CN100415245C - Post-surgery anti-accretion material capable of gelatinized in situ or by injection and preparation process thereof - Google Patents
Post-surgery anti-accretion material capable of gelatinized in situ or by injection and preparation process thereof Download PDFInfo
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- CN100415245C CN100415245C CNB200510014737XA CN200510014737A CN100415245C CN 100415245 C CN100415245 C CN 100415245C CN B200510014737X A CNB200510014737X A CN B200510014737XA CN 200510014737 A CN200510014737 A CN 200510014737A CN 100415245 C CN100415245 C CN 100415245C
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Abstract
The present invention provides post-surgery anti-accretion material of gelatinization in situ or by injection and a preparation process thereof. Polyanion water solution, gel water solution, a plasticizing and solubilizing agent, a coloring agent, an antioxidant and a preservative are uniformly mixed according to a certain proportion for obtaining transparent gel; the polyanion is combined with vegetable gel or a polysaccharide macromolecule gelatinization carrier with the base group of -SO3; prepared gelatinization material can be uniformly distributed on a wound surface without an adverse reaction to human bodies; the material effectively restrains fibrocyte growth and promotes the normal repair of tissues. The prepared anti-accretion material of gelatinization in situ is liquid in vitro and forms the gel at the body temperature by adjusting the gelatinization temperature of a system for effectively enwrapping and isolating the wound surface. A special structure enriched with surface active molecules is formed between the material and a tissue interface. In the process of an operation, only local parts are exposed for solving the difficult problems of inconvenient use of conventional membrane material or gel material, poor anti-adhesion effect, etc.
Description
Technical field
The invention belongs to medical material, particularly a kind of injectable gelization and gelatinizing-in-situ post-operation adhesion preventing material and preparation method.
Background technology
In the operation that surgical field is carried out, the problem of adhesion between the overwhelming majority relates to and prevents to organize.Adhesion is that connective fiber band and adjacent tissue or organ combine and the anomalous structure that forms, its degree can be from the very thin thin film of a slice to thick blood vessel scar tissue, it is the common clinical picture of surgical operation, also is the inevitable pathophysiological process of postoperative agglutination.Cause the reason of adhesion to comprise that operation wound, ischemia, foreign body exist, hemorrhage and wound surface exposure and bacterial infection.At obstetrics, orthopaedics or cardiothoracic surgery tissue adhesion is ubiquitous problem.The complication that is caused by peritoneal adhesion mainly comprises intestinal obstruction, infertility and chronic pelvic pain etc., becomes an operating difficult problem.The use of minimally invasive surgery enforcement, Drug therapy and anti isolated material (antiadhesive barrier) etc. all can be played the purpose that reduces adhesion.In the whole bag of tricks of anti, adopting adherence preventing material is the main at present method that adopts as spacer after surgery, and wherein biodegradable absorbing material is used widely.Commercial now post-operation adhesion preventing product mainly contains three kinds: the one, and U.S. W.L.Gore﹠amp; The Gore-Tex post-operation adhesion preventing film of Associates company, its main component is a polytetrafluoroethylene (PTFE), but PTFE is a kind of inert material, can't degrade in human body, must could take out by second operation, it is very not convenient to use, and curative effect is limited; The 2nd, U.S. Johnson﹠amp; The INTERDEED of Johnson company (TC-7), it is the barrier that is absorbed by the degradable that oxidized regenerated cellulose constitutes; But its blood compatibility is relatively poor, and the existence meeting of blood significantly reduces its effect.The 3rd, Genzyme company
The Seprafilm adherence preventing material is made by hyaluronic acid and carboxymethyl cellulose blend, is one of adherence preventing material that clinical research is maximum and the proof preventing adhesiving effect is best, now by drugs approved by FDA, is used for clinical operation.But hyaluronic price is higher, and the Seprafilm operability is bad, meets water and can be out of shape or dissolve, so in the clinical operation enforcement certain difficulty is arranged.The shortcoming of Antiadhesive film material is that tissue adherence is poor, must still be difficult to implementation and operation in edge by sutured, thereby use is subjected to certain restriction.
