CN104861177A - Hydrogel material with thrombin-responsive thrombolysis capacity and preparation method thereof - Google Patents
Hydrogel material with thrombin-responsive thrombolysis capacity and preparation method thereof Download PDFInfo
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- CN104861177A CN104861177A CN201510204456.4A CN201510204456A CN104861177A CN 104861177 A CN104861177 A CN 104861177A CN 201510204456 A CN201510204456 A CN 201510204456A CN 104861177 A CN104861177 A CN 104861177A
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- 239000000017 hydrogel Substances 0.000 title claims abstract description 35
- 230000002537 thrombolytic effect Effects 0.000 title claims abstract description 33
- 239000000463 material Substances 0.000 title claims abstract description 27
- 229960004072 thrombin Drugs 0.000 title claims abstract description 19
- 108090000190 Thrombin Proteins 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 230000004043 responsiveness Effects 0.000 claims abstract description 13
- 230000000694 effects Effects 0.000 claims description 24
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 17
- 229920001184 polypeptide Polymers 0.000 claims description 16
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 16
- 239000000243 solution Substances 0.000 claims description 16
- 238000004132 cross linking Methods 0.000 claims description 14
- 239000000178 monomer Substances 0.000 claims description 13
- 239000000758 substrate Substances 0.000 claims description 12
- 239000002953 phosphate buffered saline Substances 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 7
- 229920002554 vinyl polymer Polymers 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 239000003999 initiator Substances 0.000 claims description 6
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 238000010526 radical polymerization reaction Methods 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 claims description 4
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 claims description 4
- 230000009471 action Effects 0.000 claims description 3
- 239000000872 buffer Substances 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 150000008431 aliphatic amides Chemical group 0.000 claims description 2
- -1 aliphatic diamine Chemical class 0.000 claims description 2
- 230000000975 bioactive effect Effects 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- JRKICGRDRMAZLK-UHFFFAOYSA-L persulfate group Chemical group S(=O)(=O)([O-])OOS(=O)(=O)[O-] JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 claims description 2
- 208000007536 Thrombosis Diseases 0.000 abstract description 13
- 210000004369 blood Anatomy 0.000 abstract description 3
- 239000008280 blood Substances 0.000 abstract description 3
- 230000007774 longterm Effects 0.000 abstract description 2
- 230000007547 defect Effects 0.000 abstract 1
- 230000015271 coagulation Effects 0.000 description 6
- 238000005345 coagulation Methods 0.000 description 6
- 102100033571 Tissue-type plasminogen activator Human genes 0.000 description 5
- 108050006955 Tissue-type plasminogen activator Proteins 0.000 description 5
- 230000002785 anti-thrombosis Effects 0.000 description 5
- 239000003146 anticoagulant agent Substances 0.000 description 5
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical group CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 3
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical group [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000011435 rock Substances 0.000 description 3
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- XUUXCWCKKCZEAW-YFKPBYRVSA-N Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N XUUXCWCKKCZEAW-YFKPBYRVSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 125000005395 methacrylic acid group Chemical group 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229960000103 thrombolytic agent Drugs 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 239000004160 Ammonium persulphate Substances 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229910001870 ammonium persulfate Inorganic materials 0.000 description 1
- 235000019395 ammonium persulphate Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 230000001723 fibrinogenic effect Effects 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001453 nonthrombogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention discloses a hydrogel material with thrombin-responsive thrombolysis capability and a preparation method thereof. The material has thrombolysis capacity with thrombin responsiveness (thrombus responsiveness), avoids the defect that a series of complications are caused by long-term exposure of active molecules in the traditional thrombolysis material, and has application prospect in the aspect of implanting blood contact materials into human bodies.
Description
Technical field
The present invention relates to biological medical polymer material and chemical field, be specifically related to a kind of material with responsiveness corroded rock mass with and preparation method thereof.
Background technology
The generation that material causes thrombus causes human body to implant the failed one of the main reasons of blood contacting devices application, the main approach of current this problem of solution introduces antithrombotic acitivity molecule in the material, as heparin and Profibrinolysin etc., and then realize material to the suppression of Coagulation test or the dissolving to nascent thrombus.But the long-term exposure of antithrombotic acitivity molecule will inevitably cause the dysfunction of blood system, with serious complication, as hemorrhage etc. in organized.Desirable antithrombotic acitivity material should have thrombus responsiveness, and namely only start antithrombotic mechanism when Coagulation test occurs, this also more meets the operating mode of human body self function point analysis mechanism.
