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WO2017088177A1 - Mussel adhesive protein product, and use thereof in preventing and suppressing neuronal inflammation - Google Patents

Mussel adhesive protein product, and use thereof in preventing and suppressing neuronal inflammation Download PDF

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Publication number
WO2017088177A1
WO2017088177A1 PCT/CN2015/095798 CN2015095798W WO2017088177A1 WO 2017088177 A1 WO2017088177 A1 WO 2017088177A1 CN 2015095798 W CN2015095798 W CN 2015095798W WO 2017088177 A1 WO2017088177 A1 WO 2017088177A1
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Prior art keywords
mussel mucin
mussel
neuroinflammation
mucin
mefp
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PCT/CN2015/095798
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French (fr)
Chinese (zh)
Inventor
高敏
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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/CN2015/095798 priority Critical patent/WO2017088177A1/en
Publication of WO2017088177A1 publication Critical patent/WO2017088177A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/12Aerosols; Foams

Definitions

  • the present invention relates generally to the fields of pharmaceuticals, medical products, health care products, and food technology, and more particularly to mussel mucin products and their use in preventing and inhibiting neuroinflammation.
  • the nervous system is a functional regulation system that plays a leading role in the human body. It is composed of brain, spinal cord, cranial nerve, spinal nerve and vegetative nerve, and various ganglia. It can coordinate the activities of various organs and systems in the body and make it complete. Integrated and interacted with the external environment.
  • Neuroinflammation refers to the inflammation or deterioration of nerves or nerve groups.
  • the symptoms vary with the disease. There are many causes of neuroinflammation, including nerve injuries such as nearby fractures and direct blows; nerve infections such as diabetes and blood cancer. And gout, etc.; mercury, lead, methanol and other poisoning; lack of vitamin B group in the diet, the general symptoms of neuroinflammation are pain, tenderness, tingling, infected nerve itching and loss of consciousness, partial infection of redness and severe spasm.
  • 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; and (2) containing 3,4 dihydroxyphenylalanine (DOPA, dopa). The cells and tissues of the human body are negatively charged.
  • Mussel mucin interacts with cells by electrostatic interaction between its own positive charge and the negative charge of human cells and tissues Closely integrated with the organization to play a protective and therapeutic role.
  • 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 mussel mucin solution state, or are stored as lyophilized powder formulations and dissolved prior to use. Their primary 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.
  • the treatment of neuritis is mainly to prevent and relieve symptoms. It is usually treated according to the cause of inflammation of the nerves to relieve symptoms. However, the treatment of neuroinflammation is slow and the treatment effect is not obvious. The average cure rate is only about 40%.
  • the mussel mucin used herein may be 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 of the natural source used herein may have a pH of 1.0 to 7.0 in an aqueous solution, and particularly may have a pH of 3.0 to 6.5 to make the therapeutic effect better.
  • the mussel mucin used herein may also be obtained by a method of biosynthesis, comprising a mixture of one or more of the known 11 mussel mucin subclasses.
  • the artificial biosynthesized mussel mucin used herein may have a pH of 1.0 to 7.0 in aqueous solution, and particularly may be in the range of pH 3.0 to 6.5 to make the therapeutic effect better.
  • the mussel mucin used herein may also be a hydrolyzed peptide obtained by hydrolysis of mussel mucin from a natural source or an artificial biosynthesis source, or a functional group-containing complex obtained by artificial synthesis. Form a peptide.
  • the mussel mucin hydrolyzed peptide or synthetic peptide used herein may have a pH of 1.0 to 7.0 in an aqueous solution, and particularly may be in the range of 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, it can cause cytotoxicity, skin irritation, etc., which is not conducive to the prevention and treatment of neuroinflammation.
  • the mussel mucin used herein can also be prepared as a liquid agent by combining it with an excipient.
  • An exemplary mussel mucin liquid preparation is prepared by dissolving or diluting mussel mucin solution mother liquor or lyophilized powder to a certain concentration or pH, and the solution for dissolving or diluting may be water, physiological saline, phosphate solution, vinegar. Acid solution, borate solution, and the like.
  • the pH of the mussel mucin in the final product may be pH 1.0-7.0, especially in the range of pH 3.0-6.5 to make the therapeutic effect better.
  • 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 be used as a main raw material to prepare a medicine using a pharmaceutically acceptable carrier.
  • the drug may be a liquid agent or a gel.
  • the drug may be administered by oral, targeted topical sustained release, targeted administration, and may be administered at a low temperature or in a heated manner.
  • 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 can be a liquid agent or a gel.
  • the medical device can be used by oral, targeted local sustained release, targeted administration, and can be administered at a low temperature or in a heated manner.
  • 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 or a gel.
  • the health supplement or food may be administered by oral, targeted topical sustained release, targeted administration, and may be administered at a low temperature or in a heated manner.
  • Another object of the invention is to provide a mussel mucin product for the prevention and treatment of neuroinflammation.
  • mussel mucin can prevent and alleviate sensory, dyskinesia and autonomic dysfunction caused by various neuroinflammatory diseases.
  • Symptoms caused by neuroinflammation often in the initial stage of the fingertip or toe end burning pain and numbness and other irritations such as paresthesia or hyperesthesia, gradually appearing sensation decline or even disappear, the distribution of sensory disturbances are gloves or socks, a small number of patients There may be deep sensory disturbances, gastrocnemius and other places often have tenderness.
  • Neurological dysfunction caused by neuroinflammation manifested as cold, pale, flushing or mild cyanosis of the extremities, less sweat or sweating, thinning of the skin, tenderness or roughness of the nails, loss of normal luster, angle Enhancement and so on.
  • the symptoms of the above three groups may be different.
  • the pain caused by nitrofurazone poisoning and arsenic poisoning is often severe; the muscle atrophy is sometimes significant in diabetic patients.
  • the severity of various clinical manifestations is also inconsistent. In the light, only the acral pain can be numb without sensory loss or dyskinesia, and the severe one can also have limb paralysis.
  • the mussel mucin of the present invention can be used to prevent sensory disorders, motor dysfunction, and autonomic dysfunction caused by neuroinflammation.
  • the mussel mucin of the invention can be used to treat sensory disorders, motor dysfunction, and autonomic dysfunction caused by neuroinflammation.
  • prevention refers to a process of intervention to relieve pain or change of a particular state of health.
  • treatment in the present invention means that countermeasures that may deviate from subjectively expected or objective general laws in the course of disease treatment are prevented in advance to avoid possible damage.
  • the mussel mucin application according to embodiment 1 or 2 wherein the mussel mucin may be obtained by extracting from mussels, comprising one of 11 known mussel mucin subclasses or Several mixtures.
  • mussel mucin application according to embodiment 1 or 2 wherein the mussel mucin is also a hydrolyzed peptide obtained by hydrolyzing mussel mucin from a natural source or an artificial biosynthesis source, or by artificial synthesis.
  • a functional peptide-containing synthetic peptide obtained in a manner.
  • the mussel mucin application according to any one of embodiments 1 to 5, wherein the mussel mucin is a liquid agent or a gel.
  • the mussel mucin application according to any one of embodiments 1 to 5, wherein the mussel mucin in the final product may be in the range of pH 1.0-7.0, particularly in the range of pH 3.0-6.5.
  • the mussel mucin application according to any one of embodiments 1-8, wherein the neuroinflammation may include sensory disturbances caused by neuroinflammation, motor dysfunction, and autonomic dysfunction.
  • composition for preventing and treating neuroinflammation, wherein the composition may be a liquid agent or a gel.
  • a medicament for preventing and treating neuroinflammation comprising mussel mucin and a pharmaceutically acceptable carrier, wherein the mussel mucin is present in a concentration of from 0.1 to 15.0 mg/ml.
  • a medical device for preventing and treating neuroinflammation comprising mussel mucin and a carrier acceptable for use in the field of medical devices, wherein the concentration of mussel mucin may be from 0.1 to 15.0 mg/ml.
  • a health care product/food for preventing and treating neuroinflammation comprising a mussel mucin and a health care product/food acceptable carrier, wherein the mussel mucin may be in a concentration of 0.1 to 15.0 mg/ml.
  • neuroinflammation comprises: peripheral nerve inflammation, facial nerve inflammation, peripheral nerve inflammation, subcutaneous neuroinflammation, ulnar neuritis, intercostal nerve inflammation, and the like.
  • neuroinflammation comprises: peripheral nerve inflammation, facial nerve inflammation, peripheral nerve inflammation, subcutaneous neuroinflammation, ulnar neuritis, intercostal nerve inflammation, and the like.
  • Example 1 Application of mussel mucin gel drug in the treatment of peripheral nerve inflammation.
  • Example 2 Application of mussel mucin liquid medical device in the treatment of peripheral neuritis.
