阅读说明：本技术 一种具有预防和治疗痤疮功效的生物多糖及其应用 (It is a kind of to have effects that prevent and treat the biological polyoses of acne and its application ) 是由 郭宏亮 庄秀园 叶榛 林檬 朱勤健 王轩 于 2018-05-23 设计创作，主要内容包括：本发明提供了一种具有预防和治疗痤疮功效的生物多糖及其应用。具体地,本发明提供了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。所述β-葡聚糖有明显缓解和改善痤疮,有效控制痤疮的发生,加速痤疮愈合的作用。同时所述β-葡聚糖还能增强皮肤主动防御功能,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。(Have effects that prevent and treat the biological polyoses of acne and its application the present invention provides a kind of.Specifically, the present invention provides the purposes of beta glucan, are used to prepare a preparation or composition, the preparation or composition are for preventing and/or treating acne.The beta glucan is relieved and improves acne, effectively controls the generation of acne, accelerates the effect of acne healing.The beta glucan can also enhance skin Initiative Defense function simultaneously, antibacterial, anti-inflammatory and reparation skin, skin and mucosa inflammation or other inflammatory disease of the skin are treated or prevented, patient skin drying or skin red capillary, reduction of patient skin allergy, microgroove, color spot or fuel-displaced are improved.)

1. a kind of purposes of beta glucan, which is characterized in that be used to prepare a preparation or composition, the preparation or composition are used In prevention and/or treatment acne.

2. purposes as described in claim 1, which is characterized in that the beta glucan is β -1,3- glucan, it is preferable that described Beta glucan is the beta-1,3-dextran with β -1,6- branch.

3. purposes as described in claim 1, which is characterized in that the structure of the beta glucan is shown in formula I,

Wherein, l is the integer of 0-50, preferably 0-10, more preferably 0-3, more preferably 1-2, more preferably 1；The integer that m is >=0, compared with It is goodly 0-19, preferably 0-4, is more preferably 0-1, is more preferably 0；The integer that n is >=3, preferably 30-60000, more Good ground 100-10000.

4. purposes as described in claim 1, which is characterized in that the degree of branching of the beta glucan is 0.02-0.8, preferably 0.1-0.5, preferably 0.25-0.4.

5. purposes as described in claim 1, which is characterized in that the par of the monosaccharide unit of the side chain of the beta glucan ≤ 20, it is more preferably 1 more preferably≤1.5 preferably≤3 preferably≤5.

6. purposes as described in claim 1, which is characterized in that molecular weight >=2kD of the beta glucan, preferably 2kD- 40000kD, more preferably 20kD-20000kD.

7. purposes as described in claim 1, which is characterized in that the beta glucan is selected from the group: schizophyllum commune beta glucan, perfume (or spice) Mushroom beta glucan, pyrenomycetes beta glucan, grifola frondosa beta-glucose, polysaccharide of picking up the ears, mushroom beta glucan, yeast beta-dextran, Avenabeta glucosan, or combinations thereof.

8. purposes as described in claim 1, which is characterized in that described to prevent and/or treat acne to include: to prevent the life of acne At, improve or alleviate acne symptom or accelerate acne subside healing or improve acne scars (acne print) or accelerate acne scar Trace (acne print) subsides.

9. purposes as described in claim 1, which is characterized in that the preparation or composition contain (a) beta glucan；And appoint (b) of choosing pharmaceutically, on cosmeceutical or the acceptable carrier of weapon exercises or excipient.

10. purposes as described in claim 1, which is characterized in that the preparation or composition are also used to prevent and/or treat skin Skin mucosal inflammation or other inflammatory disease of the skin.

11. a kind of preparation, which is characterized in that the preparation contains (a) beta glucan；And (b) pharmaceutically, on cosmeceutical, Or the acceptable carrier of weapon exercises or excipient.

12. preparation as claimed in claim 11, which is characterized in that the preparation also contains (c) second active constituent, and described Two active constituents are the treatment acne active constituent different from the beta glucan, or treatment skin and mucosa inflammation or other skins The active constituent of disease.

13. preparation as claimed in claim 11, which is characterized in that the preparation is for preventing and/or treating acne.

14. a kind of composition product, which is characterized in that the composition product includes:

(1) first pharmaceutical composition, first pharmaceutical composition contain (a) first active constituent, first active constituent For beta glucan；(b) pharmaceutically acceptable carrier；And

(2) second pharmaceutical compositions, second pharmaceutical composition are abundance type acne treatment drug or skin and mucosa inflammation or other skins The therapeutic agent of skin disease.

Technical field

The present invention relates to field of biotechnology more particularly to it is a kind of have effects that prevent and treat acne biological polyoses and It is applied.

Background technique

Acne is a kind of chronic inflammation disease for involving pilosebaceous follicle, Chang Yinqi skin lesion.The main original of pathogenesis of acne Cause, including endocrine disorder, follicular keratosis is abnormal, then causes clogging of pores, is that chance is created in the infection of propionibacterium acnes, Cause scytitis.Currently, it for the treatment of acne, generally controls sebum secretion, improve dyskeratosis, bacterial-infection resisting, And anti-inflammatory etc..Common abundance type acne treatment drug such as antibiotic, vitamin A acid, benzoyl peroxide and plant sterilization is antibacterial Ingredient etc., though inhibiting propionibacterium acnes can be reached, there are drug resistance, the problems such as irritation is big and dependence, seriously Affect the therapeutic effect of acne.In addition, this kind of sterilised products are easily destroyed the skin surface flora ecological balance, to cause more Serious skin problem.The effect for the treatment of acne currently on the market ingredient is typically all fungicide, what these ingredients can only be simple Bactericidal effect is played, and anti-inflammatory effects are limited, the reparation to skin is even more no effect.

