CN111905141A - Solid composition for preparing medical adhesive and medical adhesive prepared from solid composition - Google Patents
Solid composition for preparing medical adhesive and medical adhesive prepared from solid composition Download PDFInfo
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- CN111905141A CN111905141A CN202010725067.7A CN202010725067A CN111905141A CN 111905141 A CN111905141 A CN 111905141A CN 202010725067 A CN202010725067 A CN 202010725067A CN 111905141 A CN111905141 A CN 111905141A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/043—Mixtures of macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0031—Hydrogels or hydrocolloids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
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Abstract
The invention belongs to the technical field of biomedical materials, and particularly relates to a solid composition for preparing a medical adhesive and the medical adhesive prepared by the solid composition. The invention selects plant polysaccharide to modify aldehyde group through oxidation reaction, and further cross-links with amino-containing high polymer material in the presence of water or buffer solution to prepare the medical adhesive. The used materials are widely applied to the fields of medical treatment, food and the like, have good biocompatibility, can be degraded and metabolized in vivo, and have low cost and wide sources; the formed hydrogel type medical adhesive with the three-dimensional network structure has good application potential in the aspects of tissue adhesion, filling, sealing, hemostasis and the like.
Description
Technical Field
The invention belongs to the technical field of biomedical materials, and particularly relates to a solid composition for preparing a medical adhesive and the medical adhesive prepared by the solid composition.
Background
In recent years, with the vigorous development of Chinese economy, the industrialization level is promoted year by year, and the number of accidental injury accidents is increased. In addition to the war and natural disasters, a large number of wounded persons are caused, and the wounds caused by various factors such as traffic accident injury, falling injury, mechanical injury, sharp injury, falling injury, sprain and the like are very common in daily work.
Trauma generally refers to injury to any tissue (e.g., skin, muscle) of the human body caused by external mechanical action, which can result in the rupture and damage of organ structures, cells, blood vessels, biological membranes, etc. All wounds, including those resulting from surgical procedures, require immediate closure and repair to prevent infection and promote healing.
Suturing is the most common technique for achieving wound closure and repair, typically with sutures or staples. Sutures have excellent tensile strength and low cracking rates, most commonly. However, common problems with suturing are inevitable penetration of surrounding tissue, nerve damage and possible post-operative adhesions, and ischemia and necrosis of local tissue due to capillary damage. Therefore, in the urgent clinical need, medical adhesives have emerged to replace traditional suturing techniques or as a means of supplementing suturing.
Medical adhesives, mainly including tissue adhesives, hemostats, and tissue sealants, have found widespread use in clinical procedures. Tissue adhesives may be broadly defined as any substance having in situ polymerization properties that can cause tissue to adhere to tissue or tissue and non-tissue surfaces, control bleeding (hemostatic agents), and act as a barrier to gas and liquid leakage (sealant). Ideal biomedical adhesives need to meet the requirements of biocompatibility, biodegradability, mechanical compliance with underlying tissues, acceptable swelling index, and storage stability. In particular, the following features should be provided: safe and nontoxic, and is easy to sterilize and prepare; has fluid properties, is easy to use at a wound site; the gel can be quickly cured in a physiological environment, and bleeding and operation time are reduced; has excellent tissue adhesion performance and can keep stable in a specific time; original mechanical properties are maintained in the healing process; the degradation time is proper, and degradation products are nontoxic.
Currently, the medical adhesives commonly used in the market are mainly classified into several categories, such as cyanoacrylate derivatives, polyethylene glycol, polyurethane, etc., and particularly, the above substances in the form of polymer hydrogel. The cyanoacrylate adhesive has the advantages of fast filming, high adhesion, etc. But the mechanical property is poor, and the skin-care patch is easy to break when being used for a long incision or a skin fold. In addition, its degradation products cause tissue toxic reactions and are usually applied only to the epidermis. Polyethylene glycols are
DuraSealTMAnd the like, generally multi-arm polymers containing functional groups capable of reacting with amino/thiol groups on tissue proteins, which are highly adhesive, biocompatible, and biodegradable. However, it is expensive and the gel has a high swelling degree and tends to locally press the tissue. Representative of the polyurethanes are
Also possesses good biosafety and in vivo degradation properties, but requires a long time for crosslinking (typically 25 minutes). It can be seen that the preparation of medical adhesives meeting clinical requirements remains a non-trivial challenge.
