CN104031361A - Temperature sensitive hydrogel, and preparation method and application thereof - Google Patents
Temperature sensitive hydrogel, and preparation method and application thereof Download PDFInfo
- Publication number
- CN104031361A CN104031361A CN201310072360.8A CN201310072360A CN104031361A CN 104031361 A CN104031361 A CN 104031361A CN 201310072360 A CN201310072360 A CN 201310072360A CN 104031361 A CN104031361 A CN 104031361A
- Authority
- CN
- China
- Prior art keywords
- temperature
- plga
- peg
- lactide
- glycollide
- 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.)
- Granted
Links
Landscapes
- Polyesters Or Polycarbonates (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a temperature sensitive hydrogel. The temperature sensitive hydrogel is a PLGA-PEG-PLGA triblock copolymer, wherein a mass ratio of lactide to glycolide in the above PLGA copolymer is 2-4:1, and a ratio of the total mass of lactide and glycolide to PEG is 1-2:1. The invention also discloses a preparation method of the temperature sensitive hydrogel, and an application of the temperature sensitive hydrogel in endoscopic submucosal dissection. The temperature sensitive hydrogel can increase the mucosal protrusion height and prevent the diffusion of a musical lower layer as a marker carrier in the endoscopic submucosal dissection, so the cutting completeness in the endoscopic submucosal dissection is ensured, the perforating and bleeding risks are reduced, the operation safety and efficiency are improved, and the pains of patients are mitigated.
Description
Technical field
The present invention relates to medical technical field, be specifically related to a kind of temperature-sensitive hydrogel and its preparation method and application.
Background technology
PLA-PEG-PLA (PLGA-PEG-PLGA) triblock copolymer, after injection, due to the variation of temperature, copolymer solution changes semi-solid gel into by original solution in vivo.Meanwhile, PLGA-PEG-PLGA has bio-compatibility and biodegradable, because its synthetic raw material and degraded product lactic acid thereof, oxyacetic acid, PEG are the eubolism products in human body, therefore has good bio-compatibility; In purification process without with an organic solvent, the various types of organic solvent residual problem like having run in macromolecular compound leaching process before having solved, and reduced organic solvent pollution in production process and the problem such as inflammable, explosive; Oppositely thermo-sensitivity, at certain aqueous solution (as 25%, w/w) (as 25 DEG C) at ambient temperature, exists with liquid state, and gel occurs rising temperature (as reaching 30～60 DEG C), forms semi-solid hydrogel.
Cancer of the stomach is one of modal malignant tumour in world wide, and according to statistics in 2000, annual new cancer of the stomach 870,000 examples in the whole world, accounted for 9% of all new cases of cancers, are only second to lung cancer, mammary cancer and intestinal cancer, occupy the 4th.Approximately there are every year 640000 people because of mortality of gastric carcinoma, occupy the 2nd of the cancer cause of the death.Malignant tumour is the second largest cause of the death of Chinese population, and mortality of gastric carcinoma occupies mortality of malignant tumors first place, is to threaten one of malignant tumour that China's people's life health is the most serious.Because PD is fast, after discovery symptom, if do not treated, 90% above patient is dead in 1 year.Surgical operation remains current primary treatment means, but that by surgical operation, cancer of the stomach is effected a radical cure only accounts for 1/3, postoperative 5 years survival rates only 25%, major cause is failing to pinpoint a disease in diagnosis early gastric cancer, mistaken diagnosis, the clinical symptom of early gastric cancer is not obvious, extensive observational study points out that approximately 70% early gastric cancer patient is without anaemia, the symptoms such as dysphagy and weight alleviate, correct diagnosis and rational disposal of grasping precancerous lesion, particularly to dysplasia severe or doubtful canceration, the treatment means that adopts excision or scope to process, the limited medical resource of health to patient and China is all significant.
Endoscopic submucosal dissection (endoscopic submucosal dissection, ESD) is the new technology of minimally-invasive treatment early gastric cancer and precancerous lesion under a kind of scope safely and effectively.ESD can the larger focus of complete resection, provide pathological diagnosis material, for new approach has been opened up in the diagnosis and treatment of early gastric cancer and precancerous lesion.The marker using in ESD art is now to add the height of methylene blue marker to ooze Glycerin Fructose solution, in surgical procedure, easily occurs methylene blue diffusion, Marks Illegible, protuberance DeGrain phenomenon.Under scope, the complication of ESD treatment comprises pain, hemorrhage and perforation.How comparatively gentle post-operative pain degree is, and hemorrhage is modal complication, and perforation is the complication of hazard level maximum.
