CN113663120B

CN113663120B - Hemostatic sponge cushion core and preparation method thereof

Info

Publication number: CN113663120B
Application number: CN202111144981.3A
Authority: CN
Inventors: 王纯斌; 王纯保; 肖亚兰
Original assignee: Guilin Fukangsen Medical Devices Co ltd
Current assignee: Guilin Fukangsen Medical Devices Co ltd
Priority date: 2021-09-28
Filing date: 2021-09-28
Publication date: 2022-10-28
Anticipated expiration: 2041-09-28
Also published as: CN113663120A

Abstract

The invention discloses a hemostatic sponge pad core and a preparation method thereof, wherein hemostatic sponge is smeared on a water absorption pad in a foaming stage and does not disappear after being dried, and further the hemostatic sponge pad core can be prepared into functional dressing with adhesive plaster, and is suitable for hemostasis and wound protection after body surface dialysis and operation of a human body.

Description

Hemostatic sponge cushion core and preparation method thereof

[ technical field ] A

The invention relates to the technical field of polymer medical materials, in particular to a hemostatic sponge cushion core and a preparation method thereof.

[ background ] A method for producing a semiconductor device

The hemostatic sponge is used for rapidly stopping bleeding, inhibiting bacteria and resisting infection, absorbing a large amount of blood and tissue seepage and accelerating wound healing. The normal hemostasis of the body mainly depends on the structure and function of the intact blood vessel wall, the effective quality and quantity of blood platelets and the activity of normal blood coagulation factors, wherein the effects of the blood platelets with negative charges and the blood coagulation factors are the main. The hemostatic sponge is a hemostatic material which is fine, porous and positively charged, and can immediately adhere and aggregate platelets when contacting human blood, so that the blood forms thrombus and blocks wounds, various factors related to blood coagulation are released, and the blood forms stable fibrin polymers under the combined action of endogenous and exogenous blood coagulation paths, so that blood clots are formed, and the purpose of wound hemostasis is achieved.

The hemostatic sponge is mainly used for wound surface hemostasis and operation wound healing in surgery, obstetrics and gynecology, orthopedics, stomatology and other operations; first-aid hemostasis treatment for superficial burn, scald, accidental wound, battlefield rescue, industrial and mining accident wound and the like. According to different parts, selecting hemostatic sponge with corresponding shape or cutting into required shape under aseptic condition, and applying after gently kneading. In wound emergency treatment and surgical operation, wound bleeding and bleeding are frequently encountered problems, the life is threatened by the massive loss of blood, and meanwhile, the bleeding or bleeding is a natural microbial culture medium, so that the infection probability is increased, and the success rate of the operation is reduced. Good hemostasis techniques are the key to successful surgery, so surgical hemostasis is one of the cores of surgical techniques. Temporarily controlling bleeding, covering and binding the wound as soon as possible, isolating the wound from the outside to reduce the infection chance and creating good wound surface conditions for debridement. The ideal hemostatic material should have the characteristics of rapid hemostasis, no irritation, no acute toxicity, no chronic toxicity, no teratogenicity, carcinogenicity and the like, and has controllable degradation speed meeting different requirements and excellent biocompatibility.

The hemostatic sponge is mainly classified into absorbable gelatin hemostatic sponge, chitosan hemostatic sponge, collagen hemostatic sponge, etc. according to different materials. With the research and development of biomedical polymer materials such as natural polymer materials like cellulose and chitin and synthetic polymer materials like polyvinyl alcohol and collagen, the application and development of hemostatic materials have been greatly improved:

1. gelatin: the absorbable gelatin sponge is the most common hemostatic material in clinic at present, has long use history, more definite use effect and low price, can be applied, wrapped and embolized by using a mode, and is suitable for trauma and bleeding, bleeding and deep trauma of surgery. The gelatin hemostatic product is a safe and reliable product on the whole, has no antigenicity, does not produce anaphylactic reaction, and has no inflammatory reaction to surrounding tissues when being packed with a wound. However, the gelatin hemostatic product has the disadvantages that the mechanical property is poor, the gelatin hemostatic product is easy to damage after encountering blood, and the traction capacity of platelets for blood cells is very weak, so that the gelatin hemostatic product is difficult to stop for large wound bleeding. It has poor adhesion, is easy to fall off, and is also not easy to fix on the wound surface of the internal organ. In addition, when the gelatin sponge promotes blood coagulation, the activation of blood coagulation factors in body blood is needed to be realized, so the hemostatic effect on patients with blood coagulation mechanism disorder is not ideal, and a high-performance gelatin hemostatic product is obtained by compounding the gelatin hemostatic product with other types of hemostatic materials.