Adhesion capability is a central property of medical adhesives. Polymeric hydrogels achieve stable adhesion to tissue surfaces in two general ways: one is to form an interpenetrating network with the surrounding tissue, mechanically locking the material in place. For example, an adhesive containing acrylate can be rapidly polymerized in situ to form a three-dimensional network structure under the action of light and a photoinitiator. Another way is to introduce specific functional groups on the polymer skeleton, and these groups can be cross-linked with amino groups and sulfhydryl groups on the tissue surface by means of amidation, esterification, Michael addition, Schiff base, click chemistry, etc. The main researches are the three functional groups of N-hydroxysuccinimide, aldehyde group and dopamine. The stability of the N-hydroxysuccinimide fragment is poor, and ester bonds are easy to break under the alkaline environment, so that the efficacy is influenced. The catechol fragment of dopamine has good adhesiveness, but only in animal body research, no product is on the market, and the safety of the product has risk. In contrast, aldehyde groups are an ideal tissue adhesion group.
In addition, the medical adhesives of the existing polymer hydrogels are both two liquid components, and the two liquid components are directly mixed when needed, and the polymer hydrogel is formed after the completion of the gelation, but the polymer hydrogels are not easy to transport and store, the transportation cost is high, and the stability of chemical substances in a solution state is poor.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide a solid composition for preparing a medical adhesive and the medical adhesive prepared by the solid composition, wherein the solid composition comprises an aldehyde-based natural polysaccharide and an amino-containing polymer material, and when the solid composition is contacted with water, the aldehyde-based natural polysaccharide and the amino-containing polymer material in the solid composition can undergo Schiff base reaction to realize the preparation of the polymer hydrogel medical adhesive. The solid composition for preparing the medical adhesive has the characteristics of good stability, easy transportation and storage, low cost and the like, and the prepared medical adhesive has good adhesiveness and biocompatibility, can be degraded and absorbed in vivo, has the functions of tissue adhesion, filling, sealing and hemostasis, and can replace the conventional medical adhesive with two liquid-phase components.
The invention provides the following technical scheme:
a solid composition for preparing a medical adhesive, the composition comprising an aldehydic natural polysaccharide and an amino-containing polymeric material.
According to the invention, the mass ratio of the aldehyde natural polysaccharide to the amino high polymer material is 7/10-15/10, such as 7/10, 8/10, 9/10, 10/10, 11/10, 12/10, 13/10, 14/10 and 15/10.
According to the invention, the content of aldehyde groups in the aldehydized natural polysaccharide is 20-100%, and the higher the content of aldehyde groups in the aldehydized natural polysaccharide is, the quicker the gelling is realized, and the stronger the viscosity is.
According to the invention, the natural polysaccharide in the aldehyde-based natural polysaccharide is selected from one or a mixture of more than two of corn starch, potato starch, wheat starch, rice starch, pregelatinized starch, etherified starch (such as carboxymethyl starch (also called sodium carboxymethyl starch)), esterified starch (such as acetate starch), cross-linked starch, dextrin, sodium alginate, carboxymethyl cellulose and hydroxyethyl cellulose. The natural polysaccharide has the advantages of wide source, low cost, good biocompatibility, safety, no toxicity and the like.
According to the invention, the aldehyde-based natural polysaccharide is prepared by the following method:
(a) mixing natural polysaccharide, water and absolute ethyl alcohol to form a mixed solution; then adding sodium periodate aqueous solution for oxidation reaction; and (3) optionally adding ethylene glycol into the reaction system to stop the reaction, and preparing the aldehyde-based natural polysaccharide.