Summary of the invention
In order to solve deficiency of the prior art, the invention provides a kind of injectable gelization and gelatinizing-in-situ post-operation adhesion preventing material and preparation method.
The component and the weight percent content of injectable gelization and gelatinizing-in-situ post-operation adhesion preventing material are as follows:
(1) composition of gel rubber system A:
1%～5% contains-SO
3The polyanion 20%～80% of group
1%～5% gel solution 80%～20%;
(2) other components contents: following content is for being the weight percentage of benchmark with gel rubber system A;
Plasticising solubilizing agent 1%～2%
Coloring agent 0～0.05%
Antioxidant 0.01%～0.03%
Antiseptic 0.01%～0.03%.
Polyanion of the present invention preferably contains-SO
3The polyanion of group comprises sulfated chitosan (CSSO
3), cellulose sulfuric acid ester, starch sulphate or dextran sulfate, also can be above both or three's intermingling material.
Gel can be selected the natural polysaccharide plant gum for use, as Konjac glucomannan, locust bean gum, carrageenin, tara gum, xanthan gum, pectin, karaya, tragacanth gum, carboxymethyl chitosan, carboxymethyl cellulose, carrageenan, gelatin, sodium alginate or starch etc.
Glycerol, sorbitol, mannitol, xylitol, Polyethylene Glycol, sodium lauryl sulphate (SLS), dimethyl polysiloxane, dodecylbenzene sodium sulfonate, glycerin mono-fatty acid ester, sorbitan monooleate (Span80), polyethylene glycol stearate diester (PD-6000), lecithin, glyceryl stearate or dioctyl alkyl succinic acid sodium etc. are selected in the plasticising solubilizing agent for use.
Coloring agent can be selected from edible pigment such as riboflavin, anthocyanidin, carotene or Rhizoma Curcumae Longae etc.
Antioxidant can select for use epicatechol gallate, Herba Rosmarini Officinalis, carotene, phytic acid, ascorbic acid, tea polyphenols, monascus red pigment, cacao color or phospholipid etc.
Antiseptic is selected from sodium benzoate, P-hydroxybenzoic acid sodium, potassium sorbate or propyl p-hydroxybenzoate etc.
The gel rubber material of the present invention's preparation has high viscoelasticity, hydrophilic, becomes the colloid network structure after the imbibition, can form the permeability barrier film around wound surface, has given play to the fluid impedance effect, protection damaged tissues re-epithelialization; Can in body, remove by degraded simultaneously, need not sew up, still effective when blood is arranged.
By adjusting the gelling temperature of system, the adherence preventing material of the temperature-responsive Injectable in-situ gelization of body plan, external be liquid, and under body temperature, form gel.The original position hydrogel has liquid and solid-state dual function, can only do local the exposure in the operation process, has higher mechanical strength, retention time is grown (above 4 days) in vivo, the incidence rate of adhesion is descended, and adhesion seriousness also obviously reduces, and effect is better than the Antiadhesive film material.This hydrogel can significantly reduce the primary adhesion that forms after blood supply and the damage of blocking-up serous coat simultaneously.
The preparation method of injectable gel formed material of the present invention is:
(1) will contain-SO
3The polyanion of group adds quantitative distilled water, it is fully dissolved in 15～30 minutes 50～90 ℃ of following waters bath with thermostatic control, is prepared into 1%～5% polyanion aqueous solution;
(2) gel component is added quantitative distilled water, it was fully dissolved in 30～120 minutes, obtain 1%～5% gel solution 60～90 ℃ of following waters bath with thermostatic control;
(3) with polyanion solution and gel carrier solution mix homogeneously by a certain percentage, under agitation add plasticising solubilizing agent, opacifier, coloring agent, antiseptic etc. then, abundant mix homogeneously, room temperature is placed 16～24h, obtains clear gel.
Gelatinizing-in-situ post-operation adhesion preventing preparation methods of the present invention is:
(1) elder generation takes by weighing respectively and contains-SO
3The polyanion of group and gel rubber system;
(2) add quantitative distilled water more respectively, it was fully dissolved in 30～120 minutes, the solution for preparing is mixed in proportion 50～90 ℃ of following waters bath with thermostatic control;
(3) under agitation add plasticising solubilizing agent, opacifier, coloring agent, antiseptic, mix homogeneously, room temperature is placed 16～24h, gets gelatinizing-in-situ post-operation adhesion preventing material.