  • Example 3 Application of mussel mucin liquid medicine in the treatment of facial neuritis.
  • a mussel mucin solution having a concentration of 5.0 mg/ml was taken and diluted 5 times with 0.001% acetic acid to a mussel mucin content of 1.0 mg/ml to obtain a mussel mucin liquid medicine.
  • Example 4 Application of mussel mucin gel drug in the treatment of facial neuritis.
  • Ten patients with acute facial neuritis diagnosed by neurologists were enrolled in the study.
  • the clinical manifestations of the patients were one-sided facial expression tendon accompanied by mandibular angle or pain behind the ear.
  • the selected patients were randomly divided into the control group and the experimental group.
  • the control group was treated with a blank gel without mussel mucin.
  • the test group was treated with the above mussel mucin gel drug.
  • the two groups were used 3 times a day for external use, so that the affected area could be evenly covered.
  • Example 5 Application of mussel mucin liquid medicine in the treatment of peripheral neuritis.
  • a mussel mucin solution having a concentration of 20.0 mg/ml was prepared and diluted 10 times with 0.05% citric acid to a mussel mucin content of 2.0 mg/ml to obtain a mussel mucin liquid medicine.
  • the control group was treated with 0.05% citric acid.
  • the test group was treated with the above mussel mucin liquid medicine. The two groups were used 3 times a day for external use, so that the affected area could be evenly covered.
  • Example 6 Application of mussel mucin gel health supplement in the treatment of peripheral neuritis.
  • mice Ten patients with peripheral neuritis diagnosed by neurologists were enrolled in the study.
  • the clinical manifestations were sympathetic abnormalities (pain, numbness, allergies) in the distal part of the limb.
  • the dyskinesia included hypotonia, hypotonia, and decreased tendon reflex. Or disappear, autonomic dysfunction, including cold skin and pale skin.
  • the selected patients were randomly divided into the control group and the experimental group.
  • the control group was treated with a gel without mussel mucin
  • the experimental group was treated with the above mussel mucin liquid medicine.
  • the two groups were used 3 times a day for external use, so that the affected area could be evenly covered.
  • Example 7 Application of mussel mucin liquid medical device in the treatment of subcutaneous neuritis.
  • the mussel mucin solution was taken, diluted with physiological saline, and the pH was adjusted to pH 6.0 with acetic acid to obtain a mussel mucin liquid medical device, wherein the mussel mucin concentration was 3 mg/ml.
  • Example 8 Application of mussel mucin gel medical device in the treatment of subcutaneous neuritis.
  • a mussel mucin solution Taking a mussel mucin solution, mixing the preparation with hydroxypropylmethylcellulose and glycerol at a mass ratio of 3:2:1, and adjusting the pH to pH 6.2 with citric acid to obtain a mussel mucin gel medical device.
  • the mussel mucin concentration was 3 mg/ml.
  • Example 9 Application of mussel mucin liquid medical device in the treatment of ulnar neuritis.
  • the mussel mucin solution was mixed with propylene glycol in a ratio of 2:1 by volume, and the pH was adjusted to pH 5.0 with acetic acid to obtain mussel mucin liquid health care product, wherein the mussel mucin concentration was 2.0 mg/ml.
  • Example 10 Application of mussel mucin gel drug in the treatment of intercostal neuritis.
  • a mussel mucin solution was taken, and carboxymethylcellulose and glycerin were added in a volume ratio of 2:1:1 to obtain a mussel mucin hydrogel drug, wherein the mussel mucin concentration was 2.5 mg/ml.
  • a total of 12 patients with intercostal neuritis diagnosed by neurologists were enrolled in the study.
  • the clinical manifestations of the patients were along the chest ribs, from the back through the flank, to the painful mass and tenderness at the costal cartilage in the chest.
  • the selected patients were randomly divided into the control group and the experimental group.
  • the control group was treated with a blank gel without mussel mucin.
  • the test group was treated with the above mussel mucin gel drug.
  • the two groups were used 3 times a day for external use, so that the affected area could be evenly covered.
  • Example 11 Application of mussel mucin liquid health care products in the protection of neuritis.
  • the mussel mucin solution was taken and diluted with physiological saline to prepare a mussel mucin liquid health care product, and the mussel mucin concentration was 1.0 mg/ml.
  • Myelin basic protein is extracted from the fresh sciatic nerve of cattle, and the extracted myelin basic protein is identified for biochemical and biological activity.
  • the control group was only immunized with the extracted bovine myelin basic protein, and the clinical manifestations were observed along with the pathological examination.
  • the experimental group was orally administered with mussel mucin liquid health care products every day, 2-3 ml each time, 3 times a day.
  • the inflammatory cell infiltration of the rabbits in the experimental group was caused by cervical nerve root, lumbar nerve root and cauda equina nerve damage, and the sciatic nerve was separated. The single nerve fibers were separated. The semi-thin sections and electron microscopy showed that the demyelination was the main change. No axis was found. Degeneration and lesions in the brain parenchyma. It is proved that mussel mucin liquid health care products can prevent neuroinflammation.

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Abstract

The present invention discloses a use of mussel adhesive proteins or a preparation thereof in preventing and suppressing a neuronal inflammation, and particularly discloses a use of mussel adhesive proteins or a preparation thereof in neuronal inflammation-caused sensory dysfunctions, motor dysfunctions, autonomic dysfunctions, and the like.

Description

贻贝粘蛋白产品及其预防和抑制神经炎症的应用Mussel mucin product and its application for preventing and inhibiting neuroinflammation 技术领域Technical field
本发明大体涉及药品、医疗产品、保健品及食品技术领域,更具体地,涉及贻贝粘蛋白产品及其在预防和抑制神经炎症中的应用。The present invention relates generally to the fields of pharmaceuticals, medical products, health care products, and food technology, and more particularly to mussel mucin products and their use in preventing and inhibiting neuroinflammation.
背景技术Background technique
神经系统是人体内起主导作用的功能调节系统,是由脑、脊髓、脑神经、脊神经和植物性神经以及各种神经节组成,能协调体内各器官、各系统的活动,使之成为完整的一体,并与外界环境发生相互作用。The nervous system is a functional regulation system that plays a leading role in the human body. It is composed of brain, spinal cord, cranial nerve, spinal nerve and vegetative nerve, and various ganglia. It can coordinate the activities of various organs and systems in the body and make it complete. Integrated and interacted with the external environment.
神经炎症是指神经或神经群发炎衰退或变质,其症状随病因而有所同不同,神经炎症的起因有多种,包括神经受伤如附近骨折和直接重击;神经受感染,如糖尿病、血癌和痛风等;汞铅甲醇等中毒;饮食中缺乏维生素B群等,神经炎症的一般症状是疼痛、触痛、刺痛、受感染的神经痒痛和丧失知觉、感染部分红肿以及严重的痉挛。Neuroinflammation refers to the inflammation or deterioration of nerves or nerve groups. The symptoms vary with the disease. There are many causes of neuroinflammation, including nerve injuries such as nearby fractures and direct blows; nerve infections such as diabetes and blood cancer. And gout, etc.; mercury, lead, methanol and other poisoning; lack of vitamin B group in the diet, the general symptoms of neuroinflammation are pain, tenderness, tingling, infected nerve itching and loss of consciousness, partial infection of redness and severe spasm.
贻贝粘蛋白(Mussel adhesive protein,MAP),也称作贻贝足丝蛋白(Mytilus edulis foot protein,Mefp),是海洋贝类紫贻贝(Mytilus edulis Linnaeus)、厚壳贻贝(Mytilus coruscus)、翡翠贻贝(Perna viridis)等分泌的一种特殊的蛋白质。贻贝通常成群地附着在海岸边的礁石上或者轮船的底部,有在近海耐受波浪冲击的能力。实际上贻贝几乎可以极其牢固地附着在任何材料的基底上,如金属、木材、玻璃等。贻贝具有上述特性的主要原因是其足丝腺内可生成并储存这种特殊的粘蛋白,贻贝通过足丝释放粘蛋白到岩石一类的固体表面上,形成抗水的结合,从而将自己固定。Mussel adhesive protein (MAP), also known as Mytilus edulis foot protein (Mefp), is a marine shellfish, Mytilus edulis Linnaeus, and a small shell mussel (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.
