CN100348272C - Method for preparing astringent sponge of soluble cellulose - Google Patents

Abstract

The present invention relates to a method for preparing soluble cellulose hemostatic sponge, which comprises the following steps: sodium carboxymethyl cellulose and chitosan are weighed according to the weight ratio of 2 to 6:1, the sodium carboxymethyl cellulose is prepared into a solution with the concentration of 0.5 to 3% by distilled water, the chitosan is prepared into a solution with the concentration of 1 to 5% by dilute acetic acid, and then the two solutions are uniformly mixed to obtain a mixed solution. 1 to 10 g/L of polyethylene glycol 400, 2 to 12 g/L of sucrose and 0.1 to 2 g/L of glycerol are added in the mixed solution and uniformly stirred, and after the defoaming, mixed liquid is obtained. The mixed liquid is poured into a film forming apparatus, and through freeze drying in vacuum, the sponge product of the present invention is obtained. The product prepared by the method has the advantages of low cost, good hemostatic effect and easy clinical use, and is used for hemostasis.

Description

Preparation method of soluble cellulose hemostatic sponge

technical field

The invention relates to a preparation method of a spongy material, in particular to a preparation method of a soluble cellulose hemostatic sponge.

Background technique

The rapid development of modern surgical medical technology has made great contributions to saving lives and healing the wounded. There are three major obstacles to the development of surgical operations, namely pain, wound infection, and bleeding. The problem of pain has been basically solved, and the continuous replacement of antibiotics has also basically solved the problem of wound infection. Bleeding has just become the biggest obstacle hindering the development of surgical operations. In surgical operations, whether the bleeding can be effectively stopped sometimes becomes the key to determine the success of the operation. At present, surgeons generally use ligation, suture ligation and electrocoagulation as methods for hemostasis and wound healing, but this method is not perfect. , wound edge lysis, ischemic necrosis, postoperative scar, etc.; electrocoagulation will increase tissue damage, and it is not suitable to use electrocoagulation near hollow organs and large blood vessels to stop bleeding, because it can easily cause tissue necrosis and affect healing. Therefore, for a long time, medical scientists have been actively researching to find a new method and new material that can not only quickly and effectively stop bleeding, but also simplify or even replace traditional suture techniques, and this material is non-toxic, can be completely absorbed by the body, and has no immunity. response etc. Thereby making surgery safer, improving the quality of postoperative healing, and reducing the pain of patients.

Traditional wound hemostatic materials are mainly first aid kits, four-head bands, tourniquets and bandages, etc., and sometimes a large number of sterile dressings are used to make up for the deficiency of first aid kits for hemostasis. A large number of sterile dressings are difficult to carry and sterilized to store; first aid kits and four-head bands only have sterile triangular towels and 1 to 2 small and medium-sized dressings, and the coverage and hemostasis of large-area wounds, complex wounds, and multiple wounds are not good. Use a tourniquet to control wound bleeding, but improper use of a tourniquet may result in traumatic amputation or even death. Therefore, the study of new wound first aid hemostatic materials has become the key for surgeons to successfully perform surgical operations. New wound first aid hemostatic materials often come from the application of wound hemostatic materials in the field of trauma first aid.

At present, many kinds of wound hemostatic materials have been developed at home and abroad, mainly including: fibrin glue, collagen, chitosan, microporous inorganic materials such as zeolite, etc., α-cyanoacrylate (cyanoacrylate) tissue glue etc. Fibrin glue and collagen hemostatic materials are biological products extracted from humans or animals, which are expensive, increase the burden of hospitalization for patients, and have potential safety issues of blood-derived biological products; chitosan hemostatic materials have limited hemostatic effect and are The hemostatic effect of extensive bleeding wounds is not ideal; the zeolite hemostatic process will generate a lot of heat; and α-cyanoacrylate tissue glue has tissue toxicity and irritation to varying degrees.

Sodium carboxymethyl cellulose (NaCMC) is the earliest developed and applied cellulose derivative made from natural fiber materials. Sodium carboxymethyl cellulose has good biocompatibility, is non-toxic, non-irritating, and can be completely degraded. Studies have found that sodium carboxymethylcellulose has an excellent triple hemostatic effect, and its hemostatic process is achieved through the synergistic effect of physical, chemical and physiological hemostasis. When in contact with blood, sodium carboxymethylcellulose absorbs the water in the blood and swells to form a viscose-like substance, which increases the viscosity and concentration of the blood and slows down the flow rate. Due to the production of viscous bodies, it can fill the wound surface gap, close the capillary ends, and achieve the purpose of hemostasis; at the same time, sodium carboxymethyl cellulose has a significant affinity for hemoglobin, and forms an insoluble covering or filling with Fe ²⁺ in the blood, making the wound surface hemostasis; in addition, the dissolved sodium cellulose releases negative ions (equivalent to 4 times that of general hemostatic materials), which can also activate a variety of coagulation factors, agglomerate platelets, and play a role in coagulation, thereby achieving the purpose of hemostasis and improving the surgical efficiency. post-healing quality. But the existing fibrous hemostatic product gelatin sponge still has higher cost, unsatisfactory hemostatic effect and inconvenient clinical use.

