CN104958790A - Composite membrane for preventing postoperative adhesion - Google Patents

Composite membrane for preventing postoperative adhesion Download PDF

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Publication number
CN104958790A
CN104958790A CN201510447812.5A CN201510447812A CN104958790A CN 104958790 A CN104958790 A CN 104958790A CN 201510447812 A CN201510447812 A CN 201510447812A CN 104958790 A CN104958790 A CN 104958790A
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composite membrane
adhesion
chitin
polysaccharide
hyaluronic acid
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CN201510447812.5A
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CN104958790B (en
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蒋革
罗锋
赵琦
王金星
吴艳华
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Dalian University
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Dalian University
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Abstract

The invention relates to a composite membrane for preventing postoperative adhesion, and belongs to the technical field of membranes. The composite membrane comprises polysaccharide, hyaluronic acid, hydroxyethyl starch, glycerinum and sodium chloride at the weight ratio of (15-40) to (3-5) to (1-40) to (45-75) to (25-30), wherein the polysaccharide is chitin, chitosan or chitin polysaccharide. The prepared composite membrane has the beneficial effects that the prepared composite membrane can stably cover the surface of a wound in a long-acting manner; and the target of preventing adhesion to other organs or tissues is reached through a physical barrier.

Description

Prevent the composite membrane of postoperative intestinal adhesion
Technical field
The present invention relates to a kind of composite membrane preventing postoperative intestinal adhesion, belong to technical field of membrane.
Background technology
Tissue adhesion (adhesion) is the wound caused by inflammation, friction, operation etc., produces excess fibre tissue or hemorrhage formation clot over the course for the treatment of, makes periphery internal organs produce the phenomenon of adhesion with tissue.This phenomenon is very easy to occur at surgical site infections such as human abdominal cavity, cardiovascular, spinal column, osteoarthrosis, gynecologics.Wherein the incidence rate of the position adhesion of abdominal cavity and pelvic cavity is up to more than 90%, and the female acyesis patient of about 20% is caused by pelvic adhesion, and the adhesion of 30% has manifest symptom, and as chronic pelvic pain, what intestinal adhesion caused feels sick, flatulence and constipation etc.Tissue adhesion not only brings great misery to patient, have a strong impact on its normally work and life, and long-term medical expense brings huge financial burden to patient and family thereof.In order to solve tissue adhesion problem, relevant technical worker both domestic and external carries out unremitting effort always, adopts various measure to prevent and treat, such as modus operandi; Removing Fibrin exudation thing; Separately intestinal tube surface, injects air etc.Although these methods can play the effect of prevention of postoperative adhesion, but effect is not affirmed, in order to reach prevention of postoperative adhesion object, need life-time service strong dose thing, this makes the danger had side effects or disease is issued licence can obtain beneficial effect often beyond their prevention of intestinal adhesions.
Along with going deep into of research, adherence preventing material comes out successively, and is progressively applied to clinical, and wherein representational is exactly hyaluronic acid.Hyaluronic acid (Haluronic acid, HA) has another name called Hyaluronic Acid, hyaluronic acid is a kind of acid mucopolysaccharide, the linear polysaccharide structure be made up of the repetitive structure of N-acylamino-glucose and D-Glucose aldehydic acid, the molecular structure of its uniqueness and physicochemical property demonstrate multiple important physiological function in body, as lubricating joint, regulate the permeability of blood vessel wall, Function protein matter, Water-Electrolyte diffusion and running, promote wound healing etc.Because hyaluronic acid is present in the soft connective tissue of most of animal body, therefore there is biocompatibility and nontoxic characteristic, be widely used in countries such as Japan, the U.S..Pharmaceutically hyaluronic acid is applied to eye drop, surgical material and injection.4th, 141, No. 973 United States Patent (USP) is published because hyaluronic acid not only can suppress hemorrhage, and granulocyte can be suppressed to move and phagocytosis, there is good antiinflammatory action, thus there is preventing tissue adhesion effect.But because it easily decomposes by body absorption in vivo, limit preventing tissue adhesion effect.Easily decompose in vivo to improve hyaluronic acid, (patent No. is 6 to United States Patent (USP), 387, 413B1) take hyaluronic acid grafting macromolecular compound (Carboxymethyl cellulose, CMC) method has delayed its decomposition rate in vivo, although the cellulose in Antiadhesive film prepared by the method is natural macromolecular material, but because it is not biological substance in vivo, when being injected in vivo, react with some materials in body, thus initiation untoward reaction, add in upper body not to the enzyme that it decomposes, therefore it is hydrolyzed, after oxidation processes, could use in vivo.