According to the invention, the method further comprises the steps of:
(b) repeatedly filtering and washing the aldehyde-group natural polysaccharide solid by using a mixed solvent of water and absolute ethyl alcohol, filtering and washing by using absolute ethyl alcohol for the last time, and drying in vacuum.
According to the invention, in step (a), the volume ratio of the water to the absolute ethyl alcohol is 1: 1.
According to the invention, in the step (a), the mass fraction of the natural polysaccharide in the mixed solution is 5-15%.
According to the invention, in step (a), the mass ratio of the sodium periodate to the natural polysaccharide is 3/10-3/2, and the volume of the sodium periodate aqueous solution is half of the sum of the volumes of water and absolute ethyl alcohol.
According to the invention, in step (a), the oxidation reaction is preferably carried out at room temperature in the absence of light for 4 to 24 hours.
According to the invention, in step (a), the reaction is stopped by adding an amount of ethylene glycol equimolar to the amount of sodium periodate.
According to the invention, in the step (b), the vacuum drying temperature is 40-60 ℃ and the time is 6-24 h.
According to the invention, the amino polymer material is selected from one of gelatin, collagen, sericin, chitosan, serum albumin, diamino polyethylene glycol and four-arm aminated polyethylene glycol.
The solid composition for preparing the medical adhesive comprises the aldehydic natural polysaccharide and the amino-containing high polymer material, and the two components have stable performance in a solid state and do not react; this greatly increases its transport capacity and transport costs, avoiding possible formation of impurity components in the liquid component.
When the solid composition for preparing the medical adhesive is required to be prepared to obtain the medical adhesive, the solid composition can be in a paste state after being contacted and mixed with water or buffer solution, and can be gelatinized within a few minutes after being coated on a required part, so that the solid composition is convenient to use.
The present invention also provides a method for preparing the above solid composition for preparing a medical adhesive, the method comprising;
mixing the aldehyde natural polysaccharide and the amino-containing high polymer material to obtain the solid composition for preparing the medical adhesive.
According to the present invention, the mixing is not particularly defined, and a suitable mixing method may be selected depending on the amount of the desired solid composition, and for example, the aldehydic natural polysaccharide and the amino group-containing polymeric material may be physically mixed in a high-speed mixer; or adding the aldehyde natural polysaccharide and the amino-containing high polymer material into absolute ethyl alcohol, mixing and stirring at room temperature, carrying out suction filtration to obtain solid powder, and carrying out vacuum drying to realize the preparation of the solid composition for preparing the medical adhesive.
According to the invention, in the mixing process, the controllable gelling time can be realized by adjusting the proportional relation between the solid composition and water, wherein the gelling time is shortened when the addition amount of water is less, and the gelling time is prolonged when the addition amount of water is more; the medical staff can adjust the proportional relation of the solid composition and the water according to the actual operation condition.
The invention also provides the application of the solid composition for preparing the medical adhesive, which is used for preparing the medical adhesive.
The invention also provides a medical adhesive which is prepared from the solid composition for preparing the medical adhesive.
According to the present invention, the medical adhesive is prepared by mixing water or a buffer solution with the above-mentioned solid composition for preparing a medical adhesive.
According to the invention, the water is selected from purified water, deionized water, water for injection;
the pH value of the buffer solution is 6-8.
According to the invention, in the mixing process, the aldehyde-based natural polysaccharide and the amino-containing high polymer material are crosslinked in a medium environment of water or buffer solution through Schiff base reaction to form the hydrogel type medical adhesive.
According to the invention, the mass ratio of the water or the buffer solution to the aldehyde-based natural polysaccharide is 2/1-200/1.
The invention also provides the application of the medical adhesive in tissue adhesion, filling, sealing and hemostasis.
