WO2017011983A1 - Protéine de moule à action adhésive indiquée pour la protection cutanée et de l'appendice cutané - Google Patents

Protéine de moule à action adhésive indiquée pour la protection cutanée et de l'appendice cutané Download PDF

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Publication number
WO2017011983A1
WO2017011983A1 PCT/CN2015/084493 CN2015084493W WO2017011983A1 WO 2017011983 A1 WO2017011983 A1 WO 2017011983A1 CN 2015084493 W CN2015084493 W CN 2015084493W WO 2017011983 A1 WO2017011983 A1 WO 2017011983A1
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WIPO (PCT)
Prior art keywords
skin
mussel mucin
mussel
accessory organs
mucin
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PCT/CN2015/084493
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English (en)
Chinese (zh)
Inventor
高敏
Original Assignee
江阴市本特塞缪森生命科学研究院有限公司
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Priority to PCT/CN2015/084493 priority Critical patent/WO2017011983A1/fr
Publication of WO2017011983A1 publication Critical patent/WO2017011983A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings

Definitions

  • the present invention generally relates to the fields of daily chemical products, cosmetics, medical devices, pharmaceuticals, disinfecting products, health care products, and the like, and relates to the use of mussel mucin or a preparation thereof for protecting skin and skin accessory organs.
  • the skin As the body's first physiological defense line and the largest organ, the skin always participates in the functional activities of the body, maintaining the unity of the body and the natural environment. Any abnormality of the body can also be reflected on the skin surface.
  • the skin consists of the epidermis, dermis, and subcutaneous tissue, and contains many accessory organs such as hair, sweat glands, sebaceous glands, nails, toenails, and blood vessels, lymphatic vessels, nerves, and muscles.
  • the skin has near-perfect physiological protection functions, such as barrier function, sensory function, body temperature regulation, absorption, secretion and excretion, which play an important role in maintaining the health of the body.
  • the skin and its appendages are susceptible to damage from ultraviolet rays, radiation (such as electromagnetic waves, radiation, computer radiation, etc.), hot objects, frostbite caused by low temperature objects, sea water, environmental pollution, and hot dyeing agents.
  • radiation such as electromagnetic waves, radiation, computer radiation, etc.
  • hot objects frostbite caused by low temperature objects, sea water, environmental pollution, and hot dyeing agents.
  • UVB Ultraviolet light
  • UVB UVB in sunlight can cause redness, swelling, burning, burning, edema, skin desquamation and other damage to the skin and skin accessory organs; causing hair yellowing, splitting, easy to break, dry Inelastic, and can not be repaired once the damage.
  • Radiation such as ionizing radiation, including radiotherapy, has a certain therapeutic effect on malignant tumors, but there will be some degree of skin reaction, such as: erythema, burning and itching, desquamation, congestion, edema, blisters, exudation, erosion, Ulcer, skin atrophy, telangiectasia, lymphatic drainage disorders, dark brown spots, pigmentation, etc.
  • Scalding is a problem of skin redness, blisters, peeling, tissue necrosis, ulceration, ulcers, etc. caused by skin contact with objects above body temperature.
  • Frostbite is a local injury to the skin and skin accessory organs caused by cold and dampness. It is cold, pale, hard, numbness or loss, redness and congestion, heat, itching, burning pain, blisters, edema, severe pain, and tissue necrosis.
  • the salt in the sea and the chlorine in the swimming pool can damage the scalp and cause inflammatory reactions such as enlarged pores, and the hair will become dry.
  • the main pollutants in the air are sulfur dioxide, nitrogen oxides, particulate pollutants, and acid rain.
  • Nitrogen-containing pollutants such as sulfur dioxide, nitrous oxide (N 2 O), nitrogen monoxide (NO), nitrogen dioxide (NO 2 ), and nitrogen trioxide (N 2 O 3 ) are highly irritating to human skin.
  • Granular pollutants are large in number and complex in composition. They can be carriers of toxic substances or other pollutants, which can easily cause skin inflammation, large pores, red hair follicles, pigmentation and other problems.
  • Hair dyes have the effect of changing the color of hair, containing toxic and harmful substances such as metals, oxides, p-phenylenediamine, etc., causing scalp allergies, redness, itching and the like.
  • the thioglycolic substances in the perm agent are harmful to the hair, scalp and hair follicles, causing the scales to be damaged, which may cause the hair to become yellow, brittle, detached, tarnished and elastic.
