CN104861214A - Pullulan containing injectable hydrogel and preparation method thereof - Google Patents
Pullulan containing injectable hydrogel and preparation method thereof Download PDFInfo
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- CN104861214A CN104861214A CN201510269822.4A CN201510269822A CN104861214A CN 104861214 A CN104861214 A CN 104861214A CN 201510269822 A CN201510269822 A CN 201510269822A CN 104861214 A CN104861214 A CN 104861214A
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Abstract
The invention relates to a preparation method of pullulan containing injectable hydrogel. The preparation method comprises steps as follows: pullulan is dissolved in deionized water, a cross-linking agent solution is added for stirring reaction, a reaction liquid is subjected to water bath heating to prepare hydrogel, the prepared hydrogel is immersed and washed by pyrogen-free water and a phosphate buffered solution sequentially, and injectable particles are prepared by a granulator. With the adoption of a chemical crosslinking method, two adjacent hydroxyl groups in pullulan with different molecular weights are in butt joint with epoxy groups at two ends of BDDE (1,4-butanediol diglycidyl ether), a butting polymer is formed, the polymer reacts at the temperature of 50 DEG C to form the jelly-like hydrogel, the hydrogel can be prepared to form millimeter-scale particles by the granulator, the particles are used for the injectable hydrogel, and the pullulan containing injectable hydrogel has the advantages of high stability, good biological performance and avoidance of surgical trauma.
Description
Technical field
The present invention relates to a kind of hydrogel, be specifically related to a kind of pulullan polysaccharide injection aquagel and preparation method thereof.
Background technology
The design of hydrogel and develop into there is the focus of multi-functional high molecular polymer for tissue repair research.Pulullan polysaccharide is a kind of polymer substance of irreducibility, the outer neutral polysaccharide of the water-soluble born of the same parents secreted by Aureobasidium pullulans (Aureobasidium pullulans), it has nontoxicity, security, solvability, stability, oilness, binding property, solidifiability, overlay film, decomposability, improves the character such as physical property, is widely used in the fields such as food, medicine, light industry, chemical industry and oil.Because pulullan polysaccharide has good toxicological harmless effect, water-soluble, dispersed, water absorbability, makeup can be used for viscosity additive; In price well below hyaluronic acid, but its effect is very nearly the same with hyaluronic acid.
Amphipathic grafting or block polymer are owing to self-assembly can form nanoparticle or nanometer bundle in aqueous, and good biocompatibility, can be used as Soft-tissue operation material and be applied to field of tissue engineering technology.
Summary of the invention
The object of this invention is to provide a kind of pulullan polysaccharide injection aquagel and preparation method thereof, adopt Chemical Crosslinking Methods preparation to have more the higher skin packing material of degradability, biocompatibility, security and implant frame material.
Implementation procedure of the present invention is as follows:
A preparation method for pulullan polysaccharide injection aquagel, comprises the following steps:
(1) be dissolved in deionized water by pulullan polysaccharide and obtain the pulullan polysaccharide solution that quality volume fraction is 50 ~ 300mg/mL, it is 0 ~ 27 DEG C that temperature controls;
(2) add the linking agent Isosorbide-5-Nitrae butanediol diglycidyl ether solution that massfraction is 1 ~ 10%, stir, it is 20 ~ 30 DEG C that temperature controls; Wherein, the mass ratio of pulullan polysaccharide and linking agent is 300 ~ 1800:1 ~ 40;
(3) reaction solution is obtained hydrogel at 45 ~ 55 DEG C of reaction 3 ~ 6h;
(4) obtained hydrogel embathes 2 ~ 6 days with apirogen water and phosphate buffer soln in succession, makes injectable particle with nodulizer.
Above-mentioned pulullan polysaccharide is the outer neutral polysaccharide of water-soluble born of the same parents of Aureobasidium pullulans secretion, and molecular weight is 100000g/mol ~ 530000g/mol; The pH of phosphate buffer soln is 7.4.
Specifically, the preparation method of above-mentioned pulullan polysaccharide injection aquagel comprises the following steps:
(1) be dissolved in deionized water by pulullan polysaccharide, obtain the pulullan polysaccharide solution 6mL that quality volume fraction is 50 ~ 300mg/mL, it is 0 ~ 27 DEG C that temperature of reaction controls, and reacts 0.5 ~ 1h under agitation;
(2) add 0.1 ~ 0.35mL, massfraction be 1 ~ 10% linking agent Isosorbide-5-Nitrae butanediol diglycidyl ether solution, temperature of reaction control be 20 ~ 30 DEG C, react 0.2 ~ 0.5h under agitation;
(3) reaction solution is put in 3 ~ 6h in 50 DEG C of thermostat water baths, obtained hydrogel;
(4) obtained hydrogel embathes 2 ~ 6 days with apirogen water and phosphate buffer soln in succession, makes injectable particle with nodulizer.
