CN105288601B - A kind of application being embedded with blood coagulation relevant enzyme hydrogel microsphere - Google Patents
A kind of application being embedded with blood coagulation relevant enzyme hydrogel microsphere Download PDFInfo
- Publication number
- CN105288601B CN105288601B CN201410310437.5A CN201410310437A CN105288601B CN 105288601 B CN105288601 B CN 105288601B CN 201410310437 A CN201410310437 A CN 201410310437A CN 105288601 B CN105288601 B CN 105288601B
- Authority
- CN
- China
- Prior art keywords
- blood coagulation
- relevant enzyme
- microballoon
- alginate
- hydrogel
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention discloses a kind of applications for being embedded with blood coagulation relevant enzyme hydrogel microsphere.Microspherulite diameter 100-1000 microns obtained, uniform particle diameter (CV < 20%), blood coagulation relevant enzyme is evenly distributed in hydrogel microsphere, the mass ratio 1:3-4:1 of blood coagulation relevant enzyme and sodium alginate in microballoon, the drugloading rate of blood coagulation relevant enzyme is loaded with the hydrogel microsphere of blood coagulation relevant enzyme for blood, the process of setting of blood plasma in 25%-80% after water removal.
Description
Technical field
The present invention relates to a kind of application of hydrogel microsphere, especially a kind of hydrogel microsphere for being embedded with blood coagulation relevant enzyme
Application in blood clotting.
Background technique
The presently disclosed method for blood (or blood plasma) solidification is the direct solidification using blood coagulation relevant enzyme, this
Method is only applicable to the condensation of a small amount of static sample or relatively fine pipeline.But if it is the very big lumen system of diameter, and
In the case where having positive pressure propulsion, it is difficult to realize the quick solidification and target tube of the blood (or blood plasma) of flowable state in a short time
Effective closure of chamber.
Summary of the invention
In view of the above-mentioned problems, the present invention mutually ties the biochemical procoagulant activity of fibrin ferment and the blocking action of hydrogel microsphere
It closes, proposes a kind of hydrogel microsphere for being embedded with blood coagulation relevant enzyme in the application of coagulation process.It is characterized by: hydrogel microsphere
Main component be alginate material, 100-1000 microns of microspherulite diameter, it is related to contain blood coagulation for uniform particle diameter (CV < 20%)
The mass ratio 1:3-4:1 of blood coagulation relevant enzyme and sodium alginate in the Sodium Alginate Hydrogel Films microballoon of enzyme, blood coagulation relevant enzyme after water removal
Drugloading rate in 25%-80%, be loaded with the hydrogel microsphere of blood coagulation relevant enzyme for one of following three kinds of situations or two kinds or more；
A, the pipe blocking containing fibrin primary liquid flow process in pipeline；
Or, B, containing fibrin primary liquid in pipeline one or two of flow process with upper pipeline open end envelope
It closes；
Or, C, the condensation containing fibrin primary liquid.
Wherein, the liquid containing fibrinogen includes in vitro blood or blood plasma.
The obstruction containing fibrinogen liquid line, open end closing and the liquid condensation of the flowing include physics-
The synergy of chemistry；
Physical action include microballoon mechanical blockage and the rapid water swelling of hydrogel after reinforce obstruction sealing process；Chemistry
Effect refers to that blood coagulation relevant enzyme acts on fibrinogen and causes the closing of bring obstruction and condensation effects after liquid solidification.
The hydrogel microsphere is particularly suitable for existing containing fibrinogen in certain pressure (60-150mmHg)
One of situation of the pipe blocking of working fluid, the closing of pipeline open end or liquid condensation or two kinds or more.
Blood coagulation relevant enzyme in the hydrogel microsphere, including one or both of fibrin ferment or hemagglutinase.
In the alginate hydrogel microballoon, alginate molecular weight 10kDa-2000kDa, the alginate includes
One of alginic acid calcium salt or alginic acid barium salt or two kinds can also include or not comprising in alginic acid sodium salt or sylvite simultaneously
It is a kind of or two kinds.
