CN105709216B - A kind of human-like collagen oral mucosa reparation liquid - Google Patents

A kind of human-like collagen oral mucosa reparation liquid Download PDF

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CN105709216B
CN105709216B CN201510883488.1A CN201510883488A CN105709216B CN 105709216 B CN105709216 B CN 105709216B CN 201510883488 A CN201510883488 A CN 201510883488A CN 105709216 B CN105709216 B CN 105709216B
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collagen
human
oral mucosa
liquid
phase
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CN105709216A (en
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范代娣
马晓轩
严建亚
王淑英
常海燕
王小军
杨婵媛
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SHAANXI GIANT BIOGENE TECHNOLOGY Co Ltd
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SHAANXI GIANT BIOGENE TECHNOLOGY Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/20—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing organic materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/24—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
    • A61L15/325—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents

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  • Proteomics, Peptides & Aminoacids (AREA)
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Abstract

The present invention relates to medical treatment/beauty treatment instrument fields, and in particular to a kind of human-like collagen oral mucosa reparation liquid can promote human-like collagen rapid transdermal to absorb.Human-like collagen oral mucosa of the invention, which repairs liquid, to be used for oral mucosa reparation in medical treatment/beauty treatment fields.It includes human-like collagen, carbomer, glycerol, polysorbate80 and water that human-like collagen oral mucosa of the invention, which repairs liquid,.

