CN104327310B - Antiadhesive film that a kind of ultrasonic technique processes and preparation method thereof - Google Patents

Abstract

The present invention relates to a kind of Antiadhesive film and preparation method thereof.The Antiadhesive film of the present invention is stuck with paste liquid by carboxymethyl starch and is mixed by supersound process with gelatinized corn starch liquid.The Antiadhesive film clinical effectiveness of the present invention is excellent, safety is good, biodegradable, and preparation method is simple, low for equipment requirements, with low cost, can apply and large-scale industrial production.

Description

Anti-adhesion film treated by ultrasonic process and preparation method thereof

technical field

The invention relates to the technical field of medical materials, in particular to an anti-adhesion film and a preparation method thereof.

Background technique

Adhesions are abnormal structures where fibrous bands of connective tissue join together with adjacent tissues or organs. Adhesion formation is universal, and it is reported that 50% to 100% of abdominal and pelvic surgeries can lead to different degrees of adhesions. Clinically serious complications caused by adhesions include intestinal obstruction, infertility, and chronic pelvic pain, which increase the difficulty of reoperation and the potential for further complications. Therefore, the prevention of postoperative adhesions is a very important topic in the surgical field. Clinically, the physical barrier effect of anti-adhesion materials is generally used to prevent the occurrence of adhesion symptoms.

At present, the existing anti-adhesion materials include the following: modified chitosan, hyaluronic acid, and carboxymethyl cellulose.

Modified chitosan is a relatively common anti-adhesion material. It has excellent biological barrier properties and tissue compatibility. It can be applied to tissue wounds to prevent postoperative tissue adhesion. Due to its biocompatibility and tissue degradability, chitosan can be used as an ideal postoperative anti-adhesion agent theoretically after being made into a film. However, the purity of chitin gum currently used in clinical practice is not high enough, and its anti-adhesion effect is poor, and the degradation rate is difficult to control artificially. The degradation of chitin is also affected by the level of lysozyme in the human body, and the absorption effect is unpredictable. Therefore, the application area is narrow. Past studies on the prevention of postoperative adhesions were limited to the prevention of adhesive ileus during abdominal surgery. Furthermore, because of ophthalmic adverse reactions and mass incidents, it is being urgently stopped by SFDA.

The basic principle of hyaluronic acid is based on the good biocompatibility, physical (rheological) properties and unique biological actions of hyaluronic acid and cross-linked hyaluronic acid molecules. However, natural hyaluronic acid cannot achieve the ideal effect in preventing adhesion due to its short retention time at the implant site. Cross-linked hyaluronic acid has good biocompatibility and a long retention time in tissues. Since then, the application of cross-linked hyaluronic acid as an effective preparation for preventing and reducing postoperative adhesions has attracted widespread attention. However, due to the high price of hyaluronic acid, the cost of medical treatment for patients is high, and hyaluronic acid is mostly of animal origin, which has immunogenicity problems in the body, and the process of extraction and purification of hyaluronic acid is complicated, so it is very difficult to maintain high purity , and there will be heavy metal residues, which will lead to human poisoning after implantation.

Carboxymethyl cellulose is a kind of cellulose ether, and its sodium salt is usually used. It has good biocompatibility, can be completely degraded and absorbed in the body, and the degraded products are non-toxic, have no side effects, are not irritating to the peritoneum, and can reduce the incidence of postoperative adhesions in the abdominal cavity and alleviate adhesions. However, carboxymethyl cellulose absorbs and degrades quickly (4 days), which is far less than the time for wound healing. It usually needs to be modified by adding plasticizers before it can be applied clinically, but the degradation rate has not yet been controlled.

In the previous patent application (patent number: ZL201410629763.2), the applicant disclosed an anti-adhesion film made of carboxymethyl starch paste and starch paste, which has good safety and biodegradability On this basis, after further research, the applicant found that if an ultrasonic step was added in the preparation process, its anti-adhesion and biodegradability could be further improved.

Contents of the invention

The purpose of the present invention is to overcome the deficiencies of the above-mentioned prior art, and to provide a preparation of a medical absorbable anti-adhesion film that can self-adhere to the surgical wound site to form a physical barrier, prevent the formation of adhesion, and self-degrade and absorb during the wound healing process. method.

A technical scheme of the present invention is:

An anti-adhesion film is formed by mixing carboxymethyl starch paste and starch paste.