The preparation method of the hydrogel microsphere includes the following steps:
A, compound concentration 10-30g/L sodium alginate soln；
B, blood coagulation relevant enzyme is dissolved into the sodium alginate soln of step A preparation, the concentration of blood coagulation relevant enzyme is 10-
40g/L is to get the sodium alginate soln containing blood coagulation relevant enzyme；
C, gel bath, one kind containing total concentration 5-30g/L calcium chloride or barium chloride or two in coagulation bath are prepared
Kind, gel bath also contains one of total concentration 1-20g/L sodium chloride or potassium chloride or two kinds；Gel bath is also
Containing total concentration 0.5-20g/L sodium citrate or sodium phosphate or one of disodium hydrogen phosphate or sodium dihydrogen phosphate or two kinds with
On；Gel bath also contains one of total concentration 1-30g/L tween or F68 or two kinds；
D, high-pressure electrostatic off field, the sodium alginate soln containing blood coagulation relevant enzyme that step B is prepared is formed uniformly
Jet droplets, drop enter step in the coagulation bath solution of C preparation, and gelation reaction occurs to get blood coagulation relevant enzyme is embedded with
Alginate hydrogel microballoon.
The alginate hydrogel microballoon for being embedded with blood coagulation relevant enzyme can be further anti-with said polycation solution crosslinking
It answers, forms polyelectrolyte complex film in microsphere surface, form the alginate-polycation microballoon for being embedded with blood coagulation relevant enzyme,
Specific steps are as follows:
1) the alginate hydrogel microballoon for being embedded with blood coagulation relevant enzyme is put into said polycation solution, microballoon and poly-
The volume ratio of cationic solution is 1:2-1:10, and rotation concussion allows microballoon to be in even suspension state in the solution, carries out poly- electricity
Solution matter complex reaction 2-60 minutes；
2) microballoon is separated with polycation reaction solution, is collected microballoon, is obtained after physiological saline cleaning and be embedded with blood coagulation phase
Close alginate-polycation microballoon of enzyme；
Wherein, polycation includes chitosan and its derivative, α or ε polylysine, poly ornithine, poly arginine, polyamine
And its derivative, polyamide and its derivative, polyimides and its derivative and any of the above-described one or two or more kinds of poly- sun from
One of copolymer of son or two kinds or more, for the molecular weight of polycation molecules in 1kDa-500kDa, said polycation solution is dense
Spend 0.2-20g/L.
The hydrogel microsphere for being embedded with blood coagulation relevant enzyme can realize that blood coagulation relevant enzyme is applying ring according to application demand
The slow controlled release in border.
Advantages of the present invention:
1. the obstruction containing fibrinogen liquid line that the alginate hydrogel microballoon for carrying fibrin ferment is used to flow,
Open end closing and liquid condensation.The function and effect of more simple gel micro-ball or simple fibrin ferment are compared, and the present invention has played water
The effect that the physical effect of gel micro-ball and the chemical effect of fibrin ferment are combined.Wherein, physical effect includes the machinery of microballoon
Reinforce obstruction sealing process after obstruction and the rapid water swelling of hydrogel；Chemical action refers to that blood coagulation relevant enzyme acts on fibrin
Original causes the closing of bring obstruction and condensation effects after liquid solidification.Therefore, the alginate for being loaded with fibrin ferment in the present invention
It is solidifying that hydrogel microsphere can give full play to the obstruction containing fibrinogen liquid line to flowing, open end closing and liquid
The application effect of knot.
2. due to can be realized external sustained release.Therefore, the biochemical of fibrin ferment is promoted into coagulation function and alginate hydrogel
The physical blockage effect of microballoon combines, and realizes the flowing containing fibrinogen existing for certain pressure (60-150mmHg)
Pipe blocking, open end closing and the liquid condensation of liquid.
3. technique preparation process mild condition of the invention, is easy to the holding of blood coagulation correlation enzyme bioactivity.
4. the blood coagulation relevant enzyme embedding process that the present invention uses is direct in alginate hydrogel microballoon preparation process
Blood coagulation relevant enzyme is embedded into microballoon, the encapsulation rate of blood coagulation relevant enzyme is up to 90% or more, the drugloading rate height after water removal to 25%-
80%.
Detailed description of the invention
Attached drawing 1: the modeling of the new zealand white rabbit arteria renalis and microballoon embolism image；
A: normal kidney image；
B: image after renal blood vessels damage modeling (red arrow show bleeding after damage)；
C: using image after microballoon embolism damaged arteries, stopped bleeding is shown；
D: 10min checks angiography and shows no bleeding after embolism, and fibrin ferment microballoon embolism stops blooding successfully.