Has the advantages that:
the invention selects plant polysaccharide to modify aldehyde group through oxidation reaction, and further cross-links with amino-containing high polymer material in the presence of water or buffer solution to prepare the medical adhesive. The used materials are widely applied to the fields of medical treatment, food and the like, have good biocompatibility, can be degraded and metabolized in vivo, and have low cost and wide sources; the formed hydrogel type medical adhesive with the three-dimensional network structure has good application potential in the aspects of tissue adhesion, filling, sealing, hemostasis and the like.
The invention also improves the prior art for oxidizing natural polysaccharide, simplifies the purification method and greatly saves the production cost and time. In the prior art, a single water solvent is generally used for oxidation reaction, and the purification of oxidized polysaccharide product needs dialysis and freeze drying steps. Dialysis is carried out for at least 2 days, the freeze-drying step is also long, generally 1-2 days, and the cost of large-scale freeze-drying equipment in the industrial production process is extremely high. The invention adopts the mixed solvent of water and ethanol, can separate the solid phase and the liquid phase by simple centrifugation or filtration, and then uses the mixed solvent to rapidly wash the solid to remove micromolecular byproducts. Finally, the solid is washed by absolute ethyl alcohol to replace water absorbed in the solid, and oxidized natural polysaccharide powder can be obtained under conventional vacuum drying. By adopting the method, the whole purification time can be shortened to less than one day from at least three or four days, and expensive freeze drying equipment is avoided, thereby laying a foundation for large-scale industrial production of the technology.
The raw materials for preparing the medical adhesive can be stored in a solid powder form, so that the stability of the adhesive can be improved, and the transportation cost can be reduced. The existing two-component adhesives are generally two-liquid phase systems, and are mixed and applied to wounds through a Y-shaped double-bore syringe when in use. However, the polysaccharide material is unstable in property in a solution state, is easy to degrade and breed bacteria, and needs to be added with a stabilizer and a preservative, so that the application of the natural polysaccharide solution in the biological field is limited. The medical adhesive of the invention can effectively ensure the stable performance of the polysaccharide material only by mixing the two solid powders in advance and storing the two solid powders in a solid form without adding extra auxiliary agents. The solid composition can be applied to an affected part and waits for gelling after a certain amount of water or buffer solution is added and uniformly stirred before use, gelling time of the solid composition is proper, gelling can be realized within proper time, proper preparation time can be reserved for medical workers, and blockage of a mixer due to too short gelling time is avoided.
Detailed Description
The present invention will be described in further detail with reference to specific examples. It is to be understood that the following examples are only illustrative and explanatory of the present invention and should not be construed as limiting the scope of the present invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.
The experimental methods used in the following examples are all conventional methods unless otherwise specified; reagents, materials and the like used in the following examples are commercially available unless otherwise specified.
Example 1
(1) 2g of wheat starch is added into 30mL of mixed solvent of purified water/absolute ethyl alcohol with the same volume, 1g of sodium periodate is dissolved in 15mL of purified water and added into a mixed system for oxidation reaction. And after the reaction is carried out for 12 hours in a dark place at room temperature, adding ethylene glycol with the same molar amount as sodium periodate to stop the reaction, carrying out suction filtration, repeatedly carrying out suction filtration and washing on the solid by using a purified water/ethanol mixed solvent, carrying out suction filtration by using absolute ethyl alcohol for the last time, and carrying out vacuum drying at 60 ℃ for 12 hours to obtain the formylated wheat starch, wherein the measured aldehyde content is 43.2%.
(2) Adding 1g of aldehyde wheat starch and 1g of gelatin into 30mL of absolute ethanol, mixing and stirring for 10min at room temperature, carrying out suction filtration to obtain solid powder, and carrying out vacuum drying for 6h at 40 ℃ to obtain the solid composition for preparing the medical adhesive.
(3) 1.5g of the solid composition for preparing the medical adhesive is added into 6mL of purified water, stirred uniformly, kept stand at room temperature and can be formed into gel within 10 min.
