CN1086145C - Tissue leading regeneration collagen film - Google Patents
Tissue leading regeneration collagen film Download PDFInfo
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- CN1086145C CN1086145C CN94118836A CN94118836A CN1086145C CN 1086145 C CN1086145 C CN 1086145C CN 94118836 A CN94118836 A CN 94118836A CN 94118836 A CN94118836 A CN 94118836A CN 1086145 C CN1086145 C CN 1086145C
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Abstract
The present invention provides a tissue guiding regeneration collagen membrane which is a novel medical membrane material used for tissue repair. The present invention is the membrane-shaped medical material which is prepared by the following: collagen protein extracted from mammal connective tissue by the enzyme digesting method is used as a basic raw material, and is shaped by a coating, spraying or freeze-drying method, and chemical cross-linking modification is carried out. The tissue guiding regeneration membrane has the advantages of excellent physical and chemical properties, good biological compatibility, organism absorption, convenient operation, etc., and overcomes the disadvantages that the material in the same class has high toxic side effects, is unabsorbable, needs to be taken out in a secondary operation, etc. The material can be widely used for the tissue repair of all departments of the clinical medicine, and particularly, the effect of guiding/inducing the periodontal tissue regeneration is obvious.
Description
The present invention relates to a kind of medical tissue guiding regeneration membrane goods that promote wound healing, particularly relating to a kind of is the medical tissue guiding regeneration collagen film and the manufacture method thereof of stock with the collagen protein.
Guided tissue regeneration's material is developed country and a kind of brand-new material that occurs along with the development of biological membrane technique of area in recent years.As a kind of brand-new treatment means that promotes the tissue regeneration healing; it utilizes protection, obstruct, the guiding/inducing action of membrane material to arrive tissue regeneration or reconstruction on ideal form and the function cleverly, and the limitation of traditional operation therapy has been broken in the rise of this technology.This key problem in technology is the application of guided tissue regeneration's film, present regeneration membrane material such as the poly tetrafluoroethylene that uses, referring to " New Attachment Formation intheHuman Periodontium by Guide Tissue Regeneration " (JanGottlowet al, Journal of Clinical Periodontology, 13:604-616,1986) and " New Attachment Achieved by Guided TissueRegeneration inBeagle Dogs " (R.G.Caffesse et al, Journalof Periodontology, 59 (9): 589-594).Because poly tetrafluoroethylene is a kind of nondegradable macromolecular material, can not be organized absorption, need second operation to take out, increased the chance of wound, generally be difficult to be accepted by the patient.Therefore, state such as Japan has begun the research of collagen regeneration film in recent years, referring to " The Histopathological Study of PeriodontolTissue Regeneration Using Atelocollagen " (Nippon ShishubyoGaishi, 1990 March; 32 (1): 1-25), " Electron MicroscopicObservation for PeriodontolTissue Regeneration afterImplantation of AtelocollagenMembrane " (Kanagawa shigaku 1990, Sep., 25 (2): 187-208), but still be in the experimentation stage.
The purpose of this invention is to provide a kind of is the method that primary raw material prepares guided tissue regeneration's film with the collagen protein that extracts from beef tendon, this method comprises the collagen protein that extracts with the protease digestion method from the connective tissue of animal, malonic acid solution-treated with 0.3-0.5% makes the collagen protein swelling, reuse concentration is the malonic acid solution adjusting solids content of 0.3-0.5% behind the mixing, obtain collagen solution, adopt then and apply, spraying or freeze-drying method molding, and make collagen cross-linking after the film forming, last after drying or the crosslinked collagen film of lyophilizing with conventional cross-linking method.
For realizing purpose of the present invention, at first mammiferous connective tissue such as beef tendon, Corii Bovis seu Bubali, pig tendon, Corii Sus domestica etc. are cut into the thick sheet of 1-2mm that is, carry out enzyme with the protein enzyme solution of 0.05%-0.25% and handle, handle the back and handle so that residual enzyme deactivation with hydrogen peroxide.The malonic acid solution that adds 0.3-0.5% then makes its swelling, and reuse concentration is 0.3% malonic acid solution adjusting solids content behind the mixing, promptly obtains collagen solution.With solids content be the 0.5-1.0% collagen solution after deaeration, adopt coated, spray is washed or the vacuum-freezing process drying and forming-film.Afterwards, equilibrium water conten in climatic chamber firmly flattens film.The molding product with the crosslinked certain hour of Chemical Crosslinking Methods (as the aldehydes cross-linking method, and the cyanate cross-linking method, the acid azide cross-linking method).Be preferably the use formaldehyde crosslinking among the crosslinked side of above-mentioned conventional chemical.After crosslinked, drying or lyophilization under the ultra-clean condition again.