(patent No. is 5 to United States Patent (USP), 017,229) published and utilize hyaluronic acid to go out hydrophobicity antiadhesion barrier technology by EDC [1-ethyl-3 (3-dimethylaminopropyl) carbodilimide hydrochloride] grafting CMC (Carboxymethyl cellulose) Polymer materialspreparation, its grafting method is combined into by positive and negative charge between compound, this Antiadhesive film is not easy to decompose, there is anti effect, but EDC chemical substance has toxicity to human body, removing it needs special handling process for a long time.
In sum, although the adherence preventing material of current exploitation has anti performance, but promote synthetic chemistry additive because the anti performance materials prepared by chemical method is difficult to remove, therefore its toxic and safety issue becomes the bottleneck of its wide clinical application of restriction.Mostly current the used anti-blocking agent in market is hydrogel, and quantity is large, and cost is high; Simultaneously because the extraneous factors such as environment can shine into active ingredient evenly, specifically can not act on wound site.
Summary of the invention
The present invention, by preparing the physical barrier effect of Novel composite membrane, reaches the tissue adhesion's phenomenon preventing Post operation from causing, and Novel composite membrane also has anti-inflammation, promotes the multi-biological effects such as wound healing simultaneously.
The invention provides a kind of composite membrane preventing postoperative intestinal adhesion, described composite membrane comprises polysaccharide, hyaluronic acid, hetastarch, glycerol, sodium chloride, the weight ratio of described polysaccharide, hyaluronic acid, hetastarch, glycerol and sodium chloride is 15 ~ 40:3 ~ 5:1 ~ 40:45 ~ 75:25 ~ 30, and described polysaccharide is chitin, chitosan or chitin polysaccharide.
The molecular weight of chitin of the present invention is preferably 0.5 × 10 5~ 2 × 10 5dalton.
The molecular weight of chitosan of the present invention is preferably 0.2 × 10 5~ 1 × 10 5dalton.
The molecular weight of chitin polysaccharide of the present invention is preferably 0.8 × 10 5~ 1.2 × 10 5dalton.
Hyaluronic molecular weight of the present invention is preferably 0.8 × 10 6~ 3 × 10 6dalton, hyaluronic viscosity is preferably 30 ~ 35dl/g.
The molecular weight of hetastarch of the present invention is preferably 7 × 10 4~ 6.7 × 10 5dalton, the water of hetastarch replaces degree and is preferably 0.4 ~ 0.75.Beneficial effect of the present invention is:
1. the composite membrane of preparation of the present invention long-actingly stable can cover wound surface, is reached prevent and other organ or tissue's adhesion objects by physical barrier;
2. the composite membrane of preparation of the present invention has anti-inflammation and promotes the effect of wound healing;
3. the composite membrane composition safety of preparation of the present invention, can be absorbed by body.
Accompanying drawing explanation
Accompanying drawing 6 width of the present invention,
Fig. 1 is the animal abdominal adhesions figure of matched group 1 group;
Fig. 2 is the adhesion site area survey map of matched group 1 group;
Fig. 3 is the animal abdominal adhesions figure of matched group 2 groups;
Fig. 4 is the adhesion site area survey map of matched group 2 groups;
Fig. 5 is the animal abdominal adhesions figure of embodiment 1 group;
Fig. 6 is the adhesion site area survey map of embodiment 1 group.
Detailed description of the invention
Following non-limiting example can make the present invention of those of ordinary skill in the art's comprehend, but does not limit the present invention in any way.
Following chitin is purchased from Pa Nier bio tech ltd, Shaanxi, and the molecular weight of chitin is 0.5 × 10 5~ 2 × 10 5dalton;
Following chitosan is purchased from Pa Nier bio tech ltd, Shaanxi, and the molecular weight that the molecular weight of chitosan is is 0.2 × 10 5~ 1 × 10 5dalton;
Following chitin polysaccharide is purchased from Pa Nier bio tech ltd, Shaanxi, and the molecular weight of chitin polysaccharide is 0.8 × 10 5~ 1.2 × 10 5dalton;
Following hyaluronic acid is purchased from Pa Nier bio tech ltd, Shaanxi, and hyaluronic molecular weight is 0.8 × 10 6~ 3 × 10 6dalton, hyaluronic viscosity is 30 ~ 35dl/g;
Following hetastarch is purchased from Pa Nier bio tech ltd, Shaanxi, and the molecular weight of hetastarch is 7 × 10 4~ 6.7 × 10 5dalton, it is 0.75 ~ 0.4 that the water of hetastarch replaces degree;
Your Thailand of following art is purchased from Beijing De Long Weir Science and Technology Ltd..
Embodiment 1
Prevent a preparation method for the chitin/hyaluronic acid composite membrane of postoperative intestinal adhesion, described preparation method comprises the steps:
1. chitin and normal saline are mixed to get 4wt% chitin normal saline solution, mixed with 10% (V/V) acetic acid by 4wt% chitin normal saline solution, 4 DEG C of standing 48h, obtain solution I;
The volume ratio of described 4wt% chitin normal saline solution and 10% (V/V) acetic acid is 1:0.85;
2. hyaluronic acid and normal saline are mixed to get 0.5wt% hyaluronic acid normal saline solution, 4 DEG C of standing 48h, obtain solution II;
3. hetastarch and normal saline are mixed to get 2wt% hetastarch normal saline solution III;
By solution I, solution II and solution III by volume 1:1:1 mix, add glycerol and obtain 5wt% solution IV, stirring 10min, ultrasonic 2min, 4 DEG C of standing 24h obtain film forming solution, 20mL film forming solution is joined in the one-tenth film container of 10cm × 10cm, uniform spreading, drying obtain smooth, bright, transparency is high, be 0.03mm chitin/hyaluronic acid composite membrane without greasy feeling, matter is soft, toughness is strong thickness.
Embodiment 2
Prevent a preparation method for the chitosan/hyaluronic acid composite membrane of postoperative intestinal adhesion, adopt chitosan to replace chitin with being distinguished as of embodiment 1.
Embodiment 3
Prevent the preparation method of the chitin polysaccharide/hyaluronic acid composite membrane of postoperative intestinal adhesion, adopt chitin polysaccharide to replace chitin with being distinguished as of embodiment 1.
Application examples 1
Intestinal adhesion is tested:
Adopt lumbar injection pentobarbital sodium (30mg/kg) anesthetized rat, when animal is quiet, breathe steadily balance, blood pressure is normal, wall is of flaccid muscles, corneal reflex blunt performance time can carry out every test operation.After Animal Anesthesia, dorsal position is fixed, cropping is sterilized, median abdominal incision is taken off under sterile working, long 3 ~ 4cm, find out caecum part after opening abdominal cavity, wiping is impaired to intestinal placenta percreta serous coat gently repeatedly for caecum portion dry gauze, and damaged area is 1.2cm × 1.2cm, show as surface and have the large blood point of needle point, light red color dyed by gauze.At the area that the damage of damage location opposite abdominal wall medication Wood-scoop is equally large.Caecum damage location is fixed on and with on the abdominal wall position of abdominal wall damage location symmetry, can be promoted that adhesion occurs, build abdominal adhesions animal model.Matched group 1 is wiping normal saline between caecum damage location and abdominal wall damage location; Matched group 2 is the safe 2mL of wiping art that between caecum damage location and abdominal wall damage location; Embodiment 1 group covers chitin/hyaluronic acid composite membrane prepared by embodiment 1 between caecum damage location and abdominal wall damage location.Then successively close abdomen, sew up.Post operation animal fasting 12h, sub-cage rearing, feedstuff is full nutrition rat grain feedstuff.Open abdomen after one week to check, draw materials, judge adhesion grade, experimental result is in table 1.
Rat adhesion situation is determined: 0 grade: completely without adhesion according to middle inspection scoring grade standard; The slight adhesion in I grade: 1 ~ 2 local, place, can separate with finger; II grade: have the adhesion of I grade, more than two places; III grade: have adhesion widely, part separation difficulty; IV grade: caecum and chamber wall close adhesion, separation difficulty.
Table 1 intestinal adhesion experimental result
Degree of adhesion Adhesion area (cm 2) Adhesion Ratio of decreased area (%)
Matched group 1 group 1.36±0.25 0
Matched group 2 groups 0.78±0.12** 42.7
Embodiment 1 group 0.29±0.17* 78.7
Embodiment 1 group and matched group 1 group of ratio, * p<0.05, matched group 2 groups and embodiment 1 group of ratio, * * p<0.05
Obtained by table 1, with matched group 1 group of ratio, tissue adhesion's degree of embodiment 1 group obviously reduces.In addition, with matched group 1 group of ratio, matched group 2 groups of adhesion areas reduce 42.7%, and embodiment 1 group of adhesion area reduces 78.7%.