目前从贻贝中鉴定得到11种粘蛋白亚类,包括mefp1、mefp-2、mefp-3、mefp-4、mefp-5、mefp-6、胶原蛋白pre-COL-P、pre-COL-D、pre-COL-NG、足丝基质蛋白PTMP和DTMP(朱曜曜等,海洋科学进展,2014,32(4):560-568)。贻贝粘蛋白具有2个结构特点:(1)含有赖氨酸,使蛋白带有高载量正电荷;(2)含有3,4二羟基苯丙氨酸(DOPA,多巴)。人体的细胞和组织带有负电荷。贻贝粘蛋白通过自身正电荷与人体的细胞和组织负电荷之间的静电相互作用与细胞 和组织紧密结合,发挥防护和治疗的作用。此外,多巴氧化生成邻位二醌,可以和未被氧化的多巴相互交联形成膜或是网状支架,促使蛋白质更加紧密、稳固地附着在人体表面,起到保护作用。贻贝粘蛋白是大分子蛋白质,在人体内完全降解的时间约为3-10天,其附着于细胞组织的能力优异,使贻贝粘蛋白可以稳固于局部,持续发挥作用。Currently, 11 mucin subclasses have been identified from mussels, including mefp1, mefp-2, mefp-3, mefp-4, mefp-5, mefp-6, collagen pre-COL-P, pre-COL-D. , pre-COL-NG, foot silk matrix proteins PTMP and DTMP (Zhu Xi et al, Advances in Marine Science, 2014, 32(4): 560-568). Mussel mucin has two structural features: (1) containing lysine, which has a high loading of positive charge; and (2) containing 3,4 dihydroxyphenylalanine (DOPA, dopa). The cells and tissues of the human body are negatively charged. Mussel mucin interacts with cells by electrostatic interaction between its own positive charge and the negative charge of human cells and tissues Closely integrated with the organization to play a protective and therapeutic role. In addition, 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.
虽然贻贝粘蛋白具有以上特点,但目前其产品应用领域非常有限。商品化的贻贝粘蛋白产品有美国BD Biosciences公司的Cell-Tak,韩国Kollodis的MAP Trix和瑞典Biopolymer的Hydrogel。这些产品或者是以贻贝粘蛋白溶液状态直接使用,或者是以冻干粉制剂保存而在使用前溶解,它们的主要应用局限于微观的细胞粘附和组织粘合剂。也有报道贻贝粘蛋白用于胎膜修复、作为抗海水腐蚀涂层、心脏载药支架等应用。Although 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 mussel mucin solution state, or are stored as lyophilized powder formulations and dissolved prior to use. Their primary 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.
神经炎的治疗以预防和缓解症状为主,通常根据引神经炎症的原因进行治疗,缓解症状,但神经炎症治疗起效缓慢、治疗效果不明显,平均治愈率仅有40%左右。The treatment of neuritis is mainly to prevent and relieve symptoms. It is usually treated according to the cause of inflammation of the nerves to relieve symptoms. However, the treatment of neuroinflammation is slow and the treatment effect is not obvious. The average cure rate is only about 40%.
发明内容Summary of the invention
本发明的一个目的是提供贻贝粘蛋白产品。It is an object of the present invention to provide a mussel mucin product.
在本文中使用的贻贝粘蛋白可以是从贻贝科(Mytilidae)双壳类软体动物中的紫贻贝(Mytilus edulis Linnaeus)、厚壳贻贝(Mytilus coruscus)或翡翠贻贝(Perna viridis)等海洋贻贝中纯化获得的、目前已知的贻贝粘蛋白11个亚类:mefp1、mefp-2、mefp-3、mefp-4、mefp-5、mefp-6、胶原蛋白pre-COL-P、pre-COL-D、pre-COL-NG、足丝基质蛋白PTMP和DTMP中的一种或多种的混合物。在本文中使用的天然来源的贻贝粘蛋白在水溶液中的酸碱度可以是pH 1.0-7.0,特别是可以在pH 3.0-6.5的范围内以使其治疗效果更佳。The mussel mucin used herein may be 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 of the natural source used herein may have a pH of 1.0 to 7.0 in an aqueous solution, and particularly may have a pH of 3.0 to 6.5 to make the therapeutic effect better.
在本文中使用的贻贝粘蛋白也可以是采用生物合成的方法获得的,包含已知的11个贻贝粘蛋白亚类中的一种或多种的混合物。在本文中使用的人工生物合成的贻贝粘蛋白在水溶液中的酸碱度可以是pH 1.0-7.0,特别是可以在pH 3.0-6.5的范围内以使其治疗效果更佳。The mussel mucin used herein may also be obtained by a method of biosynthesis, comprising a mixture of one or more of the known 11 mussel mucin subclasses. The artificial biosynthesized mussel mucin used herein may have a pH of 1.0 to 7.0 in aqueous solution, and particularly may be in the range of pH 3.0 to 6.5 to make the therapeutic effect better.
在本文中使用的贻贝粘蛋白也可以是天然来源或人工生物合成来源的贻贝粘蛋白经水解后获得的水解肽,或通过人工合成方式获得的含有功能基团的合 成肽。在本文中使用的贻贝粘蛋白水解肽或合成肽在水溶液中的酸碱度可以是pH 1.0-7.0,特别是可以在pH 3.0-6.5的范围内以使其治疗效果更佳。The mussel mucin used herein may also be a hydrolyzed peptide obtained by hydrolysis of mussel mucin from a natural source or an artificial biosynthesis source, or a functional group-containing complex obtained by artificial synthesis. Form a peptide. The mussel mucin hydrolyzed peptide or synthetic peptide used herein may have a pH of 1.0 to 7.0 in an aqueous solution, and particularly may be in the range of pH 3.0 to 6.5 to make the therapeutic effect better.
在本文中使用的贻贝粘蛋白可以采用以下制备方法获得,例如中国专利号ZL200710179491.0的一种使用混合吸附色谱分离纯化贻贝粘蛋白的方法,中国专利号ZL200710179492.5的一种使用羧甲基离子交换色谱纯化贻贝粘蛋白的方法,中国专利号ZL200910087567.6的一种使用盐析和透析分离纯化贻贝粘蛋白的方法等。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.
在本文中使用的贻贝粘蛋白可以是溶液或冻干粉形式,特别是贻贝粘蛋白在产品中的浓度可以是0.1-15.0mg/ml,当浓度过低时,贻贝粘蛋白的功效不大,当浓度过高时,可引起细胞毒性、皮肤刺激等作用,从而不利于神经炎症的预防和治疗。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, it can cause cytotoxicity, skin irritation, etc., which is not conducive to the prevention and treatment of neuroinflammation.
在本文中使用的贻贝粘蛋白也可以与辅料结合而制备成液体剂。示例性的贻贝粘蛋白液体剂是将贻贝粘蛋白溶液母液或冻干粉溶解或稀释至一定浓度或pH值制得,溶解或稀释用溶液可以是水、生理盐水、磷酸盐溶液、醋酸盐溶液、硼酸盐溶液等等。最终产品中贻贝粘蛋白的酸碱度可以是pH 1.0-7.0,特别是可以在pH 3.0-6.5的范围内以使治疗效果更佳。The mussel mucin used herein can also be prepared as a liquid agent by combining it with an excipient. An exemplary mussel mucin liquid preparation is prepared by dissolving or diluting mussel mucin solution mother liquor or lyophilized powder to a certain concentration or pH, and the solution for dissolving or diluting may be water, physiological saline, phosphate solution, vinegar. Acid solution, borate solution, and the like. The pH of the mussel mucin in the final product may be pH 1.0-7.0, especially in the range of pH 3.0-6.5 to make the therapeutic effect better.
在本文中使用的贻贝粘蛋白也可以与辅料结合而制备成凝胶剂。示例性的贻贝粘蛋白凝胶剂是将贻贝粘蛋白溶液或冻干粉与凝胶基质材料混合制得,所述凝胶基质材料可以是选自纤维素衍生物、卡波姆和海藻酸盐、西黄蓍胶、明胶、果胶、卡拉胶、结冷胶、淀粉、黄原胶、阳离子瓜尔胶、琼脂、非纤维素多糖、乙烯聚合物、丙烯酸树脂、聚乙烯醇或聚羧乙烯中之一或其任意组合。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.
本领域技术人员可以根据不同病期的临床适应症的特点来选择使用上述剂型或其他合适的剂型。One skilled in the art can select to use the above dosage forms or other suitable dosage forms depending on the characteristics of the clinical indications at different stages of the disease.
以上所有制剂都可以采用本领域周知的方法制备,详细的操作步骤可以参照例如《制剂学》。All of the above preparations can be prepared by methods well known in the art, and detailed procedures can be referred to, for example, "Pharmaceutics".
在本文中使用的贻贝粘蛋白可以作为主要原料,采用药学上可接受的载体制备药品。所述药品可以是液体剂、凝胶剂。所述药品可通过口服、定向局部缓释、靶向给药的方式使用,并且可以以低温或者加热的方式给予。The mussel mucin used herein can be used as a main raw material to prepare a medicine using a pharmaceutically acceptable carrier. The drug may be a liquid agent or a gel. The drug may be administered by oral, targeted topical sustained release, targeted administration, and may be administered at a low temperature or in a heated manner.