Example 2
(1) 2g of sodium carboxymethyl starch was added to 15mL of a mixed solvent of purified water/anhydrous ethanol of the same volume, and 0.8g of sodium periodate was dissolved in 7.5mL of purified water and added to the mixed system to conduct oxidation reaction. And after the reaction is carried out for 5 hours in a dark place at room temperature, adding ethylene glycol with the same molar amount as sodium periodate to stop the reaction, carrying out suction filtration, repeatedly carrying out suction filtration and washing on the solid by using a purified water/ethanol mixed solvent, carrying out suction filtration by using absolute ethyl alcohol for the last time, and carrying out vacuum drying at 45 ℃ for 18 hours to obtain the aldehyde carboxymethyl starch sodium, wherein the aldehyde content is measured to be 35.3%.
(2) Adding 1g of aldehyde carboxymethyl starch sodium and 0.7g of chitosan into 30mL of absolute ethyl alcohol, mixing and stirring for 7min at room temperature, carrying out suction filtration to obtain solid powder, and carrying out vacuum drying for 6h at 40 ℃ to obtain the solid composition for preparing the medical adhesive.
(3) 1.5g of the solid composition for preparing a medical adhesive described above was added to 30mL of PBS buffer having pH 6, stirred uniformly, left to stand at room temperature, and gelled in about 25 min.
Example 3
(1) 2g of sodium carboxymethyl starch was added to 15mL of a mixed solvent of purified water/anhydrous ethanol of the same volume, and 1.6g of sodium periodate was dissolved in 7.5mL of purified water and added to the mixed system to conduct oxidation reaction. And after the reaction is carried out for 12 hours in a dark place at room temperature, adding ethylene glycol with the same molar amount as sodium periodate to stop the reaction, carrying out suction filtration, repeatedly carrying out suction filtration and washing on the solid by using a purified water/ethanol mixed solvent, carrying out suction filtration by using absolute ethyl alcohol for the last time, and carrying out vacuum drying at 45 ℃ for 18 hours to obtain the aldehyde carboxymethyl starch sodium, wherein the aldehyde content is measured to be 73.6%.
(2) Adding 1g of aldehyde carboxymethyl starch sodium and 1g of chitosan into 30mL of absolute ethyl alcohol, mixing and stirring for 7min at room temperature, carrying out suction filtration to obtain solid powder, and carrying out vacuum drying for 6h at 40 ℃ to obtain the solid composition for preparing the medical adhesive.
(3) 1.5g of the solid composition for preparing a medical adhesive described above was added to 30mL of PBS buffer having pH 6, stirred uniformly, left to stand at room temperature, and gelled in about 18 min.
Example 4
(1) 2g of sodium alginate is added into 20mL of mixed solvent of purified water and absolute ethyl alcohol with the same volume, and 1.2g of sodium periodate is dissolved in 10mL of purified water and added into the mixed system for oxidation reaction. And after the reaction is carried out for 20 hours in a dark place at room temperature, adding ethylene glycol with the same molar amount as sodium periodate to stop the reaction, carrying out suction filtration, repeatedly carrying out suction filtration and washing on the solid by using a purified water/ethanol mixed solvent, carrying out suction filtration by using absolute ethyl alcohol for the last time, and carrying out vacuum drying at 50 ℃ for 18 hours to obtain the aldehyde sodium alginate, wherein the aldehyde content is measured to be 55.8%.
(2) Adding 1g of aldehyde sodium alginate and 1.2g of serum albumin into 20mL of absolute ethyl alcohol, mixing and stirring at room temperature for 10min, carrying out suction filtration to obtain solid powder, and carrying out vacuum drying at 40 ℃ for 6h to obtain the solid composition for preparing the medical adhesive.
(3) 1.5g of the solid composition for preparing a medical adhesive is added into 8mL of purified water, stirred uniformly, and kept stand at room temperature for about 12min to form gel.