Claims (6)

1. prevent the composite membrane of postoperative intestinal adhesion, it is characterized in that: described composite membrane comprises polysaccharide, hyaluronic acid, hetastarch, glycerol, sodium chloride, the weight ratio of described polysaccharide, hyaluronic acid, hetastarch, glycerol and sodium chloride is 15 ~ 40:3 ~ 5:1 ~ 40:45 ~ 75:25 ~ 30, and described polysaccharide is chitin, chitosan or chitin polysaccharide.
2. composite membrane according to claim 1, is characterized in that: the molecular weight of described chitin is 0.5 × 10 5~ 2 × 10 5dalton.
3. composite membrane according to claim 1, is characterized in that: the molecular weight of described chitosan is 0.2 × 10 5~ 1 × 10 5dalton.
4. composite membrane according to claim 1, is characterized in that: the molecular weight of described chitin polysaccharide is 0.8 × 10 5~ 1.2 × 10 5dalton.
5. composite membrane according to claim 1, is characterized in that: described hyaluronic molecular weight is 0.8 × 10 6~ 3 × 10 6dalton, hyaluronic viscosity is 30 ~ 35dl/g.
6. composite membrane according to claim 1, is characterized in that: the molecular weight of described hetastarch is 7 × 10 4~ 6.7 × 10 5dalton, it is 0.4 ~ 0.75 that the water of hetastarch replaces degree.
CN201510447812.5A 2015-07-27 2015-07-27 Prevent the composite membrane of postoperative intestinal adhesion Active CN104958790B (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108066827A (en) * 2018-02-07 2018-05-25 苏州元禾医疗器械有限公司 A kind of biomembrane for preventing postoperative tissue adhesion

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1515323A (en) * 2003-01-09 2004-07-28 成都博联医疗信息产业有限责任公司 Preparation method of flexible absorbable medical film material
CN1537641A (en) * 2003-04-18 2004-10-20 上海建华精细生物制品有限公司 Sodium hyaluronate anti-adhesion film, and its prepn. method
CN1557508A (en) * 2004-01-13 2004-12-29 都本立 Adhesion preventing membrane and its preparing method
CN1569262A (en) * 2004-05-12 2005-01-26 中国海洋大学 Carboxymethyl chitin membrane for postoperative adhesion prevention and its preparation method
CN101485897A (en) * 2008-01-14 2009-07-22 纪欣 Biocompatible hemostatic, antiblocking, healing-promoting and surgical wound-closing modified starch material
CN101669964A (en) * 2009-09-30 2010-03-17 大连大学 Surgery anti-adhesion agent and preparation method thereof
CN102380121A (en) * 2011-10-31 2012-03-21 昆明理工大学 Medical anti-adhesion material with controllable degradation and preparation method thereof

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1515323A (en) * 2003-01-09 2004-07-28 成都博联医疗信息产业有限责任公司 Preparation method of flexible absorbable medical film material
CN1537641A (en) * 2003-04-18 2004-10-20 上海建华精细生物制品有限公司 Sodium hyaluronate anti-adhesion film, and its prepn. method
CN1557508A (en) * 2004-01-13 2004-12-29 都本立 Adhesion preventing membrane and its preparing method
CN1569262A (en) * 2004-05-12 2005-01-26 中国海洋大学 Carboxymethyl chitin membrane for postoperative adhesion prevention and its preparation method
CN101485897A (en) * 2008-01-14 2009-07-22 纪欣 Biocompatible hemostatic, antiblocking, healing-promoting and surgical wound-closing modified starch material
CN101669964A (en) * 2009-09-30 2010-03-17 大连大学 Surgery anti-adhesion agent and preparation method thereof
CN102380121A (en) * 2011-10-31 2012-03-21 昆明理工大学 Medical anti-adhesion material with controllable degradation and preparation method thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108066827A (en) * 2018-02-07 2018-05-25 苏州元禾医疗器械有限公司 A kind of biomembrane for preventing postoperative tissue adhesion

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