The hydrogel of preparation method's acquisition of above-mentioned pulullan polysaccharide injection aquagel.
The present invention has the following advantages:
A kind of pulullan polysaccharide hydrogel involved in the present invention, the pulullan polysaccharide of different molecular weight and BDDE are combined the skin packing material made, the outer neutral pulullan polysaccharide of water-soluble born of the same parents that pulullan polysaccharide is the different molecular weight secreted by Aureobasidium pullulans (Aureobasidium pullulans) is raw material, employing Chemical Crosslinking Methods is made, in the pulullan polysaccharide of different molecular weight, two adjacent hydroxyls dock with the epoxy group(ing) at the two ends of BDDE, form one to graft (co) polymers.Polymkeric substance reacts to be formed and is similar to the hydrogel of g., jelly-like at 50 DEG C, makes millimetre-sized particle, use for syringeability hydrogel by nodulizer, has that stability is high, biology performance good, can avoid the advantage of operating wound.
Accompanying drawing explanation
Fig. 1 is the infrared absorption pattern of hydrogel; In figure, in A, No. 1 for molecular weight be the infrared figure of the pulullan polysaccharide of 100,000g/moL, No. 2 for molecular weight be the infrared figure of the pulullan polysaccharide of 530,000g/moL; In B, the infrared figure of No. 1 hydrogel prepared for the molecular weight pulullan polysaccharide that is 100,000g/moL, the infrared figure of No. 2 hydrogels prepared for the molecular weight pulullan polysaccharide that is 530,000g/moL; C is the infrared figure of BDDE (BDDE);
Fig. 2 is the residual quantity of BDDE in hydrogel; In figure, the residual quantity of BDDE in hydrogel prepared by the pulullan polysaccharide of A to be molecular weight be 100,000g/moL, the residual quantity of BDDE in hydrogel prepared by the pulullan polysaccharide of B to be molecular weight be 530,000g/moL;
Fig. 3 is the sample drawing of hydrogel; In figure, 1 and No. 2 is the photo figure of hydrogel; The sample drawing of No. 1 hydrogel prepared for the molecular weight pulullan polysaccharide that is 100,000g/moL; The sample drawing of No. 2 hydrogels prepared for the molecular weight pulullan polysaccharide that is 530,000g/moL;
Fig. 4 is the scanning electron microscope (SEM) photograph of hydrogel; In figure, No. 1 is the scanning electron microscope (SEM) photograph (amplifying 100 times) of hydrogel, and No. 2 is the scanning electron microscope (SEM) photograph (amplifying 250 times) of hydrogel, and No. 3 is the scanning electron microscope (SEM) photograph (amplifying 100 times) of hydrogel, and No. 4 is the scanning electron microscope (SEM) photograph (amplifying 250 times) of hydrogel; The internal structure of 1, No. 2 hydrogels prepared for the molecular weight pulullan polysaccharide that is 100,000g/moL; The internal structure of 3, No. 4 hydrogels prepared for the molecular weight pulullan polysaccharide that is 530,000g/moL;
Fig. 5 is that hydrogel is injected in the subcutaneous figure of mouse; In figure, No. 1 for molecular weight be 100, hydrogel prepared by the pulullan polysaccharide of 000g/moL is injected in the figure of mouse after subcutaneous two weeks, No. 2 for molecular weight be 530, hydrogel prepared by the pulullan polysaccharide of 000g/moL is be injected in the figure of mouse after subcutaneous two weeks, No. 3 for molecular weight be 100,000g/moL(is left) and 530,000g/moL(is right) the hydrogel prepared of pulullan polysaccharide be injected in the figure of mouse after subcutaneous two weeks, 4 are injected in the figure of subcutaneous two weeks of the mouse hydrogel of taking-up afterwards for hydrogel;
Fig. 6 be hydrogel be injected in mouse subcutaneous after H & E colored graph; In figure, 1, No. 2 hydrogels prepared for the molecular weight pulullan polysaccharide that is 100,000g/moL be injected in mouse subcutaneous after H & E tissue staining; 3, No. 4 hydrogels prepared for the molecular weight pulullan polysaccharide that is 530,000g/moL be injected in mouse subcutaneous after H & E tissue staining.