Therefore, there is an urgent need in the art to develop a kind of drug that can be effectively prevented and treated acne.

Summary of the invention

The object of the present invention is to provide a kind of drugs that can effectively treat acne.

Have effects that prevent and treat the biological polyoses of acne and its application it is a further object of the present invention to provide a kind of.

The first aspect of the present invention provides a kind of purposes of beta glucan, is used to prepare a preparation or composition, described Preparation or composition are for preventing and/or treating acne.

In another preferred example, the beta glucan is callose.

In another preferred example, the beta glucan is β -1,3- glucan, it is preferable that there is β -1, the β -1 of 6- branch, 3- glucan.

In another preferred example, the structure of the beta glucan is shown in formula I,

Wherein, l is the integer of 0-50, preferably 0-10, more preferably 0-3, more preferably 1-2, more preferably 1；M be >=0 it is whole Number, it is more preferably 0 that preferably 0-19, preferably 0-4, which are more preferably 0-1,；The integer that n is >=3, preferably 30- 60000, more preferably 100-10000.

In another preferred example, the degree of branching (DB) of the beta glucan is 0.02-0.8, preferably 0.1-0.5, preferably Ground 0.25-0.4.

In another preferred example, par≤20 of the monosaccharide unit of the side chain of the beta glucan, preferably≤5, It preferably≤3, more preferably≤1.5, is more preferably 1.

In another preferred example, the beta glucan includes the beta glucan with three screw stereo structures.

In another preferred example, the content of the beta glucan of the three screw stereos structure is 80%, 90%, 95%, is pressed The total moles meter of beta glucan.

In another preferred example, β -1 of the beta glucan, 3- main chain are the main body of three screw stereo structures.

In another preferred example, β -1 of the beta glucan, 6- branch are located at the outside of three screw stereo structures.

In another preferred example, molecular weight >=2kD of the beta glucan, preferably 2kD-40000kD, more preferably 20kD-20000kD。

In another preferred example, the molecular weight of the beta glucan can 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.

In another preferred example, the beta glucan is selected from the group: schizophyllum commune beta glucan, β-lentinan, small nut Bacterium beta glucan, grifola frondosa beta-glucose, polysaccharide of picking up the ears, mushroom beta glucan, yeast beta-dextran, avenabeta glucosan or A combination thereof.

In another preferred example, the beta glucan is schizophyllum commune beta glucan.

In another preferred example, the β-lentinan is every 5 β -1, and the main chain of 3- has 2 β -1, point of 6- Branch, and the beta glucan of 1 glucose residue of each branch.

In another preferred example, purity >=70% of the beta glucan, preferably >=90%, more preferably >=95%, more Goodly >=99%.

In another preferred example, the beta glucan is with good stability.

In another preferred example, the beta glucan is in solid-state form or liquid form, such as beta glucan solid particle or Powder or beta glucan aqueous solution.

In another preferred example, partial size≤20mm of the beta glucan particle or powder, preferably 0.001-10mm, more Good ground 0.01-5mm, more preferably 0.1-2mm.

In another preferred example, the beta glucan is completely water-soluble beta glucan.

In another preferred example, the beta glucan (particle or powder) has good water-soluble and/or natural soluble Property.

In another preferred example, solubility of the beta glucan (particle or powder) in 25 DEG C of water (100g) >= 0.0001g, preferably 0.01-50g, more preferably 0.1-10g.

In another preferred example, solubility of the beta glucan (particle or powder) in 25 DEG C of water (100g) can be 0.1-100g；0.2-90g；0.5-80g；1-50g；Alternatively, 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.

In another preferred example, the beta glucan solution is the solution of beta glucan in water, i.e. beta glucan is water-soluble Liquid.

In another preferred example, beta glucan (water) solution viscosity is big；Preferably, the β-that mass concentration is 0.5% Glucan aqueous solution (at 25 DEG C) viscosity >=40mPas, more preferably 100-10000mPas, more preferably 500-2000mPa s。

In another preferred example, beta glucan aqueous solution (25 DEG C) viscosity that the mass concentration is 0.5% can be 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。

In another preferred example, the aqueous solution for the beta glucan that the mass concentration is 1% has high clarity or high saturating Light rate, light transmittance >=50% for the beta glucan aqueous solution that the mass concentration is 1%, preferably >=80%, preferably >= 85%, more preferably >=95%；

In another preferred example, the beta glucan solution is with good stability.

In another preferred example, the prevention and/or treatment acne include: to prevent the generation of acne, improvement or alleviation Cuo Sore symptom accelerates acne recession or healing, improves acne scars (acne print) or accelerate acne scars (acne print) and subside.