Specific embodiment
Embodiment 1
[1] sodium alginate soln (concentration 15g/L) is prepared；
[2] by fibrin ferment (100mg) be dissolved into step [1] preparation sodium alginate soln in, concentration be 10g/L to get
Sodium alginate soln containing fibrin ferment；
[3] coagulation bath solution is prepared, contains calcium chloride (concentration 30g/L) in coagulation bath, sodium chloride (concentration 5g/L), phosphoric acid
Sodium dihydrogen (concentration 1g/L), tween 5g/L；
[4] high-pressure electrostatic off field, the sodium alginate soln containing fibrin ferment that step [2] are prepared is formed and is uniformly penetrated
Flow liquid drop, drop enter step in the coagulation bath solution of [3] preparation, and gelation reaction occurs, embeds after reaction 30 minutes
There is an alginate hydrogel microballoon of fibrin ferment, 500 ± 100 microns of microspherulite diameter.
[5] the alginate hydrogel microballoon for being embedded with fibrin ferment for preparing step [4], with chitosan solution (concentration
It 5g/L) is carried out under room temperature film formation reaction 10 minutes, brine 3 times, that is, obtains the alginate-shell for being embedded with fibrin ferment
Glycan microballoon.
[6] it prepares fibrinogen solution: taking fibrinogen, 0.9% sodium chloride solution is added and is prepared into containing 1g/L's
Solution.
[7] pipeline of one-to-two, two point four of three-level branch is prepared by micro-processing technology, afterbody forms long 1cm,
Diameter4 parallel pipelines, line end is open, is connected with liquid storage tank, and pass through peristaltic pump for liquid storage tank liquid
Again level-one pipeline is loaded entrance in blowback three-level branch pipeline, forms circulation loop.The fibrinogen that step [6] are prepared
Solution is placed in liquid storage tank, i.e., under wriggling pumping action, passes through three-level flow line with the flow speed stability of 10ml/s.
[8] alginate-chitosan microball for being embedded with fibrin ferment by step [5] preparation passes through capillary vessel (internal diameter
Three-level flow line afterbody is imported at the 5mm of open end for 1mm), and 0.2ml microballoon is put into flow line, is taken out
Conduit, plasma fluid solidification occurs after 30 seconds for the conduit that discovery is placed with microballoon, and does not place the pipeline of microballoon, still protects
Hold normal flow regime.
Comparative example 1
[1] it prepares fibrinogen solution: taking fibrinogen, 0.9% sodium chloride solution is added and is prepared into containing 1g/L's
Solution.
[2] method same as Example 1 is processed into identical three-level branch pipeline.
[3] three-level flow line will be imported by capillary vessel (internal diameter 1mm) with the thrombin solution of 1 equivalent of embodiment
Afterbody takes out conduit at the 5mm of open end, and Hirschfeld-Klinger reaction does not occur for each conduit after discovery 30 seconds, still maintains
In liquid storage device the solidification phenomenon of segment fluid flow occurs for normal flow regime after five minutes.
Comparative example 2
[1] method same as Example 1 is processed into identical three-level branch pipeline.
[2] will blank sodium alginate-chitosan microballoon identical with 1 partial size of embodiment by capillary vessel, (internal diameter is
Three-level flow line afterbody 1mm) is imported at the 5mm of open end, 0.2ml microballoon is put into flow line, taking-up is led
Pipe, the liquid that discovery microballoon is flowed quickly in the catheter is gone out into liquid storage tank, and does not place the pipeline of microballoon, is remained on
Keep normal flow regime.
Embodiment 2
[1] sodium alginate soln (concentration 20g/L) is prepared；
[2] fibrin ferment (50mg) is dissolved into the sodium alginate soln of step [1] preparation, concentration is 10g/L to get containing
There is the sodium alginate soln of fibrin ferment；
[3] coagulation bath solution is prepared, contains barium chloride (concentration 20g/L) in coagulation bath, sodium chloride (concentration 1g/L), phosphoric acid
Sodium dihydrogen (concentration 1g/L), tween 10g/L；
[4] high-pressure electrostatic off field, the sodium alginate soln containing fibrin ferment that step 2 is prepared forms uniform jet stream
Drop, drop enter step in the coagulation bath solution of [3] preparation, and gelation reaction occurs, and reaction is embedded with to obtain the final product after 30 minutes
The alginate hydrogel microballoon of hemagglutinase, 300 ± 100 microns of microspherulite diameter.
[5] the alginate hydrogel microballoon for being embedded with fibrin ferment for preparing step [4] is (dense with polylysin solution
Degree 0.5g/L) carries out film formation reaction 10 minutes under room temperature, brine 3 times, i.e. the acquisition alginic acid that is embedded with hemagglutinase
Salt-polylysine microballoon.
