CN101020077A - Prepn process of collagen-based surface wound repairing membrane possessing tissue induction - Google Patents

Prepn process of collagen-based surface wound repairing membrane possessing tissue induction Download PDF

Info

Publication number
CN101020077A
CN101020077A CN 200710048698 CN200710048698A CN101020077A CN 101020077 A CN101020077 A CN 101020077A CN 200710048698 CN200710048698 CN 200710048698 CN 200710048698 A CN200710048698 A CN 200710048698A CN 101020077 A CN101020077 A CN 101020077A
Authority
CN
China
Prior art keywords
collagen
parts
weight
gelatin
tissue
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
CN 200710048698
Other languages
Chinese (zh)
Other versions
CN100544774C (en
Inventor
但卫华
叶易春
曾睿
关林波
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sichuan University
Original Assignee
Sichuan University
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.)
Filing date
Publication date
Application filed by Sichuan University filed Critical Sichuan University
Priority to CNB2007100486984A priority Critical patent/CN100544774C/en
Publication of CN101020077A publication Critical patent/CN101020077A/en
Application granted granted Critical
Publication of CN100544774C publication Critical patent/CN100544774C/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Landscapes

  • Medicinal Preparation (AREA)
  • Materials For Medical Uses (AREA)

Abstract

本发明公开了一种具有组织诱导性的胶原基体表创伤修复膜的制备方法，其特点是将胶原基修复膜经过物理和化学改性，并引入含细胞生长因子的明胶基缓释微球的修复膜材料，孔径为20～200微米，孔率≥80％，拉伸强度≥1MPa，pH值为5.0～6.0，有良好的降解性和生物相容性。膜的孔结构和活性胶原成分决定了其能够充分吸收伤口渗出液，能够诱发自体细胞的粘连、增殖、分化，以及血管的长入，并且复合的缓释微球可以使细胞生长因子长时间的有效释放到伤口，明显缩短伤口愈合时间，愈合的新生组织与周围组织融合良好，避免了瘢疤的产生。本胶原基复合膜用于各种原因的机械伤、烧伤、烫伤，皮肤溃疡及其美容整形术和止血。The invention discloses a preparation method of a tissue-inducible collagen-based wound repair membrane, which is characterized in that the collagen-based repair membrane is physically and chemically modified, and gelatin-based slow-release microspheres containing cell growth factors are introduced. The repair membrane material has a pore size of 20-200 microns, a porosity of ≥80%, a tensile strength of ≥1 MPa, a pH value of 5.0-6.0, and good degradability and biocompatibility. The pore structure and active collagen components of the membrane determine that it can fully absorb wound exudate, and can induce autologous cell adhesion, proliferation, differentiation, and ingrowth of blood vessels, and the compound slow-release microspheres can make cell growth factors last for a long time. The effective release to the wound can significantly shorten the wound healing time, and the healed new tissue is well integrated with the surrounding tissue, avoiding the generation of scar. The collagen-based composite film is used for various causes of mechanical injuries, burns, scalds, skin ulcers, cosmetic plastic surgery and hemostasis.