2. And (3) chitosan: the cationic cellulose is the only polymer material which is known to exist in nature and has wide biodegradation distribution, exists in a large number in shells of insects and crustaceans and cell walls of fungi, is the second most renewable resource next to cellulose on the earth, is insoluble in water and organic solvents, and is difficult to be utilized by human bodies. The product obtained by deacetylation is called chitosan (chemical name is (1-4) -amino-2-deoxyamino-D-glucose), and can be absorbed and utilized by human body. The polysaccharide can be biosynthesized and biodegraded, has good biocompatibility with animal organ tissues and cells, is non-toxic, and the low-molecular oligosaccharide generated in the degradation process is not accumulated in vivo and has almost no immunogenicity. The chitosan hemostatic sponge is suitable for hemostasis and intractable nasal hemorrhage of various body surface wounds (such as bruise, vascular puncture, tube placement, oral cavity, ear-nose-throat operation wounds and the like) and body surface granulation wounds. The chitosan and the derivatives thereof have good biocompatibility and can be degraded in a human body, the degradation products are safe and non-toxic, the chitosan and the derivatives thereof have positive charges and have the antibacterial and anti-inflammatory effects, the sponge made of the chitosan can still keep the sponge after meeting water, and the gelatin sponge has no elasticity, so that the compression hemostasis effect of the gelatin sponge is poor; and chitosan has good effects of promoting wound healing, inhibiting the growth of fibroblasts and reducing the formation of scars. However, pure chitosan hemostatic materials are not stable in hemostatic effect against severe bleeding, and other blood coagulation factors and hemostatic materials need to be combined to improve the hemostatic effect.

3. Collagen, also known as collagen: is a group of scleroproteins which are most abundant and widely distributed in vertebrate bodies, is an important material for composing the body structures of the vertebrates, and is the most abundant protein in mammals. Collagen is composed of multiple glycoprotein molecules, is the main protein component of connective tissue, and accounts for 20-30% of total protein of body. Approximately half of the body's collagen is present in the skin, and it accounts for 70% of the dry weight of the dermis and tendons, corresponding to 6% of body weight. The collagen material has many excellent properties, such as biodegradability, low antigenicity, cell adaptability, biocompatibility, cell proliferation promoting effect, platelet aggregation accelerating effect, etc. The rapid and efficient hemostasis on the wound surface is completed. After the hemostasis process is finished, the collagen material can be automatically degraded in the body, additional dismantling is not needed, and the use is convenient.

Although both collagen and chitosan have good biocompatibility, the pure use of collagen or chitosan hemostatic material has poor mechanical properties and unsatisfactory hemostatic effect, and cannot meet the requirements of clinical operations,

[ summary of the invention ]

Aiming at the defects that the existing hemostatic sponge is generally prepared from collagen or chitosan hemostatic materials, so that the mechanical property is poor, the hemostatic effect is not ideal, the requirements of clinical operations cannot be met and the like, the invention provides the hemostatic sponge pad core and the preparation method thereof.

The purpose of the invention is realized by the following technical scheme:

the preparation method of the hemostatic sponge cushion core comprises the following steps:

1) Preparing raw materials according to the proportion: gelatin (9.5-10.5) g, distilled water (88-92) mL, 0.25% (v/v) glutaraldehyde solution (2.8-3.2) mL, 0.5% (v/v) formaldehyde (2.4-2.6) mL;

2) Pouring gelatin into distilled water, soaking for 10 minutes, heating in water bath, stirring for dissolving, adding 0.5% (v/v) formaldehyde, and stirring at high speed to obtain a liquid foam mixed solution;

3) Injecting the mixed solution obtained in the previous step into moulds with different specifications, paving water-absorbing pad cores at the bottom of the moulds, pre-freezing at-40 to-80 ℃, and then performing freeze drying to obtain the water-absorbing pad cores with sponges;

4) And (3) crosslinking the water-absorbing pad core with the sponge obtained in the previous step by adopting 0.25% (v/v) glutaraldehyde solution, washing the water-absorbing pad core with distilled water for a plurality of times after crosslinking, then carrying out freeze drying and forming again, sealing, and carrying out cobalt-60 sterilization to obtain the hemostatic sponge pad core.

In the invention:

the raw materials prepared according to the proportion in the step 1) are 10g of gelatin, 90g of distilled water, 3ml of 0.25% glutaraldehyde solution and 2.5ml of 0.5% formaldehyde.

Heating in water bath at 60-70 deg.C in step 2).

The high-speed stirring in the step 2) is stirring at 200-400rpm for 20-30min.

Washing for a plurality of times in the step 4), namely washing for 2-4 times.