Description

A kind of human-like collagen oral mucosa reparation liquid
Technical field
The present invention relates to human-like collagen dressing, and in particular to and the oral mucosa comprising human-like collagen repairs liquid, Belong to beauty/medical instruments field.
Background technique
Human-like collagen is (disclosing referring to Chinese patent application by the Fan Daidi teaching inventive of NW China university Bright book CN1371919A), therefore also referred to as Fan Shi recombined collagen or Fan Human-like Collagen (Fan ' s Human-like Collagen, FHLC).Human-like collagen has three chains, triple-helix structure, is a kind of recombinant collagen egg of high-biocompatibility It is white, it is now widely used for medical treatment or beauty treatment fields.
On the other hand, in the case that collagen casting product is repaired for such as mucous membrane of mouth, due to saliva of buccal cavity point The factors such as secrete, drink water, collagen can not long duration of action in position to be repaired, i.e. collagen can act on to be repaired The time at position is limited.For this angle, in order to improve the effect of collagen casting product, Transdermal absorption is needed Fireballing collagen casting product.But regrettably, research so far is all only the transdermal of concern collagen Absorptivity, and the Transdermal absorption speed of collagen is not paid close attention to.
Summary of the invention
In view of the above-mentioned problems in the prior art, the object of the present invention is to provide one kind can promote class people's collagen egg The reparation liquid for oral mucosa reparation that white rapid transdermal absorbs.
The starting point is placed on the Transdermal absorption speed for the collagen being never concerned before this by further investigation by inventor etc. On degree, as a result, it has been found that: for the class people formed by the auxiliary material of cooperation particular types, special ratios in human-like collagen Collagen oral mucosa repairs liquid, the rapid transdermal of human-like collagen can be promoted to absorb, so as to complete the present invention.
That is, the present invention is as follows.
1. a kind of human-like collagen oral mucosa repairs liquid comprising:
2. repairing liquid according to human-like collagen oral mucosa described in item 1, it to be used for oral mucosa reparation.
3. the human-like collagen oral mucosa according to item 1 or 2 repairs liquid, it to be used for portacaval mucositis and/or mouth The treatment and/or prevention of chamber ulcer.
4. human-like collagen oral mucosa described in any one of 1~3 is repaired liquid and is repaired in preparation for oral mucosa Purposes in multiple dressing.
5. human-like collagen oral mucosa described in any one of 1~3, which repairs liquid, is used for portacaval mucositis in preparation And/or the purposes in the dressing for the treatment of and/or the prevention of canker sore.
6. the method that human-like collagen oral mucosa described in a kind of any one of preparation 1~5 repairs liquid, this method Include:
Step A: prepare A phase, the A phase by the carbomer of 0.001~0.2 weight %, the glycerol of 3~15 weight % and The water of surplus forms；
Step B: prepare B phase, the B phase is human-like collagen liquid, and it includes make the human-like collagen mouth Transmucosal repairs the human-like collagen that the content of human-like collagen in liquid is 0.01~1 weight %, and medium is water, and described The weight ratio of human-like collagen and the water is 1:1~20；
Step C: prepare C phase, the C phase is the polysorbate80 of 0.01~1 weight %；And
Step D: the B being added in the A phase, and is heated to 80~85 DEG C, is kept the temperature 20~60 minutes, is then dropped Temperature is added the C phase and is cooled to room temperature after mixing evenly to 50~60 DEG C；With the human-like collagen oral mucosa reparation The total weight of liquid is as 100 weight %.
7. according to method described in item 6, wherein the A phase be by will be added to the water after carbomer dispersion with glycerol, and Stirring is prepared to being completely dissolved.
The present invention achieves following technical effect: being applied to human-like collagen oral mucosa of the invention is repaired liquid When skin, so that the Transdermal absorption speed of human-like collagen is accelerated, 30 minutes transdermal absorption factors of human-like collagen are significantly mentioned It is high.To which human-like collagen oral mucosa of the invention repairs liquid and is capable of providing better nourishing, stimulates oral mucosa cell Regeneration promotes the reparation of damaged oral mucous membrane.
Specific embodiment
The present invention will be described in detail With reference to embodiment.
The present invention provides a kind of human-like collagen oral mucosa reparation liquid comprising:
In the present specification, human-like collagen refers to that Chinese patent application discloses claim 1 institute of CN1371919A The recombined collagen stated has three chains, triple-helix structure, can be disclosed using such as Chinese patent application It is prepared by gene engineering expression method disclosed in CN1371919A.Human-like collagen is by the Fan Daidi of NW China university Teaching inventive, therefore also referred to as Fan Shi recombined collagen or Fan Human-like Collagen (Fan ' s Human-like Collagen, FHLC).
Carbomer is the acrylic acid of synthesis and the high molecular polymer of allyl sucrose or Allyl pentaerythritol ether.For The carbomer is not particularly limited, can be used those skilled in the art usually used in the cosmetics or medical dressing that The carbomer of Guangzhou Concho Hampshire Pharmaceutical Co., Ltd's production, CAS No:9003-01-4 can be used for example in a little carbomers.
The glycerol is not particularly limited, those skilled in the art can be used usually in cosmetics or medical dressing Used in those glycerol, can be used for example Hu'nan Erkang Pharmaceutical Co., Ltd. production glycerol, CAS No:56-81- 5。
The polysorbate80 is not particularly limited, can be used those skilled in the art usually in cosmetics or The poly- of Hu'nan Erkang Pharmaceutical Co., Ltd.'s production can be used for example in those polysorbate80s used in medical dressing Sorbitol ester 80, CAS No:9005-65-6.
When human-like collagen oral mucosa reparation liquid of the invention is applied to skin, so that human-like collagen Transdermal absorption speed is accelerated, and 30 minutes transdermal absorption factors of human-like collagen significantly improve, and reason may be due to constituting Suitable microenvironment.
