CN111729133B - Biological adhesive and preparation method and application thereof - Google Patents
Biological adhesive and preparation method and application thereof Download PDFInfo
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- CN111729133B CN111729133B CN202010573306.1A CN202010573306A CN111729133B CN 111729133 B CN111729133 B CN 111729133B CN 202010573306 A CN202010573306 A CN 202010573306A CN 111729133 B CN111729133 B CN 111729133B
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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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/041—Mixtures of macromolecular compounds
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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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2230/00—Compositions for preparing biodegradable polymers
Abstract
The invention discloses a biological adhesive and a preparation method and application thereof, wherein the biological adhesive comprises four-arm polyethylene glycol amino and four-arm polyethylene glycol succinimide succinate in a mass ratio of 1 (0.1-10). The biological adhesive disclosed by the invention has good biocompatibility, is degradable, has high adhesive capacity and can sufficiently resist the pressure of cerebrospinal fluid after being adhered to a dura mater. Moreover, the biological adhesive is convenient to operate in the operation, can be used independently, does not need to be sutured, greatly shortens the operation time and reduces the operation risk. The biological adhesive disclosed by the invention can be used for treating dural damage of special parts which cannot be effectively sutured by a conventional method, such as damage at the front part, the side part and the nerve root sleeve of a dura mater, can effectively reduce complications of spinal postoperative cerebrospinal fluid leakage, and can improve the prognosis of a patient.
Description
Technical Field
The invention relates to the field of medical adhesives, in particular to a biological adhesive and a preparation method and application thereof.
Background
The current intraoperative repair method for dura mater mainly comprises a direct suturing method and a dura mater replacing material suturing method. The direct suturing method can achieve the purpose of directly and effectively repairing the dura mater, but for the dura mater with defects in the operation, the direct suturing usually has overlarge tension and is easy to clamp and press spinal nerves, and the 'needle eye' caused by sewing a needle in the suturing process is difficult to achieve absolute watertight (waterlight) suturing. Autologous or heterologous tissues (such as muscles, fat, fascia or dura mater and the like) are used as dura mater replacement materials to be matched with tension-reducing suture to repair the dura mater with certain defects, but the dura mater replacement material suture method still cannot achieve ideal watertight suture, and scar tissue adhesion is easily formed after the dura mater replacement material suture method to cause nerve stimulation symptoms. With the development of biomedical materials, more and more novel artificial materials are applied to the repair of dural damage.
However, the existing artificial dura mater repairing material generally has the problem of weak adhesion performance, can only be used as an auxiliary adhesive but not be used independently, and can achieve the effect of watertight repairing only by covering the surface of the dura mater after the dura mater is sewed. In the practical application process, the position of dura mater damage may be located position such as the place ahead of dura mater, side or nerve root sleeve, probably leads to effectively sewing up because of reasons such as the injury position is special and dura mater suture technique is not good in the art for even if adopted dura mater to repair artifical material still there is the not good problem of repair effect, spinal column postoperative cerebrospinal fluid leaks still occasionally and takes place.
Therefore, how to provide a biological adhesive capable of effectively improving the repairing effect becomes a technical problem which needs to be solved in the field.
Disclosure of Invention
An object of the present invention is to provide a new technical solution of a bioadhesive that is effective in improving the healing effect.
According to a first aspect of the present invention, there is provided a bioadhesive.
The biological adhesive comprises four-arm polyethylene glycol amino and four-arm polyethylene glycol succinimide succinate in a mass ratio of 1 (0.1-10), wherein the molecular weight of the four-arm polyethylene glycol amino is 2000-20000 daltons, and the molecular weight of the four-arm polyethylene glycol succinimide succinate is 2000-20000 daltons.
Optionally, the mass ratio of the four-arm polyethylene glycol amino group to the four-arm polyethylene glycol succinimide succinate is 1 (0.1-1).
Optionally, the composition further comprises genipin, and the ratio of the genipin to the sum of the masses of the four-arm polyethylene glycol amino and the four-arm polyethylene glycol succinimide succinate is (0.01-1): 100.
According to a second aspect of the present invention, there is provided a method of preparing a bioadhesive.
