물
KR100889606B1 (ko) 항염증 화장료 조성물
WO2020233681A1 (zh) 具有预防和治疗激素依赖性皮炎功效的生物多糖及其应用
JP2007526325A (ja) ラクトバチルス（Ｌａｃｔｏｂａｃｉｌｌｕｓ）抽出物による皮膚の処置方法
CN106668832B (zh) 一种多肽在制备治疗肠道病毒感染药物的应用
RU2536264C2 (ru) Композиция для наружного применения на коже, содержащая соль и сахар в качестве активных ингредиентов, для предотвращения и лечения вагиноза, и ее применение
EP3049430B1 (en) Parietal fraction of propionibacterium granulosum having immunomodulating action
CN113134088B (zh) 一种含有生物多糖的组合物及其应用
JPH0873342A (ja) 覆盆子抽出物含有皮膚外用剤または浴用剤
CN109498543B (zh) 可调节皮肤微生态平衡的组合物及其应用以及包含其的润肤乳和润肤乳的制备方法
Knapczyk et al. Simple tests demonstrating the antimycotic effect of chitosan
CN105581974A (zh) 一种外用组合物
KR20160128990A (ko) 피부에서 외부 자극에 대한 반응을 진정시키기 위한 제제 및 이러한 반응을 진정시키는 방법
CN1401365A (zh) 一种中药保健药物
CN108403764B (zh) 一种用于治疗颜面再发性皮炎的外用制剂及制备方法
CN111449997A (zh) 一种使用绿藻提取物作为主要活性成分的化妆品
WO2021051685A1 (zh) 一种用于清除hpv的复合制剂
FR3091650A1 (fr) Produit pour le traitement de dysbioses
JP7475873B2 (ja) ディフェンシン発現促進剤
CN117860604A (zh) 一种低聚木糖在制备改善皮肤毛孔且抗衰护肤品中的应用
CN1481892A (zh) 蛤蚧疗肺片
CN114377054A (zh) 青钱柳叶或其提取物在制备预防和/或治疗痤疮的药物或化妆品中的用途
CN117752604A (zh) 用于治疗寻常型痤疮的复方微乳凝胶制剂及制备方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19807653

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19807653

Country of ref document: EP

Kind code of ref document: A1