Summary of the invention
The present invention will solve the technical problem that lacks the marker carrier that swells successful and can peel off completely in current Endoscopic submucosal dissection (ESD), a kind of temperature-sensitive hydrogel is provided, this temperature-sensitive hydrogel is PLA-PEG-PLA (PLGA-PEG-PLGA) triblock copolymer of temperature-induced type gelatinizing-in-situ, use the serve as a mark injection carrier of thing methylene blue of this PLGA-PEG-PLGA copolymer solution, can guarantee to cut in ESD operation complete, and can reduce perforation and hemorrhage risk, improve security and the efficiency of operation, alleviate patient's misery.
In addition, also need to provide a kind of preparation method of temperature-sensitive hydrogel and the application in Endoscopic submucosal dissection thereof.
In order to solve the problems of the technologies described above, the present invention is achieved through the following technical solutions:
In one aspect of the invention, a kind of temperature-sensitive hydrogel is provided, described temperature-sensitive hydrogel is PLGA-PEG-PLGA triblock copolymer, wherein, PLGA is hydrophobicity PLGA, PEG is hydrophilic polyglycol polymkeric substance, and in described PLGA multipolymer, rac-Lactide (LA) is 2～4: 1 with the mass ratio of glycollide (GA), and described rac-Lactide and the quality of glycollide sum and the mass ratio of PEG i.e. (LA+GA)/PEG are 1～2: 1.
Preferably, in described PLGA multipolymer, the mass ratio of rac-Lactide and glycollide is 2.5: 1; The quality of described rac-Lactide and glycollide sum and the mass ratio of PEG i.e. (LA+GA)/PEG are 2: 1.
Preferably, described PEG polymkeric substance comprises PEG1000 and PEG1500, and the mass ratio of this PEG1000 and PEG1500 is 1: 1.
In another aspect of this invention, provide a kind of preparation method of temperature-sensitive hydrogel, comprised the following steps:
(1) after PEG1000 and PEG1500 are mixed with certain mass ratio, vacuum back-flow 2～4 hours at suitable temperature, removes the moisture content in PEG1000 and PEG1500;
(2) add rac-Lactide, glycollide, the lower outside temperature of the condition that vacuumizes be heated to 80～100 DEG C 5～20 minutes to dissolution of solid, the mass ratio of the described rac-Lactide adding and glycollide is 2～4: 1, and the quality of this rac-Lactide and glycollide sum and the mass ratio of PEG total amount are 1～2: 1;
(3) be cooled to after room temperature, add catalyzer, with reflux condensate device 120～160 DEG C of reactions of temperature outside 6～12 hours, stop heating and vacuumize 20～40 minutes, be cooled to room temperature, obtain product P LGA-PEG-PLGA triblock copolymer.
Preferably, in step (3) afterwards, also comprise the steps (4):
In ice bath, dissolve products therefrom with distilled water, be heated to 60～90 DEG C and produce precipitation, abandoning supernatant, repeat this Solution and precipitation operation 2～4 times, remove unreacted glycollide, rac-Lactide and low-molecular weight copolymer, collect not water-soluble precipitation, must remove the PLGA-PEG-PLGA triblock copolymer product after impurity.
Preferably, in step (4) afterwards, also comprise the steps (5):
By after products therefrom vacuum lyophilization in cryopreservation.
Preferably, in one embodiment of the invention, the rac-Lactide in step (2) and the mass ratio of glycollide are 2.5: 1, and the quality of this rac-Lactide and glycollide sum and the mass ratio of PEG total amount are 2: 1, in step (3), 142 DEG C of reactions of temperature outside 8 hours.
In another aspect of this invention, also provide the application of above-mentioned temperature-sensitive hydrogel, for the preparation of the marker carrier in Endoscopic submucosal dissection.
Front at Endoscopic submucosal dissection (ESD), the triblock copolymer solution of the present invention that contains 0.2%wt concentration methylene blue marker is injected into the submucosa of early gastric cancer diseased region by endoscopic injection pin, under 37 DEG C of body temperature conditions, in one minute, copolymer solution can change to semi-solid gel shape, remain on intra-operative mucosal protrusion, can prevent that marker methylene blue is in submucosal diffusion, increase the accuracy of operation.And copolymer solution of the present invention is applied in ESD operation as methylene blue marker carrier, can reduce bleeding risk, increases bump height, is conducive to operation and carries out smoothly.