Another technical scheme of the present invention is:

A preparation method for an anti-adhesion film, comprising the steps of:

(1) Preparation of carboxymethyl starch paste: mix carboxymethyl starch with water to make starch milk, add glycerin, and gelatinize at 160°C;

(2) Preparation of starch paste: dissolve starch in distilled water and put it in a water bath at 80°C; add a crosslinking agent therein and stir;

(3) Preparation of anti-adhesion film: add the starch paste prepared in step (2) to the carboxymethyl starch paste prepared in step (1), stir evenly, process by ultrasonic waves, and pour the solution into Put it into the mold, dry it in an oven, and put the prepared film in a vacuum bag for later use.

Preferably, the crosslinking agent used in step 2 is one or more of acrolein, formaldehyde, sodium trimetaphosphate, and polyvinyl alcohol.

Preferably, the ratio of starch paste to carboxymethyl starch paste in step (3) is 2:1-1:3.

Preferably, the ratio of carboxymethyl starch to water in step (1) is 1g: 20ml to 1g: 40ml.

Preferably, the oven temperature in step (3) is 50°C.

Preferably, the parameters for ultrasonic treatment in step (3) are set as follows: 400W-450W power for 4-5 minutes, 3s for 3s and 3s for rest.

Another technical scheme of the present invention is:

The application of the anti-adhesion film of the invention in preventing wound adhesion and promoting wound healing.

The invention has the following advantages: the anti-adhesion film of the invention has excellent clinical effect, good safety, biodegradability, simple preparation method, low requirement for equipment, low cost, and can be applied to large-scale industrial production.

detailed description

The present invention will be described in further detail below through examples, but the scope of protection of the present invention is not limited to the content.

Example 1

Prepare anti-adhesion film, comprises the steps:

(1) Preparation of carboxymethyl starch paste: mix carboxymethyl starch with a certain amount of water (the ratio of starch to water is 1g: 20mL) to make starch milk, take 50g of starch milk, and add 5g of glycerin to it , at 160°C, gelatinize for 50min;

(2) Preparation of starch paste: dissolve 5 g of starch in 50 mL of distilled water, put it in a water bath at 80° C. for 30 min; add 2 ml of polyvinyl alcohol solution (concentration: 20 g/L) to it, and stir for 30 min;

(3) Preparation of anti-adhesion film: add the starch paste prepared in step (2) to the carboxymethyl starch paste prepared in step (1) (the ratio of the two is 1:1), stir evenly, and place In the ultrasonic cell pulverizer, 400w power is applied for 5min (3s for 3s and 3s for rest). Then add distilled water to it until the glass rod is almost free from wires, and let the solution stand until the bubbles disappear. The solution was poured into a glass dish (mold) by casting method, and dried in an oven at 50° C. for 48 hours. The prepared membranes were placed in vacuum bags for later use.

Example 2

Prepare anti-adhesion film, comprises the steps:

(1) Preparation of carboxymethyl starch paste: mix carboxymethyl starch with a certain amount of water (the ratio of starch to water is 1g: 20mL) to make starch milk, take 50g of starch milk, and add 5g of glycerin to it , at 160°C, gelatinize for 50min;

(2) Preparation of starch paste: dissolve 5 g of starch in 50 mL of distilled water, put it in a water bath at 80° C. for 30 min; add 3 ml of acrolein aqueous solution (concentration: 15 g/L) to it, and stir for 30 min;

(3) Preparation of anti-adhesion film: add the starch paste prepared in step (2) to the carboxymethyl starch paste prepared in step (1) (the ratio of the two is 1:1), stir evenly, and place In the ultrasonic cell pulverizer, 450w power is applied for 4min (3s for 3s and 3s for rest). Then add distilled water to it until the glass rod is almost free from wires, and let the solution stand until the bubbles disappear. The solution was poured into a glass dish (mold) by casting method, and dried in an oven at 50° C. for 48 hours. The prepared membranes were placed in vacuum bags for later use.

Example 3

Prepare anti-adhesion film, comprises the steps:

(1) Preparation of carboxymethyl starch paste: mix carboxymethyl starch with a certain amount of water (the ratio of starch to water is 1g: 20mL) to make starch milk, take 50g of starch milk, and add 5g of glycerin to it , at 160°C, gelatinize for 50min;

(2) Preparation of starch paste: dissolve 5 g of starch in 50 mL of distilled water, put it in a water bath at 80° C. for 30 min; add 2 ml of formaldehyde therein, and stir for 30 min;

(3) Preparation of anti-adhesion film: add the starch paste prepared in step (2) to the carboxymethyl starch paste prepared in step (1) (the ratio of the two is 1:1), stir evenly, and place In the ultrasonic cell pulverizer, 400w power is applied for 5min (3s for 3s and 3s for rest). Then add distilled water to it until the glass rod is almost free from wires, and let the solution stand until the bubbles disappear. The solution was poured into a glass dish (mold) by casting method, and dried in an oven at 50° C. for 48 hours. The prepared membranes were placed in vacuum bags for later use.