Description

Has the preparation method of organizing epigamic collagen matrix surface wound repairing membrane
Technical field
The present invention relates to a kind of have organize epigamic collagen matrix surface wound repairing membrane preparation methods, belong to the preparation field of medical material.
Background technology
Skin is the natural cover for defense of human body, to keeping the stable of internal milieu and stoping the microorganism invasion to play an important role.If skin is subjected to large tracts of land damage, then can cause many parts even general problem, as metabolism aggravation, moisture and protein excessively scatter and disappear, immune system disorder etc., the serious entail dangers to life of going back.Rebuilding or recovering skin barrier function is the final goal of body surface trauma care, before reaching this target, the Wound dressing of a function admirable can temporarily play the partial function of skin, an environment that helps wound healing is provided, wait for the wound surface epithelization or carry out the transition to and rebuild permanent skin barrier [Xu Weishi, Le Jiafen. [M] repairs in burn wound. Wuhan: Hubei science tech publishing house, 2000].In general, the body surface wound is meant mechanical injury, burn, scald and the skin ulcer etc. of a variety of causes, and the performance of body surface wound is that the disease of skin is decreased.As everyone knows, in all wounds, people's body surface wound is occupied very big ratio, according to incompletely statistics, body surface wound case, China is annual about more than 1,500 ten thousand person-times, wherein, 3,000,000 person-times of mechanical injury, 1,200 ten thousand person-times of burn, scald and skin ulcers etc.The body surface wound has caused secular, many-sided misery to the patient, and the patient is in the low-quality life all the time.Research and development have significant curative effect and medical skill that has no side effect and medical material, are the problems that medical circle and material circle are paid close attention to always.
Number of research projects mainly concentrates on the development aspect of natural dermal substitute and artificial dermis both at home and abroad, and its representational product is artificial skin, collagen gel and medical collagen film etc.Yet, a large amount of experimentatioies and clinical and experimental study result show, material ubiquities such as existing artificial skin, collagen gel and medical collagen film the mechanics poor performance, mouldability is bad and can not infection etc. problems [Liu Dewu. modern dressing progress. Chinese clinical rehabilitation, 2002,6 (22): 3436～3437. in refined virtuous. application present situation and the progress of collagen in Graftskin. and Chinese leather, 2005,34:8～12.].
At present, commercialization is applied to clinical skin wound covering has: epidermal sheet, acellular dermal matrix, collagen sponge membrane, collagen gel film etc.1. epidermal sheet: this diaphragm (KC) shortcoming is to get patient's skin biopsy specimen, the time that needs 2-3 week, lack the corium composition, diaphragm poor frangible [O ' ConnerNE, Malliken JB, Bankaclilegcls, et al.Grafting of burns with cultured epitheliunt prepared fromautologous epidermal cells[J] .Lancet, 1981,1:75-78].2. acellular dermal matrix: its shortcoming is the antigenic substance that possible contain not Ex-all, and the danger of virus spread is arranged, and the material hole connectivity is poor.3. collagen sponge membrane: as Chinese patent 94118836.1 and 01134743.0, its shortcoming is not contain cell in the material to give birth to the sub-factor, and poor mechanical property, can not infection; Chinese patent 200510022581.X though directly added somatomedin in the material, does not introduce the microsphere sustained-release technology, and somatomedin easily loses biological activity.4. collagen gel: as Chinese patent 02117585.3 and 03130382.X, shortcoming is the production process complexity, and collagen gel can shrink about 80%, and opposing degraded by collagenase ability is subject to viral infection and immunological rejection, and fragility is big, the operation technique difficulty.
Summary of the invention
The present invention seeks to provides a kind of preparation method of organizing epigamic collagen matrix surface wound repairing membrane that has at the deficiencies in the prior art.Be characterized in collagen base repair membrane process physics and chemical modification, and introduce the repair membrane material of the gelatin-based sustained-release micro-spheres that contains cell growth factor, the aperture is 20～200 microns, porosity 〉=80%, hot strength 〉=1MPa, pH value is 5.0～6.0, and good degradability and biocompatibility are arranged.
Purpose of the present invention is realized that by following technical measures wherein said raw material umber is parts by weight except that specified otherwise.
Have and organize the preparation method of epigamic collagen matrix surface wound repairing membrane may further comprise the steps:
(1) extraction of collagen: with 1 part of animal skin or cartilage or tendon tissue, adopting concentration is 20～100 parts of 1～3% acetums, 0.01～0.05 part of pepsin, pH value of solution 2.0～3.0 is in 4～24 ℃ of temperature, extracted in the rotary drum 6～12 hours, centrifugalize is then saltoutd, purification, obtain medical collagen, lyophilizing is standby;
(2) preparation of gelatin-based sustained-release micro-spheres: Oleum Ricini, liquid paraffin or the olive oil that will contain surfactant 1～3wt% place there-necked flask to be preheated to 40～50 ℃ for 50～100 parts, stirring and dripping concentration down is 5～20 parts of 5～10% gelatin-based aqueous solutions, use ice bath instead after forming water-in-oil emulsion, continue to stir 10～20min, in emulsion, add 30～50 parts of acetone, stir 30～60min, adding concentration is 1～3 part of 1～5% glutaraldehyde, reaction 1～2h.The gelatin-based microsphere that obtains with acetone wash, isopropyl alcohol is washed, centrifugalize, air-dry, again the gelatine microsphere immersion is contained in 0.25～1% glutaraldehyde, in 4～24 ℃ of temperature, stir process 12～20h, centrifugalize, thus obtained microsphere, steeps microsphere in the cell growth factor that contains 50～500ng/ml to remove the glutaraldehyde that does not have reaction at last with the washing of 10～50mM glycine, through lyophilizing, obtain the slow release gelatine microsphere;
(3) preparation of collagen basement membrane: with concentration is 40～70 parts of 0.5～2% collagens, 60～30 parts of additives place mould to adopt freeze-drying pore-creating film forming, are lyophilized into the membrane process condition: first section temperature-40 ℃, 1.5 ℃/min of rate of temperature fall, constant temperature time 5h; Second section temperature-30 ℃, 1 ℃/min of heating rate, constant temperature time 10h; The 3rd section temperature-20 ℃, 1 ℃/min of heating rate, constant temperature time 10h; The 4th section temperature-10 ℃, 1 ℃/min of heating rate, constant temperature time 10h; 20 ℃ of the 5th section temperature, 1 ℃/min of heating rate, constant temperature time 5h;
(4) modification of film and microsphere is compound: the collagen basal lamina material that (3) are made placed 100～150 ℃ of vacuum heat of temperature 2～24 hours for 1～2 part, and is cross-linking modified in 50～100 parts of cross-linking agent solutions then, is respectively the Na of 0.1～1.0mol/L with concentration 2HPO 4(pH8.0～9.1), 1～2mol/L NaCl, 5～50mmol/L glycine, distilled water clean repeatedly, the sustained-release micro-spheres that (2) are made evenly is sprayed on the film after disperseing with phosphate buffer (PBS) more again, compound lyophilizing obtains collagen matrix surface wound repairing membrane;
(5) post processing: above-mentioned wound repairing membrane sterile packaged is carried out irradiation sterilization in packing bag for medical use, adopt cobalt-60, sterilizing dose 25～50kGy.
Wherein, surfactant is tween 80 or Arlacel-80.
In the gelatin-based aqueous solution of preparation microsphere, gelatin is 60～100 parts, 0～40 part of collagen, 0～40 part of chitosan.
Cell growth factor is at least a in basic fibroblast growth factor (bFGF), transforming growth factor (TGF-β 1), endothelial cell growth factor (ECGF) (VEGF), the epithelical cell growth factor (EGF).
Additive is at least a in chitosan, chondroitin sulfate, hyaluronic acid, heparin, dermatan sulfate, heparin sulfate, polylactic acid, polyvinyl alcohol, the medical polyurethane.
Cross-linking agent is 1-ethyl-3-(3-dimethyl amine propyl group)-carbodiimides, glutaraldehyde, dialdehyde starch, diglycidyl ether of ethylene glycol, propanetriol-diglycidyl-ether, genipin, myrica extract, wattle extract, 1, any in the own diisocyanate of 6-.
Epigamic collagen matrix surface wound repairing membrane is organized in having that the employing method for preparing obtains.
Protocollagen matrix surface wound repairing membrane is applied to mechanical injury, burn, the scald of a variety of causes, skin ulcer, and beauty and shaping art and hemostasis.
The aperture of repair membrane material provided by the invention is 20～200 microns, porosity 〉=80%, hot strength 〉=1MPa, pH value 5.0～6.0.
The present invention has following advantage:
1. good degradability and biocompatibility.
2. the pore structure of film and active collagen composition have determined it can fully absorb wound fluid, can bring out adhesion, propagation, the differentiation of autogenous cell, and the growing into of blood vessel.
3. compound sustained-release micro-spheres can make cell growth factor effectively be discharged into wound for a long time, can obviously shorten wound healing time.
4. Yu He cambium and surrounding tissue good knitting have been avoided the generation of scar scar.
The specific embodiment
Below by implementing that the present invention is carried out concrete description; be necessary to be pointed out that at this present embodiment only is used for the present invention is further specified; can not be interpreted as limiting the scope of the invention, the person skilled in the art in this field can make some nonessential improvement and adjustment according to the content of foregoing invention.
Embodiment 1:
1. the preparation of sustained-release micro-spheres
The Oleum Ricini that will contain 1% tween 80 places there-necked flask for 50 parts, be preheated to 50 ℃, under agitation drip total concentration and be 5% gelatin: 5 parts of chitosan=9: 1 mixed solutions, stir 10min, use ice bath instead behind the formation water-in-oil emulsion, continue to stir 10min, in emulsion, add 30 parts of acetone, stir emulsion 30min, add 3 parts of 1% glutaraldehydes, pre-modification 1h.The gelatin-based microsphere that obtains is washed 2 times with acetone, and isopropyl alcohol is washed 2 times, and centrifugal (10000rmp, 15min, 4 ℃) are collected, and are air-dry.Again gelatine microsphere is immersed and contain in 0.25% glutaraldehyde and the 1% tween 80 solution, in 4 ℃ of temperature, stir process 12h, the solution that contains 10mM glycine and 1% tween 80 is put in centrifugalize, thus obtained microsphere, in 4 ℃ of temperature, stir process 1h is to remove the glutaraldehyde that does not have reaction.Wash microsphere 2 times with distillation, centrifugalize is steeped microsphere in the fibroblast growth factor that contains 50ng/ml, and lyophilizing more at last obtains slow release gelatin-based microsphere.
2. the preparation of repair membrane
With 1 part of animal skin or cartilage or tendon tissue, washing, homogenate, defat, adopting concentration is 50 parts of 3% acetic acid, 0.02 part of pepsin, pH value of solution 2.0～3.0 in 4 ℃ of temperature, extracted 8 hours centrifugalize then in the rotary drum, saltout, purification obtains medical collagen.Prepare collagen, chitosan, poly-vinyl alcohol solution then, three's weight ratio is 2: 2: 1, is mixed with collagen base blended liquid, in mould, adopt freeze-drying pore-creating film forming, be lyophilized into the membrane process condition: first section temperature-40 ℃, 1.5 ℃/min of rate of temperature fall, constant temperature time 5h; Second section temperature-30 ℃, 1 ℃/min of heating rate, constant temperature time 10h; The 3rd section temperature-20 ℃, 1 ℃/min of heating rate, constant temperature time 10h; The 4th section temperature-10 ℃, 1 ℃/min of heating rate, constant temperature time 10h; 20 ℃ of the 5th section temperature, 1 ℃/min of heating rate, constant temperature time 5h.In 0.25% glutaraldehyde solution cross-linking modified 24 hours, use 0.1mol/LNa then respectively 2HPO 4(pH9.1), 10mmol/L glycine, distilled water clean acquisition collagen basement membrane repeatedly.Again the sustained-release micro-spheres that said method is made with PBS disperse the back evenly spraying be compound on the collagen basement membrane, last lyophilizing, sterile packaged in packing bag for medical use, cobalt-60 irradiation sterilization, sterilizing dose 25kGy.
Embodiment 2:
1. the preparation of sustained-release micro-spheres
The liquid paraffin that will contain 2% Arlacel-80 places there-necked flask for 80 parts, is preheated to 50 ℃, and stirring and dripping total concentration down is 8% gelatin: 8 parts of collagen=8: 2 mixed solutions, and stir and use ice bath instead after forming water in oil emulsion, continue to stir 10min.In emulsion, add 40 parts of acetone, stir emulsion 30min, add 2 parts of 3% glutaraldehydes, pre-modification 1h.The gelatin-based complex microsphere that obtains is washed 2 times with acetone, and isopropyl alcohol is washed 2 times, and centrifugal (10000rmp, 15min, 4 ℃) are collected, and are air-dry, obtain uncrosslinked microsphere.Uncrosslinked gelatin-based complex microsphere immersion is contained in 0.5% glutaraldehyde and the 1% Arlacel-80 solution, in 4 ℃ of temperature, stir process 12h, centrifugalize, thus obtained microsphere is put into the solution that contains 20mM glycine and 1% Arlacel-80, in 14 ℃ of temperature, stir process 1h is to remove the glutaraldehyde that does not have reaction.Wash microsphere 2 times with distillation, centrifugalize is steeped microsphere in the transforming growth factor that contains 100ng/ml, and lyophilizing more at last promptly obtains slow release gelatin-based microsphere.
2. the preparation of repair membrane
Press the method for embodiment 1 and extract collagen protein, or be raw material with commercially available collagen protein, with collagen, chitosan, chondroitin sulfate, be mixed with collagen base blended liquid, three's weight ratio is 5: 5: 1, adopts freeze-drying pore-creating film forming in mould, is lyophilized into the membrane process condition: first section temperature-40 ℃, 1.5 ℃/min of rate of temperature fall, constant temperature time 5h; Second section temperature-30 ℃, 1 ℃/min of heating rate, constant temperature time 10h; The 3rd section temperature-20 ℃, 1 ℃/min of heating rate, constant temperature time 10h; The 4th section temperature-10 ℃, 1 ℃/min of heating rate, constant temperature time 10h; 20 ℃ of the 5th section temperature, 1 ℃/min of heating rate, constant temperature time 5h.Under 30 ℃ of temperature, be soaked in pH10.5 then, among the diglycidyl ether of ethylene glycol EX-810 of concentration 6%, crosslinked 24h.Then the film material is cleaned repeatedly with 10mmol/L glycine, distilled water, the sustained-release micro-spheres that said method is made disperses the even spraying in back to be compound on the collagen basement membrane last lyophilizing, sterile packaged, cobalt-60 irradiation sterilization, sterilizing dose 30kGy with PBS again.
Embodiment 3:
1. the preparation of sustained-release micro-spheres
The olive oil that will contain 3% Arlacel-80 places there-necked flask for 100 parts, be preheated to 50 ℃, stirring and dripping total concentration down is 10% gelatin: collagen: 20 parts of chitosan=8: 1: 1 mixed solutions, and stir and use ice bath instead after forming water in oil emulsion, continue to stir 10min.In emulsion, add 50 parts of acetone, stir emulsion 30min, add 1 part of 5% glutaraldehyde, pre-modification 1h.The gelatin-based complex microsphere that obtains is washed 2 times with acetone, and isopropyl alcohol is washed 2 times, and centrifugal (10000rmp, 15min, 4 ℃) are collected, and are air-dry, obtain uncrosslinked microsphere.Uncrosslinked gelatin-based complex microsphere immersion is contained in 1% glutaraldehyde and the 1% Arlacel-80 solution, in 4 ℃ of temperature, stir process 12h, the solution that contains 50mM glycine and 1% Arlacel-80 is put in centrifugalize, thus obtained microsphere, in 24 ℃ of temperature, stir process 1h is to remove the glutaraldehyde that does not have reaction.Wash microsphere 2 times with distillation, centrifugalize is steeped microsphere in the endothelial cell growth factor (ECGF) that contains 500ng/ml, and last lyophilizing promptly gets slow release gelatin-based microsphere.
2. the preparation of repair membrane
At 50 ℃ of acetate dissolution chitosans of using 0.5M down of temperature, add collagen, making the mixed liquor total concentration is 2%, collagen accounts for 40 parts of 60 parts, chitosan in the mixed solution, behind collagen and the chitosan mix homogeneously, adds concentration again and be 4 parts of 1% glutaraldehydes in blended liquid, lyophilizing film forming in mould, be lyophilized into the membrane process condition: first section temperature-40 ℃, 1.5 ℃/min of rate of temperature fall, constant temperature time 5h; Second section temperature-30 ℃, 1 ℃/min of heating rate, constant temperature time 10h; The 3rd section temperature-20 ℃, 1 ℃/min of heating rate, constant temperature time 10h; The 4th section temperature-10 ℃, 1 ℃/min of heating rate, constant temperature time 10h; 20 ℃ of the 5th section temperature, 1 ℃/min of heating rate, constant temperature time 5h.It is 110 ℃ of following vacuum heat 12 hours that the collagen basement membrane that makes is placed temperature, and the sustained-release micro-spheres that said method is made disperses the even spraying in back to be compound on the collagen basement membrane last lyophilizing, sterile packaged, cobalt-60 irradiation sterilization, sterilizing dose 50kGy with PBS again.
Embodiment 4:
1. the preparation of sustained-release micro-spheres
The Oleum Ricini that will contain 1% Arlacel-80 places there-necked flask for 90 parts, be preheated to 50 ℃, stirring and dripping total concentration down is 10% gelatin: collagen: 10 parts of chitosan=7: 2: 1 mixed solutions, and stir and use ice bath instead after forming water in oil emulsion, continue to stir 10min.In emulsion, add 50 parts of acetone, stir emulsion 30min, add 2 parts of 2% glutaraldehydes, pre-modification 1h.The gelatin-based complex microsphere that obtains is washed 2 times with acetone, and isopropyl alcohol is washed 2 times, and centrifugal (10000rmp, 15min, 4 ℃) are collected, and are air-dry, obtain uncrosslinked microsphere.Uncrosslinked gelatin-based complex microsphere immersion is contained in the solution of 0.5% glutaraldehyde and 1% Arlacel-80, in 4 ℃ of temperature, stir process 12h, centrifugalize, thus obtained microsphere is put into the solution that contains 30mM glycine and 1% Arlacel-80, in 4 ℃ of temperature, stir process 1h is to remove the glutaraldehyde that does not have reaction.Wash microsphere 2 times with distillation, centrifugalize is steeped microsphere in the epithelical cell growth factor that contains 200ng/ml, and last lyophilizing promptly gets slow release gelatin-based microsphere.
2. the preparation of repair membrane
With 10 parts of preparations of 50 parts of collagens, 40 parts of chitosans, hyaluronic acid collagen base blended liquid, in mould, adopt freeze-drying pore-creating film forming, be lyophilized into the membrane process condition: first section temperature-40 ℃, 1.5 ℃/min of rate of temperature fall, constant temperature time 5h; Second section temperature-30 ℃, 1 ℃/min of heating rate, constant temperature time 10h; The 3rd section temperature-20 ℃, 1 ℃/min of heating rate, constant temperature time 10h; The 4th section temperature-10 ℃, 1 ℃/min of heating rate, constant temperature time 10h; 20 ℃ of the 5th section temperature, 1 ℃/min of heating rate, constant temperature time 5h.The collagen basement membrane that makes was placed 110 ℃ of following vacuum heat of temperature 12 hours, be soaked in pH5.5 then and contain 50mmol/L2-N-morpholino ethane sulfonic acid (MES), 30min in 50% ethanol, again it is immersed in 50% alcoholic solution that contains 50mmol/L MES, 33mmol/L 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide [EDC], 20mmol/L N-maloyl imines (NHS) crosslinked 24h under the room temperature.Then with film material 0.1mol/L Na 2HPO 4(pH9.1), 1mol/L NaCl, 2mol/L NaCl, distilled water clean repeatedly, again the sustained-release micro-spheres that said method is made with PBS disperse the back evenly spraying be compound on the collagen basement membrane last lyophilizing, sterile packaged, cobalt-60 irradiation sterilization, sterilizing dose 40kGy.
Embodiment 5:
1. the preparation of sustained-release micro-spheres
Be 2% acetum 20ml dissolving gelatin, chitosan with concentration at normal temperatures, wherein gelatin is 9 parts, and 1 part of chitosan mixes the back and adds 20 microgram fibroblast growth factors.The gelatin-based mixed liquor that is compounded with somatomedin is added in the capryl alcohol (containing 2% Arlacel-80), stir 20min, form water in oil emulsion.Then, add 4% glutaraldehyde 1ml, the gelatin-based complex microsphere that obtains is washed 2 times with acetone, and isopropyl alcohol is washed 2 times, and centrifugal (10000rmp, 15min, 4 ℃) are collected, and are air-dry.Again the gelatin-based complex microsphere is immersed and contain in 0.75% glutaraldehyde and the 1% Arlacel-80 solution, in 4 ℃ of temperature, stir process 12h, the solution that 50ml contains 20mM glycine and 1% Arlacel-80 is put in centrifugalize, thus obtained microsphere, in 24 ℃ of temperature, stir process 1h is to remove the glutaraldehyde that does not have reaction.Wash microsphere 2 times with distillation, centrifugalize, last lyophilizing promptly gets slow release gelatin-based microsphere.
2. the preparation of repair membrane
At 50 ℃ of acetate dissolution chitosans of using 0.5M down of temperature, when 4 ℃ of temperature, add collagen, making the mixed liquor total concentration is 2%, collagen accounts for 50 parts in the mixed solution, 50 parts of chitosans adopt freeze-drying pore-creating film forming in mould, be lyophilized into the membrane process condition: first section temperature-40 ℃, 1.5 ℃/min of rate of temperature fall, constant temperature time 5h; Second section temperature-30 ℃, 1 ℃/min of heating rate, constant temperature time 10h; The 3rd section temperature-20 ℃, 1 ℃/min of heating rate, constant temperature time 10h; The 4th section temperature-10 ℃, 1 ℃/min of heating rate, constant temperature time 10h; 20 ℃ of the 5th section temperature, 1 ℃/min of heating rate, constant temperature time 5h.The collagen basal lamina material that makes placed 110 ℃ of following vacuum heat of temperature 12 hours, be soaked in pH5.5 then and contain 50mmol/LMES, 30min in 50% ethanol, again it is immersed in 50% alcoholic solution that contains 2% chondroitin sulfate, 50mmol/L MES, 33mmol/L EDC, 20mmol/LNHS crosslinked 24h under the room temperature.Then with film material 0.1mol/L Na 2HPO 4(pH9.1), 1mol/L NaCl, 2mol/L NaCl, distilled water clean repeatedly, again the sustained-release micro-spheres that said method is made with PBS disperse the back evenly spraying be compound on the collagen basement membrane last lyophilizing, sterile packaged, cobalt-60 irradiation sterilization, sterilizing dose 35kGy.
Embodiment 6:
1. the preparation of sustained-release micro-spheres
With 8 parts in gelatin of 3% acetum 20ml dissolving, 2 parts of collagens, mix the back and add 30 microgram transforming growth factors at normal temperatures.The gelatin-based mixed liquor that is compounded with somatomedin is added in the capryl alcohol (containing 2% Arlacel-80), stir 20min, form water in oil emulsion.Then, add 5% glutaraldehyde 1ml, the gelatin-based complex microsphere that obtains is washed 2 times with acetone, and isopropyl alcohol is washed 2 times, and centrifugal (10000rmp, 15min, 4 ℃) are collected, and are air-dry.Again the immersion of gelatin-based complex microsphere is contained in the solution of 1% glutaraldehyde and 1% Arlacel-80, in 4 ℃ of temperature, stir process 12h, centrifugal, thus obtained microsphere is put into the solution that 50ml contains 10mM glycine and 1% Arlacel-80, in 24 ℃ of temperature, stir process 1h is to remove the glutaraldehyde that does not have reaction.Wash microsphere 2 times with distillation, centrifugalize, last lyophilizing promptly gets slow release gelatin-based microsphere.
2. the preparation of repair membrane
Collagen, chitosan, polyurethane are mixed with collagen base blended liquid, and three's weight ratio is 3: 2: 1, adopts freeze-drying pore-creating film forming in mould, is lyophilized into the membrane process condition: first section temperature-40 ℃, 1.5 ℃/min of rate of temperature fall, constant temperature time 5h; Second section temperature-30 ℃, 1 ℃/min of heating rate, constant temperature time 10h; The 3rd section temperature-20 ℃, 1 ℃/min of heating rate, constant temperature time 10h; The 4th section temperature-10 ℃, 1 ℃/min of heating rate, constant temperature time 10h; 20 ℃ of the 5th section temperature, 1 ℃/min of heating rate, constant temperature time 5h.The collagen basement membrane that makes is placed 60 ℃ of following vacuum dry heat treatment of temperature 2 hours, improved temperature to 80 ℃ heat treatment afterwards 2 hours, improved temperature to 110 ℃ following vacuum dry heat treatment again 12 hours.The sustained-release micro-spheres that said method is made disperses the even spraying in back to be compound on the collagen basement membrane last lyophilizing, sterile packaged, cobalt-60 irradiation sterilization, sterilizing dose 40kGy with PBS.

Claims (8)

1.具有组织诱导性的胶原基体表创伤修复膜的制备方法，其特征在于该方法包括以下步骤：1. the preparation method of the tissue-inducible collagen matrix surface wound repair film is characterized in that the method may further comprise the steps: (1)胶原的提取：将动物皮肤或软骨或肌腱组织1重量份，采用浓度为1～3％醋酸溶液20～100重量份，胃蛋白酶0.01～0.05重量份，溶液pH2.0～3.0，于温度4～24℃，转鼓中提取6～12小时，然后离心分离，盐析，纯化，获得医用胶原蛋白，冻干备用；(1) Extraction of collagen: 1 part by weight of animal skin or cartilage or tendon tissue, 20-100 parts by weight of 1-3% acetic acid solution, 0.01-0.05 parts by weight of pepsin, pH 2.0-3.0 of the solution, The temperature is 4-24°C, and the extraction is carried out in a drum for 6-12 hours, then centrifuged, salted out, purified to obtain medical collagen, and freeze-dried for later use; (2)明胶基缓释微球的制备：将含有表面活性剂1～3wt％的蓖麻油、液体石蜡或橄榄油50～100重量份置于三口瓶中预热至40～50℃，搅拌下滴加浓度为5～10％的明胶基水溶液5～20重量份，形成油包水乳液后改用冰浴，继续搅拌10～20min，在乳液中加入30～50重量份丙酮，搅拌30～60min，加入浓度为1～5％戊二醛1～3重量份，反应1～2h。得到的明胶基微球用丙酮洗、异丙醇洗、离心分离，风干，再把明胶微球浸入含0.25～1％戊二醛中，于温度4～24℃，搅拌处理12～20h，离心分离，所得微球用10～50mM甘氨酸洗涤，以除去没反应的戊二醛，最后把微球泡入含50～500ng/ml的细胞生长因子中，经冻干，获得缓释明胶微球；(2) Preparation of gelatin-based sustained-release microspheres: 50-100 parts by weight of castor oil, liquid paraffin or olive oil containing 1-3 wt% of surfactant is placed in a three-necked bottle, preheated to 40-50°C, and stirred Add 5-20 parts by weight of a gelatin-based aqueous solution with a concentration of 5-10% dropwise to form a water-in-oil emulsion, then use an ice bath, continue stirring for 10-20 minutes, add 30-50 parts by weight of acetone to the emulsion, and stir for 30-60 minutes , adding 1-3 parts by weight of glutaraldehyde at a concentration of 1-5%, and reacting for 1-2 hours. The obtained gelatin-based microspheres were washed with acetone and isopropanol, centrifuged, air-dried, then immersed in gelatin microspheres containing 0.25-1% glutaraldehyde, stirred at a temperature of 4-24°C for 12-20 hours, centrifuged Separation, the obtained microspheres are washed with 10-50mM glycine to remove unreacted glutaraldehyde, and finally the microspheres are soaked in cell growth factors containing 50-500ng/ml, and freeze-dried to obtain slow-release gelatin microspheres; (3)胶原基膜的制备：将浓度为0.5～2％的胶原40～70重量份，添加剂60～30重量份，置于模具中采用冷冻干燥法造孔成膜，冻干工艺条件：第一段温度-40℃，降温速率1.5℃/min，恒温时间5h；第二段温度-30℃，升温速率1℃/min，恒温时间10h；第三段温度-20℃，升温速率1℃/min，恒温时间10h；第四段温度-10℃，升温速率1℃/min，恒温时间10h；第五段温度20℃，升温速率1℃/min，恒温时间5h；(3) Preparation of collagen basement membrane: 40-70 parts by weight of collagen with a concentration of 0.5-2%, and 60-30 parts by weight of additives, are placed in a mold and pore-formed by freeze-drying method. Freeze-drying process conditions: No. The first stage temperature is -40°C, the cooling rate is 1.5°C/min, and the constant temperature time is 5 hours; the second stage temperature is -30°C, the heating rate is 1°C/min, and the constant temperature time is 10 hours; min, the constant temperature time is 10h; the fourth stage temperature is -10℃, the heating rate is 1℃/min, and the constant temperature time is 10h; the fifth stage temperature is 20℃, the heating rate is 1℃/min, and the constant temperature time is 5h; (4)膜的改性与微球的复合：将(3)制得的胶原基膜材料1～2重量份置于温度100～150℃真空热处理2～24小时，然后在交联剂溶液50～100重量份中交联改性，分别用浓度为0.1～1.0mol/L的Na2HPO4(pH8.0～9.1)、1～2mol/L NaCl、5～50mmol/L甘氨酸、双蒸水反复清洗，再将(2)制得的缓释微球用磷酸盐缓冲液(PBS)分散后再均匀喷涂于膜上，复合冻干，获得胶原基体表创伤修复膜；(4) Modification of membrane and compounding of microspheres: place 1 to 2 parts by weight of the collagen base membrane material prepared in (3) at a temperature of 100 to 150° C. for vacuum heat treatment for 2 to 24 hours, and then in a crosslinking agent solution 50 ~100 parts by weight of cross-linking modification, respectively using Na 2 HPO 4 (pH8.0~9.1) with a concentration of 0.1~1.0mol/L, 1~2mol/L NaCl, 5~50mmol/L glycine, double distilled water Wash repeatedly, then disperse the slow-release microspheres prepared in (2) with phosphate buffered saline (PBS) and then evenly spray on the film, compound and freeze-dry to obtain a wound repair film on the surface of the collagen matrix; (5)后处理：将上述创伤修复膜无菌封装在医用包装袋内进行辐照灭菌：采用钴-60，灭菌剂量25～50kGy。(5) Post-treatment: Aseptically package the above-mentioned wound repair film in a medical packaging bag for irradiation sterilization: Cobalt-60 is used, and the sterilization dose is 25-50 kGy. 2.如权利要求1所述具有组织诱导性的胶原基体表创伤修复膜的制备方法，其特征在于表面活性剂为吐温-80或者司盘-80。2. The preparation method of tissue-inducible collagen matrix surface wound repair membrane as claimed in claim 1, characterized in that the surfactant is Tween-80 or Span-80. 3.如权利要求1所述具有组织诱导性的胶原基体表创伤修复膜的制备方法，其特征在于制备微球的明胶基水溶液中的明胶为60～100重量份，胶原0～40重量份，壳聚糖0～40重量份。3. The preparation method of the tissue-inducible collagen matrix surface wound repair film as claimed in claim 1, wherein the gelatin in the gelatin-based aqueous solution for preparing microspheres is 60 to 100 parts by weight, 0 to 40 parts by weight of collagen, 0-40 parts by weight of chitosan. 4.如权利要求1所述具有组织诱导性的胶原基体表创伤修复膜的制备方法，其特征在于细胞生长因子为碱性成纤维细胞生长因子(bFGF)、转化生长因子(TGF-β1)、内皮细胞生长因子(VEGF)、表皮细胞生长因子(EGF)中的至少一种。4. the preparation method of the tissue-inducible collagen matrix surface wound repair film as claimed in claim 1, is characterized in that cell growth factor is basic fibroblast growth factor (bFGF), transforming growth factor (TGF-β1), At least one of endothelial growth factor (VEGF) and epidermal growth factor (EGF). 5.如权利要求1所述具有组织诱导性的胶原基体表创伤修复膜的制备方法，其特征在于胶原基膜中的添加剂为壳聚糖、硫酸软骨素、透明质酸、肝素、硫酸皮肤素、硫酸肝素、聚乳酸、聚乙烯醇、医用聚氨酯中的至少一种。5. as claimed in claim 1, there is the preparation method of the tissue-inducible collagen matrix surface wound repair film, it is characterized in that the additive in the collagen base film is chitosan, chondroitin sulfate, hyaluronic acid, heparin, dermatan sulfate , heparan sulfate, polylactic acid, polyvinyl alcohol, and at least one of medical polyurethane. 6.如权利要求1所述具有组织诱导性的胶原基体表创伤修复膜的制备方法，其特征在于交联剂为1-乙基-3-(3-二甲基胺丙基)-碳化二亚胺、戊二醛、双醛淀粉、乙二醇缩水甘油醚、丙三醇缩水甘油醚、京尼平、杨梅栲胶、荆树皮栲胶、1，6-己二异氰酸盐中的任一种。6. as claimed in claim 1, there is the preparation method of tissue-inducible collagen matrix surface wound repair film, it is characterized in that cross-linking agent is 1-ethyl-3-(3-dimethylaminopropyl group)-carbide Imine, glutaraldehyde, dialdehyde starch, ethylene glycol glycidyl ether, glycerol glycidyl ether, genipin, bayberry extract, wattle extract, 1,6-hexamethylene diisocyanate of any kind. 7.采用上述方法制备得到的具有组织诱导性的胶原基体表创伤修复膜。7. The tissue-inducible collagen matrix surface wound repair membrane prepared by the above method. 8.如权利要求6所述具有组织诱导性的胶原基体表创伤修复膜用于各种原因的机械伤、烧伤、烫伤，皮肤溃疡，及其美容整形术和止血。8. As claimed in claim 6, the tissue-inducing collagen matrix surface wound repair film is used for mechanical injuries of various reasons, burns, scalds, skin ulcers, and cosmetic plastic surgery and hemostasis.
CNB2007100486984A 2007-03-23 2007-03-23 Preparation method of collagen matrix surface wound repair film with tissue induction Expired - Fee Related CN100544774C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CNB2007100486984A CN100544774C (en) 2007-03-23 2007-03-23 Preparation method of collagen matrix surface wound repair film with tissue induction

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CNB2007100486984A CN100544774C (en) 2007-03-23 2007-03-23 Preparation method of collagen matrix surface wound repair film with tissue induction

Publications (2)

Publication Number Publication Date
CN101020077A true CN101020077A (en) 2007-08-22
CN100544774C CN100544774C (en) 2009-09-30

Family

ID=38708003

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB2007100486984A Expired - Fee Related CN100544774C (en) 2007-03-23 2007-03-23 Preparation method of collagen matrix surface wound repair film with tissue induction

Country Status (1)

Country Link
CN (1) CN100544774C (en)

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101954126A (en) * 2010-09-26 2011-01-26 华南理工大学 Method for preparing bionic modified collagen tissue repair material
CN102604128A (en) * 2012-04-18 2012-07-25 吉林大学 Preparation method for gelatin nanosphere
CN103054814A (en) * 2013-01-16 2013-04-24 南京理工大学 Preparation method for polysaccharide microspheres based on medicine cross-linking
CN103285420A (en) * 2013-03-28 2013-09-11 北京桀亚莱福生物技术有限责任公司 A kind of preparation method of human biological dressing for covering burn wound wound surface
CN103536965A (en) * 2013-09-24 2014-01-29 北京大学口腔医学院 Preparation method for three-dimensional mineralized collagen bracket with strict grade structure as well as product and application of three-dimensional mineralized collagen bracket
CN103830768A (en) * 2012-11-21 2014-06-04 深圳兰度生物材料有限公司 Degradable wound repair material and preparation method thereof
CN104170815A (en) * 2013-05-22 2014-12-03 烟台正海生物技术有限公司 Method for protecting biological material before irradiation sterilization
CN105056286A (en) * 2015-07-15 2015-11-18 军事医学科学院华南干细胞与再生医学研究中心 Liquid band-aid and preparing method thereof
CN105088779A (en) * 2015-08-05 2015-11-25 广州赛莱拉生物基因工程有限公司 Collagen attachment membrane and preparation method thereof
CN106267341A (en) * 2016-08-30 2017-01-04 圆容生物医药无锡有限公司 One can organize induction bio-medical material
CN104667336B (en) * 2013-03-28 2017-01-25 北京桀亚莱福生物技术有限责任公司 Human body biological dressing for covering burn wound surfaces and applications of dressing
CN106730009A (en) * 2016-12-30 2017-05-31 广州迈普再生医学科技有限公司 A kind of bone repairing support and preparation method thereof
CN107602883A (en) * 2017-08-23 2018-01-19 四川大学 A kind of edible collagem membrane of controllable color and preparation method thereof
CN107638587A (en) * 2017-09-25 2018-01-30 凯斯蒂南京医疗器械有限公司 With tissue inducing function without scar regeneration medical dressing and preparation method thereof
CN108042840A (en) * 2017-12-28 2018-05-18 广州润虹医药科技股份有限公司 A kind of medical sponge
CN108434506A (en) * 2018-04-27 2018-08-24 夏思文 A kind of expandable sponges, the Preparation method and use of load nano controlled-release drug micelles
CN108913745A (en) * 2018-08-16 2018-11-30 余碧芝 The method for extracting active collagen and elastin laminin using pigs and cattle cartilage
CN109568663A (en) * 2018-11-27 2019-04-05 中山大学中山眼科中心 The preparation method and cornea scaffold of cornea scaffold
CN110644076A (en) * 2019-09-17 2020-01-03 南通大学 Preparation method of surface grafted recombinant epidermal growth factor nanofiber
CN111393521A (en) * 2020-03-20 2020-07-10 张培华 Extraction method of jellyfish collagen
CN112402289A (en) * 2020-10-26 2021-02-26 杜明春 A kind of biomimetic collagen solution for skin surface and preparation method and use method thereof
CN112516377A (en) * 2020-11-23 2021-03-19 铨丰科技(深圳)有限公司 Collagen microfiber hemostatic material and preparation method and use method thereof
CN113750286A (en) * 2021-09-30 2021-12-07 振德医疗用品股份有限公司 A kind of skin wound covering film and preparation method thereof
CN114010839A (en) * 2021-11-09 2022-02-08 深圳齐康医疗器械有限公司 Gradient degradation artificial dermis and preparation method and application thereof
CN114191604A (en) * 2021-12-06 2022-03-18 广东金发科技有限公司 Slow-release antibacterial microsphere hydrogel dressing and preparation method and application thereof
CN118814361A (en) * 2023-04-18 2024-10-22 东华大学 A method for preparing anti-adhesion film by electrostatic spinning