The generation of thrombus is with the generation of significant zymoplasm.Zymoplasm is as the activation form of the II factor in coagulation cascade reaction, and be the product that different coagulation pathway has, it impels the generation of scleroproein aggregate (elementary thrombus) to fibrinogenic enzymolysis.In addition zymoplasm also can feed back the thrombin activating coagulation cascade process upstream, causes the autoacceleration of Coagulation test.In a word, the generation of zymoplasm is thrombotic key character event.
Introduce zymoplasm response performance in the design of some antithrombotic reagents and pharmaceutical carrier, the position that medicine is generated at thrombus plays a role.Such as, S. the people such as Absar albumin on thrombolytics surface is polypeptide grafted by thrombin substrate, thus temporarily shelter its fibrinolytic, and active thrombolytics (Journal of Controlled Release can be discharged by the enzymolysis of polypeptide at the position that zymoplasm produces, 177,42-50,2014).The people such as such as M. A. Nakatsuka utilizes the aptamer of zymoplasm to prepare microbubble as zymoplasm responsiveness acoustic contrast agent (Biomaterials, 34,9559-9565,2013) for cross-linking set again.
Summary of the invention
Instant invention overcomes the deficiencies in the prior art, zymoplasm response performance is applied to the design of nonthrombogenic material.Because the generation of zymoplasm is namely with the generation of elementary thrombus, therefore, zymoplasm responsiveness combines with thrombolysis activity by we, has prepared the hydrogel material with thrombus responsiveness corroded rock mass.
For achieving the above object, a kind of technical scheme that the present invention adopts is: a kind of hydrogel material with zymoplasm responsiveness thrombolysis ability, it is characterized in that: using organic molecule as monomer, using thrombin substrate polypeptide as linking agent, parcel thrombolysis activity molecule while forming hydrogel by polymerization, this thrombolysis activity molecule can be fast released under zymoplasm is to the cutting action of linking agent chemical bond.
In a preferred embodiment of the present invention, the chopping speed of described cross-linking set and the concentration positive correlation of zymoplasm, the ratio of described monomer with the amount of substance of described linking agent and the chopping speed positive correlation of described cross-linking set.
In a preferred embodiment of the present invention, described organic molecule monomer can be water soluble vinyl molecule monomer.
In a preferred embodiment of the present invention, described linking agent is the thrombin substrate polypeptide of two terminal modified double bonds.
In a preferred embodiment of the present invention, the sequence of described thrombin substrate polypeptide is methacrylic acid-Gly-dPhe-Pro-Arg-Gly-Phe-Pro-Ala-Gly-Gly-Lys (methacrylic acid)
In a preferred embodiment of the present invention, described thrombolysis activity molecule is can be tissue-type plasminogen activator.
In a preferred embodiment of the present invention, the reaction conditions of radical polymerization is pH=6 ~ 8, temperature range 0 ~ 37 DEG C.
In a preferred embodiment of the present invention, the reaction conditions of radical polymerization is pH=7.4, temperature range 25 DEG C.
The another kind of technical scheme that the present invention adopts is: a kind of method prepared as hydrogel material, it is characterized in that, comprise the following steps: the thrombin substrate polypeptide solution of water-soluble vinyl monomer solution, two terminal modified double bonds, thrombolysis activity molecule and initiator system are mixed, carries out Raolical polymerizable.
In a preferred embodiment of the present invention, described water-soluble vinyl monomer solution is specially acrylamide soln.
In a preferred embodiment of the present invention, described initiator system is water soluble, redox system, and described oxygenant is persulphate, and described reductive agent is aliphatic amide or aliphatic diamine.
In a preferred embodiment of the present invention, described solution, described initiator and described bioactive molecule solution all use phosphate buffered saline.
In a preferred embodiment of the present invention, described thrombolysis activity molecule is can be tissue-type plasminogen activator.
In a preferred embodiment of the present invention, in described redox system, described oxygenant is ammonium persulphate, and described reductive agent is N, N, N ', N '-Tetramethyl Ethylene Diamine.
In a preferred embodiment of the present invention, after described Raolical polymerizable terminates, following operation can also be carried out: reaction gained hydrogel is cleaned for some time by phosphate buffered saline buffer, to obtain final product.
Accompanying drawing explanation
Fig. 1 is hydrogel material is having zymoplasm and athrombia to deposit t-PA release profiles in case;
Fig. 2 is hydrogel material is having zymoplasm and athrombia to deposit thrombolysis power curve in case;
The thrombolysis activity molecule release rate curve of hydrogel in 20U/mL concentration zymoplasm of the different degree of crosslinking of Fig. 3;
The thrombolysis activity molecule release rate curve of Fig. 4 hydrogel in different concns zymoplasm;
The relation curve of Fig. 5 thrombolysis activity molecule release mean rate and concentration of thrombin.
Embodiment
The present invention is further detailed explanation in conjunction with the accompanying drawings and embodiments now.
Technical problem to be solved by this invention is: provide a kind of and have hydrogel material of zymoplasm responsiveness thrombolysis ability and preparation method thereof.Described hydrogel can be deposited when namely thrombus generates in case at zymoplasm and occur degrade and discharge thrombolysis activity molecule, realizes the dissolving to thrombus.
As Figure 1-5:
Zymoplasm causes the mechanism of blood coagulation to be exactly that the Arg-Gly key (key namely between arginine and glycine) of the Fibrinogen (i.e. Fg albumen) cutting off solubility is by insoluble for it conversion scleroproein in vivo.
The mechanism of action that zymoplasm cuts off cross-linking set (chemical bond) is: the present invention's peptide sequence used is methacrylic-Gly-dPhe-Pro-Arg-Gly-Phe-Pro-Ala-Gly-Gly-Lys (methacrylic acid), Arg-Gly key in the middle of this polypeptide can be cut by zymoplasm enzyme, so when zymoplasm exists, linking agent can rupture, crosslinking structure is destroyed, and then release thrombolysis activity molecule.
The adjustment of hydrogel degree of crosslinking: degree of crosslinking regulates (i.e. the concentration of linking agent in institute's obtain solution) by changing the amount adding linking agent, and the more degree of crosslinking of cross-linked dosage are larger, and the gel protein rate of release that degree of crosslinking is larger is slower.
Concentration of thrombin is higher, and thrombolysis activity molecule is faster from the rate of release hydrogel.
The present invention realizes its function by following proposal:
By vinyl monomer, thrombin substrate polypeptide linking agent, thrombolysis activity molecule, catalyst system mixing, through Raolical polymerizable, obtain the hydrogel being enclosed with thrombolysis activity molecule.The linking agent of this hydrogel---thrombin substrate polypeptide, polypeptide is long-chain shape, and its chemical bond can rupture under the effect of zymoplasm, thus hydrogel is degraded and discharges thrombolysis activity molecule.
Compared with prior art, the present invention has following outstanding feature:
1. with thrombin substrate polypeptide for linking agent, prepare hydrogel by radical polymerization, hydrogel is degraded under the effect of zymoplasm.
2. hydrogel bag carries thrombolysis activity molecule, and this molecule is only released under the effect of zymoplasm, and then thrombus.
The method preparing zymoplasm responsiveness thrombolysis material provided by the invention is with water soluble vinyl molecule for monomer, with the thrombin substrate polypeptide of two terminal modified double bonds for linking agent, forms hydrogel by radical polymerization.
Below in conjunction with specific examples, the invention will be further described, but do not limit the present invention.
Embodiment 1
By the acrylamide soln that 25 μ L concentration are 150 mg/mL, 5 μ L concentration are polypeptide (sequence is methacrylic acid-Gly-dPhe-Pro-Arg-Gly-Phe-Pro-Ala-Gly-Gly-Lys (the methacrylic acid)) solution of 50mg/mL, 2.5 μ L concentration are tissue-type plasminogen activator (t-PA) solution of 1 mg/mL, 0.5 μ L N, N, N ', N '-Tetramethyl Ethylene Diamine (TEMED), and 2 μ L concentration be 500 mg/mL ammonium persulfate solution (solution all uses the phosphate buffered saline buffer (PBS) of PH=7.4 to prepare) mixing, Raolical polymerizable is carried out at 25 DEG C, 3h is cleaned by gained soak to PBS after 20 min, namely the hydrogel material of zymoplasm responsiveness corroded rock mass is obtained.
The process that hydrogel discharges t-PA under the effect of zymoplasm is tested by isotope-labelling method.As shown in Figure 1, t-PA only deposits at zymoplasm and can significantly discharge in case, and rate of release can regulate by changing degree of crosslinking.By release after solution be used for blood plasma thrombolysis test, as shown in Figure 2, only under thrombin action occur degrade and discharge t-PA hydrogel can thrombus generation after be dissolved again.
wherein in Fig. 3, the degree of crosslinking magnitude relationship of hydrogel is: A>B>C>D;
fig. 5 draws on the data basis of Fig. 4.
Above according to desirable embodiment of the present invention for enlightenment, by above-mentioned description, related personnel in the scope not departing from this invention technological thought, can carry out various change and amendment completely.The technical scope of this invention is not limited to the content on specification sheets, must determine technical scope according to right.
Claims (10)
1. one kind has the hydrogel material of zymoplasm responsiveness thrombolysis ability, it is characterized in that: using organic molecule as monomer, using thrombin substrate polypeptide as linking agent, parcel thrombolysis activity molecule while forming hydrogel by polyreaction, this thrombolysis activity molecule can be fast released under zymoplasm is to the cutting action of linking agent chemical bond.