The preparation method of the biological adhesive comprises the following steps:
(1) preparing a first solution from the four-arm polyethylene glycol amino, wherein the molecular weight of the four-arm polyethylene glycol amino is 2000-20000 daltons;
(2) preparing a second solution from the four-arm polyethylene glycol succinimide succinate, wherein the molecular weight of the four-arm polyethylene glycol succinimide succinate is 2000-20000 daltons, and the mass ratio of the four-arm polyethylene glycol amino to the four-arm polyethylene glycol succinimide succinate is 1 (0.1-10);
(3) and mixing the first solution and the second solution together to obtain the biological adhesive.
Optionally, the mass concentration of the four-arm polyethylene glycol amino group in the first solution in the step (1) is 50mg/mL-500 mg/mL;
the mass concentration of the four-arm polyethylene glycol succinimide succinate in the second solution in the step (2) is 50mg/mL-500 mg/mL.
Optionally, the mass concentration of the four-arm polyethylene glycol amino group in the first solution in the step (1) is 100mg/mL-300 mg/mL;
the mass concentration of the four-arm polyethylene glycol succinimide succinate in the second solution in the step (2) is 100mg/mL-300 mg/mL.
Optionally, the solvent of the first solution in the step (1) is one of secondary water, ultrapure water, physiological saline or phosphate buffer solution with pH of 7.4;
the solvent of the second solution in the step (2) is one of secondary water, ultrapure water, physiological saline or phosphate buffer solution with the pH value of 7.4.
Optionally, the mass ratio of the four-arm polyethylene glycol amino group in the first solution in the step (1) to the four-arm polyethylene glycol succinimide succinate in the second solution in the step (2) is 1 (0.1-1).
Optionally, the step (2) is specifically as follows:
(2-1) preparing a second precursor solution from the four-arm polyethylene glycol succinimide succinate;
(2-2) formulating genipin into a second auxiliary solution, wherein the ratio of genipin to the sum of the masses of the four-arm polyethylene glycol amino group in the step (1) and the four-arm polyethylene glycol succinimide succinate in the step (2-1) is (0.01-1): 100;
(2-3) mixing the second precursor solution and the second auxiliary solution to obtain a second solution; or
The step (2) is specifically as follows:
(2-1) mixing the four-arm polyethylene glycol succinimide succinate and genipin to obtain a second precursor mixture, wherein the mass ratio of genipin to the sum of the masses of the four-arm polyethylene glycol amino and the four-arm polyethylene glycol succinimide succinate is (0.01-1): 100;
(2-2) formulating the second precursor mixture into a second solution.
According to a third aspect of the present invention, there is provided a use of the bioadhesive of the present invention or the bioadhesive prepared by the method for preparing the bioadhesive in dural repair.
The four-arm polyethylene glycol amino and the four-arm polyethylene glycol succinimide succinate in the biological adhesive are subjected to in-situ gelling through amide bonds, so that the operation is convenient and fast in operation, and the gelling speed is high. The amino groups on the collagen and elastin on the dura mater surface can rapidly form high-strength adhesion with the four-arm polyethylene glycol succinimide succinate through amide bonds. Genipin can be further crosslinked with the four-arm polyethylene glycol amino group and residual amino groups on the protein on the surface of the dura mater, so that the gel crosslinking degree and the adhesion effect on the surface of the dura mater are enhanced, and the gel swelling rate and the degradation time are adjusted.
The biological adhesive disclosed by the invention has good biocompatibility, is degradable, has high adhesive capacity and can sufficiently resist the pressure of cerebrospinal fluid after being adhered to a dura mater. The biological adhesive is convenient to operate in the operation, can be independently used, does not need to be sutured, greatly shortens the operation time and reduces the operation risk. The biological adhesive disclosed by the invention can be used for treating dural damage of special parts which cannot be effectively sutured by a conventional method, such as damage at the front part, the side part and the nerve root sleeve of a dura mater, can effectively reduce complications of spinal postoperative cerebrospinal fluid leakage, and can improve the prognosis of a patient.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description, serve to explain the principles of the invention.