  • Mussel adhesive protein also known as Mytilus edulis foot protein (Mefp)
  • Mefp Mytilus edulis foot protein
  • Mytilus coruscus A special protein secreted by Perna viridis. Mussels are usually attached in groups to the reefs on the coast or to the bottom of the ship, and have the ability to withstand wave impacts in the offshore. In fact, mussels can be attached extremely strongly to the substrate of any material, such as metal, wood, glass, and the like. The main reason for the above characteristics of mussels is that they can form and store this special mucin in the girth of the foot. The mussels release the mucin through the foot silk to a solid surface such as rock to form a water-resistant combination. Fix yourself.
  • Mussel mucin has two structural features: (1) containing lysine, which has a high loading of positive charge; (2) containing 3,4 dihydroxyphenylalanine (DOPA, dopa). The cells and tissues of the human body are negatively charged.
  • Mussel mucin plays a protective and therapeutic role by tightly binding cells and tissues through the electrostatic interaction between its own positive charge and the negative charge of cells and tissues.
  • dopa oxidation produces ortho-dioxins, which can be cross-linked with unoxidized dopa to form a membrane or a network scaffold, which promotes the protein to adhere more closely and firmly to the surface of the human body, thereby protecting.
  • Mussel mucin is a macromolecular protein that is completely degraded in the human body for about 3-10 days. Its ability to attach to cell tissues is excellent, so that mussel mucin can be stabilized locally and continue to function.
  • mussel mucin has the above characteristics, its current application field is very limited.
  • Commercial mussel mucin products are Cell-Tak from BD Biosciences, MAP Trix from Kollodis, Korea, and Hydrogel from Biopolymer, Sweden. These products are either used directly in the form of mussel mucin solution, or are stored as lyophilized powder formulations and dissolved prior to use. Their primary field of application is limited to microscopic cell adhesion and tissue adhesives. Mussel mucin has also been reported for use in the repair of fetal membranes, as a coating against seawater corrosion, and as a drug-loaded stent for the heart.
  • Mussel mucin used herein refers to Mytilus edulis Linnaeus, Mytilus coruscus or Perna viridis from the Mytilidae bivalve mollusc. 11 subclasses of mussel mucin, currently known as purified from marine mussels: mefp1, mefp-2, mefp-3, mefp-4, mefp-5, mefp-6, collagen pre-COL- A mixture of one or more of P, pre-COL-D, pre-COL-NG, foot silk matrix proteins PTMP and DTMP.
  • the mussel mucin used herein may have a pH of from 1.0 to 7.0 in an aqueous solution, and particularly may be in the range of from pH 3.0 to 6.5 to make the therapeutic effect better.
  • the mussel mucin used herein can be obtained by the following preparation method, for example, a method for separating and purifying mussel mucin using mixed adsorption chromatography in Chinese Patent No. ZL200710179491.0, a kind of carboxy using Chinese Patent No. ZL200710179492.5 A method for purifying mussel mucin by methyl ion exchange chromatography, a method for separating and purifying mussel mucin using salting out and dialysis, Chinese Patent No. ZL200910087567.6.
  • the mussel mucin used herein may be in the form of a solution or a lyophilized powder, in particular, the concentration of mussel mucin in the product may be 0.1-15.0 mg/ml, and when the concentration is too low, the effect of mussel mucin Not large, when the concentration is too high, the cytotoxicity may be caused by the high positive charge, which is not conducive to play a protective role.
  • the mussel mucin used herein can also be prepared as a liquid agent by combining it with an excipient.
  • Exemplary mussel mucin fluid The body agent is prepared by dissolving or diluting the mother liquor or lyophilized powder of mussel mucin solution to a certain concentration or pH.
  • the solution for dissolving or diluting may be water, physiological saline, phosphate solution, acetate solution, borate. Solution and so on.
  • the pH of mussel mucin in the final product may be pH 1.0-7.0, and in particular, the therapeutic effect may be better in the range of pH 3.0-6.5.
  • the mussel mucin used herein can also be prepared as a gelling agent in combination with an excipient.
  • An exemplary mussel mucin gel is prepared by mixing a mussel mucin solution or a lyophilized powder with a gel matrix material, which may be selected from the group consisting of cellulose derivatives, carbomers, and seaweeds. Acid salt, tragacanth, gelatin, pectin, carrageenan, gellan gum, starch, xanthan gum, cationic guar gum, agar, non-cellulosic polysaccharide, ethylene polymer, acrylic resin, polyvinyl alcohol or poly One of carboxyvinyl or any combination thereof.
  • the mussel mucin used herein can also be combined with excipients to prepare a gel.
  • An exemplary mussel mucin gel is prepared by mixing a mussel mucin solution or a lyophilized powder with a gel matrix, which may include cellulose derivatives, glycerin, non-cellulosic polysaccharides, propylene glycol. One or any combination thereof.