Preferably, the working concentration of described temperature-sensitive hydrogel in Endoscopic submucosal dissection is 15%～30%.
Temperature-sensitive hydrogel of the present invention, it is a kind of PLGA-PEG-PLGA triblock copolymer of temperature-induced type gelatinizing-in-situ, this triblock copolymer is when concentration is 15～30%wt at normal temperatures, exist with liquid state, in solution, form micella, along with the rising of temperature, the hydrogen bond rupture between polymkeric substance and water, micella is assembled, and forms gel.In the time of human body temperature, this polymers soln can become semi-solid gel by rapid conversion, this characteristic has determined that this multipolymer serves as a mark carrier in the stationarity of diseased region, and this material has biodegradability and biocompatibility, can be widely used in pharmaceutical industries.
Brief description of the drawings
Below in conjunction with the drawings and specific embodiments, the present invention is further detailed explanation.
Fig. 1 is the nucleus magnetic hydrogen spectrum figure of the embodiment of the present invention 1 triblock copolymer;
Fig. 2 is the phase transformation figure of the embodiment of the present invention 2 triblock copolymers;
Fig. 3 is the mark effect of the embodiment of the present invention 3 temperature-sensitive hydrogels in isolated pig stomach and peels off design sketch.
Embodiment
The present invention has developed a kind of PLGA-PEG-PLGA triblock copolymer of temperature-induced type, in the process that this multipolymer can be changed to body temperature by room temperature in temperature, changed to semi-solid gel state by clear soln, its transition mechanisms is the certain density PLGA-PEG-PLGA aqueous solution, at normal temperature state in solution state, PLGA-PEG-PLGA forms micella in the aqueous solution, in the time that temperature is increased to 34 DEG C～39 DEG C, hydrogen bond rupture between polymkeric substance and water molecules, de-hydration occurs, thereby micella is assembled formation semi-solid gel shape.
In PLGA-PEG-PLGA triblock copolymer of the present invention, PLGA is hydrophobicity PLGA, PEG is hydrophilic polyglycol polymkeric substance, in PLGA multipolymer, the mass ratio of rac-Lactide and glycollide is 2～4: 1, and this rac-Lactide and the quality of glycollide sum and the mass ratio of PEG are 1～2: 1.
The preparation method of PLGA-PEG-PLGA triblock copolymer of the present invention, comprises the following steps:
(1) after PEG1000 and PEG1500 are mixed with certain mass ratio, vacuum back-flow 2～4 hours at suitable temperature, removes the moisture content in PEG1000 and PEG1500;
(2) add rac-Lactide, glycollide, the lower outside temperature of the condition that vacuumizes be heated to 80～100 DEG C 5～20 minutes to dissolution of solid, the rac-Lactide that this adds and the mass ratio of glycollide are 2～4: 1, and the quality of this rac-Lactide and glycollide sum and the mass ratio of PEG total amount are 1～2: 1;
(3) be cooled to after room temperature, add catalyzer, with reflux condensate device 120～160 DEG C of reactions of temperature outside 6～12 hours, stop heating and vacuumize 20～40 minutes, be cooled to room temperature, obtain product P LGA-PEG-PLGA triblock copolymer.
Preferably, in step (3) afterwards, also comprise the steps (4):
In ice bath, dissolve products therefrom with distilled water, be heated to 60～90 DEG C and produce precipitation, abandoning supernatant, repeat this Solution and precipitation operation 2～4 times, remove unreacted glycollide, rac-Lactide and low-molecular weight copolymer, collect not water-soluble precipitation, must remove the PLGA-PEG-PLGA triblock copolymer product after impurity.
Preferably, in step (4) afterwards, also comprise the steps (5):
By after products therefrom vacuum lyophilization in cryopreservation.
The PLGA-PEG-PLGA triblock copolymer bag of preparing with the present invention carries methylene blue marker, can play the effect of good fixing mark in ESD art.Experimental result demonstration, the fixing mark effect of this copolymer solution is better than physiological saline group and height oozes Glycerin Fructose solution group.