In another preferred example, described " acne " refers to a kind of chronic inflammatory skin of pilosebaceous unit, mainly It is apt to occur in teenager, with the characteristics of the pleomorphism skin lesion such as acne, papule, warts, the tubercle of clinical manifestation to be apt to occur in face, also known as Whelk.

In another preferred example, the acne includes severe acne and mild acne.

In another preferred example, the acne is selected from the group: Whiteheads, blackhead, acne papulosa, useless fellow Cuo Sore, cystic acne, acne nodosum, or combinations thereof.

In another preferred example, the preparation or composition contain (a) beta glucan；And optional (b) pharmaceutically, change Cosmetic is upper or the acceptable carrier of weapon exercises or excipient.

In another preferred example, the preparation or composition contain (a) schizophyllum commune beta glucan；And optional (b) medicine On, on cosmeceutical or the acceptable carrier of weapon exercises or excipient.

In another preferred example, the preparation or composition contain 0.0001-99wt%, preferably 0.001-90wt%, More preferably 0.01-50wt%, the more preferably beta glucan of 0.05-10wt%, by the total weight of preparation or composition.

In another preferred example, mass concentration of the beta glucan in the preparation or composition is >=1 μ g/mL, It is specifically as follows 1 μ g/mL-200mg/mL perhaps 1 μ g/mL-5mg/mL or 1 μ g/mL-1mg/mL.

In another preferred example, the preparation or composition are also used to enhance cutaneous immunisation power or Initiative Defense function.

In another preferred example, the preparation or composition be also used to prevent and/or treat skin and mucosa inflammation or other Inflammatory disease of the skin.

In another preferred example, the preparation or composition are also used to prevent and/or treat skin problem selected from the group below: Drying, red capillary, allergy, inflammation, microgroove, color spot, it is fuel-displaced, or combinations thereof.

In another preferred example, the dosage form of the composition or preparation is solid dosage forms, semisolid dosage form or liquid agent Type, such as solution, gel, cream, lotion.

In another preferred example, the composition is pharmaceutical composition or cosmetic composition, preferably external drug Dosage form.

In another preferred example, the preparation is external preparation or preparation capable of permeating skin (such as externally used solution agent, ointment, patch Deng).

In another preferred example, the preparation or composition include cosmetics, food, medical instrument or drug, are embodied Cosmetic can be effect type cosmetics.

The second aspect of the present invention, provides a kind of preparation, and the preparation includes beta glucan.

In another preferred example, the beta glucan is selected from the group: schizophyllum commune beta glucan, β-lentinan, small nut Bacterium beta glucan, grifola frondosa beta-glucose, polysaccharide of picking up the ears, mushroom beta glucan, yeast beta-dextran, avenabeta glucosan or A combination thereof.

In another preferred example, the beta glucan is schizophyllum commune beta glucan.

In another preferred example, the beta glucan is completely water-soluble beta glucan.

In another preferred example, the preparation is schizophyllum commune beta glucan, and the beta glucan is with good water-soluble Property, natural soluble and/or solubility.

In another preferred example, the beta glucan in the preparation is in solid-state form or liquid form.

It in another preferred example, include beta glucan aqueous solution in the preparation, the mass concentration of the beta glucan is 0.0001-50wt%, preferably 0.02-10wt%, more preferably 0.05-5wt%, by the total weight of beta glucan aqueous solution.

In another preferred example, in the preparation beta glucan aqueous solution content >=80wt%, preferably >=90wt%, More preferably >=95wt%, more preferably >=99wt%, more preferably >=99.5wt%, by the total weight of preparation.

In another preferred example, the beta glucan in the preparation, which has, is selected from the group one or more features:

(1) purity >=70% of the beta glucan, preferably >=90%, more preferably >=95%, more preferably >=99%；

(2) beta glucan has good water-soluble, solubility and/or natural soluble；

(3) solubility >=0.0001g/100g water of the beta glucan (solid particle or powder) in 25 DEG C of water, compared with Good ground 0.01-50g/100g water, more preferably 0.1g-10g/100g water；

(4) aqueous solution of the beta glucan has high clarity or high transparency；Preferably, the mass concentration is Light transmittance >=50% of 1% beta glucan aqueous solution, preferably >=80%, preferably >=85%, more preferably >=95%；

(5) the beta glucan solution viscosity is big；Preferably, mass concentration is (25 DEG C of beta glucan aqueous solution of 0.5% When) viscosity >=40mPas, more preferably 100-10000, more preferably 600-2000mPas；

(6) aqueous solution of the beta glucan is with good stability；And/or

(7) molecular weight >=2kD of the beta glucan, preferably 2kD-40000kD, more preferably 20kD-20000kD.

In another preferred example, the preparation contains (a) beta glucan；And (b) pharmaceutically, on cosmeceutical or device The acceptable carrier of tool class or excipient.

In another preferred example, the preparation contains 0.0001-99wt%, preferably 0.001-90wt%, more preferably 0.01-50wt%, the more preferably beta glucan of 0.05-10wt%, by the total weight of preparation.

In another preferred example, the preparation also contains (c) second active constituent, second active constituent be different from The treatment acne active constituent of the beta glucan, or the active constituent for the treatment of skin and mucosa inflammation or other skin diseases.