Example 4

Prepare anti-adhesion film, comprises the steps:

(1) Preparation of carboxymethyl starch paste: mix carboxymethyl starch with a certain amount of water (the ratio of starch to water is 1g: 20mL) to make starch milk, take 50g of starch milk, and add 5g of glycerin to it , at 160°C, gelatinize for 50min;

(2) Preparation of starch paste: dissolve 5 g of starch in 50 mL of distilled water, put it in a water bath at 80° C. for 30 min; add 3 ml of sodium trimetaphosphate aqueous solution (concentration: 17 g/L) to it, and stir for 30 min;

(3) Preparation of anti-adhesion film: add the starch paste prepared in step (2) to the carboxymethyl starch paste prepared in step (1) (the ratio of the two is 1:1), stir evenly, and place In the ultrasonic cell pulverizer, 450w power was applied for 5min (3s for 3s and 3s for rest). Then add distilled water to it until the glass rod is almost free from wires, and let the solution stand until the bubbles disappear. The solution was poured into a glass dish (mold) by casting method, and dried in an oven at 50° C. for 48 hours. The prepared membranes were placed in vacuum bags for later use.

Example 5

Prepare anti-adhesion film, comprises the steps:

(1) Preparation of carboxymethyl starch paste: mix carboxymethyl starch with a certain amount of water (the ratio of starch to water is 1g: 40mL) to make starch milk, take 50g of starch milk, and add 4g of glycerin to it , at 160°C, gelatinize for 50min;

(2) Preparation of starch paste: dissolve 5 g of starch in 50 mL of distilled water, put it in a water bath at 85° C. for 40 min; add 2 ml of polyvinyl alcohol solution (concentration: 20 g/L) to it, and stir for 30 min;

(3) Preparation of anti-adhesion film: add the starch paste prepared in step (2) to the carboxymethyl starch paste prepared in step (1) (the ratio of the two is 2:1), stir evenly, and place In the ultrasonic cell pulverizer, 400w power is applied for 4min (3s for 3s and 3s for rest). Then add distilled water to it until the glass rod is almost free from wires, and let the solution stand until the bubbles disappear. The solution was poured into a glass dish (mold) by casting method, and dried in an oven at 50° C. for 48 hours. The prepared membranes were placed in vacuum bags for later use.

Example 6

Prepare anti-adhesion film, comprises the steps:

(1) Preparation of carboxymethyl starch paste: mix carboxymethyl starch with a certain amount of water (the ratio of starch to water is 1g: 40mL) to make starch milk, take 50g of starch milk, and add 2g of glycerin to it , at 160°C, gelatinize for 50min;

(2) Preparation of starch paste: dissolve 5 g of starch in 50 mL of distilled water, put it in a water bath at 83° C. for 50 min; add 3 ml of acrolein aqueous solution (concentration: 15 g/L) to it, and stir for 30 min;

(3) Preparation of anti-adhesion film: add the starch paste prepared in step (2) to the carboxymethyl starch paste prepared in step (1) (the ratio of the two is 1:2), stir evenly, and place In the ultrasonic cell pulverizer, 400w power is applied for 5min (3s for 3s and 3s for rest). Then add distilled water to it until the glass rod is almost free from wires, and let the solution stand until the bubbles disappear. The solution was poured into a glass dish (mold) by casting method, and dried in an oven at 50° C. for 48 hours. The prepared membranes were placed in vacuum bags for later use.