Fig. 1 is a photograph of a plugged dura mater of a bioadhesive in an in vitro aqueous environment in example 5 of the present disclosure.
FIG. 2 shows the effect of the bioadhesive on the in vivo repair in example 6 of the present disclosure.
Detailed Description
Various exemplary embodiments of the present invention will now be described in detail. It should be noted that: the relative arrangement of the components and steps, the numerical expressions and numerical values set forth in these embodiments do not limit the scope of the present invention unless specifically stated otherwise.
The following description of at least one exemplary embodiment is merely illustrative in nature and is in no way intended to limit the invention, its application, or uses.
Techniques, methods, and apparatus known to one of ordinary skill in the relevant art may not be discussed in detail but are intended to be part of the specification where appropriate.
In all examples shown and discussed herein, any particular value should be construed as merely illustrative, and not limiting. Thus, other examples of the exemplary embodiments may have different values.
The biological adhesive disclosed by the invention comprises four-arm polyethylene glycol amino and four-arm polyethylene glycol succinimide succinate in a mass ratio of 1 (0.1-10).
The structural formula of the four-arm polyethylene glycol amino is shown as
Wherein m can be a number between 2 and 1000. Go toIn step (b), m can be 14-112. The molecular weight of the four-arm polyethylene glycol amino group can be 2000-20000 daltons.
The structural formula of the four-arm polyethylene glycol succinimide succinate is shown in the specification
Wherein n can be a number between 2 and 1000. Further, n can be 14-112. The molecular weight of the four-arm polyethylene glycol succinimide succinate may be 2000-20000 daltons.
The bioadhesive of the present disclosure is formed from the interaction of a four-armed polyethylene glycol amino group with a four-armed polyethylene glycol succinimide succinate via an amide bond. The biological adhesive disclosed by the invention is adhered to the surface of the dura mater by forming amide bonds with amino groups in collagen and elastin on the surface of the dura mater through four-arm polyethylene glycol succinimide succinate.
The biological adhesive disclosed by the invention has good biocompatibility, is degradable, has high adhesive capacity and can sufficiently resist the pressure of cerebrospinal fluid after being adhered to a dura mater. Moreover, the biological adhesive is convenient to operate in the operation, can be used independently, does not need to be sutured, greatly shortens the operation time and reduces the operation risk. The biological adhesive disclosed by the invention can be used for treating dural damage of special parts which cannot be effectively sutured by a conventional method, such as damage at the front part, the side part and the nerve root sleeve of a dura mater, can effectively reduce complications of spinal postoperative cerebrospinal fluid leakage, and can improve the prognosis of a patient.
In one embodiment of the bioadhesive of the present disclosure, to increase the gelling rate and pressure-bearing capacity of the bioadhesive, the mass ratio of the four-arm polyethylene glycol amino group to the four-arm polyethylene glycol succinimide succinate may be 1 (0.1-1).
Further, the mass ratio of the four-arm polyethylene glycol amino group to the four-arm polyethylene glycol succinimide succinate may be 1: 1. The mass ratio of the four-arm polyethylene glycol amino to the four-arm polyethylene glycol succinimide succinate is 1:1, so that the structure of a gel network is more regular, and the mechanical property is improved.
In one embodiment of the bioadhesive of the present disclosure, the bioadhesive may further comprise genipin. The ratio of genipin to the sum of the masses of the four-arm polyethylene glycol amino and the four-arm polyethylene glycol succinimide succinate is (0.01-1): 100.
The structural formula of the genipin is shown as
Genipin can further perform crosslinking reaction with the four-arm polyethylene glycol amino group and residual amino groups on the dura mater protein, so that the crosslinking degree and the interfacial adhesion of the gel are increased, and the swelling rate and the degradation time of the gel are further adjusted.
The preparation method of the biological adhesive comprises the following steps:
step (1): the four-arm polyethylene glycol amino group was formulated into a first solution. The molecular weight of the four-arm polyethylene glycol amino group can be 2000-20000 daltons.
In order to facilitate the use of the biological adhesive, the mass concentration of the four-arm polyethylene glycol amino group in the first solution in the step (1) is 50mg/mL-500 mg/mL.