Contents of the invention

The object of the present invention is to provide a kind of preparation method of soluble cellulose hemostatic sponge for the deficiency that existing hemostatic material exists, and described method adopts vacuum freeze-drying technology to make soluble sodium carboxymethylcellulose into sponge-like product, and product cost Low, strong hemostatic effect, convenient for clinical use.

The preparation method of soluble cellulose hemostatic sponge of the present invention, comprises the steps:

(1) Take sodium carboxymethyl cellulose and chitosan at a weight ratio of 2 to 6:1, prepare sodium carboxymethyl cellulose with distilled water into a solution with a concentration of 0.5 to 3%, and dilute chitosan with Acetic acid is prepared into a solution with a concentration of 1 to 5%, and then the two solutions are mixed evenly;

(2) Add 1-10g/L polyethylene glycol 400, 2-12g/L sucrose and 0.1-2g/L glycerin to the mixed solution obtained in step (1), stir evenly, and let it stand for defoaming;

(3) Pour the mixed solution obtained in step (2) into a film-forming device, and vacuum freeze-dry to obtain the sponge product of the present invention.

The degree of substitution of sodium carboxymethylcellulose in step (1) is 0.7 to 1.2, the degree of deacetylation of chitosan is 50 to 95%, and the film-forming device described in step (3) is polystyrene Film-forming device for material preparation.

Compared with the prior art, the present invention has the following advantages:

(1) It has a strong hemostatic effect and good biocompatibility. It degrades in the body to form a low-sugar substance that is absorbed by the human body without residue. Compared with other similar products, the production cost is low and the product performance is greatly improved. Clinical use is more convenient.

(2) Adding chitosan in the present invention has a great antibacterial and antibacterial effect, and can effectively reduce the risk of spreading blood-borne diseases.

(3) The present invention expands the application field of sodium carboxymethyl cellulose, drives the economic benefits of related enterprises, conforms to the development direction of international biological hemostatic materials, and has important social and economic benefits.

Detailed ways

The present invention will be further described in detail below in conjunction with specific embodiments.

Example 1

(1) It is 2: 1 by weight to take by weight the sodium carboxymethyl cellulose that the degree of substitution is 1.1 and the chitosan that the degree of deacetylation is 60%, it is 0.5% that the sodium carboxymethyl cellulose is mixed with distilled water The solution, chitosan is mixed with dilute acetic acid concentration and is a 1% solution, then the two solutions are mixed evenly;

(2) Add 10g/L polyethylene glycol 400, 2g/L sucrose, and 2g/L glycerin to the mixed solution obtained in step (1), and stir evenly, and let it stand for defoaming;

(3) Pour the mixed solution obtained in step (2) into a polystyrene container, and vacuum freeze-dry to obtain the sponge product of the present invention. The product is porous and relatively elastic, and the hemostasis time for rabbit ear veins is 55s, liver hemostasis time is 61s, and spleen hemostasis time is 68s.

Example 2

(1) It is 6: 1 by weight to take the chitosan that the degree of substitution is 0.7 sodium carboxymethyl cellulose and the degree of deacetylation is 50%, and the sodium carboxymethyl cellulose is mixed with distilled water to have a concentration of 1%. The solution, chitosan is mixed with dilute acetic acid concentration and is 5% solution, then two kinds of solutions are mixed;

(2) Add 8g/L polyethylene glycol 400, 12g/L sucrose, and 2g/L glycerin to the mixed solution obtained in step (1), and stir evenly, and let it stand for defoaming;

(3) Pour the mixed solution obtained in step (2) into a polystyrene container, and vacuum freeze-dry to obtain the sponge product of the present invention. The product is porous and relatively elastic, and the hemostasis time for rabbit ear veins is 50s, liver hemostasis time is 58s, and spleen hemostasis time is 57s.

Example 3

(1) It is 4: 1 by weight to take by weighing the sodium carboxymethyl cellulose that the degree of substitution is 0.9 and the chitosan that the degree of deacetylation is 95%, the sodium carboxymethyl cellulose is mixed with distilled water and is 1.5% concentration The solution, chitosan is mixed with dilute acetic acid concentration and is a 1% solution, then the two solutions are mixed evenly;

(2) Add 4g/L polyethylene glycol 400, 5g/L sucrose, and 1g/L glycerin to the mixed solution obtained in step (1), and stir evenly, and let it stand for defoaming;

(3) Pour the mixed solution obtained in step (2) into a polystyrene container, and vacuum freeze-dry to obtain the sponge product of the present invention. The product is porous and relatively elastic, and the hemostatic time for rabbit ear veins is 40s, liver hemostasis time is 51s, and spleen hemostasis time is 58s.

