CN109280396A - A kind of preparation method and application of high-biocompatibility hydrogel microsphere - Google Patents
A kind of preparation method and application of high-biocompatibility hydrogel microsphere Download PDFInfo
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Abstract
The invention discloses one kind to have high-biocompatibility hydrogel microsphere and preparation method thereof.High-biocompatibility hydrogel microsphere of the present invention is to obtain hydrogel microsphere through class suspension polymerisation and purification by mixing polysuccinimide, polypropylene glycol, aminated compounds.High-biocompatibility hydrogel microsphere provided by the invention has excellent biocompatibility, and the characteristics of functional groups special using amine functional groups, it assigns hydrogel microsphere and adsorbs negatively charged substance and heavy metal adsorption performance, it can be applied to the fields such as blood purification, medicament slow release, skin care item and water process, widen the application field of hydrogel；The preparation method of high-biocompatibility hydrogel microsphere provided by the invention is simple and convenient to operate, and material settling out is good, and scope of use is wide, has practical application value.
Description
Technical field
The present invention relates to a kind of preparation method and application of high-biocompatibility hydrogel microsphere, specifically, being to be related to
One kind high-biocompatibility hydrogel microsphere of polyasparamide derivative containing amine functional groups and its preparation method and application.
Background technique
Hydrogel be by chemical bond, ionic bond, hydrogen bond, hydrophobic interaction or physical action and one kind for being formed has parent
The high molecular polymer of the aqueous but insoluble three-dimensional net structure for giving water.Hydrogel modification is original by changing optimization hydrogel
Performance or it is compound have a new excellent performance, such as good biocompatibility, degradability, the physical chemistry for being easy to regulate and control
Property and structure etc. have tempting application prospect in fields such as biological medicine, medical health, fine chemistry industries.Give full play to water
Gel hydrophily, it is nontoxic, it the features such as good biocompatibility, and assigns hydrogel special function, meets different field
Property demand, while the application field of hydrogel is widened, it is the research direction of current hydrogel new material.
Polyaspartic acid high molecular material has that biodegradable, good biocompatibility, toxicity is low, synthesis is convenient, easy
The advantages that being bonded with drug, it is considered to be one kind quite has the biological medical polymer of application prospect.Domestic and foreign scholars are to this kind of
Material has carried out many researchs.Compared to other degradable high molecular materials, polysuccinimide (PSI) passes through L- asparagus fern ammonia
The thermal polycondensation of acid prepares, and by selecting different nucleopilic reagents to carry out ring-opening reaction to PSI, can prepare a series of side chains
The derivative of the poly-aspartate of modified with functional group.The main chain of polymer is polyaminoacid, this fundamentally guarantees that material is good
Biodegradability and biocompatibility.Secondly, L-Aspartic acid raw material is easy to get, reproducibility is good.And by changing PSI
The type and ratio of Ring Opening Reagent, can structure to polymer and property regulated and controled and designed, to realize different purposes
Purpose.
Summary of the invention
The technical problem to be solved in the present invention is that designing one kind has high-biocompatibility hydrogel microsphere, and can incite somebody to action
It is used for the fields such as blood purification, medicament slow release, skin protection cosmetics, can widen the application field of hydrogel.
The purpose of the present invention provides a kind of height that can be used for for fields such as blood purification, medicament slow release, skin protection cosmetics
Biocompatible hydrogel microballoon.
In order to achieve the object of the present invention, the present invention provides a kind of high-biocompatibility hydrogel microsphere, the high biology
Biocompatible hydrogel microballoon is to be suspended by mixing polysuccinimide, polypropylene glycol, aminated compounds through class
Polymerization and purification obtain hydrogel microsphere.The amine substance is 3- dimethylamine propylamine, N, N- dimethyl-ethylenediamine, polyethylene
Imines (PEI), ethylenediamine, diethylenetriamine, triethylene tetramine and tetraethylenepentamine, at least one of polyethylene polyamine；It is described
The average molecular weight of polysuccinimide is 700~80000；The average molecular weight of the polypropylene glycol be 200~
5000；The partial size of the high-biocompatibility hydrogel microsphere is between 0.001mm~2mm.
In aminated compounds, polyethyleneimine (PEI) preferred branched type polyethyleneimine.
It is known as suspension polymerization dissolved with the monomer of initiator in the droplet-like method for carrying out free radical polymerization that suspends in water.