The product that obtains is cut into required form, packs with aluminium foil or other flexible packing materials, uses the gamma-radiation radiation sterilization then.
The novel guided tissue regeneration film that the present invention makes relatively has no antigen with poly tetrafluoroethylene, and biocompatibility is good, can effectively suppress epithelial cell growth, and has and induce/guide defective tissue growth, distinguishing features such as degradable absorption.
Prove that through biological experiment, zoopery and clinic trial the novel guided tissue regeneration film degradation in vivo soak time that the present invention makes conforms with clinical needs, do not find that toxicity, stimulation, pyrogen and three cause reaction, and biocompatibility is good.Guided tissue regeneration of the present invention film can be widely used in the reparation that human body multi-section bit organization such as the reparation of bone cavity reparation after the excision of periodontal disease anaphase, radicular cyst, oral cavity tissue damages such as reparation, alveolar ridge increases, periodontal bone grafting operation, oral and maxillofacial surgery penetrating wound, cleft palate and artificial tooth root plantation art that the maxillofacial trauma bone is damaged and bone wound, tendon rupture, viscera perforation, middle ear mastoidectomy radical correction are damaged, and the result has all reached comparatively ideal tissue regeneration healing.
The extraction manufacture method of embodiment one 1. collagen protein:
The beef tendon water that outsourcing is come washes down, and peels off exocuticle with shears, stays Y type part.Y type beef tendon is scraped off surperficial fascia with operating scissors and single-edge blade by root, and fat and other impurity remove the V section, after staying the I section and placing refrigerator and cooled to freeze, vertically are cut into the thick tendon sheet of 1-2mm.Take by weighing 500g tendon sheet with distilled water flushing 3 times, strain driedly, add 0.1% Ficin solution 4.8g, 940B promoter 1.78g, H then
2O4800ml places 37 ℃ of incubator insulations 16 hours, takes out with behind the distilled water flushing 3 times, adds H
2The about 4000ml of O, H
2O
2About 10ml killed enzyme 20 minutes.Kill tendon sheet behind the enzyme with distilled water flushing 3-4 time, strain dried, the malonic acid solution 10000ml swelling of adding 0.5% 24 hours.Tendon sheet after the swelling was fully stirred 6 hours with food blending machine, and reuse malonic acid solution 2000-6000ml O.3% filters with 80-12O order stainless (steel) wire then to regulate viscosity, removes impurity and swelling thing not.Remove bubble in centrifugal 15 minutes with 3000 rev/mins centrifuge, promptly obtain being used to make base stock--the collagen solution of tissue leading regeneration collagen film of the present invention.2. the manufacture method of tissue leading regeneration collagen film:
Pouring the above-mentioned beef tendon collagen protein swelling solution 50-80ml that obtains with enzyme digestion into pre-packed floor space is 80 * 100mm, highly is in the politef tray of 3.5mm.Plate is placed-35 ℃ refrigerator 2 hours earlier, the dish that rapidly this is freezed after the taking-up gives on the shelf that places freezer dryer, is about 48 hours of lyophilization under the 10-100u in vacuum, after shelf temperature reaches room temperature, still must keep making it in 12 hours molding.Take out the collagem membrane of molding from freeze dryer, place relative humidity 80%, equilibrium water conten is 60 minutes in the climatic chamber that temperature is 25 ℃.The collagem membrane that this is moist places between two polyfluortetraethylene plates, flattens with smooth object such as rollers, take out to measure its thickness for O.15 ± O.05mm.
With the collagem membrane concentration of the molding that makes as stated above is 0.3%, and PH is crosslinked 60 minutes of 8.4 formalins, crosslinked back with distilled water thorough washing 3-5 time to neutrality.And then be placed in the politef tray, according to above-mentioned freeze-drying method lyophilizing, but the time all reduces by half accordingly.After taking out from freeze dryer, be placed on relative humidity 80%, equilibrium water conten is 20 minutes in the climatic chamber that temperature is 25 ℃.Once more film is placed two polyfluortetraethylene plates to flatten, measuring its thickness is 0.20 ± 0.05mm.
Cutting into different specifications according to clinical different requirement, pack with aluminium foil or other flexible packing materials, is the gamma-radiation photograph sterilization of 2,000,000 rads with dosage then, promptly obtains medical tissue guiding regeneration collagen membrane material.
Embodiment two
The beef tendon collagen protein swelling solution 50-100ml that obtains with enzyme digestion among the embodiment one is poured in the polytetrafluoroethylplastic plastic dish of pre-packed 8 * 12cm, place the air-dry film forming of super-clean environment room temperature, be 0.3% with the collagem membrane concentration that obtains then, crosslinked 60 minutes of PH8.4 formalin, crosslinked back to neutrality, places the film after crosslinked under the ultra-clean condition room temperature to dry with distilled water thorough washing 3-5 time again.Cutting into different specifications according to clinical different requirement then, pack with aluminium foil or other flexible packing materials, is the gamma-radiation photograph sterilization of 2,000,000 rads with dosage then, promptly obtains medical tissue guiding regeneration collagen membrane material.
Embodiment three
Choose and be in a good state of health, operative site does not have 18-58 year men and women's periodontal disease patient of other illness, adopt the mode of random packet, to 37 chronic periodontitis patient (attachment loss＞5mm, loosening degree＜III-, enough gingiva amounts (length and thickness) are arranged, the controlled person of Primary Care inflammation before the periodontal art) 60 tooth positions implement periodontal guiding regeneration art respectively and tradition is turned over lobe operation (each 30 example) merely, before operation, 1 week of operation back, 2 weeks, January, February, March and June observed and recorded art district situation, and do the antiplaque processing.
Operation method: oblique mastoid process otch in do at diseased region gum edge 0.5mm place, turn over trapezoidal or dihedral mucoperiosteum lobe, expose periodontal disease and decrease, thoroughly strike off granulation tissue and pathological changes cementum, finishing bone profile, a cleaning bag inwall, the N.S flushing, wound surface scratch scrape hemorrhage, get the standby regeneration collagen film of a sterilization, slightly do pruning, root to covering alveolar ridge 2-3mm by sick disfigurement attitude and size, hat side terminates in enamelo-cemental junction, and the side arrives the tooth proximal surface mid point.The gum lobe is carefully resetted, adopt penetration type suspension suture maintenance, plug is controlled agent protection art district, takes out stitches in 7-10 days.Matched group does not then have the implantation of membrane material.
Observed result: in postoperative 1-2 week, two groups of art districts all do not find obvious edema pain, and gum lobe and facing attach closely; The postoperative 1-2 month, to suffer from mobility of tooth and obviously alleviate, it is tough that the gingiva quality becomes, and part tooth position begins to occur gingival atrophy; Postoperative 3 months experimental group gums lobe and tissue apposition are more tight, visit and have examined resistance; All agomphiasis are (loosening degree is 0) all firmly, and sulcular bleeding index is 0, and existing bone was repaired phenomenon in radiograph demonstration alveolar ridge crest and dihedral bone were damaged.The regeneration of 6 crescent bones of postoperative is more obvious.
Claims (9)
1, a kind of collagen film that is used for guided tissue regeneration is characterized in that this film is a raw material by animal collagen, makes through swelling, molding, crosslinked and drying steps.
2, according to the collagen film of claim 1, wherein said animal collagen is the collagen protein of conventional preparation from the tendon of cattle.
3, a kind of manufacture method of tissue leading regeneration collagen film, this method comprises:
(1) collagen protein that from the connective tissue of animal, extracts with the protease digestion method,
(2) the malonic acid solution-treated with 0.3-0.5% makes the collagen protein swelling, behind the mixing
Reuse concentration is that the malonic acid solution of 0.3-0.5% is regulated solids content, promptly
To collagen solution,
(3) adopt coating, spraying or freeze-drying method molding,
(4) make collagen cross-linking after the film forming with conventional cross-linking method,
(5) last after drying or the crosslinked collagen film of lyophilizing.
4, according to the method for claim 3, wherein said animal connective tissue is the tendon of cattle.
5, according to the method for claim 3, the protease that wherein prepares the collagen protein use is the ficin that concentration is about 0.05%-0.25%.
6, according to the method for claim 3, wherein step (1) comprises that is used a H
2O
2Processing is with the step of inactivation residual enzyme.
7, according to the method for claim 3, wherein the solids content of step (2) gained collagen liquid is 0.5%-1.0%.
8, according to the method for claim 3, wherein in the step (3) said collagen liquid to be shaped into film method be aldehydes cross-linking method, isocyanates cross-linking method, the acid azide cross-linking method.
9, according to the method for claim 3, wherein said cross-linking method is the aldehydes cross-linking method in the step (4).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN94118836A CN1086145C (en) | 1994-12-08 | 1994-12-08 | Tissue leading regeneration collagen film |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN94118836A CN1086145C (en) | 1994-12-08 | 1994-12-08 | Tissue leading regeneration collagen film |
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| Publication Number | Publication Date |
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| CN1107742A CN1107742A (en) | 1995-09-06 |
| CN1086145C true CN1086145C (en) | 2002-06-12 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN94118836A Expired - Fee Related CN1086145C (en) | 1994-12-08 | 1994-12-08 | Tissue leading regeneration collagen film |
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| CN (1) | CN1086145C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103071189A (en) * | 2013-01-25 | 2013-05-01 | 广州华美康联生物科技有限公司 | Preparation method of collagen film for guided tissue regeneration |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AUPO331096A0 (en) * | 1996-10-29 | 1996-11-21 | Commonwealth Scientific And Industrial Research Organisation | Collagen products |
| CN101322662B (en) * | 2007-06-14 | 2010-05-26 | 浙江大学医学院附属口腔医院 | Dental implant surface extracellular matrix biomimetic modification method |
| CN101905038B (en) * | 2010-05-21 | 2013-04-10 | 中国医学科学院生物医学工程研究所 | Growth factor-loaded collagen group composite material as well as preparation method and application thereof |
| CN103750922B (en) | 2013-12-31 | 2016-07-13 | 金仕生物科技（常熟）有限公司 | The method preparing Cardiac valve prosthesis leaflet |
| CN104983724B (en) * | 2015-08-14 | 2019-02-12 | 广州赛莱拉干细胞科技股份有限公司 | A kind of collagen film and preparation method thereof |
| CN106390195B (en) * | 2016-11-16 | 2019-08-23 | 四川大学 | A kind of method of modifying of collagem membrane |
| CN106730037B (en) * | 2016-11-17 | 2019-12-13 | 北京华信佳音医疗科技发展有限责任公司 | composite collagen biological membrane and preparation method thereof |
| CN107551324B (en) * | 2017-10-27 | 2020-02-18 | 北京华信佳音医疗科技发展有限责任公司 | Preparation and application of suturable hard membrane repairing material |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4621631A (en) * | 1982-12-27 | 1986-11-11 | Behringwerke Aktiengesellschaft | Process for the production of a bonded collagen fiber sheet |
| US4725671A (en) * | 1984-12-24 | 1988-02-16 | Collagen Corporation | Collagen membranes for medical use |
| CN1051510A (en) * | 1989-11-08 | 1991-05-22 | 中国医学科学院生物医学工程研究所 | Collagen-polyvinyl alcoholic operation sutures and preparation method thereof |
-
1994
- 1994-12-08 CN CN94118836A patent/CN1086145C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4621631A (en) * | 1982-12-27 | 1986-11-11 | Behringwerke Aktiengesellschaft | Process for the production of a bonded collagen fiber sheet |
| US4725671A (en) * | 1984-12-24 | 1988-02-16 | Collagen Corporation | Collagen membranes for medical use |
| CN1051510A (en) * | 1989-11-08 | 1991-05-22 | 中国医学科学院生物医学工程研究所 | Collagen-polyvinyl alcoholic operation sutures and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103071189A (en) * | 2013-01-25 | 2013-05-01 | 广州华美康联生物科技有限公司 | Preparation method of collagen film for guided tissue regeneration |
| CN103071189B (en) * | 2013-01-25 | 2014-09-03 | 广州华美康联生物科技有限公司 | Preparation method of collagen film for guided tissue regeneration |
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| Publication number | Publication date |
|---|---|
| CN1107742A (en) | 1995-09-06 |
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