In another preferred example, the treatment acne active constituent is selected from the group: antibiotics, bacteriostatic agent class, vitamin A Acids, alpha-hydroxy acid class, plant sterilization antipathogenic composition, glucocorticoid, estrogen, progestational hormone, or combinations thereof；Specifically, such as Erythromycin, benzoyl peroxide, isotretinoin, Adapalene, azelaic acid, niacinamide, sulphur, resorcinol, salicylic acid or its group It closes.

In another preferred example, the treatment acne active constituent is selected from the group Chinese medicine and its extract: relieving superficies by cooling class, Clearing heat and promoting diuresis detoxify class, clearing away heat,cooling blood and removing toxin class, activating microcirculation and removing stasis medicinal dissipating bind class, reconcile punching appoint a class, or combinations thereof；Specifically, such as Rhizoma Atractylodis Macrocephalae, the tuber of pinellia, radix bupleuri, dried orange peel, radix paeoniae rubra, rheum officinale, glutinous rehmannia, Poria cocos, Radix Glycyrrhizae, ramulus cinnamomi, the coptis, radix scutellariae, centella, turmeric, gold and silver Flower, Fructus Forsythiae, tree peony root/skin, great burdock achene, loguat leaf, dandelion, ginseng, the root bark of white mulberry, Chinese yam, raw hawthorn, dark plum, wild chrysanthemum, life Semen coicis, stir-baked FRUCTUS GARDENIAE, the dried immature fruit of citron orange, caulis bambusae in taenian, or combinations thereof.

In another preferred example, the active constituent of the treatment skin and mucosa inflammation or other skin diseases is selected from the group: Antihistaminic, antibiotics, antifungal, steroids, immunosuppressor, vitamins, V-A acidic, detergent, protection Agent, antipruritic, keratoplastics, cutin cracking-off agent, astringent, corrosive agent, antibacterial agent, antifungal agent, antivirotic, desinsection Agent, opacifier, decolorising agent, or combinations thereof；Specifically, for example, chlorphenamine, Loratadine, astemizole, ranitidine, fill in Meter Song, methylprednisolone, nystatin, ketoconazole, clotrimazole, 5-flurocytosine, Adapalene, tripod, chloroquine, Iodine raised path between farm fields, calamine lotion, or combinations thereof.

In another preferred example, the preparation is for preventing and/or treating acne.

The third aspect of the present invention, provides a kind of composition product, and the composition product includes:

(1) first pharmaceutical composition, first pharmaceutical composition contain (a) first active constituent, first activity Ingredient is beta glucan；(b) pharmaceutically, on cosmeceutical or the acceptable carrier of weapon exercises or excipient；And

(2) second pharmaceutical compositions, second pharmaceutical composition be abundance type acne treatment drug or skin and mucosa inflammation or its The therapeutic agent of his skin disease.

In another preferred example, first pharmaceutical composition contains 0.0001-99wt%, preferably 0.001- 90wt%, more preferably 0.01-50wt%, the more preferably beta glucan of 0.05-10wt%, by the total weight of the first pharmaceutical composition Meter.

In another preferred example, the beta glucan is selected from the group: schizophyllum commune beta glucan, β-lentinan, small nut Bacterium beta glucan, grifola frondosa beta-glucose, polysaccharide of picking up the ears, mushroom beta glucan, yeast beta-dextran, avenabeta glucosan or A combination thereof.

In another preferred example, the beta glucan is the beta glucan of schizophyllum commune.

In another preferred example, the abundance type acne treatment drug contains (a) second active constituent, and second active constituent is Different from the treatment acne active constituent of the beta glucan；(b) pharmaceutically, on cosmeceutical or weapon exercises are acceptable Carrier or excipient.

In another preferred example, the abundance type acne treatment drug is selected from the group: antibiotics, bacteriostatic agent class, vitamin A acid Class, alpha-hydroxy acid class, plant sterilization antipathogenic composition, glucocorticoid, estrogen, progestational hormone, or combinations thereof；Specifically, such as it is red Mycin, benzoyl peroxide, isotretinoin, Adapalene, azelaic acid, niacinamide, sulphur, resorcinol, salicylic acid, or combinations thereof.

In another preferred example, the abundance type acne treatment drug is selected from the group Chinese medicine and its extract: relieving superficies by cooling class, heat-clearing Eliminating damp, detoxifying class, clearing away heat,cooling blood and removing toxin class, activating microcirculation and removing stasis medicinal dissipating bind class, reconcile punching appoint a class, or combinations thereof；Specifically, for example, Rhizoma Atractylodis Macrocephalae, The tuber of pinellia, radix bupleuri, dried orange peel, radix paeoniae rubra, rheum officinale, glutinous rehmannia, Poria cocos, Radix Glycyrrhizae, ramulus cinnamomi, the coptis, radix scutellariae, centella, turmeric, honeysuckle, company It sticks up, tree peony root/skin, great burdock achene, loguat leaf, dandelion, ginseng, the root bark of white mulberry, Chinese yam, raw hawthorn, dark plum, wild chrysanthemum, raw coix lacryma-jobi Benevolence, stir-baked FRUCTUS GARDENIAE, the dried immature fruit of citron orange, caulis bambusae in taenian, or combinations thereof.

