CN108359406A - A kind of preparation method of medical adhesive - Google Patents
A kind of preparation method of medical adhesive Download PDFInfo
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- CN108359406A CN108359406A CN201810104855.7A CN201810104855A CN108359406A CN 108359406 A CN108359406 A CN 108359406A CN 201810104855 A CN201810104855 A CN 201810104855A CN 108359406 A CN108359406 A CN 108359406A
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- medical adhesive
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- spider silk
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1077—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
- C09J189/00—Adhesives based on proteins; Adhesives based on derivatives thereof
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- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Adhesives Or Adhesive Processes (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention belongs to field of medical materials, and in particular to a kind of preparation method of medical adhesive.The primary raw material for the medical adhesive that the present invention is prepared is spider silk and gallic acid, spider silk has good Adhesion property, since spider silk is rich in abundant amino, it can be reacted under dicyclohexylcarbodiimide effect with gallic acid, react the high polymer of the amino acid generated, with cohesive action, and tea polyphenols are added during the reaction, it can make the specific anti-microbial property of medical adhesive, stabilizer can also be improved, the medical adhesive of the present invention has good biodegradability and biocompatibility, and raw material is cheap and easy to get, reaction raw materials are nontoxic.
Description
Technical field
The invention belongs to field of medical materials, and in particular to a kind of preparation method of medical adhesive.
Background technology
Currently used medical adhesive includes：(1) chemical adhesive：A-cyanoacrylate class binder is to find most
Early, most widely used Tissue adhesive.The characteristics of this kind of binder is that adhering speed is fast, adhesive strength is high, tissue reaction's phase
It is the principal item of clinical application to weaker.But its viscosity and polymerization speed are difficult to control, and glue-line brittleness is big, itself also has
Slight tissue toxicity.(2) biological adhesive：Refer to extracting or being prepared using biological synthesis method viscous from human or animal's blood
Property product, listed at present and applied to the clinical fibrin binder that mainly prepared by extraction.Fibrin Glue biology
Compatibility is good, but adhesion strength is not high, and manufacturing cost is high, and the risk of antibiotic property difference.
All the time, antibacterial and hemostasis are bases in surgical operation, and the reparation to biological tissue, seam, bundle are two most bases
This operation, but this traditional seam, bundle method are not only cumbersome laborious, but also it is be easy to cause bleeding and new damage, give patient
More pains are brought, so, people want to replace with gluing always or part replaces linear slit to close, and can stop thin vessels with glue spraying
Oozing of blood or closing cancer serosal surface, the positions such as blood vessel of those need to perform the operation excision or ligation are blocked with glue.Ideal medical adhesive
Should meet it is safe and non-toxic, without teratogenesis, carcinogenic, adhesive strength is good, can rapidly cure under normal temperature and pressure, has preferable biofacies
Capacitive has preferable biocidal property, can be used under the conditions of having existing for blood and tissue fluid, catabolite leachable not shadow
The features such as ringing healing and no cytotoxicity and few heat of solidification generation.Commercial medical adhesive mainly has Fibrin Glue
Water, a-cyanoacrylate etc., the safety of Fibrin Glue aquatic organism is good, but bonding force is general and expensive；Alpha-cyano third
Although olefin(e) acid ester curing rate is fast, intensity is high, there is certain bio-toxicity, modulus to be difficult to be adapted to tissue greatly.Therefore, people
Be desirable to develop a kind of biological safety is good, modulus it is adjustable to different tissues suitability is good, adhesion strength is high medical adhesive
Glutinous agent.
Invention content
The technical problems to be solved by the invention：For biological adhesive good biocompatibility, adhesion strength is not high, prepares
It is of high cost, and the problem of antibiotic property difference, provide a kind of preparation method of medical adhesive.