Of the invention so-called " class suspension polymerisation ", it is similar to suspension polymerisation, mainly by polysuccinimide, polypropylene glycol,
Aminated compounds, solvent A mixing, stirring and dissolving under the conditions of 0~40 DEG C are uniformly mixed and obtain " hydrogel reaction phase ", and will
" hydrogel reaction phase " carries out being dispersed into microspheroidal in the organic phase dissolved with dispersing agent, carries out reaction acquisition under certain condition
Hydrogel microsphere.
The present invention, as body of material, selects polypropylene glycol and aminated compounds pair using polysuccinimide
Polysuccinimide carries out open loop and cross-linking reaction, prepares hydrogel material.On the one hand, hydrogel material main body is poly- amino
Acid, this fundamentally guarantees the good biodegradability of material and biocompatibility；On the other hand, compound poly- on the hydrogel
Ethylene glycol can further improve the biocompatibility of material, including blood compatibility etc.；Furthermore compound amine on the hydrogel
Compound, can be obtained on hydrogel molecules chain modification take amine functional groups (such as primary amine group, secondary amine group, tertiary amine group and
Quaternary amines etc.), using the special characteristics of functional groups of amine functional groups, assign hydrogel material new function.
Since amine groups are easily cationized, absorption can be played with electronegative matter interaction by electrostatic interaction
Effect.The present invention introduces suitable containing the amine groups being easily cationized, Ke Yiyong on the hydrogel microsphere of biocompatibility
In blood purification (such as blood perfusion adsorbent material), endogenous and the exogenous poison with negative electricity characteristic in human body are adsorbed
Element, such as bilirubin, bile acid, protein binding toxin (indoxyl sulfate IS, sulfuric acid paracresol PCS), endotoxin etc..In addition,
By electrostatic interaction, the present invention also can be used for field of medicine release with amine groups.
In addition to this, since amine groups not only have chelation with metal cation, electrostatic interaction or hydrogen can also be passed through
Key adsorbing metal anion, to have very strong adsorption capacity to heavy metal.Therefore the present invention is in the hydrogel of biocompatibility
It introduces suitable containing the amine groups being easily cationized on microballoon, can be used for heavy metals removal field, including water process and human body
The skin care industry of skin heavy metals removal.
Another object of the present invention is to provide the height that can be used for for fields such as blood purification, medicament slow release, skin protection cosmetics
The preparation method of biocompatible hydrogel microballoon.
In order to achieve the object of the present invention, the present invention provides a kind of preparation method of high-biocompatibility hydrogel microsphere,
Include the following steps:
(a) polysuccinimide, polypropylene glycol, aminated compounds, solvent A are mixed, is stirred under the conditions of 0~40 DEG C
Dissolution is mixed, is uniformly mixed and obtains hydrogel reaction phase；
The solvent A is at least one of dimethylformamide DMF, dimethyl sulfoxide DMSO；
The polysuccinimide, polypropylene glycol, aminated compounds, solvent A mass ratio be 1:(0.01~
10): (0.01~10): (1~100).
(b) it disperses dispersing agent in solvent B, stirs 1~5h under normal temperature conditions, obtain oily phase；The dispersing agent with
Mass ratio 1:(10~1000 of solvent B)；
The dispersing agent is Tween-20, Tween-40, Tween-60, Tween-20, Tween-80, Tween-85, Span -20, Span -
40, Span -60, Span -65, at least one of Span-80；
The solvent B is at least one of hexamethylene, n-hexane, pentamethylene, pentane, normal heptane, normal octane, isooctane.
(c) hydrogel reaction is added in oily phase, mixing control particle size reacts 2 under the conditions of 20~90 DEG C
~20h cools down, and filtering obtains gel micro-ball；
The hydrogel reaction is mutually 1:(1~10 with the volume ratio of oily phase).
(4) gel micro-ball is successively used to ethyl alcohol, water washing, filters, obtains high-biocompatibility hydrogel microsphere.
High-biocompatibility hydrogel microsphere of the present invention can be applied to blood purification, medicament slow release, skin care item and water process
Equal fields.