In another preferred example, the therapeutic agent of the skin and mucosa inflammation or other skin diseases is selected from the group: anti-group Amine, antibiotics, antifungal, steroids, immunosuppressor, vitamins, V-A acidic, detergent, protective agent, Antipruritic, keratoplastics, cutin cracking-off agent, astringent, corrosive agent, antibacterial agent, antifungal agent, antivirotic, insecticide, screening Photo etching, decolorising agent, or combinations thereof；Specifically, for example, chlorphenamine, Loratadine, astemizole, ranitidine, dexamethasone, Methylprednisolone, nystatin, ketoconazole, clotrimazole, 5-flurocytosine, Adapalene, tripod, chloroquine, iodine raised path between farm fields, Calamine lotion, or combinations thereof.

In another preferred example, first pharmaceutical composition and the second pharmaceutical composition are independent or conjunction two It is one.

In another preferred example, the composition product is for treating and/or preventing acne.

In another preferred example, the composition product is cosmetics or drug.

The fourth aspect of the present invention provides a kind of method prevented and/or treat acne, comprising steps of (a) is to needs Object apply beta glucan.

In another preferred example, the beta glucan is selected from the group: schizophyllum commune beta glucan, β-lentinan, small nut Bacterium beta glucan, grifola frondosa beta-glucose, polysaccharide of picking up the ears, mushroom beta glucan, yeast beta-dextran, avenabeta glucosan or A combination thereof.

In another preferred example, the beta glucan is schizophyllum commune beta glucan.

In another preferred example, the object includes patients with acne or normal population.

It should be understood that above-mentioned each technical characteristic of the invention and having in below (eg embodiment) within the scope of the present invention It can be combined with each other between each technical characteristic of body description, to form a new or preferred technical solution.As space is limited, In This no longer tires out one by one states.

Detailed description of the invention

Fig. 1 shows the Fourier transform infrared spectroscopy figure of the schizophyllum commune beta glucan prepared in embodiment 1.

Fig. 2 shows beta glucan stability contrast, and one bottle of the left side is commercially available 1.0% avenabeta glucosan solution, the right One bottle is 1.0% schizophyllum commune beta glucan prepared by the present invention.

Fig. 3 shows influence of the schizophyllum commune beta glucan to skin.A and B is respectively a severe acne trouble in embodiment 2 Photo before person's schizophyllum commune beta glucan product on probation and after 1 month on probation.C and D is respectively the slight Cuo of another one in embodiment 2 Photo before sore and red capillary patient schizophyllum commune beta glucan product on probation and after 1 month on probation.

Fig. 4 shows that effect of the patient A before and after schizophyllum commune beta glucan product on probation compares in embodiment 4.

Fig. 5 shows that effect of the patient B before and after schizophyllum commune beta glucan product on probation compares in embodiment 4.

Fig. 6 shows that effect of the patient C before and after schizophyllum commune beta glucan product on probation compares in embodiment 4.

Fig. 7 shows that effect of the patient D before and after schizophyllum commune beta glucan product on probation compares in embodiment 4.

Specific embodiment

The present inventor after extensive and in-depth study, for the first time it was unexpectedly observed that beta glucan, especially has and naturally may be used Dissolubility, high molecular weight, highly viscous beta glucan (such as schizophyllum commune beta glucan), effectively can prevent and/or treat Acne.Experiment shows that schizophyllum commune beta glucan is relieved and improves acne, effectively controls the generation of acne, accelerates acne The effect of healing.Schizophyllum commune beta glucan can also enhance skin Initiative Defense function simultaneously, activate the skin innate immunity, antibacterial, Anti-inflammatory and reparation skin, treat or prevent skin and mucosa inflammation or other inflammatory disease of the skin, improve patient skin drying or skin Skin red capillary, reduction of patient skin allergy, microgroove, color spot or fuel-displaced.On this basis, the present invention is completed.

Term explanation

Unless otherwise defined, otherwise whole technologies used herein and scientific term all have such as fields of the present invention The normally understood identical meanings of those of ordinary skill.

As used herein, in use, term " about " means that the value can be from enumerating in mentioning the numerical value specifically enumerated Value changes not more than 1%.For example, as used herein, statement " about 100 " include 99 and 101 and between whole values (for example, 99.1,99.2,99.3,99.4 etc.).

As used herein, term " containing " or " including (including) " can be open, semi-enclosed and enclosed.It changes Yan Zhi, the term also include " substantially by ... constitute " or " by ... constitute ".

As used herein, the beta glucan that term " completely water-soluble " refers to the solid-state form, can be completely dissolved in water As beta glucan aqueous solution, i.e., solubility >=0.0001g of beta glucan in 25 DEG C of 100g water, preferably 0.01-50g, More preferably 0.1g-10g.

As used herein, term " natural soluble " refers to that beta glucan of native state itself is possessed, complete in water The property of fully dissolved formation aqueous solution." beta glucan of native state " refers to and produces to obtain (such as life using natural method Object fermentation) beta glucan, the beta glucan by any chemical modification and without by any physics and/ Or its long-chain molecule is interrupted and reduces its molecular mass by chemical and/or biological method.In another preferred example, of the invention Beta glucan is the beta glucan of native state.

As used herein, acne type includes: acne papulosa, acne pustulosa, acne nodosum, cystic acne. Specifically,

Acne papulosa: the little particle acne of inflammatory or non-inflammatory, diameter≤5mm can be dispersed or can intensively occur in flakes.