In order to solve the above technical problems, the technical solution adopted by the present invention is：
A kind of preparation method of medical adhesive, it is characterised in that；Specifically preparation process is：
(1) in mass ratio 1：20, it weighs spider silk and is added in hexafluoroisopropanol, stirring to spider silk is dissolved, metal screen
Filtering and collecting filter liquid obtains spidroin solution；
(2) gallic acid is added in three-necked flask, is put into ice bath pot, is added under nitrogen protection into three-necked flask
Dicyclohexylcarbodiimide and dropwise addition spidroin solution, control rate of addition are 3~5g/min, and water is moved into after completion of dropwise addition
In bath, it is heated to 60~80 DEG C, tea polyphenols and catalyst is added after stirring 10~20min, continue to be stirred to react 30~
50min is cooled to room temperature and discharges after reaction, obtains reactant；
(3) it will be washed with absolute ethyl alcohol after reactant rotary evaporation removal hexafluoroisopropanol, be freeze-dried after washing, you can
Obtain medical adhesive.
The mass ratio of the gallic acid and spider silk is 2：1.
The addition of the tea polyphenols is the 5~7% of spidroin solution quality.
The catalyst is sodium hydroxide, and addition is the 0.1~0.3% of spidroin solution quality.
Compared with other methods, advantageous effects are the present invention：
(1) primary raw material for the medical adhesive that the present invention is prepared is spider silk and gallic acid, and spider silk has
Good Adhesion property is rich in abundant amino in spider silk, can be with gallic acid under dicyclohexylcarbodiimide effect
It is reacted, reacts the high polymer of the amino acid of generation, tea polyphenols are added during the reaction, can not only improve medical gluing
The anti-microbial property of agent can also improve the stabilizer of adhesive；
(2) spider silk fibroin and gallic acid medical adhesive dressing obtained by the reaction in the medical adhesive that the present invention is prepared
Agent has good biodegradability and biocompatibility, and raw material is cheap and easy to get, reaction raw materials are nontoxic, building-up process is simple
List, reaction condition are mild, toxic catalyst need not be added.
Specific implementation mode
In mass ratio 1：20, it weighs spider silk and is added in hexafluoroisopropanol, stirring to spider silk is dissolved, metal screen filtering
After collect filtrate, obtain spidroin solution；2 times of gallic acid of spider yarn quality is added in three-necked flask, ice bath is put into
In pot, dicyclohexylcarbodiimide is added into three-necked flask under nitrogen protection and spidroin solution is added dropwise, control drop
Acceleration is 3~5g/min, is moved into water-bath after completion of dropwise addition, is heated to 60~80 DEG C, and spider is added after stirring 10~20min
5~7% tea polyphenols of spider's thread protein solution quality and 0.1~0.3% catalyst of spidroin solution quality, continue to stir
30~50min is reacted, is cooled to room temperature and discharges after reaction, obtain reactant；Reactant rotary evaporation removal hexafluoro is different
It is washed with absolute ethyl alcohol after propyl alcohol, is freeze-dried after washing, you can obtain medical adhesive.
Example 1
In mass ratio 1：20, it weighs spider silk and is added in hexafluoroisopropanol, stirring to spider silk is dissolved, metal screen filtering
After collect filtrate, obtain spidroin solution；2 times of gallic acid of spider yarn quality is added in three-necked flask, ice bath is put into
In pot, dicyclohexylcarbodiimide is added into three-necked flask under nitrogen protection and spidroin solution is added dropwise, control drop
Acceleration is 3g/min, is moved into water-bath after completion of dropwise addition, is heated to 60 DEG C, and addition spider silk fibroin is molten after stirring 10min
5% tea polyphenols of liquid quality and 0.1% catalyst of spidroin solution quality, continue to be stirred to react 30min, reaction terminates
Postcooling is to room temperature and discharges, and obtains reactant；It will be washed, washed with absolute ethyl alcohol after reactant rotary evaporation removal hexafluoroisopropanol
It is freeze-dried after washing, you can obtain medical adhesive.