2. hydrogel material according to claim 1, is characterized in that: the chopping speed of described cross-linking set and the concentration positive correlation of zymoplasm, the ratio of described monomer with the amount of substance of described linking agent and the chopping speed positive correlation of described cross-linking set.
3. hydrogel material according to claim 1 and 2, is characterized in that: described organic molecule monomer can be water soluble vinyl molecule monomer.
4. hydrogel material according to claim 1 and 2, is characterized in that: described linking agent is the thrombin substrate polypeptide of two terminal modified double bonds.
5. hydrogel material according to claim 1 and 2, is characterized in that: described thrombolysis activity molecule is for being tissue-type plasminogen activator.
6. hydrogel material according to claim 1, is characterized in that: described polyreaction is Raolical polymerizable, and the reaction conditions of described radical polymerization is pH=6 ~ 8, temperature range 0 ~ 37 DEG C.
7. prepare the method for hydrogel material as claimed in claim 1 for one kind, it is characterized in that, comprise the following steps: the thrombin substrate polypeptide solution of water-soluble vinyl monomer solution, two terminal modified double bonds, thrombolysis activity molecule and initiator system are mixed, carries out Raolical polymerizable.
8. preparation method according to claim 7, is characterized in that: described initiator system is water soluble, redox system, and described oxygenant is persulphate, and described reductive agent is aliphatic amide or aliphatic diamine.
9. preparation method according to claim 7, is characterized in that: described solution, described initiator and described bioactive molecule solution all use phosphate buffered saline.
10. preparation method according to claim 7, is characterized in that: can also carry out following operation after described Raolical polymerizable terminates: reaction gained hydrogel is cleaned for some time by phosphate buffered saline buffer, to obtain final product.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107519543A (en) * | 2017-08-22 | 2017-12-29 | 苏州大学 | With the fibrinolytic coating of fibrin ferment response and its application |
| CN111870698A (en) * | 2020-08-26 | 2020-11-03 | 中国药科大学 | Thrombin-responsive network polymers and uses thereof |
| WO2022021363A1 (en) * | 2020-07-31 | 2022-02-03 | 苏州大学 | Coating composition, hydrogel coating and preparation method therefor, and coated product |
| CN114099694A (en) * | 2021-11-25 | 2022-03-01 | 南京邮电大学 | Thrombin-responsive DNA nano machine and preparation method and application thereof |
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| CN101583348A (en) * | 2006-10-13 | 2009-11-18 | 梅达佛股份有限公司 | Formation of medically useful gels comprising microporous particles and methods of use |
| CN101629162A (en) * | 2009-08-26 | 2010-01-20 | 暨南大学 | Cell sheet engineering and preparation method thereof |
| CN102124346A (en) * | 2008-07-16 | 2011-07-13 | 雷迪奥米特医学公司 | Thrombin substrate and assay for determining the level of bioactive thrombin in a sample |
| CN103037845A (en) * | 2010-06-01 | 2013-04-10 | 巴克斯特国际公司 | Process for making dry and stable hemostatic compositions |
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2015
- 2015-04-27 CN CN201510204456.4A patent/CN104861177B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101583348A (en) * | 2006-10-13 | 2009-11-18 | 梅达佛股份有限公司 | Formation of medically useful gels comprising microporous particles and methods of use |
| CN102124346A (en) * | 2008-07-16 | 2011-07-13 | 雷迪奥米特医学公司 | Thrombin substrate and assay for determining the level of bioactive thrombin in a sample |
| CN101629162A (en) * | 2009-08-26 | 2010-01-20 | 暨南大学 | Cell sheet engineering and preparation method thereof |
| CN103037845A (en) * | 2010-06-01 | 2013-04-10 | 巴克斯特国际公司 | Process for making dry and stable hemostatic compositions |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107519543A (en) * | 2017-08-22 | 2017-12-29 | 苏州大学 | With the fibrinolytic coating of fibrin ferment response and its application |
| CN107519543B (en) * | 2017-08-22 | 2020-10-30 | 苏州大学 | Fibrinolytic coating with thrombin responsiveness and application thereof |
| WO2022021363A1 (en) * | 2020-07-31 | 2022-02-03 | 苏州大学 | Coating composition, hydrogel coating and preparation method therefor, and coated product |
| CN111870698A (en) * | 2020-08-26 | 2020-11-03 | 中国药科大学 | Thrombin-responsive network polymers and uses thereof |
| CN114099694A (en) * | 2021-11-25 | 2022-03-01 | 南京邮电大学 | Thrombin-responsive DNA nano machine and preparation method and application thereof |
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