Acne pustulosa: based on pimple, with the acne of inflamed papules, diameter≤5mm, useless fellow is interior to contain a large amount of purulence Liquid, it is more sticky.

Acne nodosum: on the basis of acne pustulosa, a large amount of angling object, sebum and pyocyte heap in hair follicle sebum Product keeps hair follicle sebum destructurized and forms red or light tubercle above skin surface or under the skin, infringement portion Position is deeper, and sense of touch is harder, and some of pressure has pain.

Cystic acne: based on Cystic mass not of uniform size, no point, inflammation is heavier, includes a large amount of tissue fluid, presses Tenderness sense is strong, normal ulceration pyorrhea.It is often accompanied by papule, tubercle, warts, abscess etc..

Beta glucan

Beta glucan is a kind of natural polysaccharide, can find the beta glucan of suitable multiple types in the natural environment, usually It is present in the cell wall of the bacterium of Special Category, saccharomycete, fungi (ganoderma lucidum), also is present in the coating of higher plant seed In.There are mainly two types of the production methods of beta glucan, one is directly mentioning from the fructifications fungi such as the cereal such as oat or mushroom It takes；The second is processing is extracted via to fermentation liquid, by the liquid fermentation of fungi or bacterium to obtain beta glucan.

As used herein, " beta glucan of the present invention ", " biological polyoses of the present invention " are used interchangeably, and are primarily referred to as the present invention Beta glucan described in first aspect, the beta glucan are selected from the group: schizophyllum commune beta glucan, β-lentinan, small nut Bacterium beta glucan, grifola frondosa beta-glucose, polysaccharide of picking up the ears, mushroom beta glucan, yeast beta-dextran, avenabeta glucosan or A combination thereof；Preferably schizophyllum commune beta glucan.

As used herein, " schizophyllum commune beta glucan " refers to the beta glucan from schizophyllum commune.

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

In another preferred example, molecular weight >=2kD of the beta glucan, preferably 2kD-40000kD, more preferably 20kD-20000kD。

In another preferred example, the molecular weight of the beta glucan can 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.

In another preferred example, purity >=70% of the beta glucan, preferably >=90%, more preferably >=95%, more Goodly >=99%.

In another preferred example, the beta glucan is with good stability.

In another preferred example, the beta glucan is in solid-state form or liquid form, such as beta glucan solid particle or Powder or beta glucan aqueous solution.

In another preferred example, partial size≤20mm of the beta glucan particle or powder, preferably 0.001-10mm, more Good ground 0.01-5mm, more preferably 0.1-2mm.

In another preferred example, the beta glucan (particle or powder) has good water-soluble and/or natural soluble Property.

In another preferred example, solubility of the beta glucan (particle or powder) in 25 DEG C of water (100g) >= 0.0001g, preferably 0.01-50g, more preferably 0.1-10g.

In another preferred example, solubility of the beta glucan (particle or powder) in 25 DEG C of water (100g) can be 0.1-100g；0.2-90g；0.5-80g；1-50g；Alternatively, 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.

In another preferred example, the beta glucan solution is the solution of beta glucan in water, i.e. beta glucan is water-soluble Liquid.

In another preferred example, beta glucan (water) solution viscosity is big；Preferably, the β-that mass concentration is 0.5% Glucan aqueous solution (at 25 DEG C) viscosity >=40mPas, more preferably 100-10000mPas, more preferably 500-2000mPa s。

In another preferred example, beta glucan aqueous solution (25 DEG C) viscosity that the mass concentration is 0.5% can be 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。

In another preferred example, the aqueous solution for the beta glucan that the mass concentration is 1% has high clarity or high saturating Light rate, light transmittance >=50% for the beta glucan aqueous solution that the mass concentration is 1%, preferably >=80%, preferably >= 85%, more preferably >=95%；

In another preferred example, the beta glucan solution is with good stability.

In another preferred example, the beta glucan derives from higher plant or various bacteriums, fungi.

The embodiment of the present invention specifically by taking the tunning of schizophyllum commune as an example, but not limited to this.

On the one hand a kind of the effect of beta glucan of the present invention is prevention and treatment acne ingredient is that beta glucan enhancing is normal The resilience of skin, to effectively prevent infecting for extraneous pathogenic microorganism；On the other hand, for caused by bacterium infection etc. Scytitis, beta glucan can prevent inflammation from excessively causing to damage, while can also promote the reparation of damaged skin.β-of the present invention Glucan also enhances skin Initiative Defense function, activated cell fundamental immunity function, while preventing excessive inflammation, has two-way exempt from Epidemic disease regulatory function, will not patient harm skin or make its generate drug resistance.

Preparation or composition

The present invention provides a kind of for preventing and/or treating the preparation or composition of acne, and the preparation or composition contain There is (a) beta glucan；And optional (b) pharmaceutically, on cosmeceutical or the acceptable carrier of weapon exercises or excipient.

In another preferred example, the preparation or composition contain (a) schizophyllum commune beta glucan；And optional (b) medicine On, on cosmeceutical or the acceptable carrier of weapon exercises or excipient.