In terms of blood purification, high-biocompatibility hydrogel microsphere of the invention can be reached in the way of blood perfusion
Endogenous and the exogenous toxin with negative electricity characteristic in human body are removed, such as bilirubin, bile acid, protein binding toxin (sulphur
Sour indoxyl IS, sulfuric acid paracresol PS etc.), endotoxin etc..Blood perfusion is to lead to the blood of patient by power to follow in vitro
Ring removes endogenous or exogenous poison in blood samples of patients by the adsorbent in blood perfusion device with special adsorption function
Object or morbid substance, to reach a kind for the treatment of technology of blood purification.Subject hydrogel microballoon has high bio-compatible
Property, it is contacted with blood of human body without obvious ill-effect.
In skin care item application field, high-biocompatibility hydrogel microsphere of the invention is due to stronger heavy metal
Adsorption capacity, the contact by high-biocompatibility hydrogel microsphere with skin, which effectively can be combined quickly and remove skin surface, to be had
Malicious heavy metal, the adverse reaction for avoiding oral expellant medicament from occurring.High-biocompatibility hydrogel microsphere tool of the present invention
The standby ability for combining toxic heavy metal ion, and then the accumulation and damage of toxic heavy metal in skin can be reduced, realize shield
The effect of skin, therefore, high-biocompatibility hydrogel microsphere of the present invention, can be used in drug and cosmetic formulations side
Face application: including cosmetics well known to those skilled in the art are added in above-mentioned high-biocompatibility hydrogel microsphere, according to
The dosage forms such as the creme, emulsifier or aqua suitable for external application are made in the conventional method of cosmetic field；It can also be by above-mentioned height
Biocompatible hydrogel microballoon is added carrier or excipient known to medicine field technical staff and according to the normal of medicine field
The drug suitable for being applied with is made in rule method.Application in terms of the preferred cosmetics of the present invention.The present invention provides height of the present invention
Biocompatible hydrogel microballoon is being prepared for removing harmful heavy metal ions from skin surface, to reduce toxic heavy metal
The drug of accumulation and damage in skin or the application in cosmetics, wherein the heavy metal refer to lead (Pb), cadmium (Cd),
Mercury (Hg) or their any combination.It should be appreciated by those skilled in the art that heavy metal of the present invention refers to different valence state
Heavy metallic salt.For Pb, common valence state has+4 valences and+divalent；For Cd, common valence state is 0 valence and+divalent；For Hg, often
See that valence state is+1 and+divalent.In the present invention, it is preferred to the above-mentioned heavy metal ion for+2 valence, for example, Pb2+, Cd2+, Hg2
+ etc..The present invention is provided to the drugs or cosmetics from skin surface removal harmful heavy metal ions, and it is effective that it includes pharmacodynamics
The high-biocompatibility hydrogel microsphere of the present invention of amount.Those skilled in the art should be noted that above-mentioned " pharmacy is effective
Amount " or " effective quantity " mean therapeutically effective amount, those skilled in the art according to the prior art, by simple, limited times reality
It tests and can determine its specific numerical value.
Compared with the existing technology, the invention has the advantages that and the utility model has the advantages that
1. high-biocompatibility hydrogel microsphere provided by the invention has excellent biocompatibility, and utilizes amine functional groups
Special characteristics of functional groups assigns hydrogel microsphere and adsorbs negatively charged substance and heavy metal adsorption performance, it is net to can be applied to blood
The fields such as change, medicament slow release, skin care item and water process；
2. the preparation method of high-biocompatibility hydrogel microsphere provided by the invention is simple and convenient to operate, material settling out is good, uses
Way range is wide, has practical application value.
Specific embodiment
Below according to examples of implementation, specific embodiments of the present invention will be described in further detail, but reality of the invention
It is without being limited thereto to apply mode.
Embodiment 1
(a) by 100g polysuccinimide (molecular weight 8000), 20g polypropylene glycol (molecular weight 800), 6g3-
Dimethylamine propylamine, 1200g dimethyl sulfoxide DMSO mixing, stirring and dissolving, is uniformly mixed and obtains hydrogel at 20 °C
React phase；
(b) it disperses 1g Span-80 and 1g Span -40 in 200g hexamethylene, stirs 2h under normal temperature conditions, obtain oily phase；
(c) reaction of 100ml hydrogel is added in 180ml oil phase, mixing control particle size is reacted under the conditions of 70 DEG C
10h cools down, and filtering obtains gel micro-ball；
(4) gel micro-ball is successively used to ethyl alcohol, water washing, is filtered, the high-biocompatibility water that partial size is 0.3~1mm is obtained
Gel micro-ball.