Therefore, human-like collagen oral mucosa of the invention is repaired liquid and is particularly suitable in medical treatment/beauty treatment fields for mouth Transmucosal reparation.Here, caused by the breakage of oral mucosa may be stomatitis or canker sore, therefore, class people of the invention Collagen oral mucosa, which repairs liquid, can be used for the treatment and/or prevention of stomatitis or canker sore.For medical treatment/beauty neck When the oral mucosa in domain repairs purposes, human-like collagen oral mucosa reparation liquid itself of the invention, which can be used as dressing, to be made With other kinds of dressing can also being made with other carriers or auxiliary material combination again.
The preparation method for repairing liquid for human-like collagen oral mucosa of the invention is not particularly limited, common system Preparation Method may include:
Step A: prepare A phase, the A phase by the carbomer of 0.001~0.2 weight %, the glycerol of 3~15 weight % and The water of surplus forms；
Step B: prepare B phase, the B phase is human-like collagen liquid, and it includes make the human-like collagen mouth Transmucosal repairs the human-like collagen that the content of human-like collagen in liquid is 0.01~1 weight %, and medium is water, and described The weight ratio of human-like collagen and the water is 1:1~20；
Step C: prepare C phase, the C phase is the polysorbate80 of 0.01~1 weight %；And
Step D: the B being added in the A phase, and is heated to 80~85 DEG C, is kept the temperature 20~60 minutes, is then dropped Temperature is added the C phase and is cooled to room temperature after mixing evenly to 50~60 DEG C；
Using the total weight of human-like collagen oral mucosa reparation liquid as 100 weight %.
Here, human-like collagen liquid includes the aqueous solution of human-like collagen and the aqueous dispersions of human-like collagen.
Here, the sequence of described step A, B, C are not particularly limited, can successively be carried out with random order or simultaneously into Row.
Preferably, the A phase and is stirred to being completely dissolved and is made by will be added to the water after carbomer dispersion with glycerol Standby.
Here, the mode of stirring is not particularly limited, as long as can stir evenly.
Human-like collagen oral mucosa of the invention is repaired liquid and can be placed in packing container.To composition packing container Material is not particularly limited comprising but be not limited to ceramics, glass, metal, plastics etc..Packing container can be closed or not It is closed but preferably closed.
Embodiment
Hereinafter, carrying out more specific description to the present invention by embodiment, but the present invention is not restricted by the embodiments.
Human-like collagen used in following embodiment and comparative examples is to disclose CN1371919A by Chinese patent application The Fan Human-like Collagen (amino acid sequence shown in SEQ ID NO:1 forms) of the method preparation, confirms its molecule Amount is 90kDa.
In order to observe the Transdermal absorption behavior of human-like collagen, using conventional method FITC (fluorescein Isothiocyanate, fluorescein isothiocynate) fluorescent marker has been carried out to it.
Unless otherwise instructed, " % " in following the description refers to " weight % ".
The human-like collagen oral mucosa of the invention of embodiment 1. repairs the preparation of liquid
Ingredient: carbomer 0.02%, glycerol 6%, human-like collagen 0.5%, polysorbate80 0.1%, water 93.38%.
Technological operation:
1. being first added to the water carbomer, it is then slowly added into after glycerol and is stirred continuously to being completely dispersed.Then it is added Human-like collagen aqueous solution (10 weight %), it is stirring while adding to being completely dissolved, it is heated to 80-85 DEG C, keeps the temperature 30min；
2. above-mentioned mixed liquor is cooled to 50-60 DEG C, polysorbate80 is added and is cooled to room temperature after mixing evenly.
The preparation of other human-like collagen oral mucosas of comparative example 1. reparation liquid
Ingredient: carbomer 0.5%, glycerol 2.5%, human-like collagen 0.5%, polysorbate80 1.5%, water 95%.
Technological operation:
1. being first added to the water carbomer, it is then slowly added into after glycerol and is stirred continuously to being completely dispersed.Then it is added Human-like collagen aqueous solution (10 weight %), it is stirring while adding to being completely dissolved, it is heated to 80-85 DEG C, keeps the temperature 30min；
2. above-mentioned mixed liquor is cooled to 50-60 DEG C, polysorbate80 is added and is cooled to room temperature after mixing evenly.
The measurement of 30 minutes transdermal absorption factors of collagen
Will the previous day be mentioned with depilatory agent depilation preserved skin in the mouse that laboratory adapts to feeding environment.Use is washed one's hair before testing Bath lotion or facial cleanser are to skin cleaning is carried out and with towel at preserved skin, by the class people's collagen egg of above-described embodiment and comparative example Spoken parts in traditional operas transmucosal repairs liquid, is applied at preserved skin of the same area with medical cotton stick with equal amount respectively, smears after completing just Often raising, it is when 0.5h that each group mouse 5 is only clean by Irrigation at preserved skin with clear water, using fluorescence microplate reader to cleaning solution In collagen carry out quantitative analysis, be just the failure to transdermal collagen.
Wherein, skin permeation rate calculates in this way: skin permeation rate=(the collagen total amount of smearing-fail transdermal collagen Amount)/smear collagen total amount.
Liquid is repaired for the human-like collagen oral mucosa of embodiment and comparative example, above-mentioned skin permeation rate test result is put down Mean value is respectively 45% and 29%.
It should also be noted that, it is implementable and it is unobvious violate purport of the invention under the premise of, in the present specification The combination of any technical characteristic or technical characteristic described in composition part as a certain technical solution equally can also be applied In other technical solutions；Also, it is implementable and it is unobvious violate purport of the invention under the premise of, as different technologies scheme Composition part described in can also be combined in any way between technical characteristic, to constitute other technical solutions.This Invention is also contained under above situation the technical solution as obtained from combination, and these technical solutions are equivalent to and are documented in this In specification.
Above by specific embodiment and embodiment, the present invention is described, but those skilled in the art should manage Solution, these are not intended to be defined the scope of the present invention, and the scope of the present invention should be determined by claims.
Industrial applicibility
Human-like collagen oral mucosa of the invention, which repairs liquid, can significantly improve the Transdermal absorption of human-like collagen Speed.

