A high expansion instantaneous absorption hemostatic sponge and preparation method thereof

Abstract

The invention discloses a high expansion instantaneous absorption hemostatic sponge and a preparation method thereof, comprising adding polyvinyl alcohol to water, stirring and heating to form a stable solution; adding polyvinyl alcohol acetal to glacial acetic acid, stirring to form a polyvinyl alcohol acetal stable solution, adding 1 to 5 parts of polyvinyl alcohol acetal stable solution, adding 5 to 20 parts of starch, 2 to 10 parts of glycerol, 2 to 15 parts of dimethylhydroxy silicone oil and 1 to 5 parts of polyethylene glycol to obtain a mixed solution; adding 5 to 20 parts of surfactant, 50 to 150 parts of catalyst and 75 to 150 parts of cross-linking agent, stirring and foaming at high speed; pouring into a mold, placing the mold in an oven for cross-linking and curing to obtain a polyvinyl alcohol formal sponge; cutting and cleaning the polyvinyl alcohol formal sponge to neutrality, drying and sterilizing by irradiation to obtain a high expansion instantaneous absorption hemostatic sponge. The hemostatic sponge prepared by the invention has high biological safety, strong liquid absorption capacity, excellent expansion performance, and is soft and easy to deform in a dry state.

Description

Technical Field

[0001] The invention relates to the field of medical technology, and in particular to a high-expansion instantaneous absorption hemostatic sponge and a preparation method thereof. Background Art

[0002] Hemostasis is an important part of various surgeries and trauma emergency treatment. In wound emergency treatment and surgical operations, wound bleeding and oozing are often encountered problems. Large-scale blood loss can endanger life and increase the chance of infection, thereby affecting the success rate of the operation.

[0003] Compared with traditional fiber-based hemostatic products, sponge-based hemostatic products have obvious advantages and application prospects. Polymers used as sponge materials of this type are often polyurethane (PU), polyvinyl formal (PVF), etc., among which PVF is the most widely used. For example, the prior art (CN107903428A) discloses a method for preparing a medical polyvinyl alcohol sponge with low cost and simple process, which comprises the following steps: A: completely dissolving polyvinyl alcohol in water at a temperature of 80 to 100°C to obtain a polyvinyl alcohol aqueous solution; B: adding a crosslinking agent and a catalyst to the polyvinyl alcohol aqueous solution and stirring evenly; C: pouring the solution stirred evenly in step B into a mold, placing it at 50 to 75°C for 10 to 24 hours for shaping; D: after demoulding and cleaning, a medical polyvinyl alcohol sponge is obtained. However, PVF sponge is very hard in dry state and cannot meet the softness requirements of medical sponge. When used as a hemostatic material, it can only ensure its softness by absorbing a certain amount of water in advance. This means that PVF sponge must sacrifice a certain amount of water absorption in advance when used as a hemostatic material. Summary of the invention

[0004] The purpose of the present invention is to provide a method for preparing a high-expansion instantaneous hemostatic sponge. The high-expansion instantaneous hemostatic sponge prepared by the method is a sponge-type hemostatic product with a porous structure, high water absorption capacity and rapid expansion capacity. This sponge can quickly absorb blood to concentrate components such as platelets, red blood cells and coagulation proteins to improve its coagulation ability and accelerate hemostasis. While absorbing wound bleeding, its volume will expand to more than 10 times to generate sufficient compressive force to assist in hemostasis. It has the advantages of high biological safety, strong liquid absorption capacity, excellent expansion performance, and soft and easy to deform in a dry state. Thereby solving the problem that the PVF sponge proposed in the background technology has a large hardness in a dry state and cannot meet the requirements of medical sponges for softness. When used as a hemostatic material, it can only absorb a certain amount of water in advance to ensure its softness, which makes the PVF sponge as a hemostatic material must sacrifice a certain amount of water absorption in advance.