[6] it accurately measures the sodium alginate containing the fibrin ferment-polylysine microballoon of 0.5ml step [5] preparation and weighs
Microballoon is immersed the test tube that 10ml0.9% normal saline solution is housed by (0.543g).Test tube is placed in 37 DEG C of shaking tables, revolving speed
For 50rpm.0.5ml sample is taken out from test tube respectively in preset time interval point (1h, 12h, for 24 hours, 38h, 48h, 60h, 72h)
Product solution, 4 DEG C of preservations；Fresh 0.9% normal saline solution of 0.5ml of equivalent is added after every sub-sampling in test tube.
[7] according to the titration method of the fibrin ferment freeze-dried powder in Chinese Pharmacopoeia 2010 editions two, the presetting period-is drawn
Thrombin activity unit norm curve.
[8] it takes internal diameter 1cm, the test tube of long 10cm several, is separately added into fibrinogen solution 0.9ml, set 37 DEG C of water-baths
Middle heat preservation 5 minutes measures the testing sample solution 0.1ml that step [6] save, is rapidly added in each test tube, timing immediately shakes up
In 37 DEG C of water-baths of juxtaposition, the fibrinous presetting period is observed.According to the presetting period-thrombin activity unit mark of step [7]
Directrix curve calculates the thrombin activity unit in variant time point sample.The results show that during the release of 72h, blood coagulation
Enzymatic activity stills remain in 20u/ml or more.
Embodiment 3
[1] the alginate hydrogel microballoon of fibrin ferment is embedded with according to [1-4] preparation the step of embodiment 1.
[2] animal model prepares: new zealand white rabbit, intraperitoneal injection of anesthesia, and groin preserved skin is implanted into arterial sheath, uses
Angiography catheter reaches renal artery branch (target artery) through femoral artery, abdominal aorta.
[3] abdomen exposure kidney is opened, bleeding damage model is made.
The seaweed for being embedded with fibrin ferment is slowly injected [4] angiography catheter to be sent to the embolism site of damage blood vessel proximal part after
Hydrochlorate microballoon (fibrin ferment alginate microsphere: contrast agent: 0.9% physiological saline=1:1:1).
[5] the bleeding variation after observation embolism at kidney injury, finds 5 seconds stopped bleedings after embolism, to complete
Stop blooding and withdraw from conduit after contrasted confirmation damage blood vessel embolism success, extract arterial sheath, ligatures femoral artery.Utilize microballoon embolism
Image shows stopped bleeding after damaged arteries, and 10min check angiography shows no bleeding, fibrin ferment microballoon embolism after embolism
Stop blooding successfully (see attached drawing 1).
[6] kidney is taken out after putting to death animal, makes renal tissue sections observation, discovery fibrin ferment microballoon is concentrated mainly on kidney
Arterial branch originates the proximal segment of position (drafting embolism site), can see after amplifying to the mixed thrombus sectioning image of formation
It arrives, thrombus ingredient includes microballoon, haemocyte and the fibrin being interweaved together.
Claims (8)
1. a kind of hydrogel microsphere for being embedded with blood coagulation relevant enzyme answering in product of the preparation for one of following three kinds of situations
With, it is characterised in that: three kinds of situations are as follows:
A, the pipe blocking containing fibrin primary liquid flow process in pipeline；
Or, B, one or more pipeline open ends closing containing fibrin primary liquid flow process in pipeline；
Or, C, the condensation containing fibrin primary liquid；
The main component of the hydrogel microsphere is alginate material, 100-1000 microns of microspherulite diameter, uniform particle diameter, CV <
20%, the mass ratio 1:3-4:1 of blood coagulation relevant enzyme and sodium alginate in the Sodium Alginate Hydrogel Films microballoon containing blood coagulation relevant enzyme,
The drugloading rate of blood coagulation relevant enzyme is in 25%-80% after water removal；
The preparation method of the hydrogel microsphere includes the following steps:
A, compound concentration 10-30g/L sodium alginate soln；
B, blood coagulation relevant enzyme is dissolved into step A preparation, the concentration of blood coagulation relevant enzyme is 10-40g/L to get containing solidifying
The sodium alginate soln of blood relevant enzyme；
C, gel bath is prepared, the one or two containing total concentration 5-30g/L calcium chloride or barium chloride in coagulation bath,
Gel bath also contains one of total concentration 1-20g/L sodium chloride or potassium chloride or two kinds；Gel bath also contains
There are total concentration 0.5-20g/L sodium citrate or sodium phosphate or one of disodium hydrogen phosphate or sodium dihydrogen phosphate or a variety of；Gel
Bath also contains one of total concentration 1-30g/L tween or F68 or two kinds；
D, high-pressure electrostatic off field, the sodium alginate soln containing blood coagulation relevant enzyme that step B is prepared, which is formed, uniformly to be penetrated
Flow liquid drop, drop enter step in the coagulation bath solution of C preparation, and gelation reaction occurs to get blood coagulation relevant enzyme is embedded with
Alginate hydrogel microballoon；
Blood coagulation relevant enzyme in the hydrogel microsphere, including one or both of fibrin ferment or hemagglutinase.