  • the mussel mucin used herein can also be combined with an excipient to prepare a paste.
  • An exemplary mussel mucin paste is prepared by mixing mussel mucin with a paste matrix material, which may include glycerin, petrolatum, paraffin, and the like.
  • the mussel mucin used herein can also be combined with a matrix material to form a dressing and application for the skin surface.
  • the liquid in the exemplary mussel mucin application may be a mussel mucin solution or a cellulose derivative, carbomer and alginate, tragacanth, gelatin, pectin, carrageenan, Gellan gum, starch, xanthan gum, cationic guar gum, agar, non-cellulosic polysaccharide, ethylene polymer, acrylic resin, polyvinyl alcohol or carbomer, gelatin, fish gelatin, pectin, alginate, glycerin One or more combinations of petrolatum, paraffin, polyethylene glycol, vitamins, glutathione.
  • the above mussel mucin solution or combination is immersed in a matrix material such as gauze, non-woven fabric, silk paper, and the application may be, for example, a wound patch, a mask, an eye mask, a hand mask, a foot film, or the like.
  • the mussel mucin used herein can also be made into a foaming agent.
  • An exemplary mussel mucin foaming agent is prepared by mixing a mussel mucin solution or a lyophilized powder with a foaming agent matrix, which may include hydroxypropylmethylcellulose, gelatin, and polyethylene.
  • a foaming agent matrix which may include hydroxypropylmethylcellulose, gelatin, and polyethylene.
  • the defoaming time of the foaming agent is long, and the action time is prolonged, so that the mussel mucin is more effective.
  • the mussel mucin used herein can be used as a main raw material to prepare a medicine using a pharmaceutically acceptable carrier.
  • Place The drug may be a liquid agent, a gel, a gel, a paste, an applicator, or a foaming agent.
  • the medicament can be used for in vitro use, in particular for external use on the skin.
  • the mussel mucin used herein can be used as a main raw material to prepare a medical device.
  • the term medical device as used herein refers to materials that are used directly or indirectly to the human body and other similar or related items.
  • the medical device may be a liquid agent, a gel, a gel, a paste, an applicator, or a foaming agent.
  • the medical device can be used for in vitro use, in particular for external use on the skin.
  • the mussel mucin used herein can be used as a main raw material to prepare a cosmetic using an auxiliary material which is acceptable in the field of cosmetics.
  • the cosmetic may be a liquid, a gel, a gel, a paste, an applicator, or a foaming agent.
  • the cosmetic can be used for in vitro use, in particular for topical application to the skin.
  • the mussel mucin used herein can be used as a main raw material to prepare a disinfecting product using an excipient which is acceptable in the field of disinfecting products.
  • the term disinfecting product as used herein refers to a disinfectant, a disinfecting device, a sanitary article, and a disposable medical article that chemically, physically, or biologically kill or eliminate pathogenic microorganisms in the environment.
  • the disinfecting product may be a liquid agent, a gel, a gel, a paste, an applicator, or a foaming agent.
  • the disinfecting product can be used for in vitro use, in particular for external use on the skin.
  • the mussel mucin used herein can be used as a main raw material, and a health care product or food can be prepared by using an excipient which is acceptable in the field of health care or food.
  • the health care product or food may be a liquid agent, a gel, a gel, a paste, an applicator, or a foaming agent.
  • the health supplement or food can be used for in vitro use or consumption, in particular for external use on the skin.
  • the mussel mucin used herein can be used as a main raw material to prepare a daily chemical product using an auxiliary material acceptable in the field of daily chemical products.
  • the term daily chemical product as used herein refers to technical chemicals that are used daily, including shampoos, shower gels, and the like.
  • the daily chemical product may be a liquid agent, a gel, a gel, a paste, an applicator, or a foaming agent.
  • the daily chemical product can be used for in vitro use, in particular for external use on the skin.
  • hair care and hair care products can be prepared from the mussel mucin of the present invention for protection of scalp and hair and other accessory organs.
  • Another object of the invention is to provide the use of mussel mucin products in the protection of skin and skin appendages.
  • the present invention provides the use of mussel mucin or a preparation thereof for protecting skin accessory organs such as skin and hair from ultraviolet damage and the like.
  • the present invention provides the use of mussel mucin or a preparation thereof for protecting skin and skin accessory organs from radiation (electromagnetic, radiation, computer radiation, etc.).
  • the present invention provides the use of mussel mucin or a preparation thereof for protecting a skin accessory organ such as skin and hair from a burn caused by a high temperature object or the like.