Embodiment
Below in conjunction with embodiment, the present invention will be described in detail.
A kind of pulullan polysaccharide hydrogel involved in the present invention, the outer neutral pulullan polysaccharide of water-soluble born of the same parents of the different molecular weight secreted with Aureobasidium pullulans (Aureobasidium pullulans) is for raw material, BDDE linking agent is adopted to carry out chemically crosslinked, at reaction solution being put into 50 DEG C, static placement 3-6h, prepares hydrogel.The thick product prepared, through purification process, namely adopts BDDE, unreacted pulullan polysaccharide molecule and impurity residual in apirogen water and phosphate buffer soln replacing water gel.
The outer neutral polysaccharide of water-soluble born of the same parents of what pulullan polysaccharide in raw material adopted the is different molecular weight secreted by Aureobasidium pullulans (Aureobasidium pullulans), compared with hyaluronic acid, it has, and good water solubility, reaction conditions are gentle, the remarkable advantage such as have good stability.In addition, pulullan polysaccharide itself has good biocompatibility and degradability, can be applicable to field of tissue engineering technology.
The preparation method of the pulullan polysaccharide injection aquagel that the present invention relates to, is realized by following steps:
Step one: the pulullan polysaccharide powder taking different molecular weight, is dissolved in deionized water, obtains the pulullan polysaccharide solution 6mL that quality volume fraction is 50 ~ 300mg/mL, and it is 0 ~ 27 DEG C that temperature of reaction controls, and reacts 0.5 ~ 1h under agitation;
Step 2: add 0.1 ~ 0.35mL, massfraction is the cross-linking agent solution of 1 ~ 10%, it is 20 ~ 30 DEG C that temperature of reaction controls, and reacts 0.2 ~ 0.5h under agitation;
Step 3: reaction solution is put in 3h ~ 6h in 50 DEG C of thermostat water baths, obtained hydrogel;
Step 4: obtained hydrogel embathes 2 ~ 6 days with apirogen water and phosphate buffer soln in succession, makes the injectable particle of different-grain diameter with nodulizer.
In step one, pulullan polysaccharide is the outer neutral polysaccharide of water-soluble born of the same parents of the different molecular weight secreted by Aureobasidium pullulans, and molecular weight is 100000g/mol ~ 530000g/mol.
In step 2, linking agent is Isosorbide-5-Nitrae butanediol diglycidyl ether.
In step 4, the pH of phosphate buffer soln is 7.4.
Wherein, linking agent 1,4-butanediol diglycidyl ether docks with the pulullan polysaccharide molecular chain of different molecular weight and forms polymkeric substance, graft (co) polymers is formed at 50 DEG C of temperature to the hydrogel being similar to g., jelly-like, impurity residual in apirogen water and phosphate buffer soln wash water gel and some unreacted BDDEs.Scavenging period is 2 ~ 6 days.The grade particle of different-grain diameter made by hydrogel nodulizer after purifying, then loads in syringe for injection.
Embodiment 1
Step one: the pulullan polysaccharide powder taking different molecular weight, is dissolved in deionized water, obtains the pulullan polysaccharide solution 6mL that quality volume fraction is 50mg/mL, and it is 27 DEG C that temperature of reaction controls, and reacts 0.5h under agitation;
Step 2: add 0.35mL, massfraction is the cross-linking agent solution of 1%, it is 30 DEG C that temperature of reaction controls, and reacts 0.2h under agitation;
Step 3: reaction solution is put in 6h in 50 DEG C of thermostat water baths, obtained hydrogel;
Step 4: obtained hydrogel embathes 2 days with apirogen water and phosphate buffer soln in succession, makes the injectable particle of different-grain diameter with nodulizer.
In step one, pulullan polysaccharide is the outer neutral polysaccharide of water-soluble born of the same parents of the different molecular weight secreted by Aureobasidium pullulans, and molecular weight is 380000g/mol ~ 530000g/mol.
In step 2, linking agent is Isosorbide-5-Nitrae butanediol diglycidyl ether.
In step 4, the pH of phosphate buffer soln is 7.4.