Example 2
In mass ratio 1：20, it weighs spider silk and is added in hexafluoroisopropanol, stirring to spider silk is dissolved, metal screen filtering
After collect filtrate, obtain spidroin solution；2 times of gallic acid of spider yarn quality is added in three-necked flask, ice bath is put into
In pot, dicyclohexylcarbodiimide is added into three-necked flask under nitrogen protection and spidroin solution is added dropwise, control drop
Acceleration is 4g/min, is moved into water-bath after completion of dropwise addition, is heated to 70 DEG C, and addition spider silk fibroin is molten after stirring 15min
6% tea polyphenols of liquid quality and 0.2% catalyst of spidroin solution quality, continue to be stirred to react 40min, reaction terminates
Postcooling is to room temperature and discharges, and obtains reactant；It will be washed, washed with absolute ethyl alcohol after reactant rotary evaporation removal hexafluoroisopropanol
It is freeze-dried after washing, you can obtain medical adhesive.
Example 3
In mass ratio 1：20, it weighs spider silk and is added in hexafluoroisopropanol, stirring to spider silk is dissolved, metal screen filtering
After collect filtrate, obtain spidroin solution；2 times of gallic acid of spider yarn quality is added in three-necked flask, ice bath is put into
In pot, dicyclohexylcarbodiimide is added into three-necked flask under nitrogen protection and spidroin solution is added dropwise, control drop
Acceleration is 5g/min, is moved into water-bath after completion of dropwise addition, is heated to 80 DEG C, and addition spider silk fibroin is molten after stirring 20min
7% tea polyphenols of liquid quality and 0.3% catalyst of spidroin solution quality, continue to be stirred to react 50min, reaction terminates
Postcooling is to room temperature and discharges, and obtains reactant；It will be washed, washed with absolute ethyl alcohol after reactant rotary evaporation removal hexafluoroisopropanol
It is freeze-dried after washing, you can obtain medical adhesive.
Comparative example：Certain commercially available soybean protein medical adhesive
The medical adhesive that example 1~3 and comparative example are prepared carries out following performance detection, testing result such as table 1
It is shown：
1, adhesion strength
Adhesive is added in ethyl alcohol, 60% gluing agent solution of mass fraction, curing agent NaIO4 are prepared into.
Prepare two pieces of clean pigskins and cut into 50mm × 25mm sizes, is drenched two pieces of pigskins with deionized water.It will
The gluing agent solution of 50 μ l is coated on one of pigskin, by the NaIO of certain volume4Solution is coated on other one piece of pigskin.It connects
It and the part that two pieces of pigskins are coated with solution overlaps, it is 25mm × 10mm to make the overlapping area of two pieces of pigskins, and gently
Rub it is several under make gluing agent solution and NaIO4Solution is uniformly mixed.The weight of a 100g is placed in the contact area of two pieces of pigskins
Code, and the pigskin overlapped is placed under 20 DEG C of environment after solidification 2h, measure bond strength.
2, the external degradation performance study of adhesive
According to gluing agent solution and NaIO4Liquor capacity ratio is 1:1 condition of cure, adhesive, which is prepared into thickness, is about
The sample thin film of 1mm weighs the sample thin film of certain mass, so that it is completely submerged in 50mL and contains 0.2mg/mL lipase
In PBS buffer solution, and it is put into 37 DEG C of constant temperature oscillation water-baths.Sample is taken out at regular intervals, after being rinsed with deionized water,
Vacuum drying chamber drying is put into until sample quality is constant.Sample quality after record different time is averaged in triplicate
Value.
3, antibiotic rate
Detection is to Escherichia coli antibiotic rate.