  • the present invention provides the use of mussel mucin or a preparation thereof for protecting a skin appendage such as skin and hair from frostbite caused by a low temperature object or the like.
  • the present invention provides the use of mussel mucin or a preparation thereof for protecting skin accessory organs such as skin and hair from seawater damage, and for protecting skin accessory organs such as skin and hair from environmental pollution.
  • the present invention provides the use of mussel mucin or a preparation thereof for protecting skin accessory organs such as skin and hair from damage such as hot and dyeing agents.
  • mussel mucin application according to embodiment 1, wherein the mussel mucin may be from a subclass: mefp1, mefp-2, mefp-3, mefp-4, mefp-5, mefp-6, collagen A mixture of one or more of pre-COL-P, pre-COL-D, pre-COL-NG, foot silk matrix proteins PTMP and DTMP.
  • the mussel mucin application according to embodiment 1, wherein the mussel mucin concentration may be from 0.1 to 15.0 mg/ml.
  • Mussel mucin application according to embodiment 1, wherein the mussel mucin in the final product may be in the range of pH 1.0-7.0, in particular in the range of pH 3.0-6.5.
  • skin appendages such as skin and hair from ultraviolet rays, radiation, high temperature objects, low temperature objects, Damage to seawater, environmental pollution, hot and dyed reagents.
  • compositions for protecting skin and skin accessory organs wherein the composition may be a liquid agent, a gel, a gel, a paste, an applicator or a foam. Use of the agent.
  • the mussel mucin application according to embodiment 14, wherein the hair care and hair care product can comprise a conditioner, a hair care essence water, a hair care gel, and the like.
  • Example 1 Application of mussel mucin hydrogel cosmetics in ultraviolet protection (sun protection).
  • the sun protection factor of the mussel mucin hydrogel cosmetic of this example was measured to be SPF 25. It is indicated that the mussel mucin product has the function of protecting the skin from ultraviolet rays.
  • Example 2 Application of mussel mucin liquid cosmetics in ultraviolet protection (sun protection).
  • a mussel mucin solution having a concentration of 10.0 mg/ml was taken, diluted with physiological saline, and 10 mg of vitamin C powder was added to prepare a mussel mucin liquid cosmetic, wherein the mussel mucin concentration was 2 mg/ml.
  • the sun protection factor of the mussel mucinized liquid cosmetic of the present example was measured to be SPF 15. It is indicated that the mussel mucin product has the function of protecting the skin from ultraviolet rays.
  • Example 3 Application of mussel mucin gel medical device in radiation therapy protection.
  • Example 4 Application of mussel mucin foam cosmetic in computer radiation protection.
  • Control product preparation A commercially available carboxymethyl cellulose substrate gel cosmetic product, which does not contain mussel mucin.
  • the melanin value of the observed site was measured before use, and the melanin value of the observed site was measured on the 90th day after use.
  • the melanin increased by 5.7% ⁇ 1.2% after 90 days; using the cheek of one side of the control product, the melanin increased by 12.4% ⁇ 0.9% after 90 days.
  • the increase in melanin in the control group was significantly higher than in the experimental group.
  • the mussel mucin product has the function of protecting the skin from radiation.
  • Example 5 Application of mussel mucin liquid cosmetics in the protection of environmental pollutants.
  • the melanin value of the observed site was measured before use, and the melanin value of the observed site was measured on the 180th day after use.
  • the melanin increased by 3.9% ⁇ 2.7% after 180 days; using the cheek of one side of the control product, the melanin increased by 18.4% ⁇ 1.5% after 180 days.
  • the increase in melanin in the control group was significantly higher than in the experimental group.
  • the mussel mucin product has the function of protecting the skin from environmental pollution.
  • Example 6 Application of mussel mucin liquid medical device in skin burn protection.
  • a mussel mucin solution having a concentration of 10.0 mg/ml was prepared and diluted with physiological saline to prepare a mussel mucin liquid medical device, wherein the mussel mucin concentration was 2.5 mg/ml.
  • the dry weight/wet weight of the test site of the above-mentioned mussel mucin liquid medical device applied to the right side of 20 rats was 33.4% ⁇ 3.8% on average; 20 rats were coated with physiological saline on the left side as a control.
  • the dry weight/wet weight of the part was 17.9% ⁇ 2.2% on average.
  • the edema of the test site coated with the mussel mucin liquid medical device was significantly lighter than that of the control group. It is indicated that mussel mucin products have the effect of protecting the skin from high temperature liquids.
  • Example 7 Application of mussel mucin hydrogel drug in the protection of skin frostbite.