In the preparation process of PLGA-PEG-PLGA triblock copolymer of the present invention, the D adding by further adjustment, ratio and temperature of reaction and the time of L-rac-Lactide (LA), glycollide (GA) and PEG, thereby control the phase transition temperature of triblock copolymer, the phase transition temperature of adjusting this multipolymer approaches to 37 DEG C so that this triblock copolymer be better applicable to temperature-induced type in body administration.
Further elaborate the present invention below by specific embodiment.
Embodiment 1
The present embodiment is prepared PLGA-PEG-PLGA triblock copolymer, comprises that step is as follows:
(1) cetomacrogol 1000 (PEG1000) and polyethylene glycol 1500 (PEG1500) are joined in three-necked bottle with the mass ratio of 1: 1, under rotating speed 200r/min condition, oil pump control vacuum tightness is at-0.1MPa, 145 DEG C of outer temperature, 130 DEG C of vacuum cold-water reflux 2h of interior temperature, remove the minority moisture content in PEG1000 and PEG1500;
(2) then logical high pure nitrogen is cooled to room temperature, add rac-Lactide (LA), glycollide (GA), the ratio that makes LA/GA is 2: 1, and (LA+GA)/PEG ratio is 1: 1, and the lower outside temperature of the condition that vacuumizes is heated to 100 DEG C of 5min to dissolution of solid;
(3) logical nitrogen is cooled to room temperature, adds after the sub-tin of octoate catalyst, loads onto reflux condensate device, and in 120 DEG C of reaction 6h of outer temperature, reaction solution is light yellow clarification, stops heating and vacuumizes 20min, naturally cools to room temperature;
(4) in 4 DEG C of ice baths, dissolve products therefrom with distilled water, be heated to 60 DEG C and produce precipitation, abandoning supernatant, repetitive operation 3 times, remove unreacted glycollide, rac-Lactide and low-molecular weight copolymer, collect not water-soluble precipitation and obtain the colourless and light yellow transparent products of thickness;
(5) by after products therefrom vacuum lyophilization in-20 DEG C of preservations.
Embodiment 2
The present embodiment is prepared PLGA-PEG-PLGA triblock copolymer, comprises that step is as follows:
(1) cetomacrogol 1000 (PEG1000) and polyethylene glycol 1500 (PEG1500) are joined in three-necked bottle with the mass ratio of 1: 1, under rotating speed 200r/min condition, oil pump control vacuum tightness is at-0.1MPa, 145 DEG C of outer temperature, 130 DEG C of vacuum cold-water reflux 3h of interior temperature, remove the minority moisture content in PEG1000 and PEG1500;
(2) then fill high pure nitrogen and be cooled to room temperature, add rac-Lactide (LA), glycollide (GA), the ratio that makes LA/GA is 2.5: 1, and (LA+GA)/PEG ratio is 2: 1, and the lower outside temperature of the condition that vacuumizes is heated to 90 DEG C of 10min to dissolution of solid;
(3) logical nitrogen is cooled to room temperature, adds after the sub-tin of octoate catalyst, loads onto reflux condensate device, and in 142 DEG C of reaction 8h of outer temperature, reaction solution is light yellow clarification, stops heating and vacuumizes 30min, naturally cools to room temperature;
(4) in 4 DEG C of ice baths, dissolve products therefrom with distilled water, be heated to 80 DEG C and produce precipitation, abandoning supernatant, repetitive operation 3 times, remove unreacted glycollide, rac-Lactide and low-molecular weight copolymer, collect not water-soluble precipitation and obtain the colourless and light yellow transparent products of thickness;
(5) by after products therefrom vacuum lyophilization in-20 DEG C of preservations.
Embodiment 3
The present embodiment is prepared PLGA-PEG-PLGA triblock copolymer, comprises that step is as follows:
(1) cetomacrogol 1000 (PEG1000) and polyethylene glycol 1500 (PEG1500) are joined in three-necked bottle with the mass ratio of 1: 1, under rotating speed 200r/min condition, oil pump control vacuum tightness is at-0.1MPa, 145 DEG C of outer temperature, 130 DEG C of vacuum cold-water reflux 4h of interior temperature, remove the minority moisture content in PEG1000 and PEG1500;
(2) then fill high pure nitrogen and be cooled to room temperature, add rac-Lactide (LA), glycollide (GA), the ratio that makes LA/GA is 4: 1, and (LA+GA)/PEG ratio is 1.6: 1, and the lower outside temperature of the condition that vacuumizes is heated to 80 DEG C of 20min to dissolution of solid;
(3) logical nitrogen is cooled to room temperature, adds after the sub-tin of octoate catalyst, loads onto reflux condensate device, and in 160 DEG C of reaction 12h of outer temperature, reaction solution is light yellow clarification, stops heating and vacuumizes 30min, naturally cools to room temperature;
(4) in 4 DEG C of ice baths, dissolve products therefrom with distilled water, be heated to 90 DEG C and produce precipitation, abandoning supernatant, repetitive operation 3 times, remove unreacted glycollide, rac-Lactide and low-molecular weight copolymer, collect not water-soluble precipitation and obtain the colourless and light yellow transparent products of thickness;
(5) by after products therefrom vacuum lyophilization in-20 DEG C of preservations.