Cited By (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101954126A (en) * 2010-09-26 2011-01-26 华南理工大学 Method for preparing bionic modified collagen tissue repair material
CN102604128A (en) * 2012-04-18 2012-07-25 吉林大学 Preparation method for gelatin nanosphere
CN102604128B (en) * 2012-04-18 2013-08-14 吉林大学 Preparation method for gelatin nanosphere
CN103830768A (en) * 2012-11-21 2014-06-04 深圳兰度生物材料有限公司 Degradable wound repair material and preparation method thereof
CN103054814A (en) * 2013-01-16 2013-04-24 南京理工大学 Preparation method for polysaccharide microspheres based on medicine cross-linking
CN103285420B (en) * 2013-03-28 2015-03-25 北京桀亚莱福生物技术有限责任公司 A kind of preparation method of human biological dressing for covering burn wound wound surface
CN103285420A (en) * 2013-03-28 2013-09-11 北京桀亚莱福生物技术有限责任公司 A kind of preparation method of human biological dressing for covering burn wound wound surface
CN104667336B (en) * 2013-03-28 2017-01-25 北京桀亚莱福生物技术有限责任公司 Human body biological dressing for covering burn wound surfaces and applications of dressing
CN104170815A (en) * 2013-05-22 2014-12-03 烟台正海生物技术有限公司 Method for protecting biological material before irradiation sterilization
CN104170815B (en) * 2013-05-22 2016-06-29 烟台正海生物科技股份有限公司 A kind of method before irradiation sterilization, biomaterial protected
CN103536965A (en) * 2013-09-24 2014-01-29 北京大学口腔医学院 Preparation method for three-dimensional mineralized collagen bracket with strict grade structure as well as product and application of three-dimensional mineralized collagen bracket
CN105056286A (en) * 2015-07-15 2015-11-18 军事医学科学院华南干细胞与再生医学研究中心 Liquid band-aid and preparing method thereof
CN105088779B (en) * 2015-08-05 2018-01-30 广州赛莱拉生物基因工程有限公司 A kind of collagem membrane patch and preparation method thereof
CN105088779A (en) * 2015-08-05 2015-11-25 广州赛莱拉生物基因工程有限公司 Collagen attachment membrane and preparation method thereof
CN106267341A (en) * 2016-08-30 2017-01-04 圆容生物医药无锡有限公司 One can organize induction bio-medical material
CN106730009A (en) * 2016-12-30 2017-05-31 广州迈普再生医学科技有限公司 A kind of bone repairing support and preparation method thereof
CN107602883A (en) * 2017-08-23 2018-01-19 四川大学 A kind of edible collagem membrane of controllable color and preparation method thereof
CN107602883B (en) * 2017-08-23 2020-04-28 四川大学 A kind of edible collagen film with adjustable color and preparation method thereof
CN107638587A (en) * 2017-09-25 2018-01-30 凯斯蒂南京医疗器械有限公司 With tissue inducing function without scar regeneration medical dressing and preparation method thereof
CN108042840A (en) * 2017-12-28 2018-05-18 广州润虹医药科技股份有限公司 A kind of medical sponge
CN108042840B (en) * 2017-12-28 2021-04-06 广州润虹医药科技股份有限公司 Medical sponge
CN108434506A (en) * 2018-04-27 2018-08-24 夏思文 A kind of expandable sponges, the Preparation method and use of load nano controlled-release drug micelles
CN108434506B (en) * 2018-04-27 2021-06-25 温州医科大学附属第二医院（温州医科大学附属育英儿童医院） A kind of swelling sponge loaded with nano sustained-release drug micelle, preparation method and use
CN108913745A (en) * 2018-08-16 2018-11-30 余碧芝 The method for extracting active collagen and elastin laminin using pigs and cattle cartilage
CN109568663A (en) * 2018-11-27 2019-04-05 中山大学中山眼科中心 The preparation method and cornea scaffold of cornea scaffold
CN109568663B (en) * 2018-11-27 2021-01-15 中山大学中山眼科中心 Preparation method of corneal stent material and corneal stent material
CN110644076A (en) * 2019-09-17 2020-01-03 南通大学 Preparation method of surface grafted recombinant epidermal growth factor nanofiber
CN110644076B (en) * 2019-09-17 2021-10-26 南通大学 Preparation method of surface grafted recombinant epidermal growth factor nanofiber
CN111393521A (en) * 2020-03-20 2020-07-10 张培华 Extraction method of jellyfish collagen
CN112402289A (en) * 2020-10-26 2021-02-26 杜明春 A kind of biomimetic collagen solution for skin surface and preparation method and use method thereof
CN112516377A (en) * 2020-11-23 2021-03-19 铨丰科技(深圳)有限公司 Collagen microfiber hemostatic material and preparation method and use method thereof
CN112516377B (en) * 2020-11-23 2022-05-27 铨丰科技(深圳)有限公司 Collagen microfiber hemostatic material and preparation method and use method thereof
CN113750286A (en) * 2021-09-30 2021-12-07 振德医疗用品股份有限公司 A kind of skin wound covering film and preparation method thereof
CN114010839A (en) * 2021-11-09 2022-02-08 深圳齐康医疗器械有限公司 Gradient degradation artificial dermis and preparation method and application thereof
CN114010839B (en) * 2021-11-09 2022-11-29 深圳齐康医疗器械有限公司 Gradient degradation artificial dermis and preparation method and application thereof
CN114191604A (en) * 2021-12-06 2022-03-18 广东金发科技有限公司 Slow-release antibacterial microsphere hydrogel dressing and preparation method and application thereof
CN114191604B (en) * 2021-12-06 2023-09-01 广东金发科技有限公司 Sustained-release antibacterial microsphere hydrogel dressing and preparation method and application thereof
CN118814361A (en) * 2023-04-18 2024-10-22 东华大学 A method for preparing anti-adhesion film by electrostatic spinning

Also Published As

Publication number Publication date
CN100544774C (en) 2009-09-30

Similar Documents

Publication Publication Date Title
CN100544774C (en) Preparation method of collagen matrix surface wound repair film with tissue induction
Sheokand et al. Natural polymers used in the dressing materials for wound healing: Past, present and future
Moraes et al. Bacterial cellulose/collagen hydrogel for wound healing
CN105031740B (en) A kind of biomimetic prosthetic skin with waterproof and breathable function and preparation method thereof
Jin et al. Multifunctional self-healing peptide hydrogel for wound healing
CN101773687B (en) Preparation method of composite soft-tissue patch
CN106729984A (en) A kind of Isin glue collagen repairs sponge and preparation method thereof
Cao et al. Animal tissue-derived biomaterials for promoting wound healing
KR102473363B1 (en) Spray type hydrogel wound coating preparation method and Spray type hydrogel wound coating thereof
CN107308494A (en) A kind of injection collagen, preparation method and filler
CN101695581A (en) Method for preparing human-like collagen haemostatic sponge in scale
CN104857552B (en) A kind of hemostatic adhesive bandage and preparation method thereof
CN115181226B (en) Micromolecule silk fibroin-based hydrogel and preparation method and application thereof
Chen et al. Facile fabrication of quaternized chitosan-incorporated biomolecular patches for non-compressive haemostasis and wound healing
CN102228695A (en) Method for preparing basic fibroblast growth factor sustained-release carrier
Gokarneshan Application of natural polymers and herbal extracts in wound management
CN106421868A (en) Chitosan quaternary ammonium salt porcine acellular dermal matrix dressing material and preparation method thereof
WO2017101020A1 (en) Modified dressing
CN114225118A (en) Injectable artificial dermis for promoting wound healing and preparation method and application thereof
TWI526488B (en) Chemical crosslinking composition, bio-medical material containing the same and use of the same
WO2017062072A1 (en) Biocompatible carboxymethylcellulose matrix (bcm) for hemostasis, tissue barrier wound healing, and cosmetology
CN108452366A (en) A kind of gelatin-compounded bleeding-stopping dressing of cod skin and preparation method thereof
Davis et al. Passive and interactive dressing materials
CN103705976A (en) Composite bone repair material and preparation method thereof
CN102008740B (en) Absorbable growth factor composite dressing

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20090930

Termination date: 20180323

CF01 Termination of patent right due to non-payment of annual fee