[0005] To achieve the above object, the present invention adopts the following technical solution:

[0006] A method for preparing a high-expansion instantaneous hemostatic sponge comprises the following steps:

[0007] Step a, adding polyvinyl alcohol into water, stirring, and heating to form a stable solution;

[0008] Step b, adding polyvinyl acetal to glacial acetic acid and stirring to form a stable solution of polyvinyl acetal;

[0009] Step c, adding 1 to 5 parts of the polyvinyl acetal stabilizing solution to 100 parts of the stabilizing solution obtained in step a, stirring until the mixture is uniform, to obtain a mixed solution;

[0010] Step d, adding 5 to 20 parts of starch, 2 to 10 parts of glycerol, 2 to 15 parts of dimethylhydroxy silicone oil and 1 to 5 parts of polyethylene glycol to the mixed solution obtained in step c, stirring until the mixture is uniform, to obtain a mixed solution;

[0011] Step e, adding 5 to 20 parts of a surfactant, 50 to 150 parts of a catalyst and 75 to 150 parts of a cross-linking agent to the mixed solution obtained in step d, and stirring at high speed to foam;

[0012] Step f, pouring the mixture foam obtained in step e into a mold, placing the mold in an oven for cross-linking and curing to obtain a polyvinyl formal sponge;

[0013] Step g, cutting the polyvinyl formal sponge, washing it to neutrality, drying it and sterilizing it by irradiation to obtain a high expansion instantaneous absorption hemostatic sponge.

[0014] Preferably, in step a, the average degree of polymerization of the polyvinyl alcohol is between 300 and 2600, and the degree of alcoholysis is between 60% and 99.9%.

[0015] Preferably, in step a, by weight, polyvinyl alcohol is 100 parts, water is 400-900 parts, and the heating temperature is raised to 90-99°C.

[0016] Preferably, in step b, the polyvinyl acetal is one or more combinations of polyvinyl formal resin, polyvinyl acetal resin, polyvinyl glutaraldehyde resin and polyvinyl glyoxal resin with an acetalization degree of 30 to 75%.

[0017] Preferably, in step b, the mass fraction of the polyvinyl acetal stabilizing solution is 1 to 20%.

[0018] Preferably, in step d, the molecular weight of the dimethylhydroxysilicone oil is 300-1000 Da, and the degree of polymerization of the polyethylene glycol is 300-1000.

[0019] Preferably, in step e, the surfactant is one or more of fatty alcohol polyoxyethylene ether AEO20, sodium dodecyl sulfonate, sodium dodecylbenzene sulfonate, sodium dodecyl sulfate, and OP-10; the catalyst is hydrochloric acid or sulfuric acid; and the cross-linking agent is formaldehyde.

[0020] Preferably, in step e, the foaming stirring speed is 1500-2800 rpm, and the stirring time is 5-20 min.

[0021] Preferably, in step f, the oven temperature is 65±5° C. and the curing time is greater than 5 hours.

[0022] The present invention also provides a high-expansion instantaneous absorption hemostatic sponge, which is prepared by the preparation method of the high-expansion instantaneous absorption hemostatic sponge.

[0023] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages: the preparation method of the present invention adds a small amount of polyvinyl alcohol acetal to the polyvinyl alcohol pre-foaming solution, uses the polyvinyl alcohol acetal as a chain initiator, and polyvinyl alcohol is sequentially condensed at the end of the acetal resin to form a polyvinyl alcohol formal resin with an intramolecular cross-linking structure as the main structure, and controls its degree of polymerization to achieve control of material strength, water solubility and other properties. The polyvinyl alcohol formal hemostatic sponge obtained by the preparation method of the present invention has a uniform shape, is porous, and the holes are interconnected. It has the advantages of high water absorption, fast water absorption rate, and large wet expansion rate; in particular, it is soft and easy to deform in a dry state, and can be used directly in a dry state, which not only avoids the many disadvantages of the previous hemostatic sponge that needs to absorb water in advance, but also makes the sponge's water absorption capacity fully used in trauma hemostasis, and has broad application prospects in medical fields such as surgery and trauma hemostasis. DETAILED DESCRIPTION

[0024] The technical solution of the present invention is further described below in conjunction with embodiments, but this should not be understood as the scope of the above subject matter of the present invention being limited to the following embodiments, and all technologies realized based on the above contents of the present invention belong to the scope of the present invention.

[0025] The experimental methods used in the following examples are all conventional methods unless otherwise specified, and the reagents, methods and equipment used are all conventional reagents, methods and equipment in the technical field unless otherwise specified.

[0026] Example 1

[0027] In the present embodiment 1, a high expansion instant absorption hemostatic sponge is prepared with polyvinyl formal as the main component, a small amount of polyvinyl acetal is added as a chain initiator during polymerization, and polyvinyl alcohol is sequentially condensed at the end of the acetal resin to prepare a polyvinyl formal sponge with an intramolecular cross-linked structure as the main component. The specific preparation method includes the following steps:

[0028] Add 100 parts of polyvinyl alcohol 1788 to 400 parts of water, heat to 90-99°C, stir and dissolve to form a stable solution;

[0029] Add 2 parts of 5% polyvinyl alcohol formal acetic acid solution to 100 parts of polyvinyl alcohol aqueous solution, stir until mixed evenly, add 9 parts of potato starch, 5 parts of glycerol, 10 parts of dimethylhydroxy silicone oil 300-400Da and 2 parts of polyethylene glycol PEG300, stir evenly, add 10 parts of sodium dodecylbenzene sulfonate, 100 parts of concentrated hydrochloric acid and 120 parts of formaldehyde, stir and foam at 2300rpm for 15min, pour into a mold, and place in a 65℃ oven for cross-linking and curing for more than 5 hours;

[0030] The polyvinyl formal sponge is cut, cleaned to neutrality, dried and sterilized by irradiation to obtain a high expansion instant absorption hemostatic sponge.

[0031] Example 2

[0032] In this Example 2, a high expansion instant absorption hemostatic sponge is prepared with polyvinyl formal as the main component, a small amount of polyvinyl acetal is added as a chain initiator during polymerization, and polyvinyl alcohol is sequentially condensed at the end of the acetal resin to prepare a polyvinyl formal sponge with an intramolecular cross-linked structure as the main component. The specific preparation method includes the following steps:

[0033] Add 100 parts of polyvinyl alcohol 1799 to 600 parts of water, heat to 90-99°C, stir and dissolve to form a stable solution;

[0034] Add 1 part of 10% polyvinyl alcohol acetal acetic acid solution by mass to 100 parts of polyvinyl alcohol aqueous solution, stir until mixed evenly, add 15 parts of potato starch, 10 parts of glycerol, 5 parts of dimethylhydroxy silicone oil 800-1000Da and 5 parts of polyethylene glycol PEG400, stir evenly, add 20 parts of AEO20, 50 parts of sulfuric acid (1:1) and 150 parts of formaldehyde, stir and foam at 1500rpm for 20 minutes, pour into a mold, and place in a 65℃ oven for cross-linking and curing for more than 5 hours;

[0035] The polyvinyl formal sponge is cut, cleaned to neutrality, dried and sterilized by irradiation to obtain a high expansion instant absorption hemostatic sponge.

[0036] Example 3

[0037] In this Example 3, a high expansion instant absorption hemostatic sponge is prepared with polyvinyl formal as the main component, a small amount of polyvinyl acetal is added as a chain initiator during polymerization, and polyvinyl alcohol is sequentially condensed at the end of the acetal resin to prepare a polyvinyl formal sponge with an intramolecular cross-linked structure as the main component. The specific preparation method includes the following steps:

[0038] Add 100 parts of polyvinyl alcohol 2488 to 900 parts of water, heat to 90-99°C, stir and dissolve to form a stable solution;

[0039] Add 2 parts of 10% polyvinyl alcohol glutaraldehyde acetic acid solution to 100 parts of polyvinyl alcohol aqueous solution, stir until mixed evenly, add 5 parts of corn starch, 2 parts of glycerol, 15 parts of dimethyl hydroxy silicone oil 450-550Da and 2 parts of polyethylene glycol PEG1000, stir evenly, add 5 parts of sodium dodecyl sulfate, 50 parts of concentrated sulfuric acid (1:1) and 75 parts of formaldehyde, stir and foam at 2000rpm for 18 minutes, then pour into a mold, place in a 65℃ oven for cross-linking and curing for more than 5 hours;

[0040] The polyvinyl formal sponge is cut, cleaned to neutrality, dried and sterilized by irradiation to obtain a high expansion instant absorption hemostatic sponge.

[0041] Example 4

[0042] In this Example 4, a high expansion instant absorption hemostatic sponge is prepared with polyvinyl formal as the main component, a small amount of polyvinyl acetal is added as a chain initiator during polymerization, and polyvinyl alcohol is sequentially condensed at the end of the acetal resin to prepare a polyvinyl formal sponge with an intramolecular cross-linked structure as the main component. The specific preparation method includes the following steps:

[0043] Add 100 parts of polyvinyl alcohol 117 to 400 parts of water, heat to 90-99°C, stir and dissolve to form a stable solution;

[0044] Add 5 parts of 15% polyvinyl alcohol glyoxal acetic acid solution to 100 parts of polyvinyl alcohol aqueous solution, stir until mixed evenly, add 20 parts of corn starch, 4 parts of glycerol, 2 parts of dimethylhydroxy silicone oil 800-1000Da and 3 parts of polyethylene glycol PEG400, stir evenly, add 8 parts of OP-10, 150 parts of concentrated hydrochloric acid and 100 parts of formaldehyde, stir and foam at 2800rpm for 5 minutes, then pour into the mold, place in a 65℃ oven for cross-linking and curing for more than 5 hours;

[0045] The polyvinyl formal sponge is cut, cleaned to neutrality, dried and sterilized by irradiation to obtain a high expansion instant absorption hemostatic sponge.

[0046] Example 5

[0047] In this Example 5, a high expansion instant absorption hemostatic sponge is prepared with polyvinyl formal as the main component, a small amount of polyvinyl acetal is added as a chain initiator during polymerization, and polyvinyl alcohol is sequentially condensed at the end of the acetal resin to prepare a polyvinyl formal sponge with an intramolecular cross-linked structure as the main component. The specific preparation method includes the following steps:

[0048] Add 100 parts of polyvinyl alcohol 124 into 900 parts of water, heat to 90-99°C, stir and dissolve to form a stable solution.

[0049] Add 5 parts of 5% polyvinyl alcohol formal acetic acid solution to 100 parts of polyvinyl alcohol aqueous solution, stir until mixed evenly, add 10 parts of potato starch, 8 parts of glycerol, 5 parts of dimethylhydroxy silicone oil 450-550Da and 2 parts of polyethylene glycol PEG400, stir evenly, add 16 parts of sodium dodecyl sulfate, 100 parts of concentrated hydrochloric acid and 120 parts of formaldehyde, stir and foam at 2800rpm for 10 minutes, then pour into a mold, place in a 65℃ oven for cross-linking and curing for more than 5 hours;

[0050] The polyvinyl formal sponge is cut, cleaned to neutrality, dried and sterilized by irradiation to obtain a high expansion instant absorption hemostatic sponge.

[0051] Example 6

[0052] In Example 6, a high expansion instant absorption hemostatic sponge is prepared with polyvinyl formal as the main component, a small amount of polyvinyl acetal is added as a chain initiator during polymerization, and polyvinyl alcohol is sequentially condensed at the end of the acetal resin to prepare a polyvinyl formal sponge with an intramolecular cross-linked structure as the main component. The specific preparation method includes the following steps:

[0053] Add 100 parts of polyvinyl alcohol 2099 to 900 parts of water, heat to 90-99°C and stir to dissolve to form a stable solution;

[0054] Add 1 part of 20% polyvinyl alcohol formal acetic acid solution by mass to 100 parts of polyvinyl alcohol aqueous solution, stir until mixed evenly, add 12 parts of corn starch, 10 parts of glycerol, 10 parts of dimethylhydroxy silicone oil 450-550Da and 2 parts of polyethylene glycol PEG400, stir evenly, add 12 parts of AEO20, 100 parts of concentrated hydrochloric acid and 150 parts of formaldehyde, stir and foam at 2300rpm for 20min, pour into the mold, and place in a 65℃ oven for cross-linking and curing for more than 5 hours;

[0055] The polyvinyl formal sponge is cut, cleaned to neutrality, dried and sterilized by irradiation to obtain a high expansion instant absorption hemostatic sponge.

[0056] Performance Test:

[0057] (1) Water absorption ratio: The polyvinyl alcohol formal sponge absorbs water freely without external force, and weighs it after it becomes constant. Water absorption ratio = (weight after water absorption - weight before water absorption) / weight before water absorption.

[0058] (2) Expansion ratio: The polyvinyl alcohol formal sponge is allowed to absorb water freely without external force, and the dimensional change in the thickness direction of the sponge is measured after the sponge is saturated with water. Expansion ratio = (thickness after water absorption - thickness before water absorption) / thickness before water absorption.

[0059] (3) Hardness: The hardness of the sponge in a dry state was measured using a Shore hardness tester.

[0060] (4) Compression deformation test: The polyvinyl formal sponge was cut into samples of 10*10*10 mm, and the compression force of the sponge at 50% deformation was measured using a texture analyzer.

[0061] The sponge properties of Examples 1 to 6 were measured respectively according to the above method, and the results are shown in the following table:

[0062] Group Water absorption rate (times) Expansion multiple (times) Hardness Compression force(N) Example 1 43.65 13.28 32.15 24.7 Example 2 9.57 3.62 54.62 58.2 Example 3 26.01 9.59 42.20 36.0 Example 4 32.48 11.45 38.57 29.3 Example 5 21.51 6.37 47.43 47.5 Example 6 14.58 4.04 52.38 52.1

[0063] The method of the invention is simple and easy to realize industrial production continuously and efficiently. The prepared high-expansion instantaneous absorption hemostatic sponge has uniform shape, is porous and the holes are interconnected. It has the advantages of high water absorption, fast water absorption rate, large wet expansion rate, soft and easy deformation in dry state, etc. It has broad application prospects in medical fields such as surgery and trauma hemostasis.

[0064] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Any technician familiar with the profession, without departing from the scope of the technical solution of the present invention, according to the technical essence of the present invention, any simple modification, equivalent replacement and improvement made to the above embodiment still falls within the protection scope of the technical solution of the present invention.

Claims

1. A method for preparing a high expansion instantaneous absorption hemostatic sponge, characterized in that: The following steps are involved: Step a, adding polyvinyl alcohol into water, stirring, and heating to form a stable solution; Step b, adding polyvinyl acetal to glacial acetic acid and stirring to form a stable polyvinyl acetal solution; the polyvinyl acetal is one or more combinations of polyvinyl formal resin, polyvinyl acetal resin, polyvinyl glutaraldehyde resin, and polyvinyl glyoxal resin with an acetalization degree of 30 to 75%; the mass fraction of the stable polyvinyl acetal solution is 1 to 20%; Step c, adding 1 to 5 parts of the polyvinyl acetal stabilizing solution to 100 parts of the stabilizing solution obtained in step a, stirring until the mixture is uniform, to obtain a mixed solution; Step d, adding 5 to 20 parts of starch, 2 to 10 parts of glycerol, 2 to 15 parts of dimethylhydroxy silicone oil and 1 to 5 parts of polyethylene glycol to the mixed solution obtained in step c, stirring until the mixture is uniform, to obtain a mixed solution; Step e, adding 5 to 20 parts of a surfactant, 50 to 150 parts of a catalyst and 75 to 150 parts of a cross-linking agent to the mixed solution obtained in step d, and stirring at high speed to foam; Step f, pouring the mixture foam obtained in step e into a mold, placing the mold in an oven for cross-linking and curing to obtain a polyvinyl formal sponge; Step g, cutting the polyvinyl formal sponge, washing it to neutrality, drying it and sterilizing it by irradiation to obtain a high expansion instantaneous absorption hemostatic sponge.

2. The method for preparing a high expansion instantaneous absorption hemostatic sponge according to claim 1, characterized in that: In the step a, the average polymerization degree of the polyvinyl alcohol is between 300 and 2600, and the alcoholysis degree is between 60% and 99.9%.

3. The method for preparing a high expansion instantaneous absorption hemostatic sponge according to claim 1, characterized in that: In the step a, by weight, polyvinyl alcohol is 100 parts, water is 400-900 parts, and the heating temperature is raised to 90-99°C.

4. The method for preparing a high expansion instantaneous absorption hemostatic sponge according to claim 1, characterized in that: In the step d, the molecular weight of the dimethyl hydroxy silicone oil is 300-1000 Da, and the degree of polymerization of the polyethylene glycol is 300-1000.

5. The method for preparing a high expansion instantaneous absorption hemostatic sponge according to claim 1, characterized in that: In the step e, the surfactant is one or more of fatty alcohol polyoxyethylene ether AEO20, sodium dodecyl sulfonate, sodium dodecylbenzene sulfonate, sodium dodecyl sulfate, and OP-10; the catalyst is hydrochloric acid or sulfuric acid; and the cross-linking agent is formaldehyde.

6. The method for preparing a high expansion instantaneous absorption hemostatic sponge according to claim 1, characterized in that: In the step e, the foaming stirring speed is 1500-2800 rpm, and the stirring time is 5-20 min.

7. The method for preparing a high expansion instantaneous absorption hemostatic sponge according to claim 1, characterized in that: In the step f, the oven temperature is 65±5° C. and the curing time is greater than 5 hours.

8. A high expansion instantaneous hemostatic sponge, characterized in that The invention is prepared by the preparation method according to any one of claims 1 to 7.