PLGA-PGE-PLGA triblock copolymer 2.0mg prepared by above-described embodiment 1-3, is dissolved in 0.6ml deuterochloroform, and NMR (300MHz) identifies polymer architecture, obtains desirable nuclear magnetic resonance map (seeing Fig. 1).Result shows, the chemical shift peak δ value that belongs to PLGA-PEG-PLGA is as follows: δ=5.22ppm (CH of LA), 1.50ppm (CH3of LA), 4.85ppm (CH2of GA), 3.60ppm (CH2of PEG), and 2.75ppm (OH of LA), illustrate that the present invention successfully synthesizes PLGA-PEG-PLGA triblock copolymer.
Embodiment 4
The PLGA-PEG-PLGA triblock copolymer compound concentration that uses above-described embodiment to prepare is respectively 15%, 20%, 25% and 30% aqueous solutions of polymers, together add in 10ml cillin bottle sealed membrane sealing after jumping a queue with magnetic stir bar (3mm × 8mm).After 4 DEG C of balances, cillin bottle is put in diffusion instrument, make circulator bath liquid level higher than aqueous solutions of polymers, temperature programming after startup stirring 100r/min, 4 DEG C start to heat up, 1～2 DEG C/min.Stop stirring and heating after cillin bottle is tilted 90 °, if do not flow to bottleneck in 3s, temperature is now defined as to the phase transition temperature of aqueous solutions of polymers.Each sample replicate(determination) 3 times, results averaged.
Result as shown in Figure 2, Fig. 2 is that the ratio of use LA/GA is 2.5: 1, (LA+GA)/PEG ratio is 2: 1 synthetic triblock copolymers phase transition temperature figure under different concns, along with the continuous increase of triblock copolymer substrate concentration, triblock copolymer aqueous gel temperature range expands.
Embodiment 5
The PLGA-PEG-PLGA triblock copolymer that uses above-described embodiment to prepare is mixed with the solution 10ml of 20%wt concentration, add the methylene blue of 0.02ml, this mixing solutions is injected into pig submucous lamina of stomach, ensures that isolated pig stomach is under 37 DEG C of constant temperatures, observe protuberance effect.
Use normal saline solution 10ml, add the methylene blue of 0.02ml, this mixing solutions is injected into pig submucous lamina of stomach, ensure that isolated pig stomach is under 37 DEG C of constant temperatures, observe protuberance effect.
Use the high Glycerin Fructose solution 10ml that oozes, add the methylene blue of 0.02ml, this mixing solutions is injected into pig submucous lamina of stomach, ensure that isolated pig stomach is under 37 DEG C of constant temperatures, observe protuberance effect.
The mucous membrane top layer of the gel group protuberance of injection is peeled off, peel off mucous membrane top layer along the marker edge of protuberance, observe and peel off effect.
As shown in Figure 3, what Fig. 3 (a) showed is bump height and the diffusions of different methylene blue injection of solution at pig submucous lamina of stomach to result, can be it is evident that by Fig. 3 (a), and the bump height of gel group is the most remarkable; What Fig. 3 (b) showed is the design sketch of peeling off behind mucous membrane top layer, the methylene blue diffusion area maximum of physiological saline group, and gel group not only diffusion area is little, and being marked with to be beneficial to and divesting mucous membrane top layer of gel group, can protect submucosa not accidentally injured.What Fig. 3 (c) showed is that gel group is being peeled off after stratum supravasculare, in the time that operation finishes, the gel of injection can be peeled off completely, does not have gel and remains in wound.