Further, the mass concentration of the four-arm polyethylene glycol amino group in the first solution in the step (1) is 100mg/mL-300 mg/mL.
In specific implementation, the solvent of the first solution in step (1) may be one of secondary water, ultrapure water, physiological saline or phosphate buffer solution with pH of 7.4.
Step (2): a four-arm polyethylene glycol succinimide succinate was formulated as a second solution.
In order to facilitate the use of the biological adhesive, the mass concentration of the four-arm polyethylene glycol succinimide succinate in the second solution in the step (2) is 50mg/mL-500 mg/mL.
Further, the mass concentration of the four-arm polyethylene glycol succinimide succinate in the second solution in the step (2) is 100mg/mL-300 mg/mL.
In specific implementation, the solvent of the second solution in step (2) may be one of secondary water, ultrapure water, physiological saline or phosphate buffer solution with pH of 7.4.
The mass ratio of the four-arm polyethylene glycol amino and the four-arm polyethylene glycol succinimide succinate is 1 (0.1-10). Further, the mass ratio of the four-arm polyethylene glycol amino and the four-arm polyethylene glycol succinimide succinate can be 1 (0.1-1). In specific implementation, the mass ratio of the four-arm polyethylene glycol amino group to the four-arm polyethylene glycol succinimide succinate may be 1: 1. The mass ratio of the four-arm polyethylene glycol amino to the four-arm polyethylene glycol succinimide succinate is 1:1, so that the structure of a gel network is more regular, and the mechanical property is improved.
And (3): and mixing the first solution and the second solution together to obtain the biological adhesive.
In one embodiment of the method for preparing the bioadhesive of the present disclosure, the step (2) is specifically as follows:
step (2-1): a four-armed polyethylene glycol succinimide succinate was formulated as a second precursor solution.
Step (2-2): and (3) preparing genipin into a second auxiliary solution, wherein the ratio of genipin to the sum of the masses of the four-arm polyethylene glycol amino in the step (1) and the four-arm polyethylene glycol succinimide succinate in the step (2-1) is (0.01-1): 100.
Step (2-3): and mixing the second precursor solution and the second auxiliary solution to obtain a second solution.
In one embodiment of the method for preparing the bioadhesive of the present disclosure, the step (2) is specifically as follows:
step (2-1): the four-arm polyethylene glycol succinimide succinate and genipin were mixed to obtain a second precursor mixture.
The ratio of genipin to the sum of the masses of the four-arm polyethylene glycol amino group in step (1) and the four-arm polyethylene glycol succinimide succinate in step (2-1) may be (0.01-1): 100.
Step (2-2): the second precursor mixture is formulated into a second solution.
Genipin can further perform crosslinking reaction with the four-arm polyethylene glycol amino group and residual amino groups on the dura mater protein, so that the crosslinking degree and the interfacial adhesion of the gel are increased, and the swelling rate and the degradation time of the gel are further adjusted. The addition mode of genipin can be selected by those skilled in the art according to actual conditions.
The disclosure also provides the application of the biological adhesive or the biological adhesive prepared by the preparation method of the biological adhesive in dura mater repair.
The components of the bioadhesive employed in the present disclosure are FDA approved materials with good biocompatibility. The biological adhesive disclosed by the invention has high adhesive capacity and can sufficiently resist the pressure of cerebrospinal fluid after being adhered to the dura mater. Moreover, the biological adhesive is convenient to operate in the operation, can be used independently, does not need to be sutured, greatly shortens the operation time and reduces the operation risk. Thus, the bioadhesive of the present disclosure may be used for specific site dural lesions where conventional methods are not effective for suturing, such as lesions located anterior, lateral and at the nerve root sleeve of the dura mater.
Hereinafter, the present disclosure will be described with specific examples. The experimental procedures used in the examples below are conventional unless otherwise specified, the materials and reagents used therein are commercially available, and the equipment used in the experiments are well known to those skilled in the art without otherwise specified.