Example 5
(1) 2g of sodium alginate is added into 20mL of mixed solvent of purified water and absolute ethyl alcohol with the same volume, and 2.4g of sodium periodate is dissolved in 10mL of purified water and added into the mixed system for oxidation reaction. And after the reaction is carried out for 20 hours in a dark place at room temperature, adding ethylene glycol with the same molar amount as sodium periodate to stop the reaction, carrying out suction filtration, repeatedly carrying out suction filtration and washing on the solid by using a purified water/ethanol mixed solvent, carrying out suction filtration by using absolute ethyl alcohol for the last time, and carrying out vacuum drying at 50 ℃ for 18 hours to obtain the aldehyde sodium alginate, wherein the aldehyde content is measured to be 90.1%.
(2) Adding 1g of aldehyde sodium alginate and 1.4g of serum albumin into 20mL of absolute ethyl alcohol, mixing and stirring at room temperature for 10min, carrying out suction filtration to obtain solid powder, and carrying out vacuum drying at 40 ℃ for 6h to obtain the solid composition for preparing the medical adhesive.
(3) 1.5g of the solid composition for preparing a medical adhesive is added to 8mL of purified water, stirred uniformly, and left to stand at room temperature for about 5min to form gel.
Example 6
(1) 2g of hydroxyethyl cellulose is added into a mixed solvent of 30mL of purified water/absolute ethyl alcohol with the same volume, and 2g of sodium periodate is dissolved in 15mL of purified water and added into the mixed system for oxidation reaction. Reacting at room temperature in a dark place for 18h, adding ethylene glycol with the same molar amount as sodium periodate to stop reaction, performing suction filtration, repeatedly performing suction filtration and washing on the solid by using a purified water/ethanol mixed solvent, performing suction filtration by using absolute ethanol for the last time, and performing vacuum drying at 50 ℃ for 20h to obtain the aldehyde hydroxyethyl cellulose, wherein the aldehyde content is 83.4 percent.
(2) Adding 1g of aldehyde hydroxyethyl cellulose and 1g of four-arm aminated polyethylene glycol into 15mL of absolute ethyl alcohol, mixing and stirring at room temperature for 10min, carrying out suction filtration to obtain solid powder, and carrying out vacuum drying at 40 ℃ for 8h to obtain the solid composition for preparing the medical adhesive.
(3) 1.5g of the solid composition for preparing a medical adhesive is added into 6mL of purified water, stirred uniformly, and kept stand at room temperature for about 5min to form gel.
Test example 1
The bonding ability was tested using pigskin. The pigskin was cut into strips of 2 strips of length x width 30mm x 10 mm. Before the test, purified water was added to 1.5g of the above-prepared solid composition for medical adhesive preparation, and after stirring uniformly, the mixture was applied to an area of about 10mm × 10mm at one end of the pigskin, respectively. Finally, the coated areas of 2 pigskins were butted together and placed in a humid environment under 20N pressure for 2 hours. The adhesive strength of the medical adhesive to the pigskin was tested by a universal tensile machine, and the test results are shown in the following table.
| Sample (I) | Adhesive Strength (kPa) | Sample (I) | Adhesive Strength (kPa) |
| Example 1 | 20.3 | Example 2 | 18.8 |
| Example 3 | 27.4 | Example 4 | 26.1 |
| Example 5 | 23.4 | Example 6 | 24.7 |
| Commercially available fibrin glue | 15.9 |
It can be seen that the adhesive capacity of examples 1-6 is superior to that of the commercially available fibrin glue, with good application potential.
The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiment. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A solid composition for preparing a medical adhesive, the composition comprising an aldehydic natural polysaccharide and an amino-containing polymeric material.
2. The solid composition according to claim 1, wherein the mass ratio of the aldehyde-modified natural polysaccharide to the amino polymer material is 7/10-15/10.