The present invention will contain-SO
3The polyanion of group and to contain-SO
3The plant gum of group or polysaccharide macro-molecular gelation carrier combine the adherence preventing material of body plan injectable gelization and gelatinizing-in-situ.The gelation material of preparation can be uniformly distributed in wound surface, and human body is had no adverse reaction, and effectively suppresses growth of fibroblasts, promotes the normal reparation of tissue.By adjusting the gelling temperature of system, the preparation the gelatinizing-in-situ adherence preventing material external be liquid, and under body temperature, form gel, effective parcel of wound surface and isolation are got up, and the special construction of formation surface active molecules enrichment between material and organizational interface, can only do local the exposure in the operation process, use inconvenience to solve conventional film material or gel rubber material, and a difficult problem such as preventing adhesiving effect is not good.Injectable gelization and temperature-responsive gelatinizing-in-situ adherence preventing material are not seen open report both at home and abroad as yet at present, and this adherence preventing material is particularly suitable for Minimally Invasive Surgery, laminectomy and complicated delicate procedure such as heart operation etc.
The specific embodiment
Embodiment 1: starch sulphate/gelatin/xanthan gum adherence preventing material
Take by weighing the 1g starch sulphate, add the 50ml distilled water, 50 ℃ of following waters bath with thermostatic control 20 minutes make the starch sulphate solution of 2wt%; Take by weighing the 1g gelatin, add the 50ml distilled water, 60 ℃ of following waters bath with thermostatic control 60 minutes, stirring and dissolving obtains the 2wt% gelatin solution; With two solution mix homogeneously, stir the xanthan gum solution that adds 0.5wt% down, add the riboflavin of 0.01wt%, the phospholipid of 0.01wt%, the sodium benzoate of 0.02wt% subsequently, stir, room temperature leaves standstill 24h, obtains starch sulphate/gelatin/xanthan gum adherence preventing material.
Embodiment 2: sulfated chitosan/sodium alginate/glycerol adherence preventing material
Take by weighing the 1g sulfated chitosan, add the 50ml distilled water, the chitosan sulfate ester solution of 2wt% is made in 50 ℃ of following waters bath with thermostatic control 30 minutes; Take by weighing the 0.5g sodium alginate, add the 50ml distilled water, 60 ℃ of following waters bath with thermostatic control 15 minutes, stirring and dissolving obtains the 1wt% sodium alginate soln; With two solution mix homogeneously, stir the glycerite that adds 0.5wt% down then, add the phospholipid of 0.02wt%, the sodium benzoate of 0.02wt% subsequently, stir, room temperature leaves standstill 16h, obtains sulfated chitosan/sodium alginate/glycerogel adherence preventing material.
Embodiment 3: carboxymethyl cellulose/gellan gum/Polyethylene Glycol gelatinizing-in-situ adherence preventing material.
Take by weighing 1g carboxymethyl cellulose and 0.5g gellan gum, add the 100ml distilled water, 70 ℃ of waters bath with thermostatic control, heated and stirred 120 minutes is made the carboxymethyl cellulose of 2wt% and the gellan gum blend solution of 1wt%; Stir the polyglycol solution that adds 0.5wt% down, add subsequently the Rhizoma Curcumae Longae of 0.02wt%, the Herba Rosmarini Officinalis of 0.02wt%, the potassium sorbate of 0.02wt%, stir, room temperature leaves standstill 20h, obtains carboxymethyl cellulose/gellan gum/Polyethylene Glycol gelatinizing-in-situ adherence preventing material.