2. application described in accordance with the claim 1, it is characterised in that: the liquid containing fibrinogen includes in vitro blood
Liquid or blood plasma.
3. application according to claim 1 or 2, it is characterised in that: the flowing contains fibrinogen liquid line
Pipe blocking, open end closing or liquid condensation include physical-chemical synergy；
Wherein, physical action include microballoon mechanical blockage and the rapid water swelling of hydrogel after reinforce obstruction sealing process；Change
Effect refers to that blood coagulation relevant enzyme acts on fibrinogen and causes the closing of bring obstruction and condensation effects after liquid solidification.
4. application according to claim 1 or 2, it is characterised in that: the hydrogel microsphere is suitable in 60-150mmHg
Pressure under the pipe blocking of the existing working fluid containing fibrinogen, the closing of pipeline open end or liquid condensation feelings
One of shape.
5. application described in accordance with the claim 1, it is characterised in that: in the alginate hydrogel microballoon, alginic acid salinity
Son amount 10kDa-2000kDa, the alginate includes one of alginic acid calcium salt or alginic acid barium salt or two kinds, is wrapped simultaneously
One of sodium salt containing alginic acid or sylvite or two kinds.
6. application described in accordance with the claim 1, it is characterised in that: in the alginate hydrogel microballoon, alginic acid salinity
Son amount 10kDa-2000kDa, the alginate includes one of alginic acid calcium salt or alginic acid barium salt or two kinds, is not included
One of alginic acid sodium salt or sylvite or two kinds.
7. application described in accordance with the claim 1, it is characterised in that: the alginate hydrogel for being embedded with blood coagulation relevant enzyme
Microballoon can form polyelectrolyte complex film in microsphere surface, formation is embedded with solidifying further with said polycation solution cross-linking reaction
The alginate of blood relevant enzyme-polycation microballoon, specific steps are as follows:
1) the alginate hydrogel microballoon for being embedded with blood coagulation relevant enzyme is put into said polycation solution, microballoon and poly- sun from
The volume ratio of sub- solution is 1:2-1:10, and rotation concussion allows microballoon to be in even suspension state in the solution, carries out polyelectrolyte
Complex reaction 2-60 minutes；
2) microballoon is separated with polycation reaction solution, is collected microballoon, is obtained after physiological saline cleaning and be embedded with blood coagulation relevant enzyme
Alginate-polycation microballoon；
Wherein, polycation be selected from chitosan and its derivative, α or ε polylysine, poly ornithine, poly arginine, polyamine and its
Derivative, polyamide and its derivative or one of polyimides and its derivative are a variety of, the molecule of polycation molecules
Amount is in 1kDa-500kDa, said polycation solution concentration 0.2-20g/L.
8. application described in accordance with the claim 1, it is characterised in that: the hydrogel microsphere for being embedded with blood coagulation relevant enzyme can root
According to application demand, realize blood coagulation relevant enzyme in the slow controlled release of application environment.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410310437.5A CN105288601B (en) | 2014-07-01 | 2014-07-01 | A kind of application being embedded with blood coagulation relevant enzyme hydrogel microsphere |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410310437.5A CN105288601B (en) | 2014-07-01 | 2014-07-01 | A kind of application being embedded with blood coagulation relevant enzyme hydrogel microsphere |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105288601A CN105288601A (en) | 2016-02-03 |
| CN105288601B true CN105288601B (en) | 2019-05-07 |
Family
ID=55186873
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410310437.5A Active CN105288601B (en) | 2014-07-01 | 2014-07-01 | A kind of application being embedded with blood coagulation relevant enzyme hydrogel microsphere |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105288601B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108102915A (en) * | 2018-01-08 | 2018-06-01 | 大连大学 | A kind of mediate contact co-culture system for being engineered amplification |
| CN111150879B (en) * | 2019-12-31 | 2022-06-17 | 华中科技大学鄂州工业技术研究院 | Thrombus-promoting and X-ray developing suppository and preparation method and application thereof |
| CN117085166A (en) * | 2023-08-24 | 2023-11-21 | 首都医科大学附属北京同仁医院 | Tantalum-calcium alginate thrombin microsphere and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102258481A (en) * | 2011-08-19 | 2011-11-30 | 薛巍 | Method for preparing self-assembled medicine-carried microspheres by combining high-voltage electrostatic liquid droplet method and layer-by-layer self-assembly method |
| CN102670611A (en) * | 2011-03-07 | 2012-09-19 | 中国人民解放军第三〇九医院 | Vascular targeting embolism sustained release agent of triple compound microsphere for antituberculosis drug, preparation method and applications thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101837143A (en) * | 2010-04-22 | 2010-09-22 | 胡堃 | Medicinal sustained-release and hemostatic composition and preparation method thereof |
| CN103830205B (en) * | 2014-02-28 | 2015-10-28 | 中山大学孙逸仙纪念医院 | A kind of solubilized thrombin nano-particle and its preparation method and application |
-
2014
- 2014-07-01 CN CN201410310437.5A patent/CN105288601B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670611A (en) * | 2011-03-07 | 2012-09-19 | 中国人民解放军第三〇九医院 | Vascular targeting embolism sustained release agent of triple compound microsphere for antituberculosis drug, preparation method and applications thereof |
| CN102258481A (en) * | 2011-08-19 | 2011-11-30 | 薛巍 | Method for preparing self-assembled medicine-carried microspheres by combining high-voltage electrostatic liquid droplet method and layer-by-layer self-assembly method |
Non-Patent Citations (1)
| Title |
|---|
| 凝血酶-壳聚糖海藻酸钠微球止血作用研究;王强,等;《医药导报》;20120531;578-580 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105288601A (en) | 2016-02-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6023009A (en) | Artificial pancreas | |
| CN105288601B (en) | A kind of application being embedded with blood coagulation relevant enzyme hydrogel microsphere | |
| CN107185029A (en) | A kind of macromolecule hydrogel embolism microball for wrapping up medicament-carried nano material and its preparation method and application | |
| CN106693040A (en) | Preparation method of drug-loadable polyvinyl alcohol eluted microspheres | |
| CN104338185A (en) | Carboxymethyl chitosan microsphere embolization agent and preparation method thereof | |
| KR101563968B1 (en) | Biodegradable microbeads with an improved ability to absorb antitumor agent comprising albumin and dextran sulfate and Methods for preparing thereof | |
| JP2009533340A (en) | Multi-membrane immunoisolation system for cell grafts | |
| CN109316626A (en) | A kind of preparation method of medicine-carried Gelatin embolism microsphere | |
| CN101564558A (en) | Alginate-barium sulfate microsphere, preparation method and application thereof | |
| CN107722304A (en) | Thixotroping oxycellulose solution and its medical applications | |
| CN104906049B (en) | A kind of sodium alginate micro ball vascular embolism agent and preparation method thereof | |
| CN101951971B (en) | Bioactive material coating method and tube | |
| RU2454242C1 (en) | Method for preparing herbal water-soluble polysaccharide agent for skin defect elimination and wound repair | |
| KR102348180B1 (en) | Microcarrier for Embolization and Preparation Method thereof | |
| CN106701730A (en) | Alginate hydrogel microsphere carrier containing galactosyl chitosan molecule and application thereof | |
| EP4021519A1 (en) | Alginate based particles as a temporary embolic agent | |
| CN109701071B (en) | Modified silk fibroin arterial embolism microsphere and preparation method thereof | |
| CN101401959B (en) | Producing method of glutin-chitosan-beta-tricalcium phosphate spherical honeycombed grain material | |
| WO2019172261A1 (en) | Esophageal stricture preventing material | |
| CN104645424B (en) | A kind of composite interstitial substance gel vascular occlusive agent and its preparation and application | |
| US20020151055A1 (en) | Novel artificial pancreas | |
| RU2669801C1 (en) | Polymeric material of medical purpose for embolization | |
| CN103611196B (en) | A kind of PELA/BMP-2 microsphere and preparation method thereof | |
| Ouyang et al. | Novel multi-layer APPPA microcapsules for oral delivery: preparation condition, stability and permeability | |
| WO2018070958A2 (en) | Method of forming a structure with extracellular matrix properties in the body using targeted microcapsules |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |