CN1810309A - Porous antisticking agar-collagen film and its prepn process - Google Patents

Porous antisticking agar-collagen film and its prepn process Download PDF

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Publication number
CN1810309A
CN1810309A CN 200610033792 CN200610033792A CN1810309A CN 1810309 A CN1810309 A CN 1810309A CN 200610033792 CN200610033792 CN 200610033792 CN 200610033792 A CN200610033792 A CN 200610033792A CN 1810309 A CN1810309 A CN 1810309A
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agar
collagen
porous
film
antisticking
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CN 200610033792
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CN100434123C (en
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汤顺清
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Jinan University
University of Jinan
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Jinan University
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Abstract

The preparation process of porous antisticking agar-collagen film includes mixing agar and collagen or gelatin and freeze- drying to obtain the antisticking film in 3D porous laminated structure. The porous antisticking agar-collagen film can ensure the nutrient supply essential for tissue to heal, inhibit cell proliferation and make proliferated cell unable to infiltrate healing tissue while degrading to disappear to reach the effect of ensuring tissue healing and preventing tissue proliferation and sticking.

Description

Agar and collagen porous antisticking film and preparation method thereof
Technical field
The present invention relates to biomedical material, particularly a kind of agar and collagen porous antisticking film and preparation method thereof.
The invention still further relates to the agar and the collagen porous antisticking film of described method preparation.
Background technology
Adhesion is a kind of protectiveness physiological reaction of human body restriction inflammation diffusion.Discharging the various active material by induce tissue Interstitial cells such as operation mechanicalness or chemical damage, mastocyte makes tissue produce inflammatory reaction, the blood capillary infiltration, secrete a large amount of serosity, if serosity is not absorbed, wherein the fibrin calmness causes fibrocyte and blood capillary and grows into and stick together.Adhesion is usually caused by confounding factor clinically, but is played a major role by one or more factors, and adhesion certainly mainly is that fibrocellular infiltration causes.Mainly prevent and treat at present, but also do not have a kind of ideal Antiadhesive film at present by physical barrier or two kinds of methods of chemicals (anti-angiogenic medicaments).
Tissue adhesion is a common complications in clinical, often needs second operation to handle, and is difficult to sometimes accurately hold operation opportunity and causes serious consequence, and particularly the intestinal adhesion of abdominal operation is easy to generate severe complications such as intestinal obstruction.Therefore taking the anti measure is to ensure one of key operation of the normal healing of postoperative tissue.
The research of carrying out Antiadhesive film both at home and abroad starts from the seventies, and main path is with non-porous film material or gel physical barrier art district surrounding tissue hypertrophy.This obstruct mechanism often causes nutrition supply bad, the normal healing difficulty of tissue; Adopt the higher hyaluronic acid of cost simultaneously and limited its extensive use.The anti-sticking poly lactic acid film of domestic Shandong medical device research institute, the great strong bio-medical Products Co., Ltd in Shantou, Chengdu enlightening health Pharmaceutical joint-stock company etc., the expanded PTFE of Suokang Medical Material Co., Ltd., Shanghai belongs to complete physical barrier, the biotype Antiadhesive film that vast and boundless biological holding company is preced with in Guangdong is the physical barrier state after crosslinked, product is just under development, " sticking rather the stopping " of Yantai ten thousand sharp medical products company limiteies adopts chitose as the Antiadhesive film base material, but its degradation speed is very slow, belong to physical barrier again, therefore be difficult to obtain promising result.
Abroad in the document,, after mixing the plain Pacilitaxel of angiogenesis inhibitor, be used for anti as the hyaluronate sodium and the cellulose composite membrane of GENZYME company relevant for the product and the research of Antiadhesive film.Mainly concentrate on hyaluronic acid, the nonporous film shape material of modified cellulose and other synthetic high polymer or gel reach preventing adhesiving effect as the physical barrier film; Perhaps introducing anti-angiogenic medicaments prevents to be organized in and more distinguishes hypertrophy.
Therefore, existing technology or stop the infiltration of cell to callus with the method for physical barrier, but also hinder the normal agglutination of tissue; The generation that suppresses blood vessel by chemicals stops proliferation of cells, the normal healing of same influence tissue.
Summary of the invention
The objective of the invention is to defective at the prior art existence, the preparation method of a kind of agar and collagen porous antisticking film is provided, the Antiadhesive film that obtains has three-dimensional porous interlayer structure, ensure the needed nutrition supply of the normal healing of tissue, the while inhibition of cell proliferation also makes outgrowth cell not soak into the tissue that is healing, and the disappearance of degrading in organization healing of this film is really played it and is guaranteed the normal structure healing, prevents the effect of hyperplastic tissue's adhesion.
The object of the present invention is to provide the agar and the collagen porous antisticking film of described method preparation, as a routine operation materials used of post operative treatment.
In view of the mechanism of adhesion, designed Antiadhesive film should not hinder the nutrition acquiring way and the healing of normal structure, and outgrowth cell is effectively suppressed or do not contact with art district tissue to produce adhesion.The present invention utilizes the design principle of organizational project, adopts new antiseized mechanism, uses inexpensive natural polymer, develops postoperative tissue adhesion's films such as preventing abdominal cavity and tendon.
The present invention obtains a kind of porous membrane by agar and collagen or gelatin cross-blend postlyophilization, is agar collagen porous antisticking film, is to obtain a kind of Antiadhesive film that Interstitial cells such as fibroblast, adipose cell is had the vertical isolation effect.But but film water square proliferative to the maintenance cell.
More specifically, the preparation method of agar of the present invention and collagen porous antisticking film comprises the steps:
(1) agar is dissolved in the 85-95 ℃ of hot water, and concentration is 0.8-1.5% weight, and collagen or gelatin swell in or be dissolved in the acetum or water of 0.04-0.06M, and concentration is 0.5-1.0% weight;
(2) agar after step (1) is handled and collagen or gelatin mix and pour die for molding into;
(3) put into freezer dryer ,-35---45 ℃ were descended freezing 1-3 hour, bled more than 17 hours at 0 ℃, were lyophilized into the porous antisticking film.
Described agar can be general agar and/or its purification thing; Described collagen is the collagen of its I, II type, one or more mixture in its modifier; Described gelatin is Soluble Gelatin or its modifier.
The mixing ratio of agar and collagen or gelatin is determined according to purposes, is generally mass parts 1-5: 5-1, and when for example being used for preventing intestinal adhesion, the mixing quality portion rate is 3: 1; When being used for stomach wall large tracts of land wound surface, the mixing quality portion rate is 2: 1, and is aided with lightly crosslinked; When being used for tendon, the mixing quality portion rate is 1: 1.
Use oxirane disinfection after the porous antisticking film cutting that obtains, get the finished product envelope and preserve.
If need membrane area big, the available glutaraldehyde stifling back of handling half an hour is sterilized standby.
The present invention compared with prior art has following advantage:
(1) the porous antisticking film that obtains of the inventive method is a porous material, can make the nutrition supply of healing district tissue unaffected, and the normal healing of keeping tissue is machine-processed.And existing non-porous film or gel obstruct belong to pure physical barrier, suppress the sick normal healing that the district organizes of decreasing;
(2) the inventive method cost is low since raw materials used be collagen or gelatin and agar rather than expensive hyaluronate sodium, cost is very low, post-operation adhesion preventing is operated becomes possibility as a kind of routine operation;
(3) easy to operate, this film pliability is good, can carry out crimp operation, so as convenient with paper, and there is certain randomness in gel commonly used, impact effect in the assurance on injection areas, opportunity, can select the Antiadhesive film of proper strength and degradation time according to the difference of using the position.
(4) agar of the present invention and collagen porous antisticking film are of many uses, can be used as behind tendon, abdominal cavity, pelvic cavity, intestinal, thoracic cavity, uterine cavity, fallopian tube, cervix uteri, the vertebrae plate resection nonspecificly behind the surgical operation such as cicatricial adhesion to prevent adhesion.
The specific embodiment
Embodiment 1
Preparation agar and collagen porous antisticking film
Agar is dissolved in 85 ℃ of hot water, and concentration is 1.5% weight, and the II Collagen Type VI swells in the acetum of 0.04M, and concentration is 0.5% weight;
Pour agar after step (1) processing and II Collagen Type VI into die for molding by mass ratio mixing in 1: 5;
Put into freezer dryer, descended freezing 3 hours, bled 18 hours, be lyophilized into the porous antisticking film at 0 ℃ at-35 ℃.
Porous antisticking membrane area 20cm * 10cm, thick 0.2-0.4mm.
Be used for the operation on tendon anti
Cut and be of a size of length=operation tendon length, wide=2 times tendon girth, oxirane disinfection is standby.After blood, hydrops etc. are removed in the operation back, film is rolled in the lesion, film is attached on the tendon automatically, does not have untoward reaction.
Embodiment 2
Preparation agar and collagen porous antisticking film
Agar or its purification thing are dissolved in 95 ℃ of hot water, and concentration is 0.8% weight, and Soluble Gelatin is soluble in water, and concentration is 0.6% weight;
Agar after step (1) handled or its purification thing mix by 2: 1 mass ratioes with Soluble Gelatin pours die for molding into;
Put into freezer dryer, descended freezing 1 hour, bled 20 hours, be lyophilized into the porous antisticking film at 0 ℃ at-45 ℃.With crosslinked a little less than 2% glutaraldehyde stifling half an hour.Its area 20cm * 20cm, thick 0.5mm.
Be used for the abdominal operation anti
Cut and be of a size of Zhou Jing greater than focal zone 0.5-0.8cm,, oxirane disinfection is standby.After blood, hydrops etc. are removed in the operation back, film is attached to the lesion, film is attached to automatically (generally to be fixed with 03-08# line four or 6 stitching initial stages) on the focus, has no adverse reaction.
Embodiment 3
Preparation agar and collagen porous antisticking film
Agar purification thing is dissolved in 90 ℃ of hot water, and concentration is 1.0% weight, and the collagen of I and II type swells in the acetum of 0.06M, and concentration is 0.55% weight;
Agar purification thing after step (1) handled mixes by 5: 1 mass ratioes with the collagen of I and II type pours die for molding into;
Put into freezer dryer, descended freezing hour, bled 10 hours, be lyophilized into the porous antisticking film at 0 ℃ at-40 ℃.Porous antisticking membrane area 20cm * 20cm, thick 0.2-0.4mm.
Anti-intestinal adhesion is used to perform the operation
Cut the long art district focus size that is, Zhou Jing is intestinal 1.5-2 times, and oxirane disinfection is standby.After blood, hydrops etc. are removed in the operation back, the film volume is attached to the lesion, film is attached to (4 stitching initial stages of available 03-08# line are fixed) on the focus automatically, has no adverse reaction.