In another preferred example, the preparation or composition contain 0.0001-99wt%, preferably 0.001-90wt%, More preferably 0.01-50wt%, the more preferably beta glucan of 0.05-10wt% (preferably schizophyllum commune beta glucan), by preparation or The total weight of composition.

In another preferred example, mass concentration of the beta glucan in the preparation or composition is >=1 μ g/mL, It is specifically as follows 1 μ g/mL-200mg/mlL perhaps 1 μ g/mL-5mg/mL or 1 μ g/mL-1mg/mL.

In another preferred example, the preparation contains schizophyllum commune beta glucan aqueous solution, schizophyllum commune β-Portugal in the preparation Content >=80wt% of water solution, preferably >=90wt%, more preferably >=95wt%, more preferably >=99wt%, more preferably >=99.5wt%, by the total weight of preparation.

In another preferred example, in the preparation, the matter of the schizophyllum commune beta glucan in schizophyllum commune beta glucan aqueous solution Amount concentration is 0.0001-50wt%, and preferably 0.02-10wt%, more preferably 0.05-5wt%, water-soluble by schizophyllum commune beta glucan The total weight of liquid.

In one preferred embodiment, the present invention provides a kind of for preventing and/or treating the preparation of acne, institute Stating preparation includes: beta glucan, 1,3 butylene glycol, 1,3- propylene glycol, polyethylene glycol 400, glycerol, hyaluronic acid, deionized water.

In another preferred example, the component of the preparation is as shown in table 1:

Table 1 has effects that prevent and/or treat the preparation of acne

" active constituent (the first active constituent) " in preparation or composition of the present invention refers to β-of the present invention Glucan (preferably schizophyllum commune beta glucan).

" active constituent (the first active constituent) " of the present invention, preparation and/or composition can be used for preventing and/or controlling Treat acne.

In another preferred example, described " active constituent (the first active constituent) ", preparation and/or composition are also used to prevent And/or treat skin and mucosa inflammation or other inflammatory disease of the skin.

In another preferred example, described " active constituent (the first active constituent) ", preparation and/or composition are also used to prevent And/or treatment skin problem selected from the group below: drying, red capillary, allergy, inflammation, microgroove, color spot, it is fuel-displaced, or combinations thereof.

" the second active constituent " refers to different from the active constituent of the treatment acne of the beta glucan in the present invention, or controls Treat skin and mucosa inflammation or the active constituent of other skin diseases.

" safe and effective amount " refers to: the amount of active constituent is enough to be obviously improved the state of an illness or symptom, and is unlikely to generate tight The side effect of weight.

In general, pharmaceutical composition contains 1-2000mg active constituent/agent, more preferably, containing 10-200mg active constituent/ Agent.Preferably, described is " one " for a tablet or an injection.

" pharmaceutically acceptable carrier " refers to: one or more biocompatible solids or liquid filler or gelatinous mass, They are suitable for people's use and it is necessary to have enough purity and sufficiently low toxicity.

In " compatibility " referred to herein as composition each component energy and active constituent of the invention and they between mutually Blending, and significantly reduce the drug effect of active constituent.

Pharmaceutically acceptable carrier part example has cellulose and its derivates (such as sodium carboxymethylcellulose, ethyl Sodium cellulosate, cellulose ethanoate etc.), gelatin, talcum, solid lubricant (such as stearic acid, magnesium stearate), calcium sulfate, plant Oily (such as soya-bean oil, sesame oil, peanut oil, olive oil), polyalcohol (such as propylene glycol, glycerol, mannitol, sorbierite), emulsification Agent is (such as), wetting agent (such as lauryl sodium sulfate), colorant, flavoring agent, stabilizer, antioxidant, preservative, nothing Pyrogen water etc..

In another preferred example, beta glucan of the present invention can act on shape by nonbonding with macromolecular compound or macromolecule At compound.

In another preferred example, beta glucan of the present invention can be connected by chemical bond with macromolecular compound or macromolecule It connects.The macromolecular compound can be large biological molecule such as high glycan, albumen, nucleic acid, polypeptide etc..

The method of application of active constituent or pharmaceutical composition of the invention is not particularly limited, representative method of application packet Include but be not limited to: be applied with, be oral, in tumor, rectum, parenteral (intravenous, intramuscular or subcutaneous) etc..

Solid dosage forms includes capsule, tablet, pill, powder and granule.

In these solid dosage forms, active constituent is mixed at least one conventional inert excipients or carrier, such as citric acid Sodium or Dicalcium Phosphate, or with following compositions are one or more mixes:

(a) filler or expanding material, for example, starch, lactose, sucrose, glucose, mannitol and silicic acid；

(b) adhesive, for example, hydroxymethyl cellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and Arab Glue；

(c) moisturizer, for example, glycerol；

(d) disintegrating agent, for example, agar, calcium carbonate, potato starch or tapioca, alginic acid, certain composition silicates, And sodium carbonate；

(e) retarding solvent, such as paraffin；

(f) absorbsion accelerator, for example, quaternary ammonium compound；

(g) wetting agent, such as cetanol and glycerin monostearate；

(h) adsorbent, for example, kaolin；And/or

(i) lubricant, for example, talcum, calcium stearate, magnesium stearate, solid polyethylene glycol, lauryl sodium sulfate, or Its mixture.