在本文中使用的贻贝粘蛋白可以作为主要原料,制备医疗器械。本文中使用的术语医疗器械是指直接或间接用于人体的材料及其他类似或相关的物品。 所述医疗器械可以是液体剂、凝胶剂。所述医疗器械可通过口服、定向局部缓释、靶向给药的方式使用,并且可以以低温或加热方式给予。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 can be a liquid agent or a gel. The medical device can be used by oral, targeted local sustained release, targeted administration, and can be administered at a low temperature or in a heated manner.
在本文中使用的贻贝粘蛋白可以作为主要原料,采用保健品或食品领域可接受的辅料制备保健品或食品。所述保健品或食品可以是液体剂、凝胶剂。所述保健品或食品可通过口服、定向局部缓释、靶向给药的方式使用,并且可以以低温或加热方式给予。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 or a gel. The health supplement or food may be administered by oral, targeted topical sustained release, targeted administration, and may be administered at a low temperature or in a heated manner.
本发明的另一个目的是提供贻贝粘蛋白产品用于预防和治疗神经炎症。Another object of the invention is to provide a mussel mucin product for the prevention and treatment of neuroinflammation.
出人意料地,本发明人发现贻贝粘蛋白可预防和缓解各种神经炎症引起的感觉障碍、运动障碍和植物神经功能障碍。Surprisingly, the inventors have found that mussel mucin can prevent and alleviate sensory, dyskinesia and autonomic dysfunction caused by various neuroinflammatory diseases.
神经炎症引起的感觉障碍,初期常以指端或趾端烧灼疼痛发麻等感觉异常或感觉过敏等刺激症状为主,逐渐出现感觉减退乃至消失,感觉障碍的分布呈手套或袜套式,少数病人可有深感觉障碍、腓肠肌等处常有压痛。Symptoms caused by neuroinflammation, often in the initial stage of the fingertip or toe end burning pain and numbness and other irritations such as paresthesia or hyperesthesia, gradually appearing sensation decline or even disappear, the distribution of sensory disturbances are gloves or socks, a small number of patients There may be deep sensory disturbances, gastrocnemius and other places often have tenderness.
神经炎症引起的运动功能障碍,表现为紧密肌力减退、肌张力低下、腱反射减弱或消失,个别病因(如呋喃西林)所致者反射可活跃,久病后可有肌萎缩,剧烈运动后腿部出现不适感,表现为麻木,站立不稳,脚裸处酸麻。Motor dysfunction caused by neuroinflammation, manifested as tight muscle strength, low muscle tone, reduced or disappeared tendon reflexes, reflexes caused by individual causes (such as nitrofurazone) can be active, muscle atrophy after a long illness, strenuous exercise The department showed discomfort, manifested as numbness, unstable standing, and numbness in the bare feet.
神经炎症引起的植物神经功能障碍,表现为肢端皮肤发凉、苍白、潮红或轻度发绀、少汗或多汗、皮干变薄、变嫩或粗糙指(趾)甲失去正常光泽、角化增强等。Neurological dysfunction caused by neuroinflammation, manifested as cold, pale, flushing or mild cyanosis of the extremities, less sweat or sweating, thinning of the skin, tenderness or roughness of the nails, loss of normal luster, angle Enhancement and so on.
由于病因不同,上述三组症状表现可有差异,如由呋喃西林类中毒、砷中毒等引起者疼痛常较剧烈;糖尿病引起者有时肌萎缩较显著。多种临床表现的轻重程度也不一致,轻者可仅有肢端疼痛麻木而无感觉缺失或运动障碍,重者也可有肢体瘫痪。Due to different causes, the symptoms of the above three groups may be different. For example, the pain caused by nitrofurazone poisoning and arsenic poisoning is often severe; the muscle atrophy is sometimes significant in diabetic patients. The severity of various clinical manifestations is also inconsistent. In the light, only the acral pain can be numb without sensory loss or dyskinesia, and the severe one can also have limb paralysis.
在一个方面,本发明的贻贝粘蛋白可用于预防神经炎症引起的感觉障碍、运动功能障碍和植物神经功能障碍。In one aspect, the mussel mucin of the present invention can be used to prevent sensory disorders, motor dysfunction, and autonomic dysfunction caused by neuroinflammation.
在另一个方面,本发明的贻贝粘蛋白可用于治疗神经炎症引起的感觉障碍、运动功能障碍和植物神经功能障碍。In another aspect, the mussel mucin of the invention can be used to treat sensory disorders, motor dysfunction, and autonomic dysfunction caused by neuroinflammation.
在本发明中的术语“预防”是指为解除病痛所进行的干预或改变特定健康状态的过程。The term "prevention" as used in the present invention refers to a process of intervention to relieve pain or change of a particular state of health.
在本发明中的术语“治疗”是指预先做好疾病治疗过程中可能出现偏离主观预期轨道或客观普遍规律的应对措施,避免产生可能存在的损害。 The term "treatment" in the present invention means that countermeasures that may deviate from subjectively expected or objective general laws in the course of disease treatment are prevented in advance to avoid possible damage.
具体实施方式detailed description
本发明的实施方式包括:Embodiments of the invention include:
1、贻贝粘蛋白在预防和治疗神经炎症中的应用。1. The application of mussel mucin in the prevention and treatment of neuroinflammation.
2、根据实施方式1的贻贝粘蛋白应用,其中所述贻贝粘蛋白是来自亚类:mefp1、mefp-2、mefp-3、mefp-4、mefp-5、mefp-6、胶原蛋白pre-COL-P、pre-COL-D、pre-COL-NG、足丝基质蛋白PTMP和DTMP中的一种或几种的混合物。2. The mussel mucin application according to embodiment 1, wherein the mussel mucin is from a subclass: mefp1, mefp-2, mefp-3, mefp-4, mefp-5, mefp-6, collagen pre a mixture of one or more of -COL-P, pre-COL-D, pre-COL-NG, foot silk matrix protein PTMP and DTMP.
3、根据实施方式1或2的贻贝粘蛋白应用,其中所述贻贝粘蛋白可以是采用从贻贝中提取获得的,包含已知的11个贻贝粘蛋白亚类中的一种或几种的混合物。3. The mussel mucin application according to embodiment 1 or 2, wherein the mussel mucin may be obtained by extracting from mussels, comprising one of 11 known mussel mucin subclasses or Several mixtures.
4、根据实施方式1或2的贻贝粘蛋白应用,其中所述贻贝粘蛋白可以是生物合成的方法获得的,包含已知的11个贻贝粘蛋白亚类中的一种或几种的混合物。4. The mussel mucin application according to embodiment 1 or 2, wherein the mussel mucin is obtained by a method of biosynthesis, comprising one or more of the known 11 mussel mucin subclasses mixture.
5、根据实施方式1或2的贻贝粘蛋白应用,其中所述的贻贝粘蛋白也可以是天然来源或人工生物合成来源的贻贝粘蛋白经水解后获得的水解肽,或通过人工合成方式获得的含有功能基团的合成肽。5. The mussel mucin application according to embodiment 1 or 2, wherein the mussel mucin is also a hydrolyzed peptide obtained by hydrolyzing mussel mucin from a natural source or an artificial biosynthesis source, or by artificial synthesis. A functional peptide-containing synthetic peptide obtained in a manner.
6、根据实施方式1-5中任一项的贻贝粘蛋白应用,其中所述贻贝粘蛋白浓度可以是0.1-15.0mg/ml。The mussel mucin application according to any one of embodiments 1 to 5, wherein the mussel mucin concentration may be from 0.1 to 15.0 mg/ml.
7、根据实施方式1-5中任一项的贻贝粘蛋白应用,其中所述贻贝粘蛋白可以是以液体剂或凝胶剂。The mussel mucin application according to any one of embodiments 1 to 5, wherein the mussel mucin is a liquid agent or a gel.
8、根据实施方式1-5中任一项的贻贝粘蛋白应用,其中最终产品中的贻贝粘蛋白可以是在pH 1.0-7.0的范围内,特别是在pH 3.0-6.5的范围内。The mussel mucin application according to any one of embodiments 1 to 5, wherein the mussel mucin in the final product may be in the range of pH 1.0-7.0, particularly in the range of pH 3.0-6.5.
9、根据实施方式1-8中任一项的贻贝粘蛋白应用,其中所述神经炎症可以包括神经炎症引起的感觉障碍、运动功能障碍和植物神经功能障碍。The mussel mucin application according to any one of embodiments 1-8, wherein the neuroinflammation may include sensory disturbances caused by neuroinflammation, motor dysfunction, and autonomic dysfunction.