Embodiment 2
Step one: the pulullan polysaccharide powder taking different molecular weight, is dissolved in deionized water, obtains the pulullan polysaccharide solution 6mL that quality volume fraction is 180mg/mL, and it is 14 DEG C that temperature of reaction controls, and reacts 0.7h under agitation;
Step 2: add 0.14mL, massfraction is the cross-linking agent solution of 5%, it is 25 DEG C that temperature of reaction controls, and reacts 0.3h under agitation;
Step 3: reaction solution is put in 4.5h in 50 DEG C of thermostat water baths, obtained hydrogel;
Step 4: obtained hydrogel embathes 4 days with apirogen water and phosphate buffer soln in succession, makes the injectable particle of different-grain diameter with nodulizer.
In step one, pulullan polysaccharide is the outer neutral polysaccharide of water-soluble born of the same parents of the different molecular weight secreted by Aureobasidium pullulans, and molecular weight is 240000g/mol ~ 380000g/mol.
In step 2, linking agent is Isosorbide-5-Nitrae butanediol diglycidyl ether.
In step 4, the pH of phosphate buffer soln is 7.4.
Embodiment 3
Step one: the pulullan polysaccharide powder taking different molecular weight, is dissolved in deionized water, obtains the pulullan polysaccharide solution 6mL that quality volume fraction is 300mg/mL, and it is 0 DEG C that temperature of reaction controls, and reacts 1h under agitation;
Step 2: add 0.1mL, massfraction is the cross-linking agent solution of 10%, it is 20 DEG C that temperature of reaction controls, and reacts 0.5h under agitation;
Step 3: reaction solution is put in 3h in 50 DEG C of thermostat water baths, obtained hydrogel;
Step 4: obtained hydrogel embathes 6 days with apirogen water and phosphate buffer soln in succession, makes the injectable particle of different-grain diameter with nodulizer.
In step one, pulullan polysaccharide is the outer neutral polysaccharide of water-soluble born of the same parents of the different molecular weight secreted by Aureobasidium pullulans, and molecular weight is 100000g/mol ~ 240000g/mol.
In step 2, linking agent is Isosorbide-5-Nitrae butanediol diglycidyl ether.
In step 4, the pH of phosphate buffer soln is 7.4.
Carry out scanning electron microscope analysis, sample observation and H & E staining analysis to the product of above embodiment, result is as follows:
1, the infrared absorption pattern of hydrogel as shown in Figure 1, at 1645cm
-1with 1159 cm
-1there is new absorption peak at place, is the absorption peak of carbonyl and secondary hydroxyl.Illustrate that in pulullan polysaccharide cross-linking process, docking polymerization forms new polymkeric substance.
2, as shown in Figure 2, purification time is longer, and the residual quantity of BDDE is lower for the BDDE content that hydrogel is residual after different time purification process, and still can reach standard-required after process in 2 days.
3, the sample of hydrogel packing material as shown in Figure 3, and Hydrogels is similar to the milk white gel of g., jelly-like.The sample drawing of No. 1 hydrogel prepared for the molecular weight pulullan polysaccharide that is 100,000g/moL, transparent; The sample drawing of No. 2 hydrogels prepared for the molecular weight pulullan polysaccharide that is 530,000g/moL, is creamy white.
4, the scanning electron microscope analysis of hydrogel packing material as shown in Figure 4, and hydrogel is the vesicular structure of three-dimensional network shape, arranges more regular.
5, hydrogel packing material is injected in the subcutaneous analysis of mouse as shown in Figure 5, is present in mouse subcutaneous at second week hydrogel, slightly some degraded; After hydrogel packing material is injected in mouse taking-up in subcutaneous 2 weeks, hydrogel adapts to surrounding tissue gradually.
6, hydrogel packing material be injected in mouse subcutaneous after H & E staining analysis as shown in Figure 6,1, No. 2 hydrogel injection mouse skins prepared for the molecular weight pulullan polysaccharide that is 530,000g/moL 1 week and 2 weeks; 3, No. 4 hydrogels prepared for the molecular weight pulullan polysaccharide that is 100,000g/moL are injected in mouse skin 1 week and 2 weeks.1 and No. 2 degraded is the slowest.
The hydrogel packing material that the present invention obtains shows for the experimentation on animals of Adult female ICR mouse: the hydrogel prepared with chemical crosslink technique, has good biocompatibility and histocompatibility, and degraded is slow, is suitable for tissue filling.
Content of the present invention is not limited to cited by embodiment, and the conversion of those of ordinary skill in the art by reading specification sheets of the present invention to any equivalence that technical solution of the present invention is taked, is claim of the present invention and contains.