Example 4

(1) It is 3: 1 by weight to take by weight the sodium carboxymethyl cellulose that the degree of substitution is 1.2 and the chitosan that the degree of deacetylation is 80%, the sodium carboxymethyl cellulose is mixed with distilled water and is 3% concentration The solution, chitosan is mixed with dilute acetic acid concentration and is a 1% solution, then the two solutions are mixed evenly;

(2) Add 1g/L polyethylene glycol 400, 2g/L sucrose, and 0.1g/L glycerin to the mixed solution obtained in step (1), and stir evenly, and let it stand for defoaming;

(3) Pour the mixed solution obtained in step (2) into a polystyrene container, and vacuum freeze-dry to obtain the sponge product of the present invention. The product is porous and relatively elastic, and the hemostatic time for rabbit ear veins is 58s, liver hemostasis time is 61s, and spleen hemostasis time is 60s.

Example 5

(1) It is 5: 1 by weight to take the chitosan that the degree of substitution is 0.8 sodium carboxymethyl cellulose and the degree of deacetylation is 90%, and the concentration of sodium carboxymethyl cellulose is 2% with distilled water The solution, chitosan is mixed with dilute acetic acid concentration and is 1.5% solution, then two kinds of solutions are mixed;

(2) Add 10g/L polyethylene glycol 400, 2g/L sucrose, and 2g/L glycerin to the mixed solution obtained in step (1), and stir evenly, and let it stand for defoaming;

(3) Pour the mixed solution obtained in step (2) into a polystyrene container, and vacuum freeze-dry to obtain the sponge product of the present invention. The product is porous and relatively elastic, and the hemostasis time for rabbit ear veins is 52s, liver hemostasis time is 56s, and spleen hemostasis time is 59s.

Example 6

(1) It is 5: 1 by weight to take by weight the sodium carboxymethyl cellulose that the degree of substitution is 1.0 and the chitosan that the deacetylation degree is 80%, it is 2% that the sodium carboxymethyl cellulose is mixed with distilled water The solution, chitosan is mixed with dilute acetic acid concentration and is 1.5% solution, then two kinds of solutions are mixed;

(2) Add 9g/L polyethylene glycol 400, 5g/L sucrose, and 1g/L glycerin to the mixed solution obtained in step (1), and stir evenly, and let it stand for defoaming;

(3) Pour the mixed solution obtained in step (2) into a polystyrene container, and vacuum freeze-dry to obtain the sponge product of the present invention. The product is porous and relatively elastic. The hemostasis time for rabbit ear veins is 52s, liver hemostasis time is 55s, and spleen hemostasis time is 61s.

The hemostatic effect of the products prepared in Examples 1 to 6 on rabbit ear veins, liver, and spleen is compared with the hemostatic effect of the existing gelatin sponge on rabbit ear veins, liver, and spleen, as shown in the table below:

hemostatic material Number of cases   Average hemostasis time (s) Hemostasis percentage (%) Ear the liver spleen Existing gelatin sponge of embodiment 1-6 product 3030 49±978±8 56±595±10 61±787±12 100100

As can be seen from the above table, the product of the present invention has a strong hemostatic effect, and its hemostatic time is greatly shortened compared with that of the existing gelatin sponge.

Claims (4)

1. a preparation method of soluble cellulose hemostatic sponge, is characterized in that comprising the steps: (1) Take sodium carboxymethyl cellulose and chitosan at a weight ratio of 2 to 6:1, prepare sodium carboxymethyl cellulose with distilled water into a solution with a concentration of 0.5 to 3%, and dilute chitosan with Acetic acid is prepared into a solution with a concentration of 1 to 5%, and then the two solutions are mixed evenly; (2) Add 1-10g/L polyethylene glycol 400, 2-12g/L sucrose and 0.1-2g/L glycerin to the mixed solution obtained in step (1), stir evenly, and let it stand for defoaming; (3) Pour the mixed solution obtained in step (2) into a film forming device, and freeze-dry in a vacuum to obtain a soluble cellulose hemostatic sponge. 2. The method according to claim 1, characterized in that the degree of substitution of sodium carboxymethylcellulose in step (1) is 0.7 to 1.2. 3. The method according to claim 1, characterized in that the degree of deacetylation of the chitosan in the step (1) is 50-95%. 4. The method according to claim 1, characterized in that the film-forming device described in step (3) is a film-forming device made of polystyrene material.