  • Control product preparation a gel containing no mussel mucin as a substrate for cationic guar gum.
  • the dry weight/wet weight of the test site of the above mussel mucin hydrogel drug coated on the right side of 20 rats was 33.4% ⁇ 3.8% on average; 20 rats were coated on the left side without mussel mucin
  • the dry weight/wet weight of the test site of the cationic guar gel as a control was 17.9% ⁇ 2.2% on average.
  • the edema of the test site coated with the mussel mucin product was significantly lighter than that of the control group. It is indicated that mussel mucin products have the effect of protecting the skin from high temperature liquids.
  • Example 8 Application of mussel mucoid hair gel cosmetic (essential product) in seawater protection.
  • the mucin hair care essence that is, the hair gel cosmetic, wherein the mussel mucin concentration is 1.2 mg/ml.
  • the scaly skin of the test group volunteers using the above mussel mucin hair care essence was intact, and there was no difference from the blank control of the test group.
  • the control group volunteers who did not use mussel mucin hair care essence were incomplete in the scaly rind, which was different from the control blank.
  • mussel mucin products have the effect of protecting the skin from seawater erosion.
  • Example 9 Application of mussel mucoprotein hair care liquid cosmetic (essential aquatic product) in allergy protection caused by hair dyeing.
  • mussel mucin solution Take 100ml of mussel mucin solution with a concentration of 10.0mg/ml, add 3g of glutathione, and dilute with purified water to prepare mussel mucoprotein hair care essence water, which is a hair care cosmetic.
  • the mussel mucin concentration is 3.9. Mg/ml.
  • Example 10 Application of Mussel Muscle Hair Care Gel Cosmetic (Essence Product) in allergy protection caused by perm.
  • mussel mucin solution Take 50ml of mussel mucin solution with a concentration of 10.0mg/ml, dilute with purified water, and add 10g of gelatin to prepare mussel mucoprotein hair care essence gel, which is a hair care cosmetic.
  • the mussel mucin concentration is 2.0mg/ g.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
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  • Animal Behavior & Ethology (AREA)
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Abstract

L'invention a pour objet un produit à base de protéine de moule à action adhésive et son application pour protéger la peau et l'annexe cutanée L'invention a plus particulièrement trait à une protéine de moule à action adhésive ou à sa formulation destinée à être appliquée, par exemple mais non limitativement, en vue de la protection cutanée et de l'annexe cutanée de manière à éviter toute lésion causée par la lumière ultraviolette. Par ailleurs l'application de la protéine de moule à action adhésive de l'invention permet de protéger la peau et l'annexe cutanée dans le cas de lésions cutanées provoquées par des radiations comme par exemple mais non limitativement l'électromagnétisme, les radiations et les radioémissions. Elle permet aussi de protéger la peau et l'annexe cutanée dans les différents domaines indiqués ici : dans le domaine de la cryogénie, par exemple ; notamment lors de lésions causées par l'eau salée ; ou encore en cas de lésions provoquées par la pollution environnementale, entre autres ; et, finalement sans pour autant s'y limiter, lors de lésions causées par des colorants et des réactifs à températures très élevées.
PCT/CN2015/084493 2015-07-20 2015-07-20 Protéine de moule à action adhésive indiquée pour la protection cutanée et de l'appendice cutané WO2017011983A1 (fr)

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Cited By (6)

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CN107137338A (zh) * 2017-07-07 2017-09-08 苏州蓬拓生物医学科技有限公司 一种基于表面涂层原理的毛发染色方法
CN114057833A (zh) * 2021-11-02 2022-02-18 浙江工业大学 基于减少黑色素沉淀功效的贻贝多肽、多肽粉及制备方法和应用
US11672792B2 (en) * 2017-07-05 2023-06-13 Enlitisa (Shanghai) Pharmaceutical Co., Ltd Topical formulations comprising montelukast and combinations with mussel adhesive proteins
CN116617109A (zh) * 2023-06-05 2023-08-22 广州植境生物科技有限公司 一种贻贝粘蛋白头皮修护组合物及其制备方法和应用
CN117398511A (zh) * 2023-10-18 2024-01-16 珠海市雅莎医疗器械有限公司 激光、光子术后修复的贻贝粘蛋白修护敷料及其制备方法
CN117982710A (zh) * 2024-02-18 2024-05-07 韩伟东 一种重组双蛋白医用敷料的制备方法

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CN116617109B (zh) * 2023-06-05 2024-02-20 广州植境生物科技有限公司 一种贻贝粘蛋白头皮修护组合物及其制备方法和应用
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