CN106692953A - Blue shark skin collagen compound gel preparation and preparation method and application thereof - Google Patents

Blue shark skin collagen compound gel preparation and preparation method and application thereof Download PDF

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Publication number
CN106692953A
CN106692953A CN201710063626.0A CN201710063626A CN106692953A CN 106692953 A CN106692953 A CN 106692953A CN 201710063626 A CN201710063626 A CN 201710063626A CN 106692953 A CN106692953 A CN 106692953A
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China
Prior art keywords
blue shark
collagen
gel preparation
blue
shark collagen
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Chinese (zh)
Inventor
蒋升
徐晓刚
李铁军
吴文惠
杨桥
王淑军
吕明生
缪辉南
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Shanghai Mai Lin Biomedical Engineering Technology Co Ltd
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Shanghai Mai Lin Biomedical Engineering Technology Co Ltd
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Priority to CN201710063626.0A priority Critical patent/CN106692953A/en
Publication of CN106692953A publication Critical patent/CN106692953A/en
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    • 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
    • A61K38/39Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716Glucans
    • A61K31/722Chitin, chitosan
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38Cellulose; Derivatives thereof
    • 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

Abstract

The invention discloses a blue shark skin collagen compound gel preparation. The blue shark skin collagen compound gel preparation is characterized in that the gel preparation comprises the following components by weight percent: 1-9% of blue shark skin collagen, 0.25-2.25% of chitosan, and the balance of a gel matrix. The invention further provides a preparation method of the gel preparation. The gel preparation can be used to rehabilitate a wound surface in an oral cavity.

Description

A kind of blue shark collagen plural gel preparation and preparation method and application
Technical field
The invention belongs to biomaterial for medical purpose field, it is related to a kind of gel preparation, particularly a kind of blue shark collagen egg White plural gel preparation and preparation method and application.
Background technology
Aquatic collagen protein is a kind of natural bioabsorbable polymer material, with low antigenicity, it is hemostatic, biological can inhale Receive, the skin spongy tissue of wound can be provided and continue and be slowly administered, promote granulation growth, prevent bleeding again, promote Wound healing.
Shitosan is natural alkaline polysaccharide present in nature, is the deacetylation product of chitin, and chitin is certainly Content is only second to cellulose, wide material sources in right boundary.Shitosan as a kind of natural macromolecular material, with good biofacies Capacitive, degradability, antibiotic property, promote heal property, it is nontoxic, nonirritant to mucous membrane, mucoadhesive can be promoted, in bio-medical material Material field has a wide range of applications.
Canker sore is a kind of most common mucous epithelium limitation defect as deep as corium, is most normal in diseases of oral mucosa The clinical manifestation seen, illness rate is up to 20%.Canker sore pathology changes based on the infringement of oral cavity partial mucosa ulcer, morbidity Mechanism is extremely complex, relevant with the several factors such as inherent cause, immune factor, with periodically and burning property pain feature, one Denier can continue infection after forming ulcer, cause ulcer local organization inflammation and necrosis, and course of disease delay, its cause of disease is not completely clear and definite, It is relevant with immune, heredity, mental element, vitamins shortage etc., thus medicine is more, effect is preferable not to the utmost, faces at present Without the effect method of radical cure on bed.
The content of the invention
The technical problem to be solved in the present invention is directed to the deficiencies in the prior art, it is proposed that a kind of blue shark collagen Plural gel preparation.
Present invention also offers a kind of preparation method of foregoing gel preparation.
The application repaired in the surface of a wound medicine of oral cavity is prepared present invention also offers foregoing gel preparation.
The technical problem to be solved in the present invention is achieved through the following technical solutions, a kind of blue shark collagen Plural gel preparation, is characterized in, the gel preparation is consisted of the following components in percentage by weight:
Blue shark collagen 1-9%;
Shitosan 0.25-2.25%;
Balance of gel-type vehicle.
Blue shark collagen of the present invention is prepared using following methods:
(1)Blue sharkskin is taken, subdermal muscle and adipose tissue is rejected, then as 0.5-1h is soaked in distilled water, fish-skin is cut into Size is the fish-skin block of 3-5 mm × 3-5 mm, and filtering is drained standby;
(2)By step(1)In the fish-skin block that obtains be placed in soak degreasing in 0.25-0.5 M NaOH solutions, stir 4-12h, put 8-16h is refrigerated in 4 DEG C, it is clean with distilled water flushing after taking-up;
(3)Fish-skin block after ungrease treatment is processed is placed in and desugar is soaked in 70% ethanol solution, stirs 4-6h, with steaming after taking-up Distilled water is rinsed well;
(4)By desugar treat fish-skin block crush, be placed in 0.25M glacial acetic acid solutions and soak and stir 2-6h, be placed in 4 DEG C it is cold 12h is hidden, fish-skin extract solution is obtained;
(5)The filtering of fish-skin extract solution is taken, filtrate is collected, reached to NaOH solution to the pH value of solution of 0.25-0.5M is added in filtrate 6.8-7.0, separates out to a large amount of White Flocculus, filters taking precipitate, and sediment extracts sealing after being cleaned with distilled water, freezing is dry It is dry, obtain blue shark collagen bulk extract;
(6)Blue shark collagen bulk extract is carried out into ultra-fine grinding treatment under liquid nitrogen cryogenics environment, powdery is obtained blue Shark collagen.
The molecular weight of blue shark collagen of the present invention is 100-300 KDa.
It is further preferred that the molecular weight of described blue shark collagen is 130-200 KDa.
The deacetylation of shitosan of the present invention>95%.
Gel-type vehicle of the present invention includes the raw material of following weight portion:
D-sorbite 30-40;
Glycerine 8-12;
Cellulose gum 1.3-1.6;
Methyl hydroxybenzoate sodium 0.13-0.17;
Nipasol sodium 0.09-0.11;
Citric acid 0.03-0.06;
Water 50-56.
It is further preferred that described gel-type vehicle includes the raw material of following weight portion:
D-sorbite 33-37;
Glycerine 9.5-10.5;
Cellulose gum 1.2-1.5;
Methyl hydroxybenzoate sodium 0.14-0.15;
Nipasol sodium 0.09-0.1;
Citric acid 0.05-0.06;
Water 53-55.
It is further preferred that described gel-type vehicle includes the raw material of following weight portion:
D-sorbite 35;
Glycerine 10;
Cellulose gum 1.5;
Methyl hydroxybenzoate sodium 0.15;
Nipasol sodium 0.1;
Citric acid 0.05;
Water 53.2.
Present invention also offers the preparation side of the blue shark collagen plural gel preparation described in above technical scheme Method, is characterized in, the gel preparation is adopted and prepared with the following method:Powdery indigo plant shark collagen is mixed with shitosan, is obtained Mixture, to gel-type vehicle is added in mixture, is sufficiently mixed grinding, obtains final product blue shark collagen plural gel preparation; Wherein, in adding the mixture of blue shark collagen and shitosan after each component in gel-type vehicle is fully mixed.
Blue shark collagen plural gel preparation of the present invention can be used to repair the oral cavity surface of a wound.
The present invention, by easy, efficient isoelectric precipitation law technology, extracts indigo plant with blue sharkskin leftover bits and pieces as raw material Shark collagen, is effectively utilized blue shark leftover bits and pieces, turns waste into wealth, and improves the added value of Aquatic Product Process Industry.This hair Bright blue shark collagen plural gel preparation is applied directly to oral ulcer surface in application, makes in inventive gel preparation Blue shark collagen and shitosan are the bio-medical material of natural degradable, by rational compatibility, by indigo plant Shark collagen and shitosan are used in conjunction with, while playing two kinds of effects of biomaterial, it is to avoid the disadvantage of single therapy End, with excellent biocompatibility, can be used to repair the oral cavity surface of a wound, can substantially speed up diminution canker sore diameter, mitigate Congestion and edema degree, accelerates canker sore healing, and evident in efficacy, has no adverse reaction, and mucous membrane irritation is low, and degradability is good.
Brief description of the drawings
Fig. 1 is the optics of the blue sharkskin collagen gel preparation to rat canker sore curative effect of the embodiment of the present invention 19 Microscopy results.In figure:(a)Model group;(b) high dose group;(c) middle dose group;(d)Low dose group;(e)Single glue Former protein groups;(f)Gel group;(g)Positive controls.
Specific embodiment
Below in conjunction with specific embodiment and accompanying drawing, the present invention will be described in further detail.It should be appreciated that this place is retouched The specific embodiment stated only is used to explain the present invention, is not intended to limit the present invention.
Embodiment 1, a kind of blue shark collagen plural gel preparation, the gel preparation is by following percentage by weight Component is constituted:
Blue shark collagen 9%;
Shitosan 2.25%;
Balance of gel-type vehicle.
Embodiment 2, a kind of blue shark collagen plural gel preparation, the gel preparation is by following percentage by weight Component is constituted:
Blue shark collagen 3%;
Shitosan 0.75%;
Balance of gel-type vehicle.
Embodiment 3, a kind of blue shark collagen plural gel preparation, the gel preparation is by following percentage by weight Component is constituted:
Blue shark collagen 1%;
Shitosan 0.25%;
Balance of gel-type vehicle.
Embodiment 4, a kind of blue shark collagen plural gel preparation, the gel preparation is by following percentage by weight Component is constituted:
Blue shark collagen 4%;
Shitosan 1%;
Balance of gel-type vehicle.
Embodiment 5, it is described in the blue shark collagen plural gel preparation described in embodiment 1-4 any one The preparation method of blue shark collagen is as follows:
(1)Blue sharkskin is taken, subdermal muscle and adipose tissue is rejected, then as 0.5h is soaked in distilled water, fish-skin is cut into greatly Small is the fish-skin block of 3mm × 3mm, and filtering is drained standby;
(2)By step(1)In the fish-skin block that obtains be placed in soak degreasing in 0.25M NaOH solutions, stir 4h, be placed in 4 DEG C of refrigerations 8h is clean with distilled water flushing after taking-up;
(3)Fish-skin block after ungrease treatment is processed is placed in and desugar is soaked in 70% ethanol solution, stirs 4h, with distillation after taking-up Water is rinsed well;
(4)The fish-skin block that desugar is treated is crushed, and is placed in 0.25M glacial acetic acid solutions and is soaked and stir 2h, is placed in 4 DEG C of refrigerations 12h, obtains fish-skin extract solution;
(5)The filtering of fish-skin extract solution is taken, filtrate is collected, to the NaOH solution of 0.25M is added in filtrate to pH value of solution up to 6.8, extremely A large amount of White Flocculus are separated out, and filter taking precipitate, and sediment extracts sealing after being cleaned with distilled water, freeze-drying obtains blue shark Collagen bulk extract;
(6)Blue shark collagen bulk extract is carried out into ultra-fine grinding treatment under liquid nitrogen cryogenics environment, powdery is obtained blue Shark collagen.
Embodiment 6, it is described in the blue shark collagen plural gel preparation described in embodiment 1-4 any one The preparation method of blue shark collagen is as follows:
(1)Blue sharkskin is taken, subdermal muscle and adipose tissue is rejected, then as 1h is soaked in distilled water, fish-skin is cut into size It is the fish-skin block of 5 mm × 5 mm, filtering is drained standby;
(2)By step(1)In the fish-skin block that obtains be placed in soak degreasing in 0.5 M NaOH solutions, stir 12h, be placed in 4 DEG C it is cold 16h is hidden, it is clean with distilled water flushing after taking-up;
(3)Fish-skin block after ungrease treatment is processed is placed in and desugar is soaked in 70% ethanol solution, stirs 6h, with distillation after taking-up Water is rinsed well;
(4)The fish-skin block that desugar is treated is crushed, and is placed in 0.25M glacial acetic acid solutions and is soaked and stir 6h, is placed in 4 DEG C of refrigerations 12h, obtains fish-skin extract solution;
(5)The filtering of fish-skin extract solution is taken, filtrate is collected, to adding the NaOH solution of 0.5M in filtrate to pH value of solution up to 7.0, to big Amount White Flocculus are separated out, and filter taking precipitate, and sediment extracts sealing after being cleaned with distilled water, freeze-drying obtains blue shark Collagen bulk extract;
(6)Blue shark collagen bulk extract is carried out into ultra-fine grinding treatment under liquid nitrogen cryogenics environment, powdery is obtained blue Shark collagen.
Embodiment 7, it is described in the blue shark collagen plural gel preparation described in embodiment 1-4 any one The preparation method of blue shark collagen is as follows:
(1)Blue sharkskin is taken, subdermal muscle and adipose tissue is rejected, then as 1h is soaked in distilled water, fish-skin is cut into size It is the fish-skin block of 4 mm × 4mm, filtering is drained standby;
(2)By step(1)In the fish-skin block that obtains be placed in soak degreasing in 0.4M NaOH solutions, stir 8h, be placed in 4 DEG C of refrigerations 12h is clean with distilled water flushing after taking-up;
(3)Fish-skin block after ungrease treatment is processed is placed in and desugar is soaked in 70% ethanol solution, stirs 5h, with distillation after taking-up Water is rinsed well;
(4)The fish-skin block that desugar is treated is crushed, and is placed in 0.25M glacial acetic acid solutions and is soaked and stir 4h, is placed in 4 DEG C of refrigerations 12h, obtains fish-skin extract solution;
(5)The filtering of fish-skin extract solution is taken, filtrate is collected, to adding the NaOH solution of 0.4M in filtrate to pH value of solution up to 6.9, to big Amount White Flocculus are separated out, and filter taking precipitate, and sediment extracts sealing after being cleaned with distilled water, freeze-drying obtains blue shark Collagen bulk extract;
(6)Blue shark collagen bulk extract is carried out into ultra-fine grinding treatment under liquid nitrogen cryogenics environment, powdery is obtained blue Shark collagen.
Embodiment 8, it is described in the blue shark collagen plural gel preparation described in embodiment 1-7 any one The molecular weight of blue shark collagen is 100KDa.
Embodiment 9, it is described in the blue shark collagen plural gel preparation described in embodiment 1-7 any one The molecular weight of blue shark collagen is 300 KDa.
Embodiment 10, it is described in the blue shark collagen plural gel preparation described in embodiment 1-7 any one The molecular weight of blue shark collagen is 130 KDa.
Embodiment 11, it is described in the blue shark collagen plural gel preparation described in embodiment 1-7 any one The molecular weight of blue shark collagen is 200 KDa.
Embodiment 12, it is described in the blue shark collagen plural gel preparation described in embodiment 1-11 any one Shitosan deacetylation>95%.
Embodiment 13, it is described in the blue shark collagen plural gel preparation described in embodiment 1-12 any one Gel-type vehicle including following weight portion raw material:
D-sorbite 30;
Glycerine 8;
Cellulose gum 1.3;
Methyl hydroxybenzoate sodium 0.13;
Nipasol sodium 0.09;
Citric acid 0.03;
Water 50.
Embodiment 14, it is described in the blue shark collagen plural gel preparation described in embodiment 1-12 any one Gel-type vehicle including following weight portion raw material:
D-sorbite 40;
Glycerine 12;
Cellulose gum 1.6;
Methyl hydroxybenzoate sodium 0.17;
Nipasol sodium 0.11;
Citric acid 0.06;
Water 56.
Embodiment 15, it is described in the blue shark collagen plural gel preparation described in embodiment 1-12 any one Gel-type vehicle including following weight portion raw material:
D-sorbite 33;
Glycerine 9.5;
Cellulose gum 1.2;
Methyl hydroxybenzoate sodium 0.14;
Nipasol sodium 0.09;
Citric acid 0.05;
Water 53.
Embodiment 16, it is described in the blue shark collagen plural gel preparation described in embodiment 1-12 any one Gel-type vehicle including following weight portion raw material:
D-sorbite 37;
Glycerine 10.5;
Cellulose gum 1.5;
Methyl hydroxybenzoate sodium 0.15;
Nipasol sodium 0.1;
Citric acid 0.06;
Water 55.