The above embodiment has only expressed embodiments of the present invention, and it describes comparatively concrete and detailed, but can not therefore be interpreted as the restriction to the scope of the claims of the present invention.It should be pointed out that for the person of ordinary skill of the art, without departing from the inventive concept of the premise, can also make some distortion and improvement, these all belong to protection scope of the present invention.Therefore, the protection domain of patent of the present invention should be as the criterion with claims.
Claims (10)
1. a temperature-sensitive hydrogel, it is characterized in that, described temperature-sensitive hydrogel is PLGA-PEG-PLGA triblock copolymer, wherein, PLGA is PLGA, PEG is polyethylene glycol polymer, and in described PLGA multipolymer, the mass ratio of rac-Lactide and glycollide is 2～4: 1, and described rac-Lactide and the quality of glycollide sum and the mass ratio of PEG are 1～2: 1.
2. temperature-sensitive hydrogel according to claim 1, is characterized in that, in described PLGA multipolymer, the mass ratio of rac-Lactide and glycollide is 2.5: 1.
3. temperature-sensitive hydrogel according to claim 1, is characterized in that, described rac-Lactide and the quality of glycollide sum and the mass ratio of PEG are 2: 1.
4. according to the temperature-sensitive hydrogel described in any one in claims 1 to 3, it is characterized in that, described PEG polymkeric substance comprises PEG1000 and PEG1500, and the mass ratio of this PEG1000 and PEG1500 is 1: 1.
5. a preparation method for temperature-sensitive hydrogel, is characterized in that, comprises the following steps:
(1) after PEG1000 and PEG1500 are mixed with certain mass ratio, vacuum back-flow 2～4 hours at suitable temperature, removes the moisture content in PEG1000 and PEG1500;
(2) add rac-Lactide, glycollide, the lower outside temperature of the condition that vacuumizes be heated to 80～100 DEG C 5～20 minutes to dissolution of solid, the mass ratio of the described rac-Lactide adding and glycollide is 2～4: 1, and the quality of this rac-Lactide and glycollide sum and the mass ratio of PEG total amount are 1～2: 1;
(3) be cooled to after room temperature, add catalyzer, with reflux condensate device 120～160 DEG C of reactions of temperature outside 6～12 hours, stop heating and vacuumize 20～40 minutes, be cooled to room temperature, obtain product P LGA-PEG-PLGA triblock copolymer.
6. preparation method according to claim 5, is characterized in that, in step (3) afterwards, also comprises the steps (4):
In ice bath, dissolve products therefrom with distilled water, be heated to 60～90 DEG C and produce precipitation, abandoning supernatant, repeat this Solution and precipitation operation 2～4 times, remove unreacted glycollide, rac-Lactide and low-molecular weight copolymer, collect not water-soluble precipitation, must remove the PLGA-PEG-PLGA triblock copolymer product after impurity.
7. preparation method according to claim 5, is characterized in that, in described step (2), the mass ratio of rac-Lactide and glycollide is 2.5: 1, and the quality of this rac-Lactide and glycollide sum and the mass ratio of PEG total amount are 2: 1.
8. preparation method according to claim 5, is characterized in that, in described step (3), and 142 DEG C of reactions of temperature outside 8 hours.
9. the application of temperature-sensitive hydrogel described in claim 1, is characterized in that, for the preparation of the marker carrier in Endoscopic submucosal dissection.