Embodiment 4: sulfated chitosan/carboxymethyl cellulose/carrageenan adherence preventing material
Take by weighing the 1g sulfated chitosan, add the 50ml distilled water, the chitosan sulfate ester solution of 2wt% is made in 50 ℃ of following waters bath with thermostatic control 30 minutes; Get the 1g carboxymethyl cellulose, add the 50ml distilled water, the cmc soln of 2wt% is made in 70 ℃ of following waters bath with thermostatic control 30 minutes; Take by weighing the 0.5g carrageenan, add in the 50ml distilled water, 70 ℃ of waters bath with thermostatic control, heated and stirred 120 minutes obtains the carrageenan solutions of 1wt%; Then carrageenan solutions and cmc soln are mixed, the chitosan sulfate ester solution added again, and mix homogeneously, in solution, add the Rhizoma Curcumae Longae of 0.02wt%, the phospholipid of 0.03wt%, the sodium benzoate of 0.01wt%, stir, room temperature leaves standstill 24h, obtains sulfated chitosan/carboxymethyl cellulose/carrageenan adherence preventing material.
Embodiment 5: carboxymethyl chitosan/cellulose sulfuric acid ester/gelatin adherence preventing material
Take by weighing the 1g carboxymethyl chitosan, add in the 50ml distilled water, the carboxymethyl chitosan sugar juice of 2wt% is made in 50 ℃ of following waters bath with thermostatic control 30 minutes; Take by weighing 2.5g cellulose sulfuric acid ester and gelatin (both ratios are 1/1), add the 50ml distilled water, 70 ℃ of waters bath with thermostatic control, heated and stirred 60 minutes, swelling, dissolving obtain cellulose sulfuric acid ester/aqueous gelatin solution of 5wt%.With above-mentioned 2 kinds of solution mix homogeneously, add the Rhizoma Curcumae Longae of 0.02wt%, the phospholipid of 0.03wt%, the sodium benzoate of 0.01wt%, stir, room temperature leaves standstill 23h, obtains carboxymethyl chitosan/cellulose sulfuric acid ester/gelatin adherence preventing material.
Embodiment 6: dextran sulfate/gelatin/Konjac glucomannan gelatinizing-in-situ adherence preventing material
Take by weighing the 1g dextran sulfate, 2.5g gelatin and Konjac glucomannan (both ratios are 2/1) are dissolved in the 100ml distilled water after mixing, 80 ℃ of following waters bath with thermostatic control, heated and stirred 80 minutes is dissolved, and obtains the blend solution of 2wt% dextran sulfate and 5wt% gelatin/Konjac glucomannan; Add the polyglycol solution of 0.5wt%, the phospholipid of 0.02wt%, the sodium benzoate of 0.015wt% under stirring, stir, room temperature leaves standstill 16h, obtains dextran sulfate/gelatin/Konjac glucomannan gelatinizing-in-situ adherence preventing material.
Embodiment 7: hydroxypropyl carboxy methyl cellulose/carrageenan/locust bean gum gelatinizing-in-situ adherence preventing material
Take by weighing 1g hydroxypropyl carboxy methyl cellulose, 1.5g carrageenan and locust bean gum (both ratios are 2/1) are dissolved in the 100ml distilled water 90 ℃ of waters bath with thermostatic control, heated and stirred 100 minutes is made the hydroxypropyl carboxy methyl cellulose of 2wt% and the carrageenan of 3wt%/locust bean gum blend solution; Stir and add the polyglycol solution of 0.5wt%, the anthocyanidin of 0.01wt%, the cacao color of 0.02wt%, the sodium benzoate of 0.01wt% down, stir, room temperature leaves standstill 21h, obtains hydroxypropyl carboxy methyl cellulose/carrageenan/locust bean gum gelatinizing-in-situ adherence preventing material.
Claims (10)
1. injectable gelization and gelatinizing-in-situ post-operation adhesion preventing material: component and weight percent content are as follows:
(1) composition of gel rubber system A:
1%～5% contains-SO
3The polyanion 20%～80% of group
1%～5% gel solution 80%～20%;
(2) other components contents: following content is for being the weight percentage of benchmark with gel rubber system A;
Plasticising solubilizing agent 1%～2%
Coloring agent 0～0.05%
Antioxidant 0.01%～0.03%
Antiseptic 0.01%～0.03%.
2. a kind of injectable gelization as claimed in claim 1 and gelatinizing-in-situ post-operation adhesion preventing material is characterized in that described gel is the natural polysaccharide plant gum.