Example 7

Prepare anti-adhesion film, comprises the steps:

(1) Preparation of carboxymethyl starch paste: mix carboxymethyl starch with a certain amount of water (the ratio of starch to water is 1g: 40mL) to make starch milk, take 50g of starch milk, and add 3g of glycerin to it , at 160°C, gelatinize for 50min;

(2) Preparation of starch paste: dissolve 5 g of starch in 50 mL of distilled water, put it in a water bath at 82°C for 30 min; add 2 ml of formaldehyde therein, and stir for 30 min;

(3) Preparation of anti-adhesion film: add the starch paste prepared in step (2) to the carboxymethyl starch paste prepared in step (1) (the ratio of the two is 1:1), stir evenly, and place In the ultrasonic cell pulverizer, 400w power is applied for 5min (3s for 3s and 3s for rest). Then add distilled water to it until the glass rod is almost free from wires, and let the solution stand until the bubbles disappear. The solution was poured into a glass dish (mold) by casting method, and dried in an oven at 50° C. for 48 hours. The prepared membranes were placed in vacuum bags for later use.

Example 8

Prepare anti-adhesion film, comprises the steps:

(1) Preparation of carboxymethyl starch paste: mix carboxymethyl starch with a certain amount of water (the ratio of starch to water is 1g: 40mL) to make starch milk, take 50g of starch milk, and add 2g of glycerin to it , at 160°C, gelatinize for 50min;

(2) Preparation of starch paste: dissolve 5 g of starch in 50 mL of distilled water, put it in a water bath at 80° C. for 30 min; add 3 ml of sodium trimetaphosphate aqueous solution (concentration: 17 g/L) to it, and stir for 30 min;

(3) Preparation of anti-adhesion film: add the starch paste prepared in step (2) into the carboxymethyl starch paste prepared in step (1) (the ratio of the two is 1:3), stir evenly, and place In the ultrasonic cell pulverizer, 400w power is applied for 5min (3s for 3s and 3s for rest). Then add distilled water to it until the glass rod is almost free from wires, and let the solution stand until the bubbles disappear. The solution was poured into a glass dish (mold) by casting method, and dried in an oven at 50° C. for 48 hours. The prepared membranes were placed in vacuum bags for later use.

Embodiment 9 The anti-adhesion film test effect of the present application

Carry out animal experiment with the anti-adhesion film that embodiment 1-8 makes:

26 rabbits were taken, under general anesthesia, the abdomen of the rabbits was cut open along the midline, the uterine horns were taken out, the serosa at the uterine horns was destroyed, bleeding occurred, and wounds were formed. Grouping treatment, anti-adhesion film application 16 as the experimental group (the anti-adhesion film prepared in each embodiment is used for 2 rabbits), 5 using "Baifeimi" of Beijing Bailikang Biochemical Co., Ltd. as the positive control group , 5 as a blank control group, and then the abdominal wall was sutured. After 13 days, the materials were collected for observation. It was found that there was no adhesion in the abdominal cavity of the rabbits in the experimental group, and the anti-adhesion membrane degraded significantly, with an excellent and good rate of 100%. Adhesions, the uterine horn not only produces adhesions with itself, but also has a wide range of adhesions and high adhesion strength.

It can be seen that the anti-adhesion film prepared by the method of the present application is not only significantly stronger in anti-adhesion and degradation effects than the positive control group and the blank control group, but also better than the anti-adhesion film prepared in the applicant's prior patent application (ZL201410629763.2). The effect of the anti-adhesion film is even better (the wound recovery time of the rabbit was advanced by two days).

Claims (2)

1. the preparation method of an Antiadhesive film, it is characterised in that: comprise the steps of:

(1) carboxymethyl starch sticks with paste the preparation of liquid: mixed with water by carboxymethyl starch, furnishing starch milk, adds glycerol, Under the conditions of 160 DEG C, gelatinizing；

(2) preparation of gelatinized corn starch liquid: by starch dissolution in distilled water, puts in the water-bath of 80 DEG C；It is added thereto to Cross-linking agent, stirring；

(3) preparation of Antiadhesive film: gelatinized corn starch liquid step (2) prepared adds the carboxymethyl starch prepared in step (1) Stick with paste in liquid, stir, processed by ultrasound wave, pour this solution in mould, put in baking oven dry Dry, prepared film is placed in vacuum bag standby；

The cross-linking agent used in step (2) is: one in acrylic aldehyde, formaldehyde, sodium trimetaphosphate, polyvinyl alcohol or Multiple；

The ratio that in step (3), gelatinized corn starch liquid and carboxymethyl starch stick with paste liquid is 2:1～1:3；

In step (1), carboxymethyl starch is 1g:20ml～1g:40ml with the ratio of water；

In step (3), oven temperature is 50 DEG C；

Parameter when ultrasound wave processes in step (3) is set to: 400W～450W power effect 4～5min, Effect 3s interval 3s.

2. the Antiadhesive film that the preparation method described in claim 1 prepares.