Claims (5)

1, the preparation method of a kind of agar and collagen porous antisticking film is characterized in that agar and collagen or gelatin cross-blend postlyophilization are obtained.
2, method according to claim 1 is characterized in that comprising the steps:
(1) agar is dissolved in the 85-95 ℃ of hot water, and concentration is 0.5-1.5% weight, and collagen or gelatin swell in or be dissolved in the acetum or water of 0.04-0.06M, and concentration is 0.5-1.0% weight;
(2) agar after step (1) is handled and collagen or gelatin mix and pour die for molding into;
(3) put into freezer dryer ,-35-45 ℃ freezing 1-3 hour down, bleed more than 17 hours at 0 ℃, be lyophilized into the porous antisticking film.
3, method according to claim 1 and 2 is characterized in that described agar is agar and/or its purification thing; Described collagen is the collagen of its I, II type, one or more mixture in its modifier; Described gelatin is Soluble Gelatin or its modifier.
4, method according to claim 3, the mixing ratio that it is characterized in that agar and collagen or gelatin is mass parts 1-5: 5-1.
5, the agar and the collagen porous antisticking film of the described method preparation of one of claim 1-4.
CNB2006100337928A 2006-02-23 2006-02-23 Porous antisticking agar-collagen film and its prepn process Expired - Fee Related CN100434123C (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102397587A (en) * 2010-09-08 2012-04-04 舒朝锋 Uterine cavity anti-adhesion material and preparation process and application thereof
CN103386145A (en) * 2013-07-31 2013-11-13 暨南大学 Wound healing dressing containing carrageenan, and preparation method and application of wound healing dressing
CN110384830A (en) * 2018-04-19 2019-10-29 易浦润(上海)生物技术有限公司 Has the isolation film and preparation method thereof for reactivating inner membrance substrate layer function in a kind of uterine cavity

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5906997A (en) * 1997-06-17 1999-05-25 Fzio Med, Inc. Bioresorbable compositions of carboxypolysaccharide polyether intermacromolecular complexes and methods for their use in reducing surgical adhesions
CN1403163A (en) * 2002-10-23 2003-03-19 东南大学 Absorbable fiber reinforced multilayer film material and its prepn
CN100525778C (en) * 2004-04-30 2009-08-12 天津大学 Novel post-operation antiadhesive materials and its preparation method
CN1320931C (en) * 2004-05-14 2007-06-13 中国科学院长春应用化学研究所 Dressing material containing medicine chitoholosida and its preparation method

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102397587A (en) * 2010-09-08 2012-04-04 舒朝锋 Uterine cavity anti-adhesion material and preparation process and application thereof
CN103386145A (en) * 2013-07-31 2013-11-13 暨南大学 Wound healing dressing containing carrageenan, and preparation method and application of wound healing dressing
CN103386145B (en) * 2013-07-31 2015-03-04 暨南大学 Wound healing dressing containing carrageenan, and preparation method and application of wound healing dressing
CN110384830A (en) * 2018-04-19 2019-10-29 易浦润(上海)生物技术有限公司 Has the isolation film and preparation method thereof for reactivating inner membrance substrate layer function in a kind of uterine cavity
CN110384830B (en) * 2018-04-19 2022-06-17 易浦润(上海)生物技术有限公司 Isolating membrane with function of reactivating intima-media basal layer in uterine cavity and preparation method thereof

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