Example 1
400mg of a four-armed polyethylene glycol amino group (molecular weight 20000 daltons) was weighed and dissolved in 2mL of purified water to obtain a first solution. 300mg of four-arm polyethylene glycol succinimide succinate (molecular weight 20000 daltons) and 1.2mg of genipin were weighed out and dissolved in 2mL of pure water to obtain a second solution. The first and second solutions were aspirated with a double syringe and injected simultaneously into the sample vial, after which the sample vial was inverted and the gel formation time was recorded. The time that the gel can not flow backwards is the gelling time. The gelling time was tested by inversion. The experimental result shows that the gelling time is 5-10 seconds, and the requirements of operation in the operation are met.
Example 2
250mg of four-arm polyethylene glycol amino (molecular weight 10000 Dalton) was weighed and dissolved in 1mL of pure water to obtain a first solution. 120mg of four-arm polyethylene glycol succinimide succinate (molecular weight 5000 daltons) and 0.3mg of genipin were weighed out and dissolved in 1mL of pure water to obtain a second solution. The first and second solutions were aspirated with a double syringe and injected simultaneously into the sample vial, after which the sample vial was inverted and the gel time was recorded. The time that the gel can not flow backwards is the gelling time. The gelling time was tested by inversion. The experimental result shows that the gel forming time is 5-20 seconds, and the requirements of operation in the operation are met.
Example 3
200mg of four-arm polyethylene glycol amino (molecular weight 2000 daltons) was weighed out and dissolved in 1mL of pure water to obtain a first solution. 180mg of four-arm polyethylene glycol succinimide succinate (molecular weight 2000 daltons) and 2.3mg of genipin were weighed out and dissolved in 1mL of pure water to obtain a second solution. The first and second solutions were aspirated with a double syringe and injected simultaneously into the sample vial, after which the sample vial was inverted and the gel formation time was recorded. The time that the gel can not flow backwards is the gelling time. The gelling time was tested by inversion. The experimental result shows that the gelling time is 5-10 seconds, and the requirements of operation in the operation are met.
Example 4
600mg of four-arm polyethylene glycol amino (molecular weight 10000 Dalton) was weighed and dissolved in 3mL of pure water to obtain a first solution. 600mg of four-arm polyethylene glycol succinimide succinate (molecular weight 10000 Dalton) and 0.5mg of genipin were weighed out and dissolved in 3mL of pure water to obtain a second solution. The first and second solutions were aspirated with a double syringe and injected simultaneously into the sample vial, after which the sample vial was inverted and the gel formation time was recorded. The time that the gel can not flow backwards is the gelling time. The gelling time was tested by inversion. The experimental result shows that the gelling time is 5-10 seconds, and the requirements of operation in the operation are met.
Example 5
300mg of a four-arm polyethylene glycol amino group (molecular weight 5000 daltons) was weighed and dissolved in 1mL of purified water to obtain a first solution. 280mg of four-arm polyethylene glycol succinimide succinate (molecular weight 5000 daltons) and 0.92mg of genipin were weighed out and dissolved in 1mL of pure water to obtain a second solution. The first solution and the second solution were aspirated with a double syringe and applied to the defective dura surface of the goat in an aqueous environment.
As shown in FIG. 1, the results show that the bioadhesive can effectively adhere to the dura mater, block the dural defect, and withstand 300mm water column pressure, which is much greater than the normal cerebrospinal fluid pressure range (80-180mm water column).
Example 6
2000mg of four-arm polyethylene glycol amino group (molecular weight 10000 Dalton) was weighed and dissolved in 8mL of pure water to obtain a first solution. 3000mg of four-armed polyethylene glycol succinimide succinate (molecular weight 20000 daltons) and 11.5mg of genipin were weighed out and dissolved in 8mL of purified water to obtain a second solution. And sucking the first solution and the second solution by using a double-tube syringe, and coating the first solution and the second solution on the surface of a defective dura mater of a new Zealand white rabbit dura mater defective animal model.
As shown in fig. 2, the defective dura mater can be effectively repaired during the operation, and the postoperative MR results show that the incidence of cerebrospinal fluid leakage of the bioadhesive repair group is significantly reduced compared with that of the blank group.