10、贻贝粘蛋白作为活性成分在用于预防及治疗神经炎症的组合物中的应用,其中所述组合物可以是以液体剂、凝胶剂。10. Use of mussel mucin as an active ingredient in a composition for preventing and treating neuroinflammation, wherein the composition may be a liquid agent or a gel.
11、根据实施方式10的贻贝粘蛋白应用,其中所述组合物可以是通过口服、定向局部缓释、靶向给药的方式使用。11. The mussel mucin application according to embodiment 10, wherein the composition is for use by oral, targeted local sustained release, targeted administration.
12、根据实施方式10的贻贝粘蛋白应用,其中所述组合物可以以低温或加热方式使用。 12. Mussel mucin application according to embodiment 10, wherein the composition can be used at low temperature or in a heated manner.
13、根据实施方式10的贻贝粘蛋白应用,其中所述贻贝粘蛋白可以是实施方式2-5中任一种。13. The mussel mucin application according to embodiment 10, wherein the mussel mucin is any one of embodiments 2-5.
14、一种用于预防及治疗神经炎症的药品,包括贻贝粘蛋白和药学上可接受的载体,其中贻贝粘蛋白的浓度可以是0.1-15.0mg/ml。14. A medicament for preventing and treating neuroinflammation, comprising mussel mucin and a pharmaceutically acceptable carrier, wherein the mussel mucin is present in a concentration of from 0.1 to 15.0 mg/ml.
15、一种用于预防及治疗神经炎症的医疗器械,包括贻贝粘蛋白和医疗器械领域可接受的载体,其中贻贝粘蛋白的浓度可以是0.1-15.0mg/ml。15. A medical device for preventing and treating neuroinflammation, comprising mussel mucin and a carrier acceptable for use in the field of medical devices, wherein the concentration of mussel mucin may be from 0.1 to 15.0 mg/ml.
16、一种用于预防及治疗神经炎症的保健品/食品,包括贻贝粘蛋白和保健品/食品领域可接受的载体,其中贻贝粘蛋白的浓度可以是0.1-15.0mg/ml。A health care product/food for preventing and treating neuroinflammation, comprising a mussel mucin and a health care product/food acceptable carrier, wherein the mussel mucin may be in a concentration of 0.1 to 15.0 mg/ml.
17、贻贝粘蛋白在用于预防及治疗神经炎症的药品中的应用,其中所述神经炎症可以涉及神经炎症引起的感觉障碍、运动功能障碍和植物神经功能障碍等。17. Use of mussel mucin in a medicament for preventing and treating neuroinflammation, wherein the neuroinflammation may involve sensory disturbances caused by neuroinflammation, motor dysfunction, and autonomic dysfunction.
18、根据实施方式17的贻贝粘蛋白应用,其中神经炎症可以包括:末梢神经炎症、面部神经炎症、周围神经炎症、皮下神经炎症、尺神经炎、肋间神经炎症等。18. The mussel mucin application according to embodiment 17, wherein the neuroinflammation comprises: peripheral nerve inflammation, facial nerve inflammation, peripheral nerve inflammation, subcutaneous neuroinflammation, ulnar neuritis, intercostal nerve inflammation, and the like.
19、贻贝粘蛋白在用于预防及治疗神经炎症的医疗器械中的应用,其中所述神经炎症可以涉及神经炎症引起的感觉障碍、运动功能障碍和植物神经功能障碍等。19. Use of mussel mucin in a medical device for preventing and treating neuroinflammation, wherein the neuroinflammation may involve sensory disturbance, motor dysfunction, and autonomic dysfunction caused by neuroinflammation.
20、根据实施方式19的贻贝粘蛋白应用,其中神经炎症可以包括:末梢神经炎症、面部神经炎症、周围神经炎症、皮下神经炎症、尺神经炎、肋间神经炎症等。20. The mussel mucin application according to embodiment 19, wherein the neuroinflammation comprises: peripheral nerve inflammation, facial nerve inflammation, peripheral nerve inflammation, subcutaneous neuroinflammation, ulnar neuritis, intercostal nerve inflammation, and the like.
21、贻贝粘蛋白在用于预防及治疗神经炎症的保健品或食品中的应用,其中所述神经炎症可以涉及神经炎症引起的感觉障碍、运动功能障碍和植物神经功能障碍等。21. Use of mussel mucin in a health product or food for preventing and treating neuroinflammation, wherein the neuroinflammation may involve sensory disturbance, motor dysfunction, and autonomic dysfunction caused by neuroinflammation.
22、根据实施方式21的贻贝粘蛋白应用,其中神经炎症可以包括:末梢神经炎症、面部神经炎症、周围神经炎症、皮下神经炎症、尺神经炎、肋间神经炎症等。22. The mussel mucin application according to embodiment 21, wherein the neuroinflammation comprises: peripheral nerve inflammation, facial nerve inflammation, peripheral nerve inflammation, subcutaneous neuroinflammation, ulnar neuritis, intercostal nerve inflammation, and the like.
下面将结合具体实施例对本发明作进一步说明。需要指出的是,由本发明中的贻贝粘蛋白或贻贝粘蛋白的各种制剂形成的药品、医疗器械、保健品或食品在施用于受试者后,都可以应用于上文所述的适应症并展现出上文所述的功能,在本发明范围内的所有剂型均已测试,下文中,仅仅是为说明,只在实施 例中描述了其中一少部分,然而不应将其理解为对本发明的限制。The invention will now be further described in conjunction with specific embodiments. It should be noted that the pharmaceutical, medical device, health care product or food formed by various preparations of mussel mucin or mussel mucin in the present invention can be applied to the above as described above after administration to a subject. Indications and exhibiting the functions described above, all dosage forms within the scope of the invention have been tested, hereinafter, merely for illustration, only in practice A few of them are described in the examples, however, they should not be construed as limiting the invention.
除非特殊说明,否则本发明中所使用的试剂都是市售可购买的。Unless otherwise stated, the reagents used in the present invention are commercially available.
实施例1:贻贝粘蛋白凝胶剂药品在末梢神经炎症治疗中的应用。Example 1: Application of mussel mucin gel drug in the treatment of peripheral nerve inflammation.
取羟丙基甲基纤维素10g,加入20ml去离子水,90℃温浴30min至完全溶解得到凝胶基质,另取浓度为10.0mg/ml的贻贝粘蛋白溶液2.5ml,边搅拌边加入到凝胶基质中,混合均匀后形成贻贝粘蛋白凝胶医疗器械,其中贻贝粘蛋白浓度为2.0mg/ml。Take 10g of hydroxypropyl methylcellulose, add 20ml of deionized water, warm bath at 90 °C for 30min to completely dissolve to obtain the gel matrix, and take another 2.5ml mussel mucin solution with a concentration of 10.0mg/ml, and add to the mixture while stirring. In the gel matrix, after mixing uniformly, a mussel mucin gel medical device was formed, wherein the mussel mucin concentration was 2.0 mg/ml.
收集经神经内科医生确诊的末梢神经炎患者10人进行试验,入选患者临床表现为手足及四肢麻木,伴有疼痛、无力感。入选患者随机分为对照组和试验组,对照组采用空白凝胶溶液治疗,试验组采用上述贻贝粘蛋白凝胶剂药品治疗。两组使用方法均为每日3次,外用,用量以能均匀覆盖患处。使用3日后,对照组5人的症状均未出现明显改变,试验组5人疼痛感消失,3人手足及四肢麻木症状减轻。证明贻贝粘蛋白凝胶药品可用于末梢神经炎的治疗。Ten patients with peripheral neuritis diagnosed by neurologists were enrolled in the study. The clinical manifestations of the patients were numbness of the hands, feet and limbs, accompanied by pain and weakness. The selected patients were randomly divided into the control group and the experimental group. The control group was treated with a blank gel solution, and the test group was treated with the above mussel mucin gel drug. The two groups were used 3 times a day for external use, so that the affected area could be evenly covered. After 3 days of use, the symptoms of 5 people in the control group did not change significantly. The pain in 5 people in the experimental group disappeared, and the symptoms of numbness in 3 hands, feet and limbs were alleviated. It is proved that mussel mucin gel drugs can be used for the treatment of peripheral neuritis.
实施例2:贻贝粘蛋白液体医疗器械在末梢神经炎治疗中的应用。Example 2: Application of mussel mucin liquid medical device in the treatment of peripheral neuritis.
取浓度为10.0mg/ml的贻贝粘蛋白溶液1ml,加入9ml 0.1%柠檬酸溶液,配制度为1.0mg/ml的贻贝粘蛋白液体医疗器械。Take 1 ml of mussel mucin solution at a concentration of 10.0 mg/ml, add 9 ml of 0.1% citric acid solution, and dispense a 1.0 mg/ml mussel mucin liquid medical device.