Embodiment 2
(a) by 100g polysuccinimide (molecular weight 5000), 20g polypropylene glycol (molecular weight 1000), 8g
N, N- dimethyl-ethylenediamine, 600g dimethyl sulfoxide DMSO mixing, stirring and dissolving under the conditions of 30 DEG C are uniformly mixed and obtain water-setting
Glue reacts phase；
(b) it disperses 10g Span -60 in 2000g pentamethylene, stirs 4h under normal temperature conditions, obtain oily phase；
(c) reaction of 100ml hydrogel is added in 200ml oil phase, mixing control particle size is reacted under the conditions of 60 DEG C
6h cools down, and filtering obtains gel micro-ball；
(4) gel micro-ball is successively used to ethyl alcohol, water washing, is filtered, the high-biocompatibility that partial size is 0.2~0.8mm is obtained
Hydrogel microsphere.
Embodiment 3
(a) by 100g polysuccinimide (molecular weight 10000), 2g polypropylene glycol (molecular weight 5000), 4g
Polyethyleneimine (PEI), 1000g dimethyl sulfoxide DMSO mixing, stirring and dissolving under the conditions of 30 DEG C are uniformly mixed and obtain water-setting
Glue reacts phase；
(b) it disperses 10g Span -20 in 1500g normal heptane, stirs 1h under normal temperature conditions, obtain oily phase；
(c) reaction of 100ml hydrogel is added in 300ml oil phase, mixing control particle size is reacted under the conditions of 70 DEG C
10h cools down, and filtering obtains gel micro-ball；
(4) gel micro-ball is successively used to ethyl alcohol, water washing, is filtered, the high-biocompatibility that partial size is 0.2~0.6mm is obtained
Hydrogel microsphere.
Embodiment 4
(a) by 100g polysuccinimide (molecular weight 7000), 50g polypropylene glycol (molecular weight 2000),
9g3- dimethylamine propylamine, 6g triethylene tetramine, 800g dimethylformamide DMF mixing, stirring and dissolving under the conditions of 30 DEG C,
It is uniformly mixed and obtains hydrogel reaction phase；
(b) it disperses 10g Tween-80 in 2500g normal octane, stirs 4h under normal temperature conditions, obtain oily phase；
(c) reaction of 100ml hydrogel is added in 100ml oil phase, mixing control particle size is reacted under the conditions of 75 DEG C
10h cools down, and filtering obtains gel micro-ball；
(4) gel micro-ball is successively used to ethyl alcohol, water washing, is filtered, the high-biocompatibility water that partial size is 0.2~1mm is obtained
Gel micro-ball.
Embodiment 5
(a) by 100g polysuccinimide (molecular weight 80000), 1g polypropylene glycol (molecular weight 400),
1000g tetraethylenepentamine, 100g dimethylformamide DMF mixing, stirring and dissolving under the conditions of 40 DEG C are uniformly mixed and obtain water-setting
Glue reacts phase；
(b) it disperses 10g Tween-60 in 10000g isooctane, stirs 1h under normal temperature conditions, obtain oily phase；
(c) reaction of 100ml hydrogel is added in 1000ml oil phase, mixing control particle size is anti-under the conditions of 90 DEG C
2h is answered, is cooled down, filtering obtains gel micro-ball；
(4) gel micro-ball is successively used to ethyl alcohol, water washing, is filtered, the high-biocompatibility water that partial size is 0.5~2mm is obtained
Gel micro-ball.
Embodiment 6
(a) by 100g polysuccinimide (molecular weight 700), 1000g polypropylene glycol (molecular weight 200), 1g
Polyethylene polyamine, 10000g dimethylformamide DMF mixing, stirring and dissolving under the conditions of 0 DEG C are uniformly mixed that obtain hydrogel anti-
Ying Xiang；
(b) it disperses 100g Tween-20 in 1000g n-hexane, stirs 5h under normal temperature conditions, obtain oily phase；
(c) reaction of 100ml hydrogel is added in 500ml oil phase, mixing control particle size is reacted under the conditions of 60 DEG C
20h cools down, and filtering obtains gel micro-ball；
(4) gel micro-ball is successively used to ethyl alcohol, water washing, is filtered, the high-biocompatibility that partial size is 0.001~1mm is obtained
Hydrogel microsphere.