Although some specific embodiments of the present invention have been described in detail by way of examples, it should be understood by those skilled in the art that the above examples are for illustrative purposes only and are not intended to limit the scope of the present invention. It will be appreciated by those skilled in the art that modifications may be made to the above embodiments without departing from the scope and spirit of the invention. The scope of the invention is defined by the appended claims.
Claims (6)
1. A biological adhesive for dura mater repair is characterized by comprising a four-arm polyethylene glycol amino and a four-arm polyethylene glycol succinimide succinate in a mass ratio of 1 (0.48-1.5), wherein the molecular weight of the four-arm polyethylene glycol amino is 2000-20000 daltons, and the molecular weight of the four-arm polyethylene glycol succinimide succinate is 2000-20000 daltons;
The weight ratio of genipin to the sum of the masses of the four-arm polyethylene glycol amino and the four-arm polyethylene glycol succinimide succinate is (0.01-1): 100.
2. A method of preparing the bioadhesive of claim 1 for dural repair, comprising the steps of:
(1) preparing a first solution from the four-arm polyethylene glycol amino, wherein the molecular weight of the four-arm polyethylene glycol amino is 2000-20000 daltons;
(2) preparing a second solution from the four-arm polyethylene glycol succinimide succinate, wherein the molecular weight of the four-arm polyethylene glycol succinimide succinate is 2000-20000 daltons, and the mass ratio of the four-arm polyethylene glycol amino to the four-arm polyethylene glycol succinimide succinate is 1 (0.1-1);
(3) mixing the first solution and the second solution together to obtain the biological adhesive;
the step (2) is specifically as follows:
(2-1) preparing a second precursor solution from the four-arm polyethylene glycol succinimide succinate;
(2-2) formulating genipin into a second auxiliary solution, wherein the ratio of genipin to the sum of the masses of the four-arm polyethylene glycol amino group in the step (1) and the four-arm polyethylene glycol succinimide succinate in the step (2-1) is (0.01-1): 100;
(2-3) mixing the second precursor solution and the second auxiliary solution to obtain a second solution; or
The step (2) is specifically as follows:
(2-1) mixing the four-arm polyethylene glycol succinimide succinate and genipin to obtain a second precursor mixture, wherein the mass ratio of genipin to the sum of the masses of the four-arm polyethylene glycol amino and the four-arm polyethylene glycol succinimide succinate is (0.01-1): 100;
(2-2) formulating the second precursor mixture into a second solution.
3. The preparation method according to claim 2, wherein the mass concentration of the four-arm polyethylene glycol amino group in the first solution of step (1) is 50mg/mL to 500 mg/mL;
the mass concentration of the four-arm polyethylene glycol succinimide succinate in the second solution in the step (2) is 50mg/mL-500 mg/mL.
4. The preparation method according to claim 3, wherein the mass concentration of the four-arm polyethylene glycol amino group in the first solution of step (1) is 100mg/mL-300 mg/mL;
the mass concentration of the four-arm polyethylene glycol succinimide succinate in the second solution in the step (2) is 100mg/mL-300 mg/mL.
5. The production method according to claim 2, wherein the solvent of the first solution in the step (1) is one of secondary water, ultrapure water, physiological saline or a phosphate buffer solution having a pH of 7.4;
The solvent of the second solution in the step (2) is one of secondary water, ultrapure water, physiological saline or phosphate buffer solution with the pH value of 7.4.
6. Use of the bioadhesive of claim 1 or the bioadhesive prepared by the method of any one of claims 2 to 5 in the preparation of a dural repair formulation.
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| CN102695501A (en) * | 2009-11-09 | 2012-09-26 | 聚光灯技术合伙有限责任公司 | Fragmented hydrogels |
| CN110193091A (en) * | 2018-02-27 | 2019-09-03 | 华东理工大学 | Injectable albumen/polyethylene glycol groups hydrogel material and its preparation method and application |
| CN110433344A (en) * | 2019-08-05 | 2019-11-12 | 北京诺康达医药科技股份有限公司 | The preparation method and kit of a kind of anti-adhesion gel precursor, anti-adhesion gel |
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