收集经神经内科医生确诊的末梢神经炎患者10人进行试验,入选患者临床表现为手足及四肢麻木,伴有疼痛、无力感。入选患者随机分为对照组和试验组,对照组采用0.1%柠檬酸溶液治疗,试验组采用上述贻贝粘蛋白液体医疗器械治疗。两组使用方法均为每日3次,外用,用量以能均匀覆盖患处。使用3日后,对照组5人的症状均未出现明显改变,试验组5人疼痛感消失,3人手足及四肢麻木症状减轻。证明贻贝粘蛋白液体医疗器械可用于末梢神经炎的治疗。Ten patients with peripheral neuritis diagnosed by neurologists were enrolled in the study. The clinical manifestations of the patients were numbness of the hands, feet and limbs, accompanied by pain and weakness. The selected patients were randomly divided into the control group and the experimental group, and the control group was treated with 0.1% citric acid solution. The test group was treated with the above mussel mucin liquid medical device. The two groups were used 3 times a day for external use, so that the affected area could be evenly covered. After 3 days of use, the symptoms of 5 people in the control group did not change significantly. The pain in 5 people in the experimental group disappeared, and the symptoms of numbness in 3 hands, feet and limbs were alleviated. Proof of mussel mucin liquid medical device can be used for the treatment of peripheral neuritis.
实施例3:贻贝粘蛋白液体药品在面部神经炎治疗中的应用。Example 3: Application of mussel mucin liquid medicine in the treatment of facial neuritis.
取浓度为5.0mg/ml的贻贝粘蛋白溶液,用0.001%的乙酸稀释5倍,至贻贝粘蛋白含量为1.0mg/ml,得到贻贝粘蛋白液体药品。A mussel mucin solution having a concentration of 5.0 mg/ml was taken and diluted 5 times with 0.001% acetic acid to a mussel mucin content of 1.0 mg/ml to obtain a mussel mucin liquid medicine.
收集经神经内科医生确诊的急性面部神经炎患者10人进行试验,入选患者临床表现为一侧面部表情肌瘫痪,并伴有下颌角或耳后疼痛。入选患者随机分 为对照组和试验组,对照组采用0.1%柠檬酸溶液治疗,试验组采用上述贻贝粘蛋白液体药品治疗。两组使用方法均为每日3次,外用,用量以能均匀覆盖患处。使用5日后,对照组5人的症状均未出现明显改变,试验组5人疼痛感消失,4人面部表情肌恢复正常,1人面部表情肌瘫痪状况明显改善。证明贻贝粘蛋白液体药品可用于面部神经炎的治疗。Ten patients with acute facial neuritis diagnosed by neurologists were enrolled in the study. The clinical manifestations of the patients were one-sided facial expression tendon accompanied by mandibular angle or pain behind the ear. Randomized patients For the control group and the experimental group, the control group was treated with 0.1% citric acid solution, and the test group was treated with the above mussel mucin liquid medicine. The two groups were used 3 times a day for external use, so that the affected area could be evenly covered. After 5 days of use, the symptoms of 5 people in the control group did not change significantly. The pain in 5 people in the experimental group disappeared, the facial expression muscles of 4 people returned to normal, and the facial muscles of one person showed significant improvement. It is proved that mussel mucin liquid medicine can be used for the treatment of facial neuritis.
实施例4:贻贝粘蛋白凝胶剂药品在面部神经炎治疗中的应用。Example 4: Application of mussel mucin gel drug in the treatment of facial neuritis.
取贻贝粘蛋白溶液,与瓜尔胶、丙三醇按体积比2∶1∶1混合,加入注射水,用柠檬酸调整酸碱度到pH 3.0,制备贻贝粘蛋白含量为1.5mg/ml的贻贝粘蛋白凝胶剂药品。Take the mussel mucin solution, mix with guar gum and glycerol at a volume ratio of 2:1:1, add water for injection, adjust the pH to pH 3.0 with citric acid, and prepare mussel mucin content of 1.5 mg/ml. Mussel mucin gel drug.
收集经神经内科医生确诊的急性面部神经炎患者10人进行试验,入选患者临床表现为一侧面部表情肌瘫痪,并伴有下颌角或耳后疼痛。入选患者随机分为对照组和试验组,对照组采用不添加贻贝粘蛋白的空白凝胶治疗,试验组采用上述贻贝粘蛋白凝胶剂药品治疗。两组使用方法均为每日3次,外用,用量以能均匀覆盖患处。Ten patients with acute facial neuritis diagnosed by neurologists were enrolled in the study. The clinical manifestations of the patients were one-sided facial expression tendon accompanied by mandibular angle or pain behind the ear. The selected patients were randomly divided into the control group and the experimental group. The control group was treated with a blank gel without mussel mucin. The test group was treated with the above mussel mucin gel drug. The two groups were used 3 times a day for external use, so that the affected area could be evenly covered.
使用5日后,对照组5人的症状均未出现明显改变,试验组5人疼痛感消失,面部表情肌恢复正常。证明贻贝粘蛋白凝胶剂药品可用于面部神经炎的治疗。After 5 days of use, the symptoms of 5 people in the control group did not change significantly. The pain in the experimental group disappeared and the facial expression muscles returned to normal. It is proved that mussel mucin gel medicine can be used for the treatment of facial neuritis.
实施例5:贻贝粘蛋白液体药品在周围神经炎治疗中的应用。Example 5: Application of mussel mucin liquid medicine in the treatment of peripheral neuritis.
取浓度为20.0mg/ml的贻贝粘蛋白溶液,用0.05%的柠檬酸稀释10倍,至贻贝粘蛋白含量为2.0mg/ml,得到贻贝粘蛋白液体药品。A mussel mucin solution having a concentration of 20.0 mg/ml was prepared and diluted 10 times with 0.05% citric acid to a mussel mucin content of 2.0 mg/ml to obtain a mussel mucin liquid medicine.
收集经神经内科医生确诊的运动神经炎患者10人进行试验,入选患者临床表现为肢体远端对称性感觉异常(疼痛、麻木、过敏),运动障碍包括肌力减退、肌张力低下、腱反射减弱或消失,植物神经功能障碍包括肢端皮肤发凉、苍白。入选患者随机分为对照组和试验组,对照组采用0.05%的柠檬酸治疗,试验组采用上述贻贝粘蛋白液体药品治疗。两组使用方法均为每日3次,外用,用量以能均匀覆盖患处。A total of 10 patients with motor neuron diagnosed by neurologists were enrolled in the study. The clinical manifestations were sympathetic abnormalities (pain, numbness, allergies) in the distal extremities. The dyskinesias included hypotonia, hypotonia, and decreased tendon reflexes. Or disappear, autonomic dysfunction, including cold skin and pale skin. The selected patients were randomly divided into the control group and the experimental group. The control group was treated with 0.05% citric acid. The test group was treated with the above mussel mucin liquid medicine. The two groups were used 3 times a day for external use, so that the affected area could be evenly covered.
使用2周后,对照组5人的症状均未出现明显改变,试验组5人疼痛、麻木感觉消失,3人运动功能障碍及植物神经功能障碍症状消失,2人运动功能障 碍及植物神经功能障碍症状有大幅度缓解。证明贻贝粘蛋白液体药品可用于周围神经炎的治疗。After 2 weeks of use, the symptoms of 5 people in the control group did not change significantly. The pain and numbness of 5 people in the experimental group disappeared, the symptoms of motor dysfunction and autonomic dysfunction disappeared in 3 people, and the motor dysfunction of 2 people The symptoms of autonomic dysfunction are greatly alleviated. It is proved that mussel mucin liquid medicine can be used for the treatment of peripheral neuritis.
实施例6:贻贝粘蛋白凝胶保健品在周围神经炎治疗中的应用。Example 6: Application of mussel mucin gel health supplement in the treatment of peripheral neuritis.
取贻贝粘蛋白溶液,与瓜尔胶、丙三醇按质量比为2∶1∶1混合,用生理盐水稀释,用醋酸调整酸碱度到pH 5.0得到贻贝粘蛋白水凝胶保健品,其中贻贝粘蛋白浓度为2.0mg/ml。Taking the mussel mucin solution, mixing with guar gum and glycerol at a mass ratio of 2:1:1, diluting with physiological saline, adjusting the pH to pH 5.0 with acetic acid to obtain mussel mucin hydrogel health care products, wherein The mussel mucin concentration was 2.0 mg/ml.
收集经神经内科医生确诊的周围神经炎患者10人进行试验,入选患者临床表现为肢体远端对称性感觉异常(疼痛、麻木、过敏),运动障碍包括肌力减退、肌张力低下、腱反射减弱或消失,植物神经功能障碍包括肢端皮肤发凉、苍白。入选患者随机分为对照组和试验组,对照组采用不添加贻贝粘蛋白的凝胶治疗,试验组采用上述贻贝粘蛋白液体药品治疗。两组使用方法均为每日3次,外用,用量以能均匀覆盖患处。Ten patients with peripheral neuritis diagnosed by neurologists were enrolled in the study. The clinical manifestations were sympathetic abnormalities (pain, numbness, allergies) in the distal part of the limb. The dyskinesia included hypotonia, hypotonia, and decreased tendon reflex. Or disappear, autonomic dysfunction, including cold skin and pale skin. The selected patients were randomly divided into the control group and the experimental group. The control group was treated with a gel without mussel mucin, and the experimental group was treated with the above mussel mucin liquid medicine. The two groups were used 3 times a day for external use, so that the affected area could be evenly covered.
使用2周后,对照组5人的症状均未出现明显改变,试验组5人疼痛、麻木感觉消失,2人运动功能障碍及植物神经功能障碍症状消失,3人运动功能障碍及植物神经功能障碍症状有大幅度缓解。证明贻贝粘蛋白凝胶保健品可用于周围神经炎的治疗。After 2 weeks of use, there were no significant changes in the symptoms of 5 people in the control group. The pain and numbness of 5 people in the experimental group disappeared, the symptoms of motor dysfunction and autonomic dysfunction disappeared, and 3 people had motor dysfunction and autonomic dysfunction. Symptoms have been greatly alleviated. It is proved that mussel mucin gel health products can be used for the treatment of peripheral neuritis.
实施例7:贻贝粘蛋白液体医疗器械在皮下神经炎治疗中的应用。Example 7: Application of mussel mucin liquid medical device in the treatment of subcutaneous neuritis.
取贻贝粘蛋白溶液,用生理盐水稀释,用醋酸调整酸碱度到pH 6.0得到贻贝粘蛋白液体医疗器械,其中贻贝粘蛋白浓度为3mg/ml。The mussel mucin solution was taken, diluted with physiological saline, and the pH was adjusted to pH 6.0 with acetic acid to obtain a mussel mucin liquid medical device, wherein the mussel mucin concentration was 3 mg/ml.
收集经神经内科医生确诊的皮下神经炎患者20人进行试验,入选患者临床表现为皮肤红肿、痒或大面积针刺痛。入选患者随机分为对照组和试验组,对照组采用生理盐水治疗,试验组采用上述贻贝粘蛋白液体医疗器械治疗。两组使用方法均为每日3次,外用,用量以能均匀覆盖患处。Twenty patients with subcutaneous neuritis diagnosed by neurologists were enrolled in the study. The clinical manifestations of the patients were redness, itching or large-scale needle stick pain. The selected patients were randomly divided into the control group and the experimental group, and the control group was treated with normal saline. The experimental group was treated with the above mussel mucin liquid medical device. The two groups were used 3 times a day for external use, so that the affected area could be evenly covered.
使用1周后,对照组10人的症状均未出现明显改变,试验组10人疼痛感觉、红肿、痒症状消失。证明贻贝粘蛋白液体医疗器械可用于皮下神经炎的治疗。After 1 week of use, the symptoms of 10 people in the control group did not change significantly. In the test group, 10 people felt pain, redness and itching disappeared. It is proved that mussel mucin liquid medical devices can be used for the treatment of subcutaneous neuritis.
实施例8:贻贝粘蛋白凝胶医疗器械在皮下神经炎治疗中的应用。 Example 8: Application of mussel mucin gel medical device in the treatment of subcutaneous neuritis.
取贻贝粘蛋白溶液,与羟丙基甲基纤维素和丙三醇按照质量比3∶2∶1的比例混合制剂,用柠檬酸调整酸碱度到pH 6.2得到贻贝粘蛋白凝胶医疗器械,其中贻贝粘蛋白浓度3mg/ml。Taking a mussel mucin solution, mixing the preparation with hydroxypropylmethylcellulose and glycerol at a mass ratio of 3:2:1, and adjusting the pH to pH 6.2 with citric acid to obtain a mussel mucin gel medical device. The mussel mucin concentration was 3 mg/ml.
收集经神经内科医生确诊的皮下神经炎患者20人进行试验,入选患者临床表现为皮肤红肿、痒或大面积针刺痛。入选患者随机分为对照组和试验组,对照组采用不添加贻贝粘蛋白的空白凝胶治疗,试验组采用上述贻贝粘蛋白凝胶医疗器械治疗。两组使用方法均为每日3次,外用,用量以能均匀覆盖患处。Twenty patients with subcutaneous neuritis diagnosed by neurologists were enrolled in the study. The clinical manifestations of the patients were redness, itching or large-scale needle stick pain. The selected patients were randomly divided into the control group and the experimental group. The control group was treated with a blank gel without mussel mucin. The test group was treated with the above mussel mucin gel medical device. The two groups were used 3 times a day for external use, so that the affected area could be evenly covered.
使用1周后,对照组10人的症状均未出现明显改变,试验组10人疼痛感觉、红肿、痒症状消失。证明贻贝粘蛋白凝胶医疗器械可用于皮下神经炎的治疗。After 1 week of use, the symptoms of 10 people in the control group did not change significantly. In the test group, 10 people felt pain, redness and itching disappeared. It is proved that mussel mucin gel medical instruments can be used for the treatment of subcutaneous neuritis.
实施例9:贻贝粘蛋白液体医疗器械在尺神经炎治疗中的应用。Example 9: Application of mussel mucin liquid medical device in the treatment of ulnar neuritis.
取贻贝粘蛋白溶液,与丙二醇按体积比2∶1的比例混合,用乙酸调整酸碱度到pH 5.0得到贻贝粘蛋白液体保健品,其中贻贝粘蛋白浓度2.0mg/ml。The mussel mucin solution was mixed with propylene glycol in a ratio of 2:1 by volume, and the pH was adjusted to pH 5.0 with acetic acid to obtain mussel mucin liquid health care product, wherein the mussel mucin concentration was 2.0 mg/ml.
收集经神经内科医生确诊的尺神经炎患者8人进行试验,入选患者临床表现为尺神经麻痹症状,即手尺侧部麻木、疼痛。对照组采用生理盐水配合热敷理疗治疗。试验组采用上述贻贝粘蛋白液体医疗器械治疗配合热敷理疗治疗。两组使用方法均为每日3次,外用,用量以能均匀覆盖患处。Eight patients with ulnar neuritis diagnosed by neurologists were enrolled in the study. The clinical manifestations of the patients were ulnar nerve paralysis, which was numbness and pain in the lateral side of the hand. The control group was treated with normal saline and hot compress therapy. The experimental group used the above-mentioned mussel mucin liquid medical device treatment combined with hot compress therapy. The two groups were used 3 times a day for external use, so that the affected area could be evenly covered.
使用1周后,对照组3人麻木及疼痛感略有缓解,1人症状无缓解;试验组4人疼痛症状消失,麻木症状大幅度缓解。证明贻贝粘蛋白液体医疗器械可用于尺神经炎的治疗。After 1 week of use, the numbness and pain of the control group were slightly relieved, and the symptoms of one person were not relieved. The pain symptoms of the test group disappeared and the symptoms of numbness were greatly alleviated. It is proved that mussel mucin liquid medical instruments can be used for the treatment of ulnar neuritis.
实施例10:贻贝粘蛋白凝胶药品在肋间神经炎治疗中的应用。Example 10: Application of mussel mucin gel drug in the treatment of intercostal neuritis.
取贻贝粘蛋白溶液,按体积比为2∶1∶1加入羧甲基纤维素和甘油,获得贻贝粘蛋白水凝胶药品,其中贻贝粘蛋白浓度为2.5mg/ml。A mussel mucin solution was taken, and carboxymethylcellulose and glycerin were added in a volume ratio of 2:1:1 to obtain a mussel mucin hydrogel drug, wherein the mussel mucin concentration was 2.5 mg/ml.
收集经神经内科医生确诊的肋间神经炎患者12人进行试验,入选患者临床表现为沿着胸部肋骨,由背后经过侧腹,一直到胸前肋软骨处有痛性肿块及压痛。入选患者随机分为对照组和试验组,对照组采用不添加贻贝粘蛋白的空白凝胶治疗,试验组采用上述贻贝粘蛋白凝胶药品治疗。两组使用方法均为每日3次,外用,用量以能均匀覆盖患处。 A total of 12 patients with intercostal neuritis diagnosed by neurologists were enrolled in the study. The clinical manifestations of the patients were along the chest ribs, from the back through the flank, to the painful mass and tenderness at the costal cartilage in the chest. The selected patients were randomly divided into the control group and the experimental group. The control group was treated with a blank gel without mussel mucin. The test group was treated with the above mussel mucin gel drug. The two groups were used 3 times a day for external use, so that the affected area could be evenly covered.
使用1周后,对照组6人的症状均未出现明显改变,试验6人疼痛症状消失。证明贻贝粘蛋白凝胶药品可用于肋间神经炎的治疗。After 1 week of use, the symptoms of 6 people in the control group did not change significantly, and the pain symptoms of 6 people in the test disappeared. It is proved that mussel mucin gel drugs can be used for the treatment of intercostal neuritis.
实施例11:贻贝粘蛋白液体保健品在神经炎防护中的应用。Example 11: Application of mussel mucin liquid health care products in the protection of neuritis.
取贻贝粘蛋白溶液,用生理盐水稀释,制备贻贝粘蛋白液体保健品,贻贝粘蛋白浓度为1.0mg/ml。The mussel mucin solution was taken and diluted with physiological saline to prepare a mussel mucin liquid health care product, and the mussel mucin concentration was 1.0 mg/ml.
从牛的新鲜的坐骨神经中提取髓鞘碱性蛋白,并对所提取的髓鞘碱性蛋白进行生化及生物活性鉴定后备用。另取20只新西兰白兔,雄性,体重2.5-3.0kg,随机分为对照组和试验组,每组各10只。对照组仅用所提取的牛髓鞘碱性蛋白免疫,观察临床表现并行病理检查,试验组在免疫的同时每日口服贻贝粘蛋白液体保健品,每次2-3ml,每日3次。Myelin basic protein is extracted from the fresh sciatic nerve of cattle, and the extracted myelin basic protein is identified for biochemical and biological activity. Another 20 New Zealand white rabbits, male, weighing 2.5-3.0 kg, were randomly divided into control group and experimental group, with 10 in each group. The control group was only immunized with the extracted bovine myelin basic protein, and the clinical manifestations were observed along with the pathological examination. The experimental group was orally administered with mussel mucin liquid health care products every day, 2-3 ml each time, 3 times a day.
免疫1周后观察,对照组10只白兔中有8只出现不同程度的临床症状,发病率达80%;试验组有4只出现不同程度的临床症状,发病率为40%。病理检查发现,对照组发病兔的炎细胞浸润是以颈神经根、腰神经根、马尾神经损害重于坐骨神经,单神经纤维分离,半薄切片及电镜下均发现以脱髓鞘改变为主,少数重症动物有轴索变性,脑脊膜有轻度充血及少量炎细胞浸润,脑实质内未见病变。试验组发病兔的炎细胞浸润是以颈神经根、腰神经根、马尾神经损害重于坐骨神经,单神经纤维分离,半薄切片及电镜下均发现以脱髓鞘改变为主,未发现有轴索变性及脑实质内病变。证明贻贝粘蛋白液体保健品可以预防神经炎症。 After 1 week of immunization, 8 of 10 white rabbits in the control group showed different degrees of clinical symptoms, the incidence rate reached 80%; 4 of the experimental group showed different degrees of clinical symptoms, the incidence rate was 40%. Pathological examination showed that the inflammatory cell infiltration of the rabbits in the control group was more severe than the sciatic nerve by the cervical nerve root, lumbar nerve root and cauda equina nerve. The single nerve fibers were separated, and the demyelination was mainly observed under semi-thin sections and electron microscopy. A few critically ill animals have axonal degeneration, mild congestion of the meninges and a small amount of inflammatory cell infiltration, no lesions in the brain parenchyma. The inflammatory cell infiltration of the rabbits in the experimental group was caused by cervical nerve root, lumbar nerve root and cauda equina nerve damage, and the sciatic nerve was separated. The single nerve fibers were separated. The semi-thin sections and electron microscopy showed that the demyelination was the main change. No axis was found. Degeneration and lesions in the brain parenchyma. It is proved that mussel mucin liquid health care products can prevent neuroinflammation.

Claims (11)

  1. 贻贝粘蛋白在预防及治疗神经炎症中的应用。The application of mussel mucin in the prevention and treatment of neuroinflammation.
  2. 根据权利要求1的贻贝粘蛋白应用,其中所述贻贝粘蛋白是来自亚类:mefp1、mefp-2、mefp-3、mefp-4、mefp-5、mefp-6、胶原蛋白pre-COL-P、pre-COL-D、pre-COL-NG、足丝基质蛋白PTMP和DTMP中的一种或几种的混合物。The mussel mucin application according to claim 1, wherein said mussel mucin is from a subclass: 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.
  3. 根据实施方式1的贻贝粘蛋白应用,其中所述贻贝粘蛋白浓度是0.1-15.0mg/ml。The mussel mucin application according to embodiment 1, wherein the mussel mucin concentration is 0.1 to 15.0 mg/ml.
  4. 根据实施方式1的贻贝粘蛋白应用,其中所述贻贝粘蛋白是以液体剂、凝胶剂使用。The mussel mucin application according to embodiment 1, wherein the mussel mucin is used as a liquid agent or a gelling agent.
  5. 根据实施方式1的贻贝粘蛋白应用,其中最终产品中的贻贝粘蛋白是在pH 1.0-7.0的范围内,特别是在pH 3.0-6.5的范围内。The mussel mucin application according to embodiment 1, wherein the mussel mucin in the final product is in the range of pH 1.0-7.0, particularly in the range of pH 3.0-6.5.
  6. 根据实施方式1-5中任一项的贻贝粘蛋白应用,其中所述神经炎症包括:末梢神经炎症、面部神经炎症、周围神经炎症、皮下神经炎症、尺神经炎、肋间神经炎症等。The mussel mucin application according to any one of embodiments 1 to 5, wherein the neuroinflammation comprises: peripheral nerve inflammation, facial nerve inflammation, peripheral nerve inflammation, subcutaneous neuroinflammation, ulnar neuritis, intercostal nerve inflammation, and the like.
  7. 贻贝粘蛋白作为活性成分在用于预防和治疗神经炎症的组合物中的应用,其中所述组合物是以液体剂或凝胶剂使用。Use of mussel mucin as an active ingredient in a composition for preventing and treating neuroinflammation, wherein the composition is used as a liquid or gel.
  8. 根据实施方式7的贻贝粘蛋白应用,其中所述组合物是通过口服、定向局部缓释、靶向给药的方式使用。The mussel mucin application according to embodiment 7, wherein the composition is used by oral, targeted local sustained release, targeted administration.
  9. 贻贝粘蛋白作为活性成分在用于预防和治疗神经炎症的药品中的应用。The use of mussel mucin as an active ingredient in medicines for preventing and treating neuroinflammation.
  10. 贻贝粘蛋白作为活性成分在用于预防和治疗神经炎症的医疗器械中的应用。The use of mussel mucin as an active ingredient in medical devices for preventing and treating neuroinflammation.
  11. 贻贝粘蛋白作为活性成分在用于预防和治疗神经炎症的保健品或食品中的应用。 The use of mussel mucin as an active ingredient in health care products or foods for preventing and treating neuroinflammation.
PCT/CN2015/095798 2015-11-27 2015-11-27 Mussel adhesive protein product, and use thereof in preventing and suppressing neuronal inflammation WO2017088177A1 (en)

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Publication number Priority date Publication date Assignee Title
WO2020143744A1 (en) * 2019-01-10 2020-07-16 Jiangyin Mucocare Pharmaceutical Co., Ltd. New formulations containing leukotriene receptor antagonists
EP4069715A4 (en) * 2019-12-02 2024-08-14 EnliTISA (Shanghai) Pharmaceutical Co., Ltd. PEPTIDES AND THEIR USE IN THE TREATMENT OF INFLAMMATION

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YU , FENGBIN ET AL.: "Reconstructing Spinal Dura-like Tissue Using Electrospun Poly (lactide-co-glycolide) Membranes and Dermal Fibroblasts to Seamlessly Repair Spinal Dural Defects in Goats", J BIOMATER APPL, vol. 30, no. 3, 30 September 2015 (2015-09-30), pages 311 - 326 *
ZHU, YAOYAO ET AL.: "The Research Progress on Mussel Adhesive Proteins", ADVANCES IN MARINE SCIENCE, vol. 32, no. 4, 31 October 2014 (2014-10-31), pages 560 - 570 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020143744A1 (en) * 2019-01-10 2020-07-16 Jiangyin Mucocare Pharmaceutical Co., Ltd. New formulations containing leukotriene receptor antagonists
EP4069715A4 (en) * 2019-12-02 2024-08-14 EnliTISA (Shanghai) Pharmaceutical Co., Ltd. PEPTIDES AND THEIR USE IN THE TREATMENT OF INFLAMMATION

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