3. The solid composition according to claim 1 or 2, wherein the aldehyde group content in the aldehydized natural polysaccharide is 20% to 100%;
preferably, the natural polysaccharide in the aldehyde-based natural polysaccharide is selected from one or a mixture of more than two of corn starch, potato starch, wheat starch, rice starch, pregelatinized starch, etherified starch, esterified starch, cross-linked starch, dextrin, sodium alginate, carboxymethyl cellulose and hydroxyethyl cellulose.
Preferably, the amino polymer material is selected from one of gelatin, collagen, sericin, chitosan, serum albumin, diamino polyethylene glycol and four-arm aminated polyethylene glycol.
4. The solid composition according to any one of claims 1 to 3, wherein the aldehydized natural polysaccharide is prepared by a method comprising:
(a) mixing natural polysaccharide, water and absolute ethyl alcohol to form a mixed solution; then adding sodium periodate aqueous solution for oxidation reaction; and (3) optionally adding ethylene glycol into the reaction system to stop the reaction, and preparing the aldehyde-based natural polysaccharide.
Preferably, the method further comprises the steps of:
(b) repeatedly filtering and washing the aldehyde-group natural polysaccharide solid by using a mixed solvent of water and absolute ethyl alcohol, filtering and washing by using absolute ethyl alcohol for the last time, and drying in vacuum.
5. The solid composition according to any one of claims 1 to 4, wherein in step (a), the volume ratio of water to absolute ethanol is 1: 1.
Preferably, in the step (a), the mass fraction of the natural polysaccharide in the mixed solution is 5-15%.
Preferably, in step (a), the mass ratio of the sodium periodate to the natural polysaccharide is 3/10-3/2, and the volume of the sodium periodate aqueous solution is half of the sum of the volumes of water and absolute ethyl alcohol.
Preferably, in the step (a), the oxidation reaction is preferably carried out at room temperature in a dark condition, and the time of the oxidation reaction is 4-24 h.
6. A process for preparing the solid composition of any one of claims 1-5, the process comprising;
mixing the aldehyde natural polysaccharide and the amino-containing high polymer material to obtain the solid composition for preparing the medical adhesive.
7. Use of the solid composition for the preparation of a medical adhesive according to any one of claims 1 to 5 for the preparation of a medical adhesive.
8. A medical adhesive prepared from the solid composition for preparing a medical adhesive according to any one of claims 1 to 5.
9. The medical adhesive according to claim 8, wherein the medical adhesive is prepared by a method of mixing water or a buffer solution with the solid composition for preparing a medical adhesive according to any one of claims 1 to 5.
Preferably, the water is selected from purified water, deionized water, water for injection;
preferably, in the mixing process, the aldehyde-based natural polysaccharide and the amino-containing polymer material are crosslinked in a medium environment of water or a buffer solution through Schiff base reaction to form the hydrogel medical adhesive.
Preferably, the mass ratio of the water or the buffer solution to the aldehyde-based natural polysaccharide is 2/1-200/1.
10. The medical adhesive of claim 8 for use in tissue adhesion, filling, sealing and hemostasis.
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Cited By (10)
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| CN112494711A (en) * | 2020-11-23 | 2021-03-16 | 杭州英健生物科技有限公司 | High-adhesion bi-component self-crosslinking digestive tract mucosa protective adhesive and application thereof |
| CN112843325A (en) * | 2021-01-20 | 2021-05-28 | 江苏德威兰医疗器械股份有限公司 | Medical hydrogel adhesive and preparation method and application thereof |
| CN113024847A (en) * | 2021-03-19 | 2021-06-25 | 中国科学院宁波材料技术与工程研究所 | Application of natural polysaccharide hydrogel in hemostasis field |
| CN113244442A (en) * | 2021-06-01 | 2021-08-13 | 北京化工大学 | Application of polyamino cationic compound in preparation of surface procoagulant enhanced hemostatic material |
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Application publication date: 20201110 |