Further, after the step 4) of freeze drying and molding again, adhesive plaster is pasted at the bottom of the hemostatic sponge cushion core.

The invention also relates to the hemostatic sponge cushion core prepared by the preparation method of the hemostatic sponge cushion core, which is suitable for hemostasis and wound protection after body surface dialysis and operation.

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

1. the functional layer raw materials of the existing hemostatic sponge cushion core are gelatin and high-protein products, and the hemostatic sponge is not used to prepare functional dressing capable of being provided with adhesive plaster at present.

2. The preparation method of the hemostatic sponge cushion core provides technical support for producing functional dressing, and the dried material can be cut and coiled according to different thickness requirements, so that the hemostatic sponge cushion core is convenient for mechanical production.

[ detailed description ] embodiments

The following examples are provided to further illustrate the embodiments of the present invention.

Example 1:

1) Preparing raw materials according to the proportion: 10g of gelatin, 90g of distilled water, 3ml of 0.25% glutaraldehyde solution and 2.5ml of 0.5% formaldehyde;

2) Pouring gelatin into distilled water, soaking for 10 min, heating in 65 deg.C water bath, stirring for dissolving, adding 0.5% (v/v) formaldehyde, and stirring at high speed (400rpm, 20min) to obtain foam liquid mixed solution;

4) And (2) crosslinking the water absorption pad core with the sponge obtained in the previous step by adopting 0.25% (v/v) glutaraldehyde solution, washing the crosslinked pad core for several times by using distilled water after crosslinking is finished, then carrying out freeze drying and forming again, pasting adhesive tape on the bottom of the hemostatic sponge pad core, sealing, and then sterilizing by adopting cobalt-60 to obtain the hemostatic sponge pad core.

Example 2:

1) Preparing raw materials according to the proportion: 9.5g of gelatin, 92mL of distilled water, 2.8mL of 0.25% (v/v) glutaraldehyde solution, and 2.6mL of 0.5% (v/v) formaldehyde;

2) Pouring gelatin into distilled water, soaking for 10 min, heating in water bath at 60 deg.C, stirring for dissolving, adding 0.5% (v/v) formaldehyde, and stirring at high speed (300rpm, 25min) to obtain foam liquid mixed solution;

4) And (3) crosslinking the water-absorbing pad core with the sponge obtained in the previous step by adopting 0.25% (v/v) glutaraldehyde solution, washing the crosslinked pad core for several times by using distilled water after crosslinking is finished, then carrying out freeze drying and forming again, sealing, and carrying out cobalt-60 sterilization to obtain the hemostatic sponge pad core.

Example 3:

1) Preparing raw materials according to the proportion: 10.5g of gelatin, 88mL of distilled water, 3.2mL of 0.25% (v/v) glutaraldehyde solution, and 2.4mL of 0.5% (v/v) formaldehyde;

2) Pouring gelatin into distilled water, soaking for 10 minutes, heating in 70 ℃ water bath, stirring for dissolving, adding 0.5% (v/v) formaldehyde, and uniformly stirring at high speed (200rpm, 30min) to obtain a foam liquid mixed solution;

3) Injecting the mixed solution obtained in the previous step into moulds with different specifications, paving water-absorbing pad cores at the bottom of the mould, pre-freezing at-40 to-80 ℃, and then performing freeze drying to obtain the water-absorbing pad cores with sponges;

Comparative example:

according to CN202110319395.1, a degradable hemostatic sponge, a preparation method and application thereof, and a degradable drug-loaded hemostatic sponge, the provided preparation method of the degradable hemostatic sponge comprises the following steps:

1) Weighing 100.0g of potato starch in a reaction kettle, adding 4900ml of water into the reaction kettle, setting the temperature of a jacket reaction kettle to be 80 ℃, and stirring at a constant temperature of 200rpm for 1h; reducing the temperature of a jacket reaction kettle to 50 ℃, adjusting the pH of reaction liquid to 9 by using a NaOH solution with the concentration of 1mol/L, dropwise adding 10ml of epoxy chloropropane aqueous solution into the reaction liquid by using a constant-pressure titration funnel, reacting at a high temperature for 4 hours, pouring out the reaction liquid after the reaction is finished, cooling, separating out a product by using 12.5L of absolute ethyl alcohol, washing the product by using 2L of absolute ethyl alcohol for 2-3 times, and drying at 50 ℃ for 24 hours to obtain the crosslinked modified potato starch;

2) Weighing 1.0g of carboxymethyl cellulose in 39ml of water, stirring at 400rpm in a water bath at 40 ℃ for 4 hours to completely dissolve the carboxymethyl cellulose into uniform transparent gel, adjusting the pH value of the carboxymethyl cellulose solution to 3 by using 1mol/L HCl, and cooling to room temperature for later use;