In capsule, tablet and pill, dosage form also may include buffer.

Coating and shell material preparation also can be used in the solid dosage forms, such as casing and other materials well known in the art.It May include opacifying agent, also, in this composition active constituent release can in a delayed fashion it is in the digestive tract certain It is discharged in a part.The example of adoptable embedding component is polymeric material and wax material.

Liquid dosage form includes pharmaceutically acceptable lotion, solution, suspension, syrup or tincture.Other than active constituent, Liquid dosage form may include the inert diluent routinely used in this field, such as water or other solvents, solubilizer and emulsifier, example Such as, ethyl alcohol, isopropanol, ethyl carbonate, ethyl acetate, propylene glycol, 1,3-BDO, dimethylformamide and oil, especially Cottonseed oil, peanut oil, maize germ, olive oil, castor oil and sesame oil or the mixture of these substances etc..In addition to these inertia Outside diluent, composition also may include auxiliary agent, such as wetting agent, emulsifier and suspending agent, sweetener, corrigent and fragrance.

Other than active constituent, suspension may include suspending agent, for example, ethoxylation isooctadecane alcohol, polyoxyethylene mountain The pure and mild Isosorbide Dinitrate of pears, microcrystalline cellulose, aluminium methoxide and agar or the mixture of these substances etc..

Composition may include physiologically acceptable sterile, aqueous or anhydrous solution, dispersion liquid, suspension or lotion, and use In the aseptic powdery for re-dissolving into sterile Injectable solution or dispersion liquid.It is suitable aqueous and nonaqueous carrier, diluent, molten Agent or excipient include water, ethyl alcohol, polyalcohol and its suitable mixture.

It is that the present composition of safe and effective amount is applied to mammal in need for the treatment of when using pharmaceutical composition (such as people), wherein dosage is the effective dosage pharmaceutically thought when application, for the people of 60kg weight, day is to medicament Amount is usually 1~10000mg, preferably 10~2000mg, more preferably 20~1000mg.Certainly, specific dosage be also contemplated that The factors such as medicine approach, patient health situation, within the scope of these are all skilled practitioners technical ability.

The present invention also provides a kind of composition product, the composition product includes:

(1) first pharmaceutical composition, first pharmaceutical composition contain (a) first active constituent, first activity Ingredient is beta glucan；(b) pharmaceutically, on cosmeceutical or the acceptable carrier of weapon exercises or excipient；And

(2) second pharmaceutical compositions, second pharmaceutical composition are the acne treatment different from the first pharmaceutical composition The therapeutic agent of drug or skin and mucosa inflammation or other skin diseases.

The present composition can be administered alone, or with other treatment administered in combination (as prepared in same drug In composition).

Pharmaceutical composition of the present invention can also be combined to the known other medicines for treating or improving similar symptom.Combine to When medicine, originally the administration mode of drug and dosage are remained unchanged, and subsequently or simultaneously use pharmaceutical composition of the present invention.Drug connection Pharmaceutical composition of the present invention and other one or more of known drugs are used with the period for being also included within overlapping.When medicine of the present invention When compositions and other one or more of drugs carry out drug combination, the dosage of pharmaceutical composition of the present invention or known drug can Dosage when can be than their independent medications is lower.

Main advantages of the present invention include:

(a) acne can effectively be prevented and/or be treated to beta glucan (such as schizophyllum commune beta glucan) of the present invention.

(b) side effect of beta glucan treatment acne of the present invention is very low, does not destroy the skin surface flora ecological balance, no Meeting patient harm skin makes its generate drug resistance.

(c) beta glucan of the present invention can be not only used for preventing and/or treating acne, can also enhance skin Initiative Defense function Can, activated cell fundamental immunity function, while preventing excessive inflammation has two-way immunoloregulation function, can with antibacterial, anti-inflammatory and Repair skin, prevention and/or treatment skin and mucosa inflammation or other inflammatory disease of the skin, drying, red capillary, allergy, inflammation, thin Line, color spot, fuel-displaced etc..

(d) beta glucan of the present invention can further enhance prevention and/or treatment effect in conjunction with other treatment acne drug Fruit has synergistic effect.

(e) beta glucan (preferably schizophyllum commune beta glucan) of the present invention is the biological polyoses in pure natural source, has been had Complete soluble or natural soluble, and without the modification or modification of any chemistry and/or physics.

(f) beta glucan of the present invention completely remains the three-dimensional conformation of three spirals, has preferably prevention and/or treatment Cuo Sore activity.

(g) beta glucan of the present invention has splendid stability, can coexist with most of substances and keep its activity, because And application field is extensive, can be used in combination with other abundance type acne treatment drugs or skin care item, while preventing and treating acne, Improve skin quality.

Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention Rather than it limits the scope of the invention.In the following examples, the experimental methods for specific conditions are not specified, usually according to conventional strip Part, such as Sambrook et al., molecular cloning: laboratory manual (New York:Cold Spring Harbor Laboratory Press, 1989) condition described in, or according to the normal condition proposed by manufacturer.Unless otherwise stated, no Then percentage and number are weight percent and parts by weight.

Experimental method used in following embodiments is conventional method unless otherwise specified.

Material as used in the following examples, reagent, equipment etc., are commercially available unless otherwise specified.