Claims (7)

1. a kind of human-like collagen oral mucosa repairs liquid comprising:
Wherein, the human-like collagen is Fan Human-like Collagen.
2. human-like collagen oral mucosa according to claim 1 repairs liquid, it to be used for oral mucosa reparation.
3. human-like collagen oral mucosa according to claim 1 or 2 repairs liquid, be used for portacaval mucositis and/or The treatment and/or prevention of canker sore.
4. human-like collagen oral mucosa according to any one of claims 1 to 3, which repairs liquid, is used for oral mucosa in preparation Purposes in the dressing of reparation.
5. human-like collagen oral mucosa according to any one of claims 1 to 3, which repairs liquid, is used for oral mucosa in preparation Purposes in the dressing of scorching and/or canker sore treatment and/or prevention.
6. a kind of method for preparing human-like collagen oral mucosa according to any one of claims 1 to 3 and repairing liquid, the party Method includes:
Step A: prepare A phase, the A phase is by the carbomer of 0.001~0.2 weight %, the glycerol and surplus of 3~15 weight % Water composition；
Step B: preparing B phase, and the B phase is human-like collagen liquid, and it includes make the human-like collagen oral cavity viscous Film repairs the human-like collagen that the content of human-like collagen in liquid is 0.01~1 weight %, and medium is water, and the class people The weight ratio of collagen and the water is 1:1~20；
Step C: prepare C phase, the C phase is the polysorbate80 of 0.01~1 weight %；And
Step D: the B being added in the A phase, and is heated to 80~85 DEG C, is kept the temperature 20~60 minutes, is then cooled to 50~60 DEG C, the C phase is added and is cooled to room temperature after mixing evenly；Liquid is repaired with the human-like collagen oral mucosa Total weight is as 100 weight %.
7. according to the method described in claim 6, wherein, the A phase be by will be added to the water after carbomer dispersion with glycerol, And it stirs to being completely dissolved and prepares.
CN201510883488.1A 2015-12-04 2015-12-04 A kind of human-like collagen oral mucosa reparation liquid Active CN105709216B (en)

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CN106492267B (en) * 2016-11-25 2021-09-17 陕西巨子生物技术有限公司 Human-like collagen anorectal mucosa repair gel
CN106902381B (en) * 2017-03-23 2020-07-21 陕西慧康生物科技有限责任公司 Recombinant human collagen stock solution, dressing and preparation method thereof
CN108813631A (en) * 2018-04-27 2018-11-16 西安巨子生物基因技术股份有限公司 Human-like collagen oral solution and preparation method thereof
CN110787288A (en) * 2019-12-25 2020-02-14 郑州康金瑞健康产业有限公司 Medical collagen oral ulcer protective gel and preparation method thereof

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