3) Weighing 2.0g of cross-linked modified potato starch in 58ml of water, stirring and dissolving at normal temperature for 20min to ensure that the cross-linked starch absorbs water and is saturated, pouring the cross-linked modified potato starch into a carboxymethyl cellulose solution, stirring at 400rpm for 30min to uniformly mix, adjusting the pH of the solution to 6 by using 1mol/L HCl after uniform mixing, and standing for more than 12h to remove bubbles in the solution;

4) Pouring the mixed solution into a precooling mold, standing for 30min, covering a mold cover, placing the mold cover in a freezing refrigerator at the temperature of minus 40 ℃ for prefreezing for 4h, removing the mold cover after prefreezing is finished, and placing the mold carrying the sample in a freezing drying box for freezing and drying for 72h at the temperature of minus 60 ℃ and minus 0.1MPa to obtain the degradable starch hemostatic sponge.

Experimental example 1:

the hemostatic sponges obtained in the examples and the hemostatic sponges obtained in the comparative examples were placed in water, and the dissolution was observed:

	whether the hemostatic sponge can be completely dissolved in water of 36.2 ℃ within 6 hours or not by 1 g
		Example 1	Is that
Example 2	Is that
		Example 3	Is that
Comparative example	Whether or not

As can be seen from the above table, the hemostatic sponge of the pad core of the hemostatic sponge obtained in the example can be completely dissolved in water at 36.2 ℃ for 6 hours in 1 g of the hemostatic sponge of the pad core of the hemostatic sponge, while the hemostatic sponge of the comparative example cannot be completely dissolved in 6 hours.

Experimental example 2:

based on example 1, the effect of different amounts of 0.25% (v/v) glutaraldehyde solution added on the dissolution of the hemostatic sponge in water of the resulting hemostatic sponge pad core was investigated:

from the above table, the adding amount of 0.25% (v/v) glutaraldehyde solution affects the dissolution of the hemostatic sponge of the obtained hemostatic sponge pad core in water, the adding amount of 0.25% (v/v) glutaraldehyde solution is in the range of (2.8-3.2) mL, 1 gram of hemostatic sponge of the obtained hemostatic sponge pad core can be completely dissolved within 6 hours in water at 36.2 ℃, and the other added amounts of hemostatic sponge of the obtained hemostatic sponge pad core cannot be completely dissolved, and the analysis reason is that too much 0.25% (v/v) glutaraldehyde solution is added, which causes too tight connection of different tissue components in the hemostatic sponge of the hemostatic sponge pad core, thereby affecting the solubility of the hemostatic sponge pad core in water; too little addition of 0.25% (v/v) glutaraldehyde solution results in loose connection of different tissue components in the hemostatic sponge of the hemostatic sponge pad core, which affects the hemostatic effect of the hemostatic sponge pad core, so that the addition of 0.25% (v/v) glutaraldehyde solution is suitable in the range of (2.8-3.2) mL.

The above description is intended to describe in detail the preferred embodiments of the present invention, but the embodiments are not intended to limit the scope of the claims of the present invention, and all equivalent changes and modifications made within the technical spirit of the present invention should fall within the scope of the claims of the present invention.

Claims

1. Hemostatic sponge pad core, its characterized in that: the preparation method comprises the following steps:

1) Preparing raw materials according to the proportion: gelatin (9.5-10.5) g, distilled water (88-92) mL, 0.25% v/v glutaraldehyde solution (2.8-3.2) mL, 0.5% v/v formaldehyde (2.4-2.6) mL;

2) Pouring gelatin into distilled water, soaking for 10 min, heating in water bath at 60-70 deg.C, stirring for dissolving, adding 0.5% v/v formaldehyde, stirring at high speed, and stirring at 200-400rpm for 20-30min;

4) And (2) crosslinking the water-absorbing pad core with the sponge obtained in the previous step by adopting 0.25% v/v glutaraldehyde solution, washing the water-absorbing pad core with distilled water for 2-4 times after crosslinking, then carrying out freeze drying and forming again, pasting an adhesive tape on the bottom of the hemostatic sponge pad core, sealing, and then carrying out cobalt-60 sterilization to obtain the hemostatic sponge pad core, wherein in water at 36.2 ℃,1 g of hemostatic sponge of the hemostatic sponge pad core is completely dissolved within 6 hours.

2. The hemostatic sponge cushion core according to claim 1, wherein: the raw materials prepared according to the proportion in step 1) are gelatin 10g, distilled water 90g, 0.25% v/v glutaraldehyde solution 3ml, 0.5% formaldehyde 2.5 ml.