Reference examples 1
Referring to the preparation method of embodiment 1, aminated compounds dimethylamine propylamine is not added during the preparation process, directly preparation is high
Biocompatible hydrogel microballoon.Synthesis process is as follows,
(a) by 100g polysuccinimide (molecular weight 8000), 20g polypropylene glycol (molecular weight 800),
1200g dimethyl sulfoxide DMSO mixing, stirring and dissolving, is uniformly mixed and obtains hydrogel reaction phase at 20 °C；
(b) it disperses 1g Span-80 and 1g Span -40 in 200g hexamethylene, stirs 2h under normal temperature conditions, obtain oily phase；
(c) reaction of 100ml hydrogel is added in 180ml oil phase, mixing control particle size is reacted under the conditions of 70 DEG C
10h cools down, and filtering obtains gel micro-ball；
(4) gel micro-ball is successively used to ethyl alcohol, water washing, is filtered, the high-biocompatibility water that partial size is 0.3~1mm is obtained
Gel micro-ball.
For the high-biocompatibility hydrogel microsphere that multiple embodiments above and corresponding reference examples respectively obtain, according to
Secondary absorption property evaluation, haemolysis and platelet adhesion reaction etc. of having carried out is evaluated.
(1) heavy metal adsorption performance
High-biocompatibility hydrogel microsphere made from the embodiment of the present invention 1 to 6 is placed in 150mL containing Cd2+, Pb2+ and Hg2+
Water in carry out being adsorbed and removed metal ion, wherein in water the content of Cd2+, Pb2+ and Hg2+ ion be 10ppm, add height
Biocompatible hydrogel microballoon is 2g, and 30 minutes are vibrated on constant temperature oscillator, and (temperature is 36 DEG C, oscillation rate 60r/
Min), supernatant is taken, after membrane filtration, with the concentration of residual heavy metal ion in ICP-OES analysis supernatant, experiment knot
Fruit is as shown in table 1.
The absorption property of the heavy metal of 1 embodiment of table and control sample hydrogel microsphere
| Cd2+ adsorption rate | Hg2+ adsorption rate | Pb2+ adsorption rate | |
| Embodiment 1 | 85.9% | 78.1% | 89.2% |
| Embodiment 2 | 86.5% | 71.2% | 88.3% |
| Embodiment 3 | 83.4% | 71.1% | 77.6% |
| Embodiment 4 | 87.9% | 72.8% | 85.9% |
| Embodiment 5 | 86.2% | 72.5% | 82.6% |
| Embodiment 6 | 89.2% | 70.5% | 89.8% |
| Reference examples 1 | 10.5% | 12.5% | 15.3% |
It can be seen that, the high-biocompatibility hydrogel microsphere of Examples 1 to 6 has various heavy metal ion from 1 result of table
There is preferable selective absorption performance, removal rate can reach 70% or more；Examples 1 to 6 is made in test discovery, the method for the present invention
High-biocompatibility hydrogel microsphere it is very fast to the rate of adsorption of heavy metal, adsorption dynamics adsorption kinetics is very good, substantially exists
Balance can be reached within 10min.And in control examples, the high-biocompatibility hydrogel microspheres of reference examples to heavy metal from
The adsorption rate of son is lower than the high-biocompatibility hydrogel microsphere for being Examples 1 to 6.
(2) plasma adsorption performance evaluation
Take concentration for 300 μm of ol/L total bilirubins, the sulfuric acid paracresol PCS of indoxyl sulfate IS, 50mg/L of 50mg/L respectively
Plasma solutions 20ml, above-described embodiment and the resulting high-biocompatibility hydrogel microsphere 2ml of reference examples is added, at 37 DEG C
After concussion 2 hours, the variation of adsorbed material is measured respectively, as a result referring to following table 1.
The plasma adsorption performance data of 2 embodiment of table and reference examples hydrogel microsphere
As can be seen from the results in the table that the high-biocompatibility hydrogel microsphere of Examples 1 to 6 is to various bilirubin, albumen knot
Nucleotoxin (IS, PCS) all has preferable selective absorption performance, hence it is evident that is better than control sample；And Examples 1 to 6 and reference examples
Hydrogel microsphere all have lower protein adsorption rate, show preferable blood compatibility.
(2) haemolysis and platelet adhesion reaction evaluation are as follows:
Haemolysis and platelet adhesion test are tested according to GB/T16886.4-2003 and GB/T16175-1996.As a result referring to
Following table 2.
The hydrogel microsphere haemolysis and platelet adhesion reaction of 3 embodiment of table and reference examples evaluate data
As can be seen from the results in the table that the high-biocompatibility hydrogel microsphere of Examples 1 to 6 and reference examples all have it is lower
Hemolysis rate and platelet adhesion reaction rate, show preferable blood compatibility.Meanwhile it is micro- to high-biocompatibility hydrogel of the present invention
Ball carries out the biocompatibilities such as cytotoxicity, thrombosis, blood coagulation, complement activation, immunity and is detected, and all shows excellent
Biocompatibility result.
It should be understood that although carrying out particularly shown and description to the present invention with reference to its illustrative embodiment,
It should be understood by those skilled in the art that without departing substantially from by spirit and model of the invention as defined in the claims
Under conditions of enclosing, any combination of various embodiments can be carried out in the variation for wherein carrying out various forms and details.
Claims (3)
1. a kind of high-biocompatibility hydrogel microsphere, it is characterised in that: the high-biocompatibility hydrogel microsphere is to pass through
Polysuccinimide, polypropylene glycol, aminated compounds are mixed, obtain hydrogel through class suspension polymerisation and purification
Microballoon；
The amine substance is 3- dimethylamine propylamine, N, N- dimethyl-ethylenediamine, polyethyleneimine (PEI), ethylenediamine, diethyl
Alkene triamine, triethylene tetramine and tetraethylenepentamine, at least one of polyethylene polyamine；
The average molecular weight of the polysuccinimide is 700 ~ 80000；
The average molecular weight of the polypropylene glycol is 200 ~ 5000；
The partial size of the high-biocompatibility hydrogel microsphere is between 0.001mm ~ 2mm.
2. a kind of preparation method of high-biocompatibility hydrogel microsphere according to claim 1, which is characterized in that including
Following steps:
(a) polysuccinimide, polypropylene glycol, aminated compounds, solvent A are mixed, is stirred under the conditions of 0 ~ 40 DEG C
Dissolution is mixed, is uniformly mixed and obtains hydrogel reaction phase；
The solvent A is at least one of dimethylformamide DMF, dimethyl sulfoxide DMSO；
The polysuccinimide, polypropylene glycol, aminated compounds, solvent A mass ratio be 1:(0.01 ~ 10):
(0.01 ~ 10): (1 ~ 100)；
(b) it disperses dispersing agent in solvent B, stirs 1 ~ 5h under normal temperature conditions, obtain oily phase；
Mass ratio 1:(10 ~ 1000 of the dispersing agent and solvent B)；
The dispersing agent is Tween-20, Tween-40, Tween-60, Tween-20, Tween-80, Tween-85, Span -20, Span -
40, Span -60, Span -65, at least one of Span-80；
The solvent B is at least one of hexamethylene, n-hexane, pentamethylene, pentane, normal heptane, normal octane, isooctane；
(c) hydrogel reaction being added in oily phase, mixing control particle size reacts 2 ~ 20h under the conditions of 20 ~ 90 DEG C,
Cooling, filtering, obtains gel micro-ball；
The hydrogel reaction is mutually 1:(1 ~ 10 with the volume ratio of oily phase)；
(4) gel micro-ball is successively used to ethyl alcohol, water washing, filters, obtains high-biocompatibility hydrogel microsphere.
3. the high-biocompatibility hydrogel microsphere is in blood purification, medicament slow release, skin care item and water according to claim 1 ~ 2
The application of process field.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111333840A (en) * | 2020-04-06 | 2020-06-26 | 刘云晖 | Amino acid polymer with intrinsic self-repairing property and preparation method thereof |
| CN111939126A (en) * | 2019-05-15 | 2020-11-17 | 上海交通大学医学院附属第九人民医院 | Cationic liposome, dispersion liquid containing same, and preparation method and application thereof |
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| CN111333840B (en) * | 2020-04-06 | 2023-10-27 | 安徽东凯生物科技股份有限公司 | Intrinsic self-repairing amino acid polymer and preparation method thereof |
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