Claims (5)
1. a preparation method for pulullan polysaccharide injection aquagel, is characterized in that comprising the following steps:
(1) be dissolved in deionized water by pulullan polysaccharide and obtain the pulullan polysaccharide solution that quality volume fraction is 50 ~ 300mg/mL, it is 0 ~ 27 DEG C that temperature controls;
(2) add the linking agent Isosorbide-5-Nitrae butanediol diglycidyl ether solution that massfraction is 1 ~ 10%, stir, it is 20 ~ 30 DEG C that temperature controls; Wherein, the mass ratio of pulullan polysaccharide and linking agent is 300 ~ 1800:1 ~ 40;
(3) reaction solution is obtained hydrogel at 45 ~ 55 DEG C of reaction 3 ~ 6h;
(4) obtained hydrogel embathes 2 ~ 6 days with apirogen water and phosphate buffer soln in succession, makes injectable particle with nodulizer.
2. the preparation method of pulullan polysaccharide injection aquagel according to claim 1, is characterized in that: pulullan polysaccharide is the outer neutral polysaccharide of water-soluble born of the same parents of Aureobasidium pullulans secretion, and molecular weight is 100000g/mol ~ 530000g/mol.
3. the preparation method of pulullan polysaccharide injection aquagel according to claim 3, is characterized in that: the pH of phosphate buffer soln is 7.4.
4. the preparation method of pulullan polysaccharide injection aquagel according to claim 1, is characterized in that:
(1) be dissolved in deionized water by pulullan polysaccharide, obtain the pulullan polysaccharide solution 6mL that quality volume fraction is 50 ~ 300mg/mL, it is 0 ~ 27 DEG C that temperature of reaction controls, and reacts 0.5 ~ 1h under agitation;
(2) add 0.1 ~ 0.35mL, massfraction be 1 ~ 10% linking agent Isosorbide-5-Nitrae butanediol diglycidyl ether solution, temperature of reaction control be 20 ~ 30 DEG C, react 0.2 ~ 0.5h under agitation;
(3) reaction solution is put in 3 ~ 6h in 50 DEG C of thermostat water baths, obtained hydrogel;
(4) obtained hydrogel embathes 2 ~ 6 days with apirogen water and phosphate buffer soln in succession, makes injectable particle with nodulizer.
5. the pulullan polysaccharide injection aquagel that obtains of preparation method according to claim 1.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107022091A (en) * | 2017-03-31 | 2017-08-08 | 福州大学 | A kind of preparation method of multiple response self-healing hydrogel |
| CN112280061A (en) * | 2020-11-19 | 2021-01-29 | 南京瑞贝西生物科技有限公司 | Preparation method of magnetic polysaccharide-based hydrogel |
| US11319566B2 (en) | 2017-04-14 | 2022-05-03 | Capsugel Belgium Nv | Process for making pullulan |
| US11576870B2 (en) | 2017-04-14 | 2023-02-14 | Capsugel Belgium Nv | Pullulan capsules |
-
2015
- 2015-05-26 CN CN201510269822.4A patent/CN104861214A/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| STJEPAN KRESIMIR KRACUN ET AL.: ""A new generation of versatile chromogenic substrates for high-throughput analysis of biomass-degrading enzymes"", 《 BIOTECHNOLOGY FOR BIOFUELS》 * |
| XIAN LI ET AL.: ""Novel multifunctional PB and PBH hydrogels as soft filler for tissue engineering"", 《JOURNAL OF MATERIALS CHEMISTRY B》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107022091A (en) * | 2017-03-31 | 2017-08-08 | 福州大学 | A kind of preparation method of multiple response self-healing hydrogel |
| CN107022091B (en) * | 2017-03-31 | 2019-05-07 | 福州大学 | A kind of preparation method of multiple response self-healing hydrogel |
| US11319566B2 (en) | 2017-04-14 | 2022-05-03 | Capsugel Belgium Nv | Process for making pullulan |
| US11576870B2 (en) | 2017-04-14 | 2023-02-14 | Capsugel Belgium Nv | Pullulan capsules |
| US11878079B2 (en) | 2017-04-14 | 2024-01-23 | Capsugel Belgium Nv | Pullulan capsules |
| CN112280061A (en) * | 2020-11-19 | 2021-01-29 | 南京瑞贝西生物科技有限公司 | Preparation method of magnetic polysaccharide-based hydrogel |
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Application publication date: 20150826 |