Embodiment 17, it is described in the blue shark collagen plural gel preparation described in embodiment 1-12 any one Gel-type vehicle including following weight portion raw material:
D-sorbite 35;
Glycerine 10;
Cellulose gum 1.5;
Methyl hydroxybenzoate sodium 0.15;
Nipasol sodium 0.1;
Citric acid 0.05;
Water 53.2.
Embodiment 18, the preparation of the blue shark collagen plural gel preparation described in embodiment 13-17 any one Method is as follows:Blue shark collagen is mixed with shitosan, mixture is obtained, to gel-type vehicle is added in mixture, fully Mixed grinding, obtains final product blue shark collagen plural gel preparation;Wherein, after each component in gel-type vehicle is fully mixed In adding the mixture of blue shark collagen and shitosan.
Embodiment 19, experimental example, shadow of the blue shark collagen plural gel preparation to Rat Experimental canker sore Ring.
1st, test medicine
The blue shark collagen plural gel preparation of embodiment of the present invention 1-3, wherein:The preparation of blue shark collagen Method is using the method described in embodiment 7;The molecular weight of blue shark collagen is 150KDa;The deacetylation > of shitosan 95%;Gel-type vehicle is made up of the raw material of following weight portion:D-sorbite 35, glycerine 10, cellulose gum 1.5, methyl hydroxybenzoate sodium 0.15th, Nipasol sodium 0.1, citric acid 0.05, water 53.2;The preparation method of the plural gel preparation of blue shark collagen Using the method described in embodiment 18.
2nd, experimental animal
Male SD rat, 200~220 g, the western pul-Bi Kai experimental animals Co., Ltd in Shanghai.
3rd, experimental technique
Healthy SD male rat 48 is taken, 7 groups, every group 8 are randomly divided into.Respectively:Model group;Test medicine group:3 Dosage group(High dose group:Blue shark collagen 9%, shitosan 2.25% adds 100 mL gel-type vehicles;Middle dose group:It is blue Shark collagen 3%, shitosan 0.75% adds 100 mL gel-type vehicles;Low dose group:Blue shark collagen 1%, shell Glycan 0.25% adds 100 mL gel-type vehicles);Negative control:Single collagen group(Blue shark collagen 3% is added 100 mL gel-type vehicles)With gel controls group(Gel-type vehicle is not added with any auxiliary material);Positive drug is compareed:Recombinant human epidermal growth because Sub- gel(Huanuowei Gene Pharmaoy Co Ltd, Guilin, lot number:201412102A).
10% chloraldurate of rat(3 mL/kg)Anesthesia, with the cm of internal diameter 0.4, the plastic tube of 3 cm long(One end plug cotton Flower, in case solution spills), to 35% glacial acetic acid solution is filled in pipe, cotton end will be filled in rat lower lip inner side mucous membrane table 60s is vertically fixed in face, you can it was observed that lower lip locally has blush, is observed after 24h, ulcer is occurred, model is to be successfully established.
Oral cavity ulcer area is observed after modeling 24h, and starts administration, administration 2 times daily, model group is not administered.Before administration Physiological saline is dipped in cotton balls and gently wipe rat oral surfaces, be applied to mouth with the small corresponding medicine of medicine bale-out about 100mg respectively Chamber ulcer surface, 30min fasting for solids and liquids after administration.Daily observation oral cavity skin surface situation, and in before administration, administration after the 1st day, 3rd day, the 7th day, the 10th day and the 12nd day, slide measure determined that ulcer is long and width, calculates ulcer area(Area=length × wide × 3.14 / 4).
After administration 12 days, model group and each administration group take 6 and visually observe the lighter rat anesthesia execution of ulcer, take one Part lip ulcer and surrounding tissue sample, are fixed with 10% formalin, conventional dehydration, specimens paraffin embedding slices, HE dyeing, light microscopic The changes in histopathology of lower observation chronic ulcer tissue.
5th, statistical method
Using the software data processings of SPSS 17.0, data are represented with mean+SD(± SD), Dan Yin is used between group Plain variance analysis(one-way ANOVA)Check the conspicuousness of difference, P<0.05 has statistical significance for difference.
6th, experimental result
Starting appearance part in model group canker sore rat lower lip at mucous membrane has blush, and surface is in greyish white after forming ulcer Color, around there is congestion and edema, is slightly recessed, and ulcer is more serious, and 1-3 days ulcer diameters of modeling slightly have expansion, subsequent canker sore Gradually mitigate.
After blue shark collagen plural gel preparation is administered 1 day, ulcer surface expands unobvious;After medication 3 days, ulcer Surface begins with pseudomembrane covering, and ulcer diameter reduces;After medication 12 days, pseudomembrane comes off, and fresh surface of a wound exposure, ulcer surface substantially contracts Small, ulcer heals successively.Blue each dosage group of shark collagen plural gel preparation can reduce ulcer diameter, administration the 3rd My god, the 7th day, the 10th day and the 12nd day, ulcer area and model group comparing difference have statistical significance(P < 0.05), and Effect has certain dose-dependence.Influence to ulcer area the results are shown in Table 1, the influence optical microphotograph to ulcer area Sem observation result is shown in Fig. 1.
As seen from Figure 1, the 12nd day after modeling, model group canker sore site tissue damage is heavier, ulcer spot tissue Necrosis is also more apparent, it is seen that granulation tissue and fibrosis;Each dosage group of ocean collagen plural gel preparation and the positive Control group canker sore site tissue damage is lighter, and degree of necrosis significantly mitigates, and granulation tissue and fibrosis are formed substantially.It is single Collagen group and gel group canker sore site tissue have healed, and degree of necrosis is light, granulation tissue and fibrosis formed compared with Substantially.
The blue shark collagen plural gel preparation of table 1. to experimental rat canker sore area influence (n= 8,±s)
Note:Compare with model group, * P<0.05, * * P< 0.01
7th, conclusion
Result shows that inventive gel preparation can substantially mitigate rat canker sore area and its degree of necrosis, with model group Compare, administration has pole significant difference on the 3rd day(P < 0.01).From pathological section result, ocean fish skin collagen egg White each dosage group canker sore site tissue damage of plural gel preparation is lighter, and degree of necrosis significantly mitigates, granulation tissue and fibre Dimensionization forms obvious.Experimental result is pointed out:Indigo plant shark collagen plural gel preparation of the invention has repairs the oral cavity surface of a wound Effect.

Claims (9)

1. a kind of blue shark collagen plural gel preparation, it is characterised in that the gel preparation is by following percentage by weight Component composition:
Blue shark collagen 1-9%;
Shitosan 0.25-2.25%;
Balance of gel-type vehicle.
2. blue shark collagen plural gel preparation according to claim 1, it is characterised in that described blue shark The preparation method of collagen is as follows:
(1)Blue sharkskin is taken, subdermal muscle and adipose tissue is rejected, then as 0.5-1h is soaked in distilled water, fish-skin is cut into Size is the fish-skin block of 3-5 mm × 3-5 mm, and filtering is drained standby;
(2)By step(1)In the fish-skin block that obtains be placed in soak degreasing in 0.25-0.5 M NaOH solutions, stir 4-12h, put 8-16h is refrigerated in 4 DEG C, it is clean with distilled water flushing after taking-up;
(3)Fish-skin block after ungrease treatment is processed is placed in and desugar is soaked in 70% ethanol solution, stirs 4-6h, with steaming after taking-up Distilled water is rinsed well;
(4)By desugar treat fish-skin block crush, be placed in 0.25M glacial acetic acid solutions and soak and stir 2-6h, be placed in 4 DEG C it is cold 12h is hidden, fish-skin extract solution is obtained;
(5)The filtering of fish-skin extract solution is taken, filtrate is collected, reached to NaOH solution to the pH value of solution of 0.25-0.5M is added in filtrate 6.8-7.0, separates out to a large amount of White Flocculus, filters taking precipitate, and sediment extracts sealing after being cleaned with distilled water, freezing is dry It is dry, obtain blue shark collagen bulk extract;
(6)Blue shark collagen bulk extract is carried out into ultra-fine grinding treatment under liquid nitrogen cryogenics environment, powdery is obtained blue Shark collagen.
3. blue shark collagen plural gel preparation according to claim 1 and 2, it is characterised in that described indigo plant The molecular weight of shark collagen is 100-300 KDa.
4. blue shark collagen plural gel preparation according to claim 1, it is characterised in that described shitosan Deacetylation>95%.
5. blue shark collagen plural gel preparation according to claim 1, it is characterised in that described gel base Matter includes the raw material of following weight portion:
D-sorbite 30-40;
Glycerine 8-12;
Cellulose gum 1.3-1.6;
Methyl hydroxybenzoate sodium 0.13-0.17;
Nipasol sodium 0.09-0.11;
Citric acid 0.03-0.06;
Water 50-56.
6. blue shark collagen plural gel preparation according to claim 5, it is characterised in that described gel base Matter includes the raw material of following weight portion:
D-sorbite 33-37;
Glycerine 9.5-10.5;
Cellulose gum 1.2-1.5;
Methyl hydroxybenzoate sodium 0.14-0.15;
Nipasol sodium 0.09-0.1;
Citric acid 0.05-0.06;
Water 53-55.
7. the blue shark collagen plural gel preparation according to claim 5 or 6, it is characterised in that described is solidifying Gel matrix includes the raw material of following weight portion:
D-sorbite 35;
Glycerine 10;
Cellulose gum 1.5;
Methyl hydroxybenzoate sodium 0.15;
Nipasol sodium 0.1;
Citric acid 0.05;
Water 53.2.
8. the preparation method of a kind of blue shark collagen plural gel preparation as described in claim 1-7 any one, Characterized in that, the gel preparation is adopted and prepared with the following method:Blue shark collagen is mixed with shitosan, must be mixed Thing, to gel-type vehicle is added in mixture, is sufficiently mixed grinding, obtains final product blue shark collagen plural gel preparation.
9. a kind of blue shark collagen plural gel preparation as claimed in claim 1 is preparing reparation oral cavity surface of a wound medicine In application.
CN201710063626.0A 2017-02-03 2017-02-03 Blue shark skin collagen compound gel preparation and preparation method and application thereof Pending CN106692953A (en)

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CN108298855A (en) * 2018-02-07 2018-07-20 安徽宇力环保科技有限公司 A kind of preparation method of waterproofing agent for pearlite heat-insulation plate
CN108455895A (en) * 2018-02-07 2018-08-28 安徽宇力环保科技有限公司 A kind of hydrophober and preparation method thereof for external-wall heat-insulation material
CN109908395A (en) * 2018-08-17 2019-06-21 上海昊海生物科技股份有限公司 A kind of sharkskin natural medical collagen protein sponge preparation method
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
CN111067921A (en) * 2020-01-20 2020-04-28 蓝佳堂生物医药(福建)有限公司 Preparation method of hydrogel for oropharynx

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CN107441479A (en) * 2017-08-08 2017-12-08 广东海洋大学 Marine active peptide/chitin burn ointment for treating scald and preparation method thereof
CN107441479B (en) * 2017-08-08 2018-12-21 广东海洋大学 Marine active peptide/chitin burn ointment for treating scald and preparation method thereof
CN108298855A (en) * 2018-02-07 2018-07-20 安徽宇力环保科技有限公司 A kind of preparation method of waterproofing agent for pearlite heat-insulation plate
CN108455895A (en) * 2018-02-07 2018-08-28 安徽宇力环保科技有限公司 A kind of hydrophober and preparation method thereof for external-wall heat-insulation material
CN109908395A (en) * 2018-08-17 2019-06-21 上海昊海生物科技股份有限公司 A kind of sharkskin natural medical collagen protein sponge preparation method
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
CN111067921A (en) * 2020-01-20 2020-04-28 蓝佳堂生物医药(福建)有限公司 Preparation method of hydrogel for oropharynx

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Application publication date: 20170524