3. a kind of injectable gelization as claimed in claim 2 and gelatinizing-in-situ post-operation adhesion preventing material is characterized in that described containing-SO
3The polyanion of group is one or more a mixture of sulfated chitosan, cellulose sulfuric acid ester, starch sulphate or dextran sulfate.
4. a kind of injectable gelization as claimed in claim 2 and gelatinizing-in-situ post-operation adhesion preventing material is characterized in that described natural polysaccharide plant gum is Konjac glucomannan, locust bean gum, carrageenin, tara gum, xanthan gum, pectin, karaya, tragacanth gum, carboxymethyl chitosan, carboxymethyl cellulose, carrageenan, gelatin, sodium alginate or starch.
5. a kind of injectable gelization as claimed in claim 1 and gelatinizing-in-situ post-operation adhesion preventing material is characterized in that described plasticising solubilizing agent is glycerol, sorbitol, mannitol, xylitol, Polyethylene Glycol, sodium lauryl sulphate, dimethyl polysiloxane, dodecylbenzene sodium sulfonate, glycerin mono-fatty acid ester, sorbitan monooleate, polyethylene glycol stearate diester, lecithin, glyceryl stearate or dioctyl alkyl succinic acid sodium.
6. a kind of injectable gelization as claimed in claim 1 and gelatinizing-in-situ post-operation adhesion preventing material is characterized in that described coloring agent is the edible pigment.
7. a kind of injectable gelization as claimed in claim 1 and gelatinizing-in-situ post-operation adhesion preventing material, it is characterized in that described antioxidant be epicatechol gallate, Herba Rosmarini Officinalis, carotene, phytic acid, ascorbic acid, tea polyphenols, monascus red pigment, cacao color or phospholipid.
8. a kind of injectable gelization as claimed in claim 1 and gelatinizing-in-situ post-operation adhesion preventing material is characterized in that described antiseptic is sodium benzoate, P-hydroxybenzoic acid sodium, potassium sorbate or propyl p-hydroxybenzoate.
9. the preparation method of a kind of injectable gel formed material as claimed in claim 1 is characterized in that:
(1) will contain-SO
3The polyanion of group adds quantitative distilled water, it is fully dissolved in 15～30 minutes 50～90 ℃ of following waters bath with thermostatic control, is prepared into 1%～5% polyanion aqueous solution;
(2) gel component is added quantitative distilled water, it was fully dissolved in 30～120 minutes, obtain 1%～5% gel solution 60～90 ℃ of following waters bath with thermostatic control;
(3) with polyanion solution and gel carrier solution mix homogeneously by a certain percentage, under agitation add plasticising solubilizing agent, opacifier, coloring agent, antiseptic then, abundant mix homogeneously, room temperature is placed 16～24h, obtains clear gel.
10. a kind of gelatinizing-in-situ post-operation adhesion preventing preparation methods as claimed in claim 1 is characterized in that:
(1) elder generation takes by weighing respectively and contains-SO
3The polyanion of group and gel rubber system;
(2) add quantitative distilled water more respectively, it was fully dissolved in 30～120 minutes, the solution for preparing is mixed in proportion 50～90 ℃ of following waters bath with thermostatic control;
(3) under agitation add plasticising solubilizing agent, opacifier, coloring agent, antiseptic, mix homogeneously, room temperature is placed 16～24h, gets gelatinizing-in-situ post-operation adhesion preventing material.
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| CN105199122A (en) * | 2015-11-05 | 2015-12-30 | 广西大学 | Preparation method of hemicellulose and gelatin composite biofilm |
| CN108066819B (en) * | 2017-12-01 | 2020-06-05 | 浙江大学 | High-strength natural polymer hydrogel film and preparation method thereof |
| CN114832043A (en) * | 2022-05-11 | 2022-08-02 | 季华实验室 | Preparation method of yellow hydrogel line for traumatology department |
| CN115737915A (en) * | 2022-12-01 | 2023-03-07 | 刘玉增 | Injectable bone filling material and preparation method thereof |
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| CN1569024A (en) * | 2004-04-30 | 2005-01-26 | 天津大学 | Novel post-operation antiadhesive materials and its preparation method |
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