Table 1：
| Detection group | Bond strength (KPa) | Degradable time (day) | Antibiotic rate (%) |
| Example 1 | 180 | 14 | 99% |
| Example 2 | 198 | 15 | 99% |
| Example 3 | 205 | 15 | 99% |
| Comparative example | 164 | 10 | 53% |
Claims (4)
1. a kind of preparation method of medical adhesive, it is characterised in that；Specifically preparation process is：
(1) in mass ratio 1：20, it weighs spider silk and is added in hexafluoroisopropanol, stirring to spider silk is dissolved, metal screen filtering
After collect filtrate, obtain spidroin solution；
(2) gallic acid is added in three-necked flask, is put into ice bath pot, two rings is added into three-necked flask under nitrogen protection
Spidroin solution is added dropwise in hexyl carbodiimide, and control rate of addition is 3~5g/min, and water-bath is moved into after completion of dropwise addition
In, 60~80 DEG C are heated to, tea polyphenols and catalyst is added after stirring 10~20min, continues to be stirred to react 30~50min, instead
It is cooled to room temperature and discharges after answering, obtain reactant；
(3) it will be washed, be freeze-dried after washing, you can obtained with absolute ethyl alcohol after reactant rotary evaporation removal hexafluoroisopropanol
Medical adhesive.
2. a kind of preparation method of medical adhesive according to claim 1, it is characterised in that：The gallic acid and
Spider silk mass ratio is 2：1.
3. a kind of preparation method of medical adhesive according to claim 1, it is characterised in that：Described in step (3)
The addition of tea polyphenols is the 5~7% of spidroin solution quality.
4. a kind of preparation method of medical adhesive according to claim 1, it is characterised in that：Described in step (3)
Catalyst is sodium hydroxide, and addition is the 0.1~0.3% of spidroin solution quality.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810104855.7A CN108359406A (en) | 2018-02-02 | 2018-02-02 | A kind of preparation method of medical adhesive |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810104855.7A CN108359406A (en) | 2018-02-02 | 2018-02-02 | A kind of preparation method of medical adhesive |
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| Publication Number | Publication Date |
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| CN108359406A true CN108359406A (en) | 2018-08-03 |
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ID=63004266
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| Application Number | Title | Priority Date | Filing Date |
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| CN201810104855.7A Pending CN108359406A (en) | 2018-02-02 | 2018-02-02 | A kind of preparation method of medical adhesive |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019146761A1 (en) * | 2018-01-26 | 2019-08-01 | 小島プレス工業株式会社 | Flocked product and production method therefor |
| CN110711264A (en) * | 2018-06-26 | 2020-01-21 | 杨佼佼 | Composite material, medical adhesive, preparation method and application thereof |
| CN112226179A (en) * | 2020-10-15 | 2021-01-15 | 吉林大学 | Water-based adhesive and preparation method thereof |
| WO2021065854A1 (en) * | 2019-09-30 | 2021-04-08 | Ｓｐｉｂｅｒ株式会社 | Adhesive |
-
2018
- 2018-02-02 CN CN201810104855.7A patent/CN108359406A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019146761A1 (en) * | 2018-01-26 | 2019-08-01 | 小島プレス工業株式会社 | Flocked product and production method therefor |
| JP2021080305A (en) * | 2018-01-26 | 2021-05-27 | 小島プレス工業株式会社 | Flocked product and production method thereof |
| JP7029748B2 (en) | 2018-01-26 | 2022-03-04 | 小島プレス工業株式会社 | Flocked products and their manufacturing methods |
| CN110711264A (en) * | 2018-06-26 | 2020-01-21 | 杨佼佼 | Composite material, medical adhesive, preparation method and application thereof |
| CN110711264B (en) * | 2018-06-26 | 2022-08-23 | 杨佼佼 | Composite material, medical adhesive, and preparation method and application thereof |
| WO2021065854A1 (en) * | 2019-09-30 | 2021-04-08 | Ｓｐｉｂｅｒ株式会社 | Adhesive |
| CN112226179A (en) * | 2020-10-15 | 2021-01-15 | 吉林大学 | Water-based adhesive and preparation method thereof |
| CN112226179B (en) * | 2020-10-15 | 2021-06-15 | 吉林大学 | Water-based adhesive and preparation method thereof |
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Application publication date: 20180803 |
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