WO2017028025A1 - 贻贝粘蛋白产品及其抑制粘膜炎症的应用 - Google Patents

贻贝粘蛋白产品及其抑制粘膜炎症的应用 Download PDF

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Publication number
WO2017028025A1
WO2017028025A1 PCT/CN2015/087011 CN2015087011W WO2017028025A1 WO 2017028025 A1 WO2017028025 A1 WO 2017028025A1 CN 2015087011 W CN2015087011 W CN 2015087011W WO 2017028025 A1 WO2017028025 A1 WO 2017028025A1
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WIPO (PCT)
Prior art keywords
mussel mucin
cancer
mucosal inflammation
mussel
inflammation
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PCT/CN2015/087011
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English (en)
French (fr)
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
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by 江阴市本特塞缪森生命科学研究院有限公司 filed Critical 江阴市本特塞缪森生命科学研究院有限公司
Priority to PCT/CN2015/087011 priority Critical patent/WO2017028025A1/zh
Priority to PCT/CN2016/095364 priority patent/WO2017028777A1/zh
Priority to US15/751,551 priority patent/US10485848B2/en
Priority to MA042629A priority patent/MA42629A/fr
Priority to JP2018501271A priority patent/JP6816098B2/ja
Priority to DK16836641.7T priority patent/DK3335739T3/da
Priority to AU2016309397A priority patent/AU2016309397B2/en
Priority to MX2018000654A priority patent/MX2018000654A/es
Priority to CN201680041312.4A priority patent/CN108348636B/zh
Priority to SG11201800578YA priority patent/SG11201800578YA/en
Priority to EP16836641.7A priority patent/EP3335739B1/en
Priority to CA2995549A priority patent/CA2995549C/en
Priority to KR1020187003844A priority patent/KR20180033517A/ko
Publication of WO2017028025A1 publication Critical patent/WO2017028025A1/zh
Priority to HK18116071.8A priority patent/HK1257176A1/zh
Priority to US16/589,346 priority patent/US11458190B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • 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
    • A61K38/1767—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
    • C—CHEMISTRY; METALLURGY
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    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
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    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
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    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
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Definitions

  • the present invention relates generally to the fields of pharmaceuticals, cosmetics, medical products, disinfecting products, health care products, foods, and daily chemical products, and more particularly to mussel mucin products and their use in inhibiting mucosal inflammation.
  • the mucous membrane is the inner wall of various organs such as digestion, respiration, excretion, and reproduction in the body, and the surface of the mucus is kept moist by mucus, specifically including the moist lining of the oral cavity, the nasal cavity, the intestine, the vagina, the intestine, and the like.
  • Inflammation is a defensive response of the body to stimuli, manifested as redness, swelling, heat, pain and dysfunction.
  • the damage factor directly or indirectly causes destruction of tissues and cells, and on the other hand, through inflammation and hyperemia and exudation reactions, dilution, killing and surrounding damage factors.
  • the damaged tissue is repaired and healed by the regeneration of parenchymal and interstitial cells. Therefore, it can be said that inflammation is a unified process of injury and damage resistance.
  • 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 through its own positive charge and static between the human body's cells and tissue negative charges Electrical interactions are tightly bound to cells and tissues to provide protection and treatment.
  • 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.
  • 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 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 treatment of mucosal inflammation.
  • 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 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 prepared as 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.
  • the drug may be a liquid agent, a gel, or a foaming agent.
  • the medicine can be administered orally, by sublingual (sublingual), perfusion (rectal administration), dripping (eye), spraying (mouth, nose), inhalation (mouth, nose), spraying (mouth, nose, ear, cervix) Etc., laparoscopic (uterine cavity, abdominal cavity, etc.), targeted local sustained release, targeted administration, and can be administered at 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 may be a liquid agent, a gel, or a foaming agent.
  • the medical device can pass through the mouth Oral, sublingual (sublingual), perfusion (rectal administration), instillation (eye), spray (mouth, nose), inhalation (mouth, nose), spraying (mouth, nose, ear, cervix, etc.), endoscope It is used in a manner of (uterine cavity, abdominal cavity, etc.), 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 to prepare a cosmetic using an auxiliary material which is acceptable in the field of cosmetics.
  • the cosmetic may be a liquid, a gel, or a foaming agent.
  • the cosmetic can be administered orally, by sublingual (sublingual), perfusion (rectal administration), dripping (eye), spraying (mouth, nose), inhalation (mouth, nose), spraying (mouth, nose, ear, cervix) Etc., laparoscopic (uterine cavity, abdominal cavity, etc.), targeted local sustained release, targeted administration, and can be administered at low temperature or in a heated manner.
  • 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 gelling agent, or a foaming agent.
  • the disinfecting product can be administered orally, by sublingual (sublingual), perfusion (rectal administration), dripping (eye), spraying (mouth, nose), inhalation (mouth, nose), spraying (mouth, nose, ear, Cervical, etc., laparoscopic (uterine cavity, abdominal cavity, etc.), targeted local sustained release, targeted administration, and can be administered at 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 supplement or food may be a liquid, a gel, or a foam.
  • the health care product or food can be administered orally, by sublingual (sublingual), perfusion (rectal administration), dripping (eye), spraying (mouth, nose), inhalation (mouth, nose), spraying (mouth, nose, Ear, cervix, etc.), laparoscopic (uterine cavity, abdominal cavity, etc.), targeted local sustained release, targeted administration, and can be administered at low temperature or heating.
  • 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 for daily use, including shampoos, shower gels, and the like.
  • the daily chemical product may be a liquid agent, a gel agent, or a foaming agent.
  • the daily chemical product can be administered orally, by sublingual (sublingual), perfusion (rectal administration), dripping (eye), spraying (mouth, nose), inhalation (mouth, nose), spraying (mouth, nose, ear) , cervix, etc.), laparoscopic (uterine cavity, abdominal cavity, etc.), targeted local sustained release, targeted administration, and can be administered at low temperature or heating.
  • Another object of the invention is to provide an application of a mussel mucin product to inhibit mucosal inflammation.
  • mussel mucin can alleviate redness, edema, subcutaneous tissue fluid exudation, and mucosal damage caused by various mucosal inflammations.
  • mucosal inflammations include oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagitis, gastritis, enteritis, cervicitis, endometritis, and inflammation caused by inhalation injuries.
  • Oral mucositis is a disease that occurs in the oral cavity or soft tissue.
  • the clinical manifestation is oral mucosal disease refers to the damage of the oral mucosa.
  • the specific symptoms are: mouth ulceration, dry tongue, hoarseness, dry mouth and bitterness, and then oral lichen planus.
  • Oral diseases such as stomatitis, recurrent aphthous ulcers, cheilitis, etc., lead to eating difficulties, unbearable oral pain, uncomfortable, and once the disease is triggered, it will recur and be more serious than once.
  • Oral mucositis can lead to a variety of complications in the body, directly affecting the patient's health and life. At present, clinically, the symptoms are often controlled by Western medicine, but it is difficult to cure. It has been listed as one of the major problems of oral diseases.
  • Rhinitis a nasal inflammatory disease, is inflammation of the nasal mucosa caused by viruses, bacteria, allergens, various physical and chemical factors, and certain systemic diseases.
  • the main pathological changes of rhinitis are nasal mucosal congestion, swelling, exudation, hyperplasia, atrophy or necrosis.
  • Otitis media is an inflammatory reaction of the middle ear mucosa and is an inflammatory lesion involving all or part of the structure of the middle ear (including the eustachian tube, tympanic cavity, sinus sinus, and mastoid air chamber).
  • Conjunctivitis is a general term for the inflammatory reaction of the conjunctival tissue under the influence of the outside and the body's own factors. Although conjunctivitis itself does not have a serious effect on vision, it can cause vision damage when its inflammation affects the cornea or causes complications. According to the condition and course of conjunctivitis, it can be divided into acute, subacute and chronic; according to the cause, it can be divided into bacterial, viral, chlamydia, fungal and allergic; according to the characteristics of conjunctival lesions, Divided into acute follicular conjunctivitis, chronic follicular conjunctivitis, membranous and pseudomembranous conjunctivitis. The clinical manifestations of conjunctivitis are conjunctival hyperemia and increased secretion.
  • Pharyngitis is inflammation of the pharyngeal mucosa and its lymphoid tissue. Acute pharyngitis is often part of the upper respiratory tract infection and is often caused by viral infections. The lesion can be characterized by acute simple pharyngitis and acute suppurative pharyngitis. Chronic pharyngitis can be divided into chronic simple pharyngitis, chronic hypertrophic pharyngitis and chronic atrophic pharyngitis.
  • Laryngitis is inflammation of the laryngeal mucosa and submucosal tissue. It is characterized by clinical cough and laryngeal swelling, warming and pain. According to the cause and clinical course, it can be divided into primary and secondary, acute and chronic laryngitis. Clinically, acute catarrhal laryngitis is common and often complicated by pharyngitis.
  • Tracheitis is an inflammatory change of the trachea and bronchus caused by infection or non-infectious factors.
  • the secretion of mucus is increased.
  • the activity of respiratory enzymes in the epithelial villus of the trachea is reduced due to the lack of negative ions, which affects the secretion function of the alveoli and the ventilation and exchange of the lungs.
  • Gas function Clinically, it is characterized by long-term cough, cough or wheezing.
  • Esophagitis refers to inflammation caused by edema and congestion due to irritation or injury in the superficial or deep tissues of the esophageal mucosa.
  • Chemical stimuli include stomach acid, bile, spirits, and strong acids, alkalis, drugs, etc.
  • physical stimuli include hot foods, beverages, esophageal foreign bodies (fishbone, etc.) incarceration, long-term placement of nasogastric tubes.
  • Tuberculosis, fungal (candida) or viral infection can also cause esophagitis due to localized damage to the esophagus due to chemotherapy or radiation therapy, or a decrease in the patient's own resistance.
  • Gastritis is an acute and chronic inflammation of the gastric mucosa caused by a variety of different causes, often accompanied by epithelial damage, mucosal inflammatory response and epithelial regeneration.
  • Acute simple gastritis refers to acute extensive or localized acute inflammation of the gastric mucosa caused by various extrinsic and intrinsic factors. Symptoms and signs of acute simple gastritis vary from disease to cause, and their causes are diverse, including acute stress, drugs, ischemia, bile reflux, and infection. Clinically, acute simple gastritis is divided into acute erosive gastritis, acute suppurative gastritis, and acute corrosive gastritis.
  • Chronic gastritis refers to various chronic gastric mucosal inflammatory lesions caused by different causes, and its incidence rate ranks first among various stomach diseases. Common are chronic superficial gastritis, chronic erosive gastritis and chronic atrophic gastritis. Chronic gastritis mucosal intestinal metaplasia, often involving the cardia, accompanied by loss of G cells and decreased secretion of gastrin, may also involve the body, accompanied by loss of acid secretion glands, leading to a decrease in gastric acid, pepsin and endogenous factors .
  • Enteritis is intestinal inflammation and colitis caused by bacteria, viruses, fungi, and parasites.
  • Clinical manifestations include abdominal pain, diarrhea, septic flushing or mucus pus and blood. Some patients may have a feeling of fever, so it is also known as infectious diarrhea.
  • Enteritis is divided into acute and chronic according to the length of the disease. Common clinical symptoms are chronic bacterial dysentery, chronic amoebic dysentery, schistosomiasis, non-specific ulcerative colitis and limited enteritis.
  • Cervical mucositis or cervicitis lesions are confined to the cervical mucosa and submucosal tissue, the appearance of the cervix is very smooth, the cervix is blocked by purulent secretions, sometimes the cervical mucosa hyperplasia protrudes to the mouth, visible cervix Congestive redness. Cervical hypertrophy can be caused by hyperemia, edema, inflammatory cell infiltration and connective tissue hyperplasia of the cervical mucosa and submucosal tissue.
  • Endometritis is an inflammatory change in the structure of the endometrium caused by various causes.
  • the uterine cavity has good drainage conditions and periodic endometrial ablation, so that there is very little chance of inflammation staying in the endometrium for a long time, but Inflammatory treatment of the acute phase is not complete, or the source of infection is often present, and inflammation can be repeated.
  • Endometritis can be divided into acute endometritis and chronic endometritis.
  • Inflammation caused by inhalation injury refers to inhalation of high heat vapor, accidental drinking of boiling water, head and neck burns caused by inhalation of flame or dry hot air to cause mucosal burns.
  • the initial appearance of the lesion is mucosal congestion, edema, erosion, cellulose exudation, and the formation of white membrane.
  • Mucosal edema begins at 1-2 hours after injury and reaches a peak at 4-8 hours. After 2-3 days, the edema gradually subsides, and the leucorrhea falls off to form ulcers of varying depths. In severe cases, local tissue necrosis and even perforation of the esophagus or trachea.
  • the mussel mucin of the present invention can be used for the treatment of oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagitis, gastritis, enteritis, cervicitis, endometritis, inhalation Inflammation caused by injury, etc.
  • the mussel mucin of the present invention can be used to inhibit oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagitis, gastritis, enteritis, cervicitis, endometritis, etc.
  • 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.
  • the mussel mucin application according to any one of embodiments 1 to 5, wherein the mucosal inflammation is selected from the group consisting of: oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagus Inflammation, gastritis, enteritis, cervicitis, endometritis, inflammation caused by inhalation injury, etc.
  • the mucosal inflammation is selected from the group consisting of: oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagus Inflammation, gastritis, enteritis, cervicitis, endometritis, inflammation caused by inhalation injury, etc.
  • the mussel mucin application according to any one of embodiments 1 to 5, wherein the mucosal inflammation is selected from the group consisting of: oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagitis, Oral cancer, nasopharyngeal cancer, middle ear cancer, conjunctival cancer, throat cancer, tracheal cancer, esophageal cancer, gastric cancer, intestinal cancer, cervical cancer, endometrial cancer, etc. caused by gastritis, enteritis, cervicitis, endometritis, etc. .
  • composition may be by oral administration, sublingual (sublingual), perfusion (rectal administration), instillation (eye), spray (mouth, nose), Inhalation (mouth, nose), spraying (mouth, nose, ear, cervix, etc.), endoscopy (uterine cavity, abdominal cavity, etc.), targeted local sustained release, targeted administration.
  • a medicament for the treatment of mucosal inflammation 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 treating mucosal inflammation comprising a 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 cosmetic for treating mucosal inflammation comprising mussel mucin and a carrier acceptable for the cosmetic field, wherein the concentration of mussel mucin may be from 0.1 to 15.0 mg/ml.
  • a disinfecting product for the treatment of mucosal inflammation comprising a mussel mucin and a carrier acceptable for the field of disinfecting products, wherein the concentration of mussel mucin may be from 0.1 to 15.0 mg/ml.
  • a health care product/food for treating mucosal inflammation comprising mussel mucin and a health care/food-acceptable carrier, wherein the concentration of mussel mucin may be from 0.1 to 15.0 mg/ml.
  • a daily chemical product for the treatment of mucosal inflammation comprising a mussel mucin and a carrier acceptable for use in the field of daily chemical products, wherein the mussel mucin concentration may be from 0.1 to 15.0 mg/ml.
  • mucosal inflammation can be selected from the group consisting of: oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagitis, gastritis , enteritis, cervicitis, endometritis, inflammation caused by inhalation injury.
  • mucosal inflammation can be selected from the group consisting of: oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, Oral cancer, nasopharyngeal cancer, middle ear cancer, conjunctival cancer, throat cancer, tracheal cancer, esophageal cancer, gastric cancer, intestinal cancer, cervical cancer, intrauterine caused by esophagitis, gastritis, enteritis, cervicitis, endometritis Membrane cancer and the like.
  • a medical device for treating mucosal inflammation wherein the mucosal inflammation can be selected from the group consisting of: oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagitis, Gastritis, enteritis, cervicitis, endometritis, inflammation caused by inhalation injury, etc.
  • a medical device for treating mucosal inflammation wherein the mucosal inflammation may be selected from the group consisting of: oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagitis, Oral cancer, nasopharyngeal cancer, middle ear cancer, conjunctival cancer, throat cancer, tracheal cancer, esophageal cancer, gastric cancer, intestinal cancer, cervical cancer, endometrial cancer, etc. caused by gastritis, enteritis, cervicitis, endometritis, etc. .
  • mucosal inflammation may be selected from the group consisting of: oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagitis, gastritis , enteritis, cervicitis, endometritis, inflammation caused by inhalation injury.
  • mussel mucin in a cosmetic for treating mucosal inflammation, wherein the mucosal inflammation can be selected from the group consisting of: oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagitis, gastritis Oral cancer, nasopharyngeal cancer, middle ear cancer, conjunctival cancer, throat cancer, tracheal cancer, esophageal cancer, gastric cancer, intestinal cancer, cervical cancer, endometrial cancer, etc. caused by enteritis, cervicitis and endometritis.
  • mussel mucin in a disinfecting product for treating mucosal inflammation, wherein the mucosal inflammation can be selected from the group consisting of: oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagitis, Gastritis, enteritis, cervicitis, endometritis, inflammation caused by inhalation injury, etc.
  • a disinfecting product for treating mucosal inflammation wherein said mucosal inflammation may be selected from the group consisting of: oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagitis, Oral cancer, nasopharyngeal cancer, middle ear cancer, conjunctival cancer, throat cancer, tracheal cancer, esophageal cancer, gastric cancer, intestinal cancer, cervical cancer, endometrial cancer, etc. caused by gastritis, enteritis, cervicitis, endometritis, etc. .
  • mucosal inflammation may be selected from the group consisting of: oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagus Inflammation, gastritis, enteritis, cervicitis, endometritis, inflammation caused by inhalation injury Symptoms, etc.
  • mucosal inflammation may be selected from the group consisting of: oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagus Oral cancer, nasopharyngeal cancer, middle ear cancer, conjunctival cancer, throat cancer, tracheal cancer, esophageal cancer, gastric cancer, intestinal cancer, cervical cancer, endometrium caused by inflammation, gastritis, enteritis, cervicitis, endometritis Cancer, etc.
  • mussel mucin in a daily chemical product for treating mucosal inflammation, wherein the mucosal inflammation can be selected from the group consisting of: oral mucositis, rhinitis, otitis media, conjunctivitis, pharyngitis, laryngitis, bronchitis, esophagitis Oral cancer, gastroenteritis, enteritis, cervicitis, endometritis, etc., oral cancer, nasopharyngeal cancer, middle ear cancer, conjunctival cancer, throat cancer, tracheal cancer, esophageal cancer, stomach cancer, intestinal cancer, cervical cancer, endometrial cancer Wait.
  • Example 1 Application of mussel mucin liquid medical device in the treatment of compound aphthous ulcer.
  • 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 medical device.
  • the two groups were used 3 times a day, spraying the affected area after meals, spraying 2-3 times each time until the affected area was completely covered with 0.1% citric acid solution or mussel mucin water.
  • Solution medical device coverage In the medical device group spraying mussel mucin aqueous solution, the pain of the affected area was significantly weakened within 5-15 minutes, and the visual analog VAS score decreased from 5.0-7.0 to 1.0-3.0 before treatment, and the analgesic time lasted for 2-7 hours. There was no change in the VAS score of the affected area before and after the control group. As the use time prolonged, the duration of analgesia was prolonged, and the interval of use was prolonged, showing no dependence.
  • Example 2 Application of mussel mucin gel medical device in the treatment of compound aphthous ulcer.
  • Twenty patients with light a compound aphthous ulcer diagnosed by experts in oral mucosa were enrolled in the study.
  • the number of ulcers in the selected patients was greater than 5, and the ulcer site was not limited.
  • the largest ulcer was selected as the target ulcer.
  • the target ulcer diameter was less than 1 cm.
  • the selected patients were randomly divided into the control group and the experimental group.
  • the control group was treated with a blank gel matrix containing no mussel mucin
  • the experimental group was treated with a mussel mucin gel medical device.
  • the two groups were used three times a day. After the meal, the affected area was sprayed, and each time the spray was applied 2-3 times until the affected area was completely covered by a blank gel or mussel mucin gel medical device.
  • the pain in the affected area was significantly weakened within 5-13 minutes, from the visual analog VAS score of 5.0-7.0 to 1.0-3.0 before treatment, and the analgesic time lasted for 2-9 hours. There was no change in the VAS score of the affected area before and after the control group. As the use time prolonged, the duration of analgesia was prolonged, and the interval of use was prolonged, showing no dependence.
  • Example 3 Application of mussel mucin liquid daily chemical product in the treatment of rhinitis.
  • a mussel mucin solution having a concentration of 0.5 mg/ml was taken and diluted 5 times with 0.001% acetic acid to a mussel mucin content of 0.1 mg/ml to obtain a mussel mucin liquid daily product.
  • Example 4 Application of mussel mucin liquid medicine in the treatment of rhinitis.
  • a mussel mucin solution having a concentration of 2.0 mg/ml was diluted 10 times with 0.05% citric acid to a mussel mucin content of 0.2 mg/ml to obtain a mussel mucin liquid medicine.
  • Ten patients with rhinitis were enrolled and confirmed by otolaryngologists.
  • the patient showed nasal congestion and salivation, and the salivation was sticky or sticky.
  • the patient is administered by nebulized inhalation every day, and the mussel mucin liquid medicine is inhaled once a day.
  • Ten patients had different degrees of nasal congestion relief after using mussel mucin liquid medicine for 3 days. After 7 days of use, the nasal congestion of all patients was alleviated, and all patients had no pus or mucous nasal discharge. It is proved that the mussel mucin liquid medicine of the present invention can be used for the treatment of rhinitis.
  • Example 5 Application of mussel mucin gel disinfectant product in the treatment of otitis media.
  • Example 6 Application of mussel mucin liquid medicine in the treatment of otitis media.
  • a mussel mucin solution was prepared by taking a 5 mg/ml mussel mucin solution, adding an equal volume of 0.001% acetic acid to 2.5 mg/ml, and a solution pH of 3.0 to prepare a mussel mucin liquid medicine having a mussel mucin content of 2.5 mg/ml.
  • Example 7 Application of mussel mucin liquid medical device in the treatment of conjunctivitis.
  • 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 hydrogel health supplement in the treatment of pharyngitis.
  • Example 9 Application of mussel mucin gel drug in the treatment of laryngitis.
  • 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 drug, wherein The mussel mucin concentration was 3 mg/ml.
  • Example 10 Application of mussel mucin liquid health care product in the treatment of tracheitis.
  • 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 3.0 mg/ml.
  • bronchitis Twelve patients with bronchitis were enrolled. The clinical manifestations were cough, cough, and asthma. The patient was diagnosed by a respiratory doctor before being admitted to the group. The patient was treated with aerosol inhalation for 30 minutes each time, once a day. After 3 days of use, the patient's cough was reduced and the amount of cough was reduced. After 7 days of use, all patients had no cough and one patient was still accompanied by a mild cough. It is proved that the mussel mucin liquid health care product of the present invention can be used for the treatment of bronchitis.
  • Example 11 Application of mussel mucin liquid medicine in the treatment of esophagitis.
  • the mussel mucin solution was taken and diluted with an aqueous borate solution to obtain a mussel mucin liquid agent having a pH of 5.5, wherein the mussel mucin concentration was 2.5 mg/ml.
  • Example 12 Application of mussel mucin hydrogel drug in the treatment of gastritis.
  • 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.
  • the mussel mucin hydrogel drug is further wrapped in a gastric-soluble coating material to form a gastric-soluble sustained-release administration preparation.
  • Twenty patients with gastritis were enrolled in the study.
  • the patients were enrolled in the gastroscope of the digestive department.
  • the selected patients were orally administered a gastric-soluble sustained-release preparation containing a mussel mucin hydrogel drug once a day, one capsule at a time.
  • gastroscopy showed that the ulcer surface of the subjects had different degrees of healing.
  • gastroscopy was performed, and the ulcer surface of the subject was completely healed.
  • Example 13 Application of mussel mucin liquid medicine in the treatment of acute enteritis.
  • the mussel mucin freeze-dried powder was prepared, and a 1.0 mg/ml aqueous solution was prepared by using physiological saline, and the pH was adjusted to 5.8 with acetic acid to obtain a mussel mucin liquid medicine.
  • the mussel mucin liquid medicine is further wrapped in an enteric coating material to form an enteric sustained-release preparation.
  • Example 14 Application of mussel mucin gel disinfectant product in the treatment of cervicitis.
  • the mussel mucin solution was taken, mixed with glycerol in a volume ratio of 1:1, and the pH was adjusted to 4.8 with acetic acid to obtain a mussel mucin gel disinfecting product.
  • Example 15 Application of mussel mucin gel medical device in the treatment of cervicitis.
  • the mussel mucin solution is mixed with gelatin and alginate at a mass ratio of 4:1:1, and the pH is adjusted to 4.8 with acetic acid to obtain a mussel mucin gel medical device, wherein mussel mucin concentration It is 5.0 mg/mL.
  • Shellin products can be used in the treatment of cervicitis.
  • Example 16 Application of mussel mucin foam medical device in the treatment of cervicitis.
  • the mussel mucin solution was mixed with hydroxypropylmethylcellulose at a mass ratio of 4:1, and the pH was adjusted to 4.8 with acetic acid to obtain a mussel mucin foam medical device, wherein the mussel mucin concentration was 5 mg. /mL.
  • Example 17 Application of mussel mucin liquid medicine in the treatment of endometritis.
  • the mussel mucin solution was taken and diluted to 3 mg/ml with 0.1% citric acid, and the pH of the solution was 6.5 after dilution to obtain a mussel mucin liquid medicine.
  • the catheter After the drug solution has entered the uterine cavity, the catheter is pulled out, and the supine or gluteal high bed is placed for 1-2 hours. 1 time a day. After 10 days of use, the pelvic region of the patient had no pain and the leucorrhea became normal, demonstrating that the mussel mucin drug of the present invention can be used for the treatment of endometritis.
  • Example 18 Application of mussel mucin liquid medicine in the treatment of inhalation injury.
  • a mussel mucin solution of 10.0 mg/ml was diluted 2 times with acetic acid to a mussel mucin concentration of 5.0 mg/ml, and the pH of the solution was 6.8, to obtain a mussel mucin liquid medicine.

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Abstract

本发明公开了贻贝粘蛋白或其制剂抑制粘膜炎症的应用。所述粘膜炎症包括口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎、吸入性损伤引起的炎症等；以及由上述炎症引起的口腔癌、鼻咽癌、中耳癌、结膜癌、咽喉癌、气管癌、食管癌、胃癌、肠癌、宫颈癌、子宫内膜癌等。

Description

贻贝粘蛋白产品及其抑制粘膜炎症的应用 技术领域
本发明大体涉及药品、化妆品、医疗产品、消毒产品、保健品、食品以及日化产品技术领域，更具体地，涉及贻贝粘蛋白产品及其在抑制粘膜炎症中的应用。
背景技术
粘膜是体内的消化、呼吸、排泄、生殖等各器官的内壁，由粘液保持其表面湿润，具体地包括口腔、鼻腔、肠管、阴道、肠道等与外界相通体腔的湿润衬里。
炎症是机体对于刺激的一种防御反应，表现为红、肿、热、痛和功能障碍。在炎症过程中，一方面损伤因子直接或间接造成组织和细胞的破坏，另一方面通过炎症充血和渗出反应，稀释、杀伤和包围损伤因子。同时通过实质和间质细胞的再生使受损的组织得以修复和愈合。因此可以说炎症是损伤和抗损伤的统一过程。
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。
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。
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。
发明内容
本发明的一个目的是提供贻贝粘蛋白产品。
在本文中使用的贻贝粘蛋白是指从贻贝科(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中的一种或几种的混合物。在本文中使用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。
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。
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，从而不利于粘膜炎症的治疗。
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的范围内治疗效果更佳。
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。
在本文中使用的贻贝粘蛋白还可以制备成泡沫剂。示例性的贻贝粘蛋白泡沫剂是由贻贝粘蛋白溶液或冻干粉与发泡剂基质混合制得，所述发泡剂基质材料可以包括羟丙甲基纤维素、明胶、聚乙二醇十二烷基硫酸钠、脂肪醇聚氧乙烯醚磺酸钠、玉米麸质粉、丙烯酰胺之一或其任意组合。特别有益的是，泡沫剂在消泡过程中释放压力，更有利于贻贝粘蛋白在患处的附着、渗透和起效。同时泡沫剂消泡时间长，延长了作用时间，使贻贝粘蛋白起效更加显著。
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。
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》。
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、泡沫剂。所述药品可通过口服、含化(舌下)、灌注(直肠给药)、滴入(眼)、喷雾(口、鼻)、吸入(口、鼻)、喷涂(口、鼻、耳、宫颈等)、腔镜(宫腔、腹腔等)、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。
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、泡沫剂。所述医疗器械可通过口 服、含化(舌下)、灌注(直肠给药)、滴入(眼)、喷雾(口、鼻)、吸入(口、鼻)、喷涂(口、鼻、耳、宫颈等)、腔镜(宫腔、腹腔等)、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。
在本文中使用的贻贝粘蛋白可以作为主要原料，采用化妆品领域可接受的辅料制备化妆品。所述化妆品可以是液体剂、凝胶剂、泡沫剂。所述化妆品可通过口服、含化(舌下)、灌注(直肠给药)、滴入(眼)、喷雾(口、鼻)、吸入(口、鼻)、喷涂(口、鼻、耳、宫颈等)、腔镜(宫腔、腹腔等)、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。
在本文中使用的贻贝粘蛋白可以作为主要原料，采用消毒产品领域可接受的辅料制备消毒产品。本文中使用的术语消毒产品是指用化学、物理、生物的方法杀灭或者消除环境中病原微生物的消毒剂、消毒器械、卫生用品和一次性使用的医疗用品。所述消毒产品可以是液体剂、凝胶剂、泡沫剂。所述消毒产品可通过口服、含化(舌下)、灌注(直肠给药)、滴入(眼)、喷雾(口、鼻)、吸入(口、鼻)、喷涂(口、鼻、耳、宫颈等)、腔镜(宫腔、腹腔等)、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。
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、泡沫剂。所述保健品或食品可通过口服、含化(舌下)、灌注(直肠给药)、滴入(眼)、喷雾(口、鼻)、吸入(口、鼻)、喷涂(口、鼻、耳、宫颈等)、腔镜(宫腔、腹腔等)、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。
在本文中使用的贻贝粘蛋白可以作为主要原料，采用日化产品领域可接受的辅料制备日化产品。本文中所使用的术语日化产品是指平日常用的科技化学制品，包括洗发水、沐浴露等。所述日化产品可以是液体剂、凝胶剂、泡沫剂。所述日化产品可通过口服、含化(舌下)、灌注(直肠给药)、滴入(眼)、喷雾(口、鼻)、吸入(口、鼻)、喷涂(口、鼻、耳、宫颈等)、腔镜(宫腔、腹腔等)、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。
本发明的另一个目的是提供贻贝粘蛋白产品抑制粘膜炎症的应用。
出人意料地，本发明人发现贻贝粘蛋白可缓解各种粘膜炎症引起的红肿、水肿、皮下组织液渗出、粘膜损伤。
常见的粘膜炎症有口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎、吸入性损伤引起的炎症等。
口腔粘膜炎是发生在口腔或软组织的疾病，临床表现为口腔粘膜病指口腔内粘膜的损坏，具体症状为：口舌溃烂，舌体干裂，声音嘶哑，口干口苦，继而引发口腔扁平苔癣，口腔炎，复发性口疮，唇炎等口腔疾患，导致饮食困难，口腔疼痛难忍，苦不堪言，而且一旦病情引发，便反复发作且一次比一次严重。口腔粘膜炎可导致体内多种并发症，直接影响病患的身体健康及生活工作。目前，临床上对此病症常施以西药控制症状，但难以根治，被医界列为口腔病重大难题之一。
鼻炎即鼻腔炎性疾病，是病毒、细菌、变应原、各种理化因子以及某些全身性疾病引起的鼻腔黏膜的炎症。鼻炎的主要病理改变是鼻腔黏膜充血、肿胀、渗出、增生、萎缩或坏死等。
中耳炎是中耳粘膜的炎症性反应，是累及中耳(包括咽鼓管、鼓室、鼓窦及乳突气房)全部或部分结构的炎性病变。
结膜炎是结膜组织在外界和机体自身因素的作用下发生的炎性反应的统称。虽然结膜炎本身对视力影响并不严重，但是当其炎症波及角膜或引起并发症时，可导致视力的损害。根据结膜炎的病情及病程，可分为急性、亚急性和慢性三类；根据病因又可分为细菌性、病毒性、衣原体性、真菌性和变态反应性等；根据结膜的病变特点，可分为急性滤泡性结膜炎、慢性滤泡性结膜炎、膜性及假膜性结膜炎等。结膜炎临床表现为结膜充血及分泌物增多等。
咽炎是咽粘膜及其淋巴组织的炎症。急性咽炎常为上呼吸道感染的一部分，多由病毒感染引起。病变可表现为急性单纯性咽炎和急性化脓性咽炎。慢性咽炎可分为慢性单纯性咽炎、慢性肥厚性咽炎和慢性萎缩性咽炎。
喉炎是喉粘膜及粘膜下层组织的炎症。临床上以剧咳及喉部肿胀、增温和疼痛为特征。依病因和临床经过可分为原发性和继发性、急性与慢性喉炎。临床上则以急性卡他性喉炎为多见，且常与咽炎并发。
气管炎是由于感染或非感染因素引起的气管、支气管黏膜炎性变化，黏液分泌增多，因缺乏负离子而使气管黏膜上皮绒毛内呼吸酶的活性降低，影响肺泡的分泌功能及肺的通气和换气功能。临床上以长期咳嗽、咳痰或伴有喘息为主要特征。
食管炎即食道炎，泛指食管粘膜浅层或深层组织由于受到刺激或损伤，发生水肿和充血而引发的炎症。化学性刺激包括胃酸、胆汁、烈酒以及强酸、强碱、药物等；物理性刺激包括烫的食物、饮料，食管异物(鱼刺等)嵌顿，长期放置鼻胃管等。由于化学治疗、放射治疗导致食管局部受损，或病患本身抵抗力下降导致结核杆菌、真菌(念珠菌)或病毒感染亦可引发食管炎。
胃炎是多种不同病因引起的胃黏膜急性和慢性炎症，常伴有上皮损伤、黏膜炎症反应和上皮再生。急性单纯性胃炎指各种外在和内在因素引起的急性广泛性或局限性的胃黏膜急性炎症。急性单纯性胃炎的症状体征因病因不同而不尽相同，其病因多样，包括急性应激、药物、缺血、胆汁反流和感染等。临床上将急性单纯性胃炎分为急性糜烂性胃炎、急性化脓性胃炎、急性腐蚀性胃炎。慢性胃炎是指不同病因引起的各种慢性胃黏膜炎性病变，其发病率在各种胃病中居首位。常见的有慢性浅表性胃炎、慢性糜烂性胃炎和慢性萎缩性胃炎。慢性胃炎黏膜肠上皮化生，常累及贲门，伴有G细胞丧失和胃泌素分泌减少，也可累及胃体，伴有泌酸腺的丧失，导致胃酸，胃蛋白酶和内源性因子的减少。
肠炎是细菌、病毒、真菌和寄生虫等引起的小肠炎和结肠炎。临床表现主要有腹痛、腹泻、稀水便或黏液脓血便。部分病患可有发热等感觉，故亦称感染性腹泻。肠炎按病程长短不同，分为急性和慢性两类。临床常见的有慢性细菌性痢疾、慢性阿米巴痢疾、血吸虫病、非特异性溃疡性结肠炎和限局性肠炎等。
宫颈粘膜炎或称宫颈管炎，病变局限于宫颈管粘膜及粘膜下组织，宫颈阴道部外观很光滑，宫颈外口有脓性分泌物堵塞，有时宫颈管粘膜增生向外口突出，可见宫颈口充血发红。由于宫颈管粘膜及粘膜下组织充血、水肿、炎性细胞浸润和结缔组织增生，可使宫颈肥大。
子宫内膜炎是各种原因引起的子宫内膜结构发生炎性改变。宫腔有良好的引流条件及周期性内膜剥脱，使炎症极少机会长期停留于子宫内膜，但如 急性期炎症治疗不彻底，或经常存在感染源，则可反复发作炎症。子宫内膜炎可分为急性子宫内膜炎和慢性子宫内膜炎。
吸入性损伤引起的炎症是指吸入高热蒸气、误饮沸水，头颈烧伤者因吸入火焰或干热空气致黏膜烧伤。病变初起表现为黏膜充血、水肿、糜烂、有纤维素渗出、形成白膜。黏膜水肿于伤后1-2小时开始，4-8小时达高峰，2-3天后水肿逐渐消退，白膜脱落形成深浅不等的溃疡。严重者局部组织坏死，甚至造成食管或气管穿孔。
在一个方面，本发明的贻贝粘蛋白可用于治疗口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎、吸入性损伤引起的炎症等。
在另一个方面，本发明的贻贝粘蛋白可用于抑制口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎等引起的口腔癌、鼻咽癌、中耳癌、结膜癌、咽喉癌、气管癌、食管癌、胃癌、肠癌、宫颈癌、子宫内膜癌等。
具体实施方式
本发明的实施方式包括：
1、贻贝粘蛋白在治疗粘膜炎症中的应用。
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。
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可以是0.1-15.0mg/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可以是以液体剂、凝胶剂或泡沫剂使用。
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。
6、根据实施方式1-5中任一项的贻贝粘蛋白应用，其中所述粘膜炎症可以选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管 炎、胃炎、肠炎、宫颈炎、子宫内膜炎、吸入性损伤引起的炎症等。
7、根据实施方式1-5中任一项的贻贝粘蛋白应用，其中所述粘膜炎症可以选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎等引起的口腔癌、鼻咽癌、中耳癌、结膜癌、咽喉癌、气管癌、食管癌、胃癌、肠癌、宫颈癌、子宫内膜癌等。
8、贻贝粘蛋白作为活性成分在用于治疗粘膜炎症的组合物中的应用，其中所述组合物可以是以液体剂、凝胶剂或泡沫剂使用。
9、根据实施方式9的贻贝粘蛋白应用，其中所述组合物可以是通过口服、含化(舌下)、灌注(直肠给药)、滴入(眼)、喷雾(口、鼻)、吸入(口、鼻)、喷涂(口、鼻、耳、宫颈等)、腔镜(宫腔、腹腔等)、定向局部缓释、靶向给药的方式使用。
10、根据实施方式9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。
11、一种用于治疗粘膜炎症的药品，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。
12、一种用于治疗粘膜炎症的医疗器械，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。
13、一种用于治疗粘膜炎症的化妆品，包括贻贝粘蛋白和化妆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。
14、一种用于治疗粘膜炎症的消毒产品，包括贻贝粘蛋白和消毒产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。
15、一种用于治疗粘膜炎症的保健品/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。
16、一种用于治疗粘膜炎症的日化产品，包括贻贝粘蛋白和日化产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。
17、贻贝粘蛋白在用于治疗粘膜炎症的药品中的应用，其中所述粘膜炎症可以选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎、吸入性损伤引起的炎症等。
18、贻贝粘蛋白在用于治疗粘膜炎症的药品中的应用，其中所述粘膜炎症可以选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、 食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎等引起的口腔癌、鼻咽癌、中耳癌、结膜癌、咽喉癌、气管癌、食管癌、胃癌、肠癌、宫颈癌、子宫内膜癌等。
19、贻贝粘蛋白在用于治疗粘膜炎症的医疗器械中的应用，其中所述粘膜炎症可以选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎、吸入性损伤引起的炎症等。
20、贻贝粘蛋白在用于治疗粘膜炎症的医疗器械中的应用，其中所述粘膜炎症可以选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎等引起的口腔癌、鼻咽癌、中耳癌、结膜癌、咽喉癌、气管癌、食管癌、胃癌、肠癌、宫颈癌、子宫内膜癌等。
21、贻贝粘蛋白在用于治疗粘膜炎症的化妆品中的应用，其中所述粘膜炎症可以选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎、吸入性损伤引起的炎症等。
22、贻贝粘蛋白在用于治疗粘膜炎症的化妆品中的应用，其中所述粘膜炎症可以选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎等引起的口腔癌、鼻咽癌、中耳癌、结膜癌、咽喉癌、气管癌、食管癌、胃癌、肠癌、宫颈癌、子宫内膜癌等。
23、贻贝粘蛋白在用于治疗粘膜炎症的消毒产品中的应用，其中所述粘膜炎症可以选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎、吸入性损伤引起的炎症等。
24、贻贝粘蛋白在用于治疗粘膜炎症的消毒产品中的应用，其中所述粘膜炎症可以选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎等引起的口腔癌、鼻咽癌、中耳癌、结膜癌、咽喉癌、气管癌、食管癌、胃癌、肠癌、宫颈癌、子宫内膜癌等。
25、贻贝粘蛋白在用于治疗粘膜炎症的保健品或食品中的应用，其中所述粘膜炎症可以选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎、吸入性损伤引起的炎 症等。
26、贻贝粘蛋白在用于治疗粘膜炎症的保健品或食品中的应用，其中所述粘膜炎症可以选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎等引起的口腔癌、鼻咽癌、中耳癌、结膜癌、咽喉癌、气管癌、食管癌、胃癌、肠癌、宫颈癌、子宫内膜癌等。
27、贻贝粘蛋白在用于治疗粘膜炎症的日化产品中的应用，其中所述粘膜炎症可以选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎、吸入性损伤引起的炎症等。
28、贻贝粘蛋白在用于治疗粘膜炎症的日化产品中的应用，其中所述粘膜炎症可以选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎等引起的口腔癌、鼻咽癌、中耳癌、结膜癌、咽喉癌、气管癌、食管癌、胃癌、肠癌、宫颈癌、子宫内膜癌等。
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、化妆品、消毒产品、保健品或食品、日化产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。
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。
实施例1：贻贝粘蛋白液体医疗器械在复方阿弗他溃疡治疗中的应用。
取浓度为10.0mg/ml的贻贝粘蛋白溶液1ml，加入9ml0.1％柠檬酸溶液，配制度为1.0mg/ml的贻贝粘蛋白水溶液医疗器械。收集经口腔粘膜科专家确诊的20例轻型复方阿弗他溃疡病患进行试验，入选病患溃疡数目大于5个，溃疡部位不限，选择最大的溃疡作为靶溃疡观察，靶溃疡直径小于1cm。
入选病患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医疗器械治疗。两组使用方法均为每日3次，饭后喷涂患处，每次喷涂2-3次至患处完全被0.1％柠檬酸溶液或贻贝粘蛋白水 溶液医疗器械覆盖。喷涂贻贝粘蛋白水溶液医疗器械组中，5-15分钟内患处疼痛明显减弱，从治疗前视觉模拟VAS评分5.0-7.0下降到1.0-3.0，止痛时间可持续2-7小时。对照组喷涂前后患处疼痛VAS评分无变化。随着使用时间延长，止痛持续时间延长，使用间隔延长，未表现出任何依赖性。
连续喷涂5天后，试验组6例病患溃疡部位均痊愈，对照组1例病患溃疡部位痊愈。连续喷涂7天后，试验组全部病例均痊愈对照组3例痊愈(参见表1)。
表1：
观察指标 对照组 试验组
平均起效时间(min) - 8.1±1.2
使用前VAS平均评分 5.6±1.0 5.9±0.9
使用后VAS平均评分 5.0±0.8 1.7±0.6
平均止痛持续时间(h) - 5.2±1.1
平均愈合时间(天) 10.5±1.9 5.9±1.2
实施例2：贻贝粘蛋白凝胶医疗器械在复方阿弗他溃疡治疗中的应用。
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1.0mg/ml。
收集经口腔粘膜科专家确诊的20例轻型复方阿弗他溃疡病患进行试验，入选病患溃疡数目大于5个，溃疡部位不限，选择最大的溃疡作为靶溃疡观察，靶溃疡直径小于1cm。
入选病患随机分为对照组和试验组，对照组采用不含贻贝粘蛋白的空白凝胶基质治疗，试验组采用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，饭后喷涂患处，每次喷涂2-3次至患处完全被空白凝胶或贻贝粘蛋白凝胶医疗器械覆盖。喷涂贻贝粘蛋白凝胶医疗器械组中，5-13分钟内患处疼痛明显减弱，从治疗前视觉模拟VAS评分5.0-7.0下降到1.0-3.0，止痛时间可持续2-9小时。对照组喷涂前后患处疼痛VAS评分无变化。随着使用时间延长，止痛持续时间延长，使用间隔延长，未表现出任何依赖性。
连续喷涂5天后，试验组7例病患溃疡部位均痊愈，对照组3例病患溃疡部位痊愈。连续喷涂7天后，试验组全部病例均痊愈对照组5例痊愈(参见表2)。
表2
观察指标 对照组 试验组
平均起效时间(min) - 7.6±1.0
使用前VAS平均评分 5.3±1.4 5.8±0.9
使用后VAS平均评分 5.0±1.1 1.3±0.7
平均止痛持续时间(h) - 7.3±1.8
平均愈合时间(天) 8.0±1.6 4.7±1.6
实施例3：贻贝粘蛋白液体日化产品在鼻炎治疗中的应用。
取浓度为0.5mg/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0.1mg/ml，得到贻贝粘蛋白液体日化产品。
收集鼻炎病患10例，经耳鼻喉科专家确诊后入组试验。病患表现有鼻塞、流涕现象，且流涕为粘稠性或粘脓性。病患每天用贻贝粘蛋白液体日化产品清洗鼻腔，早晚各1次。10例病患在使用贻贝粘蛋白液体日化产品5天后均出现不同程度的鼻塞缓解现象。至使用10天后，全部病患鼻塞情况均得到缓解，全部受试病患均无粘脓性或粘液性鼻涕现象。证明本发明的贻贝粘蛋白液体日化产品可用于鼻炎的治疗。
实施例4：贻贝粘蛋白液体药品在鼻炎治疗中的应用。
取浓度为2.0mg/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0.2mg/ml，得到贻贝粘蛋白液体药品。
收集鼻炎病患10例，经耳鼻喉科专家确诊后入组试验。病患表现有鼻塞、流涕现象，且流涕为粘稠性或粘脓性。病患每天采用雾化吸入方式给药，吸入贻贝粘蛋白液体药品，每日1次。10例病患在使用贻贝粘蛋白液体药品3天后均出现不同程度的鼻塞缓解现象。至使用7天后，全部病患鼻塞情况均得到缓解，全部受试病患均无粘脓性或粘液性鼻涕现象。证明本发明的贻贝粘蛋白液体药品可用于鼻炎的治疗。
实施例5：贻贝粘蛋白凝胶剂消毒产品在中耳炎治疗中的应用。
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消毒产品。
收集10例急性化脓性中耳炎病患，经耳鼻喉科专家确诊后入组试验。病患表现有耳痛、耳内有脓液流出现象。病患每天使用贻贝粘蛋白凝胶剂消毒产品，每日3次。10例病患在使用贻贝粘蛋白凝胶剂消毒品3天后均未再出现耳痛症状，且耳内脓液减少。至使用7天后，全部病患均无脓液流出现象。证明本发明的贻贝粘蛋白凝胶消毒产品可用于中耳炎的治疗。
实施例6：贻贝粘蛋白液体药品在中耳炎治疗中的应用。
取5mg/ml贻贝粘蛋白溶液，加入等体积的0.001％乙酸稀释至2.5mg/ml，溶液酸碱度为pH 3.0，制备贻贝粘蛋白含量2.5mg/ml的贻贝粘蛋白液体药品。
收集10例急性化脓性中耳炎病患，经耳鼻喉科专家确诊后入组试验。病患表现有耳痛、耳内有脓液流出现象。病患每天使用贻贝粘蛋白液体药品，每日3次。10例病患在使用贻贝粘蛋白液体药品3天后均未再出现耳痛症状，且耳内脓液减少。至使用7天后，全部病患均无脓液流出现象。证明本发明的液体药品可用于中耳炎的治疗。
实施例7：贻贝粘蛋白液体医疗器械在结膜炎治疗中的应用。
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。
入选15例结膜炎病患，表现为结膜充血，水样分泌物，眼部有刺激感，经眼科医生确认后入组。采用上述贻贝粘蛋白液体医疗器械滴至眼部患处，每日4次。喷涂贻贝粘蛋白液体医疗器械后，30分钟内患处刺激感减弱，使用该器械第1天减轻刺激时间可持续2-5小时。连续喷涂5天后，刺激感消失，结膜充血情况减弱，分泌物减少。连续喷涂上述贻贝粘蛋白液体医疗器械7天后，全部病患刺激和结膜充血情况均消失，分泌物情况恢复正常。证明本发明的贻贝粘蛋白液体医疗器械可用于结膜炎的治疗。
实施例8：贻贝粘蛋白水凝胶保健品在咽炎治疗中的应用。
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。
入选16例急性咽炎病患，表现为咽干、瘙痒、微痛、灼热感及异物感，继而有咽痛，多为灼痛，同时伴有粘膜充血，经耳鼻喉科医生确认后入组。采用上述贻贝粘蛋白水凝胶保健品喷涂患处，每日3次，饭后使用。喷涂该贻贝粘蛋白水凝胶保健品后，8-20分钟内患处瘙痒或疼痛感减弱，止痛时间可持续3.5-4.0小时。连续使用5天后，咽部疼痛感均消失，咽部粘膜充血情况恢复正常。证明本发明的贻贝粘蛋白水凝胶保健品可用于咽炎的治疗。
实施例9：贻贝粘蛋白凝胶药品在喉炎治疗中的应用。
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药品，其中贻贝粘蛋白浓度3mg/ml。
入选10例急性喉炎病患，表现为喉部干燥、刺痛、烧灼感、异物感等，经耳鼻喉科医生确认后入组。采用上述贻贝粘蛋白凝胶药品喷涂患处，每日3次，饭后使用。喷涂该贻贝粘蛋白凝胶药品后，7-16分钟内患处瘙痒或疼痛感减弱，止痛时间可持续3.0-4.0小时。连续使用5天后，喉部疼痛感、烧灼感及异物感均消失。证明本发明的贻贝粘蛋白药品可用于喉炎治疗。
实施例10：贻贝粘蛋白液体保健品在气管炎治疗中的应用。
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3.0mg/ml。
收集12例气管炎病患，临床表现为咳嗽、咳痰，并伴有气喘，病患经呼吸科医生确诊后方可入组试验。病患采用雾化吸入的方式治疗，每次30分钟，每日1次。使用3天后病患咳嗽减轻，咳痰量减少。至使用7天后，全部病患均无咳痰现象，1名病患仍伴有轻微咳嗽。证明本发明的贻贝粘蛋白液体保健品可用于气管炎的治疗。
实施例11：贻贝粘蛋白液体药品在食管炎治疗中的应用。
取贻贝粘蛋白溶液，用硼酸盐水溶液稀释得到贻贝粘蛋白液体剂，酸碱度为pH 5.5，其中贻贝粘蛋白浓度为2.5mg/ml。
收集20例食管炎病患进行试验，病患经食管镜检查表现为食管粘膜充血、水肿、表面糜烂及浅小溃疡，经消化内科大夫确诊后入组。病患采用食管镜给药，每日2次，每次3ml。在治疗第3天食管表面溃疡渗出及充血程度均由开始时的3分下降至2分(评分标准参见表3)。治疗第7天食管表面溃疡渗出及充血程度下降至1分。至治疗第10天食管表面溃疡渗出及充血程度降为0分。证明贻贝粘蛋白液体药品可用于食管炎的治疗。
表3
Figure PCTCN2015087011-appb-000001
实施例12：贻贝粘蛋白水凝胶药品在胃炎治疗中的应用。
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。进一步将贻贝粘蛋白水凝胶药品包裹在胃溶性包衣材料中形成胃溶性缓释给药制剂。
收集20例胃炎病患进行试验，病患经消化内科大夫胃镜检查确诊后入组。入选病患口服包含贻贝粘蛋白水凝胶药品的胃溶性缓释给药制剂，每日1次，每次1粒。治疗3天后胃镜检查，受试者胃部溃疡面均不同程度愈合趋势。 治疗5天后胃镜检查，受试者胃部溃疡面全部愈合。
实施例13：贻贝粘蛋白液体药品在急性肠炎治疗中的应用。
取贻贝粘蛋白冻干粉，用生理盐水配制成1.0mg/ml水溶液，用乙酸调整酸碱度为pH 5.8，获得贻贝粘蛋白液体药品。进一步将贻贝粘蛋白液体药品包裹在肠溶性包衣材料中形成肠溶性缓释给药制剂。
收集10例急性肠炎病患，临床表现为恶心、呕吐、腹泻，经肠镜检查后由消化内科大夫确诊为急性肠炎后入组。入组病患口服包含贻贝粘蛋白的肠溶性缓释给药制剂，每日1次，每次1粒。治疗2天后，病患恶心、呕吐、腹泻情况均得到缓解，证明贻贝粘蛋白液体药品可用于急性肠炎的治疗。
实施例14：贻贝粘蛋白凝胶剂消毒产品在宫颈炎治疗中的应用。
取贻贝粘蛋白溶液，与丙三醇按照1∶1的体积比混合，用乙酸调整酸碱度为pH 4.8，获得贻贝粘蛋白凝胶消毒产品。
收集12例宫颈炎病患，临床表现为阴道分泌物增多，粘液脓性，分泌物刺激可引起外阴瘙痒及灼热感。病患经妇科大夫确诊后入组试验。入选病患每日喷涂贻贝粘蛋白凝胶剂消毒产品，每日2次。治疗1周后病患分泌物恢复正常，无瘙痒或其它不适感，证明贻贝粘蛋白凝胶剂消毒产品可用于宫颈炎的治疗。
实施例15：贻贝粘蛋白凝胶剂医疗器械在宫颈炎治疗中的应用。
取贻贝粘蛋白溶液，与明胶和海藻酸盐按照质量比4∶1∶1的比例混合，用乙酸调整酸碱度为pH 4.8，获得贻贝粘蛋白凝胶剂医疗器械，其中贻贝粘蛋白浓度为5.0mg/mL。
收集10例宫颈炎病患，临床表现为阴道分泌物增多，粘液脓性，分泌物刺激可引起外阴瘙痒及灼热感。病患经妇科大夫确诊后入组试验。入选病患每日先以0.1％高锰酸钾溶液清洗阴道，再将贻贝粘蛋白凝胶剂医疗器械喷涂于宫颈区，每日1次。治疗1周后病患进行巴氏涂片检查，7例病患宫颈部位细胞均正常，3例病患检查仍有少量炎性细胞。至治疗10天，全部病患巴氏涂片检查均正常，分泌物恢复正常，无瘙痒或其它不适感，表明本发明的贻 贝粘蛋白产品可用于宫颈炎的治疗。
实施例16：贻贝粘蛋白泡沫剂医疗器械在宫颈炎治疗中的应用。
取贻贝粘蛋白溶液，与羟丙甲基纤维素按照质量比4∶1的比例混合，用乙酸调整酸碱度为pH 4.8，获得贻贝粘蛋白泡沫剂医疗器械，其中贻贝粘蛋白浓度为5mg/mL。
收集10例宫颈炎病患，临床表现为阴道分泌物增多，粘液脓性，分泌物刺激可引起外阴瘙痒及灼热感。病患经妇科大夫确诊后入组试验。入选病患每日先以0.1％高锰酸钾溶液清洗阴道，再将贻贝粘蛋白泡沫剂医疗器械喷涂于宫颈区，每日1次。治疗1周后对病患进行巴氏涂片检查，全部病患宫颈部位细胞均正常，病患分泌物恢复正常，无瘙痒或其它不适感。表明本发明的贻贝粘蛋白产品可用于宫颈炎的治疗，且以泡沫剂使用时，效果更佳。
实施例17：贻贝粘蛋白液体药品在子宫内膜炎治疗中的应用。
取贻贝粘蛋白溶液，用0.1％柠檬酸稀释至3mg/ml，稀释后溶液pH值为6.5，得到贻贝粘蛋白液体药品。
收集15例子宫内膜炎病患，临床表现为盆腔区域疼痛、白带增多，经妇科大夫确诊为子宫内膜炎后入组试验。采用上述贻贝粘蛋白液体药品宫腔内给药，操作前先以双合诊查清子宫大小及位置，外阴阴道消毒、探测宫腔深度后，将灭菌导尿管自宫口送入宫腔，以小于宫腔深度0.5cm，将选定的药物经导尿管缓慢注入宫腔，待药液全部进入宫腔后，拔出导尿管，平卧或臀高位卧床1-2小时，每日1次。使用10天后受试病患盆腔区域已无疼痛感，白带趋于正常，证明采用本发明的贻贝粘蛋白药品可以用于子宫内膜炎的治疗。
实施例18：贻贝粘蛋白液体药品在吸入性损伤治疗中的应用。
取10.0mg/ml的贻贝粘蛋白溶液用乙酸稀释2倍至贻贝粘蛋白浓度为5.0mg/ml，溶液pH值为6.8，得到贻贝粘蛋白液体药品。
收集10例因吸入高温蒸气、火焰或干热气体导致的吸入性损伤病患，临床表现为粘膜充血、水肿、糜烂，有纤维素渗出，形成白膜。经耳鼻喉科大 夫确诊后入组试验，采用上述贻贝粘蛋白液体药品治疗。采用雾化吸入方式给药，每日1次，每次30分钟。在治疗第2天，吸入性损伤导致的水肿开始消退，膜脱落形成溃疡。在治疗第8天，全部病例溃疡愈合，平均愈合时间为6.9±1.2天。证明本发明的贻贝粘蛋白液体药品可用于吸入性损伤的治疗。

Claims (14)

  1. 贻贝粘蛋白在治疗粘膜炎症中的应用。
  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。
  3. 根据权利要求1的贻贝粘蛋白应用，其中所述贻贝粘蛋白浓度为0.1-15.0mg/ml。
  4. 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以液体剂、凝胶剂或泡沫剂使用。
  5. 根据权利要求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。
  6. 根据实施方式1-5中任一项的贻贝粘蛋白应用，其中所述粘膜炎症选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎、吸入性损伤引起的炎症等。
  7. 根据实施方式1-5中任一项的贻贝粘蛋白应用，其中所述粘膜炎症选自：口腔粘膜炎、鼻炎、中耳炎、结膜炎、咽炎、喉炎、气管炎、食管炎、胃炎、肠炎、宫颈炎、子宫内膜炎等引起的口腔癌、鼻咽癌、中耳癌、结膜癌、咽喉癌、气管癌、食管癌、胃癌、肠癌、宫颈癌、子宫内膜癌等。
  8. 贻贝粘蛋白作为活性成分在用于治疗粘膜炎症的组合物中的应用，其中所述组合物是以液体剂、凝胶剂或泡沫剂使用。
  9. 根据实施方式9的贻贝粘蛋白应用，其中所述组合物是通过口服、舌下、灌注、滴眼、鼻腔喷雾、口腔喷雾、腔镜、定向局部缓释、靶向给药的方式使用。
  10. 贻贝粘蛋白作为活性成分在用于治疗粘膜炎症的药品中的应用。
  11. 贻贝粘蛋白作为活性成分在用于治疗粘膜炎症的化妆品中的应用。
  12. 贻贝粘蛋白作为活性成分在用于治疗粘膜炎症的消毒产品中的应用。
  13. 贻贝粘蛋白作为活性成分在用于治疗粘膜炎症的保健品或食品中的应用。
  14. 贻贝粘蛋白作为活性成分在用于治疗粘膜炎症的日化产品中的应用。
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