10. application according to claim 9, is characterized in that, the working concentration of described temperature-sensitive hydrogel in Endoscopic submucosal dissection is 15%～30%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310072360.8A CN104031361B (en) | 2013-03-07 | 2013-03-07 | temperature-sensitive hydrogel and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310072360.8A CN104031361B (en) | 2013-03-07 | 2013-03-07 | temperature-sensitive hydrogel and its preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104031361A true CN104031361A (en) | 2014-09-10 |
| CN104031361B CN104031361B (en) | 2016-08-10 |
Family
ID=51462370
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310072360.8A Active CN104031361B (en) | 2013-03-07 | 2013-03-07 | temperature-sensitive hydrogel and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104031361B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113358615B (en) * | 2021-06-01 | 2023-05-12 | 张慧敏 | Application of Melan and sodium fluorescein double staining method in living cell imaging |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101333294A (en) * | 2007-06-28 | 2008-12-31 | 信谊药厂 | Biodegradable triblock copolymer with invertible thermal gelling property |
-
2013
- 2013-03-07 CN CN201310072360.8A patent/CN104031361B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101333294A (en) * | 2007-06-28 | 2008-12-31 | 信谊药厂 | Biodegradable triblock copolymer with invertible thermal gelling property |
Non-Patent Citations (1)
| Title |
|---|
| 王晶等: "生物降解聚合物PLGA-PEG-PLGA的合成及表征", 《沈阳药科大学学报》, vol. 22, no. 5, 30 September 2005 (2005-09-30), pages 348 - 351 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113358615B (en) * | 2021-06-01 | 2023-05-12 | 张慧敏 | Application of Melan and sodium fluorescein double staining method in living cell imaging |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104031361B (en) | 2016-08-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zhang et al. | Tough hydrogel bioadhesives for sutureless wound sealing, hemostasis and biointerfaces | |
| CN104689381A (en) | Hydrogel composition for gastrointestinal submucosal injection and application of hydrogel composition | |
| CN104645356B (en) | The thermotropic hydrogel and preparation method thereof of a kind of X-ray development | |
| CN104448261B (en) | High performance polymer amount poly (l-lactic acid) synthesis technique | |
| CN102068719A (en) | Adhesion prevention material formed by physical crosslinking hydrogel composition and preparation method and application thereof | |
| CN104758256A (en) | Docetaxel nano polymer micelle freeze-drying preparation and preparation method thereof | |
| CN105147342A (en) | Device system and method for tissue displacement or separation | |
| CN105287362B (en) | Thermotropic hydrogel and the preparation method and application thereof of the one kind containing selenium or tellurium | |
| Yuan et al. | 5-Fluorouracil loaded thermosensitive PLGA–PEG–PLGA hydrogels for the prevention of postoperative tendon adhesion | |
| CN108853610A (en) | Radiopaque polymer for medical device | |
| CN105708789B (en) | A kind of medicament-carrying nano-fiber microballoon/hydrogel composites and its preparation method and application | |
| CN103055354A (en) | Biodegradable medical surgery anti-adhesion membrane and preparation method thereof | |
| CN102264399A (en) | Polymer compositions of dihydroxyacetone and uses thereof | |
| CN108926531A (en) | A kind of reduction and the nano-micelle of pH dual responsiveness and the preparation method and application thereof | |
| CN101864061B (en) | Microwave irradiation method for preparing star polycaprolactone-polylactic acid block copolymer | |
| CN103992465B (en) | biodegradable terpolymer | |
| CN104031361A (en) | Temperature sensitive hydrogel, and preparation method and application thereof | |
| Yazar et al. | Safety and reliability of microsurgical free tissue transfers in paediatric head and neck reconstruction–a report of 72 cases | |
| Gazet | Parks' coloanal pull-through anastomosis for severe, complicated radiation proctitis | |
| Ma et al. | Injectable shear-thinning sodium alginate hydrogels with sustained submucosal lift for endoscopic submucosal dissection | |
| KR101297363B1 (en) | Composition comprising local injection preparation for endoscopic mucosal resection | |
| Saget et al. | Temporary restoration of digestive continuity after laparoscopic gastric bypass to allow endoscopic sphincterotomy and retrograde exploration of the biliary tract | |
| Nam et al. | Role of primary closure after transoral robotic surgery for tonsillar cancer | |
| Isomoto et al. | Endoscopic submucosal dissection in the era of proton pump inhibitors | |
| CN111110926A (en) | Injectable colored gel pad for alimentary canal mucosa layering and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Gao Shen Inventor after: Wang Xiaoyu Inventor after: Zhang Lijuan Inventor after: Dai Ziyuan Inventor after: Tai Zongguang Inventor after: Gao Yuan Inventor after: Gu Fenfen Inventor after: Hu Chuling Inventor after: Gong Chunai Inventor after: Xia Qingming Inventor after: Zhang Min Inventor after: Zhu Quangang Inventor after: Jin Zhendong Inventor after: Liu Qingqing Inventor after: Gao Jing Inventor after: Shi Xingang Inventor after: Liu Feng Inventor after: Liu Jiyong Inventor before: Gao Shen Inventor before: Wang Xiaoyu Inventor before: Zhang Lijuan Inventor before: Dai Ziyuan Inventor before: Tai Zongguang Inventor before: Zhang Min Inventor before: Zhu Quangang Inventor before: Jin Zhendong Inventor before: Liu Qingqing Inventor before: Gao Jing Inventor before: Shi Xingang Inventor before: Liu Feng Inventor before: Liu Jiyong |
|
| COR | Change of bibliographic data | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |