CN102755282A - Temperature sensitive injectable drug-loading controlled release system - Google Patents
Temperature sensitive injectable drug-loading controlled release system Download PDFInfo
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- CN102755282A CN102755282A CN2012101793872A CN201210179387A CN102755282A CN 102755282 A CN102755282 A CN 102755282A CN 2012101793872 A CN2012101793872 A CN 2012101793872A CN 201210179387 A CN201210179387 A CN 201210179387A CN 102755282 A CN102755282 A CN 102755282A
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Abstract
The invention discloses a temperature sensitive injectable drug-loading controlled release system, which comprises a star-shaped poly-lactic-co-glycolic acid-methoxy polyethylene glycol segmented copolymer and a simulated body fluid, and the content of the copolymer accounts for 15-40 weight by percent. The drug-loading controlled release system exists in a state of liquid which can freely flow in or below room temperature, is rapidly changed into oyster white physical crosslinking hydrogel which cannot flow at a human body temperature, and expresses a reversible sol- gel conversion behavior; the drug-loading controlled release system can uniformly disperse a loaded drug, and exists in a state of liquid which can freely flow in or below room temperature and gel which cannot freely flow at the body temperature; as a vagina drug-loading controlled release system, the temperature sensitive injectable drug-loading controlled release system has the characteristics that contraceptive compound estrogen, progestogen and an anti-inflammation drug are loaded into a copolymer hydrogel carrier by adopting a solution blending method, and the prepared drug-loading system serves as a birth control spraying agent; the drug-loading system is sprayed into vagina after women menses, and is shaped into mesh gel and attached into a wall, and the drug is slowly and controllably released and have an effect of birth control.
Description
Technical field
The invention belongs to biodegradable polymer and medicine sustained release field, be specifically related to a kind of temperature sensitivity injectable medicine carrying Controlled Release System, the present invention is particularly useful for as injectable vagina medicine carrying Controlled Release System.
Background technology
Along with growth in the living standard and science and technology development, people to various short-terms flexibly the birth-control measures demand increasing, also more active to the research of the flexible birth-control measures of vagina.Vaginal jellies is the research focus as the carrier of various medicines in the past few decades always, and the scientific achievement that the various contraceptives of its coating and vagina antibacterial etc. are obtained has promoted the progress and the bio-medical material subject development of female pathology, reproduction safety.At present; Be applied to PPOX-polyethylene glycol oxide-PPOX ternary block polymer etc. that vaginal jellies that contraceptive coat to discharge mainly contains hydroxyethyl-cellulose, hydroxypropyl cellulose, methylcellulose, polycarbophil, sodium alginate, sodium carboxymethyl cellulose and temperature sensitivity; Former kinds of macromolecular materials need be at the external vaginal jellies for preparing medicine carrying when medicine coats; Implant intravaginal then; And then reaching the purpose of release, the mode of this implantation may cause the subject discomfort sense.And PPOX-polyethylene glycol oxide-PPOX ternary block polymer is different on method for preparing; It at room temperature is free-pouring colloidal sol owing to have temperature sensitive property, and medicine adds under this state; What under body temperature (37 ℃), be formed with certain intensity immediately can not the free-flow gel; Utilize the special sol-gel transition performance of this high polymer, can adopt injection or the method for spraying into to accomplish the placement of medicine-carried system, can not cause subject discomfort or pain.But above-mentioned several kinds can not degradation in vivo vaginal jellies after drug release is accomplished, can pile up in intravaginal, thereby stop up vagina.Within a short period of time complete degradability, can satisfy the temperature-sensitive macromolecular that the drug release treatment requires simultaneously should be the good method that addresses these problems.
Recent two decades comes; Fully biodegradable property temperature-sensitive macromolecular as bio-medical material be applied to that controlled delivery of pharmaceutical agents discharges, the aspects such as regeneration of the propagation of cell and tissue become various countries scientist's research focus, polyester-Polyethylene Glycol block or graft copolymer are particularly common.It is the copolymer of the thermosensitive degradable of block with polyester (PLGA) with Polyethylene Glycol (PEG) that people such as Jeong B. have synthesized a series of, for example, and linear ternary block polymer PEG-PLGA-PEG (Jeong B.et al.; Advanced Drug Delivery Reviews.2002; 54,37 – 51), graft copolymer PLGA-g-PEG and PEG-g-PLGA (Jeong B.et al., Chem.Commun.; 2001,1516 – 1517; Jeong B.et al., J.Phys.Chem.B2003,107; 10032-10039.), the certain density aqueous solution of the amphipathic high polymer of this type has temperature sensitive property, promptly at room temperature is mobile liquid phase; And fast transition is can not mobile gel under body temperature; Show as reversible sol-gel transition phenomenon, have excellent biological compatibility and biological degradability simultaneously, be suitable as the carrier material of injection preparation.In control drug release research, serve as to discharge medicine (Jeong B.et al., J.Controlled Release with hydrophilic medicament Ketoprofen and hydrophobic drug Spironolactone; 2000; 63,155-163), finding has solubilization effect to hydrophobic drug; Medicine is released to the master with diffusion in early days, and the later stage discharges with diffusion follows the stable master that is released to that degrades.(Zentner GM.et al. such as Zentner; J.Controlled Release; 2001; 72, be that catalyst has synthesized the linear temperature sensitive property block copolymer of PLGA-PEG-PLGA ternary and its exploitation is become commodity ReGel (copolymer concentration is 23wt%) through the mode of ring-opening polymerisation with the stannous octoate 203-215).People such as Zou Peng have reported a kind of synthetic method of temperature sensitive property star four arm PLGA-mPEG block copolymers; This copolymer aquagel has in sol-gel transition performance, the good body and external biological degradation property, body in biocompatibility (Peng Z.et al.; J.Mater.Chem.; 2012,22,6316-6326).Ding Jiandong etc. disclose a kind of degradable temperature sensitive physical aquagel and preparation method thereof in CN 1823726A; Through stannous iso caprylate, calcium hydride or zinc powder is catalyst, is that macromole evocating agent has synthesized the linear temperature sensitive property block copolymer of PLGA-PEG-PLGA ternary with the Polyethylene Glycol.Present above-mentioned thermo-responsive hydro gel is mainly used in field of tissue engineering technology such as sustained release and the cell culture of bioactive substances such as insulin, ciclosporin A, paclitaxel, testosterone, indomethacin, gene and tissue adhesion prevents.Seldom there is bibliographical information in sustained release field at contraceptive, and the sustained release of particularly female, progestogen and three kinds of compound contraceptions of indomethacin antibiotic medicine is not seen bibliographical information.
Summary of the invention
The object of the present invention is to provide a kind of temperature sensitivity injectable medicine carrying Controlled Release System; Described medicine carrying Controlled Release System can the contained medicine of homodisperse, exist with free-pouring liquid form in room temperature or below the room temperature, under body temperature not existing by free-pouring gel form.
A kind of temperature sensitivity injectable medicine carrying Controlled Release System provided by the invention is characterized in that, star poly (glycolide-lactide)-poly glycol monomethyl ether block copolymer and human body simulation liquid, and the mass percentage content of said copolymer is 15-40%.
As a kind of improvement of technique scheme, said human body simulation liquid is the simulation vaginal secretion, and contained medicine is the mixture of ethinylestradiol, gestodene and indomethacin, and contained medicine is the 0.01-8wt% of system's gross mass.
The temperature sensitivity injectable medicine carrying Controlled Release System that the present invention proposes is compared with existing biodegradable temperature-sensitive hydrogel has following characteristics:
The important composition composition star poly (glycolide-lactide) (PLGA) of medicine carrying Controlled Release System-poly glycol monomethyl ether (mPEG) block copolymer shows as how much topological structure on molecular structure regular, symmetrical; Cause this medicine carrying Controlled Release System to have lower viscosity, higher copolymer concentration and higher medicine covering amount at low temperatures, still keep degradation speed faster simultaneously.
As vagina medicine carrying Controlled Release System; Coat estrogen (ethinylestradiol), progestogen (gestodene) and antibiotic medicine (indomethacin) simultaneously; The effect of short-term contraception (once spraying into vagina) or long-term contraception (spraying into vagina once in every month) can be reached, the effect of antiinflammatory can be played again.
The medicine carrying Controlled Release System that the present invention proposes only just shows the sol-gel transition characteristic in the 10-45wt% concentration range.When excessive concentration, its room temperature and below the room temperature can not mobile gel state form existing, the transformation of gel-sol can only take place along with the raising of temperature; When concentration is crossed when low; Cold sol-thermosol-sedimentary transformation can only take place in its raising along with temperature; Without the gel form process, so above-mentioned two kinds of situations all are not suitable for the coating of medicine, and when copolymer concentration is 10-45wt%; The sol-gel transition characteristic can take place in its raising along with temperature; Concrete transition phenomenon is cold sol (low temperature)-gel (body temperature)-thermosol (higher temperature)-deposition (higher temperature), is convenient to injection operation so the high polymeric solution system in this concentration range can be used for the medicine coating, and more suitable concn is 15-40wt%.
The medicine carrying Controlled Release System that the present invention proposes can through with estrogen (ethinylestradiol), progestogen (gestodene or levonorgestrel) and antibiotic medicine (indomethacin) with blended mode coating medicine.The solvent of polymer is the simulation vaginal secretion.The rate of release of combination drug can be controlled through adjusting the lactide and the amount of substance ratio of Acetic acid, hydroxy-, bimol. cyclic ester and the factors such as concentration of copolymer.The drug loading of gel does not have strict restriction, only if drug loading influences the sol-gel transition behavior of copolymer solution.Route of administration can be that vagina medicine carrying Controlled Release System sprays into vagina or subcutaneous injection.
Compare with the other medicines controlled release carrier, the temperature sensitive property of the degradable medicine carrying Controlled Release System that the present invention proposes has following characteristics:
1. but the medicine carrying Controlled Release System has complete degradability, syringeability in the intelligent short time simultaneously.
2. important composition composition star poly (glycolide-lactide) (PLGA) in the medicine carrying Controlled Release System-poly glycol monomethyl ether (mPEG) block copolymer is made up of hydrophilic block mPEG and hydrophobicity block PLGA; Have amphipathicly, it can be self-assembled into the micelle (20-50nm) of Nano grade in specific solvent.
3. important composition composition star poly (glycolide-lactide) (PLGA) in the medicine carrying Controlled Release System-poly glycol monomethyl ether (mPEG) block copolymer is star-like macromolecules chain topological structure on molecular structure; Regular, symmetrical; Cause the medicine carrying Controlled Release System to have lower viscosity, higher copolymer concentration and higher medicine covering amount, still keep degradation speed faster simultaneously.
4. important composition composition star poly (glycolide-lactide) (PLGA) in the medicine carrying Controlled Release System-poly glycol monomethyl ether (mPEG) block copolymer is made up of synthesized polymer material fully, and each block composition has good biocompatibility.
5. medicine carrying Controlled Release System neutral; Its degradation behavior is mainly the hydrolysis of ester bond, and product is micromolecule lactic acid, glycolic and poly glycol monomethyl ether, and the above two are metabolized to carbon dioxide through tricarboxylic acid cycle and water is discharged; The latter is discharged by urine through kidney, to the human body safety non-toxic.
6. through adjustment poly glycol monomethyl ether shared mass fraction and the amount of substance ratio of molecular weight size, lactide and Acetic acid, hydroxy-, bimol. cyclic ester and next sol-gel transition temperature, degradation rate and the rate of releasing drug of regulating this medicine carrying Controlled Release System arbitrarily of factors such as concentration of copolymer.
7. the medicine carrying Controlled Release System has than solubilization effect hydrophobic drug, has improved the dissolubility of medicine in copolymer solution.
8. as vagina medicine carrying sustained release system, adopt that solution blended process is female with the contraceptive compound recipe, progestogen (ethinylestradiol, gestodene) and antibiotic medicine (indomethacin) be written into the copolymer aquagel carrier, the drug-loading system of preparation is as the birth control spray.In woman month sprayed into after intact, it formed netted gel and is attached to wall, slowly controllably discharges medicine, can reach the effect of short-term contraception (once spraying into vagina) or long-term contraception (spraying into vagina once in every month), can play the effect of antiinflammatory again.
Description of drawings
Fig. 1 is the rheological curve that the medicine carrying Controlled Release System raises with temperature under variable concentrations;
Fig. 2 is the drug test mobile phase mixed proportion curve that HPLC is confirmed;
Fig. 3 be three kinds of medicines go out peak sequencing curve;
Fig. 4 is the cumulative release curve of indomethacin, gestodene and ethinylestradiol;
Fig. 5 is the Higuchi model matched curve of ethinylestradiol.
The specific embodiment
Medicine carrying Controlled Release System of the present invention comprises star poly (glycolide-lactide) (PLGA)-poly glycol monomethyl ether (mPEG) block copolymer, the human body simulation liquid of temperature sensitivity, is used for the contained medicine of embedding.
The content of hydrophobic block PLGA in the important composition star poly (glycolide-lactide) (PLGA) of medicine carrying Controlled Release System-poly glycol monomethyl ether (mPEG) block copolymer is 55-85wt%; The content of hydrophilic block mPEG is 15-45wt%; More suitable consists of; The content of hydrophobic block PLGA is 60-75wt%, and the content of hydrophilic block mPEG is 25-40wt%.
Among the hydrophobic block PLGA of the important composition star poly (glycolide-lactide) (PLGA) of medicine carrying Controlled Release System-poly glycol monomethyl ether (mPEG) block copolymer, lactide content is 0-100mol%, and glycolide content is 0-100mol%; More suitable consists of, and lactide content is 50-90mol%, and glycolide content is 10-50mol%.
The number-average molecular weight of the hydrophilic block mPEG of the important composition star poly (glycolide-lactide) (PLGA) of medicine carrying Controlled Release System-poly glycol monomethyl ether (mPEG) block copolymer is 350-1000, and more suitable molecular weight is 350-750.
Medicine carrying Controlled Release System provided by the invention not only can be used as the medicine carrying Controlled Release System; Also can be used as the Controlled Release System of other medicines; The aqueous solution of its 15-40wt%, simulated solution or other simulated solution (PBS buffer, simulated body fluid, simulated uterine fluid) are free-pouring liquid colloidal sol in room temperature or below the room temperature, and fast transition is not free flowable gel under human body temperature.
When as vagina medicine carrying Controlled Release System; Medicine (ethinylestradiol, gestodene and indomethacin) evenly is embedded in the simulation vaginal secretion of any vagina medicine carrying Controlled Release System; In room temperature or below the room temperature is free-pouring liquid colloidal sol, and fast transition is not free flowable medicine carrying gel under human body temperature.
The content of the important composition star poly (glycolide-lactide) (PLGA) of said medicine carrying Controlled Release System-poly glycol monomethyl ether (mPEG) block copolymer is 15-40wt%, and said content of medicines is 0.01-8wt%, and surplus is a solvent.
Medicine in the said vagina medicine carrying Controlled Release System is that the composite contraception medicine is female, progestogen (ethinylestradiol, gestodene, levonorgestrel) and antibiotic medicine indomethacin.
Through instance the medicine carrying Controlled Release System is described below.The present invention not only limits to following examples.
Embodiment 1
Star poly (glycolide-lactide) (PLGA)-poly glycol monomethyl ether (mPEG) block copolymer; The lactide molar ratio is 90% in its poly (glycolide-lactide) (PLGA) block; The Acetic acid, hydroxy-, bimol. cyclic ester molar ratio is 10%; With its simulation vaginal secretion that is dissolved in 2-4 ℃ fully, being mixed with concentration is 30wt% radial copolymer solution.It is the above-mentioned radial copolymer solution of 30wt% that 2.0mg ethinylestradiol, 4.80mg gestodene and 12mg indomethacin are dissolved in 1ml concentration, prepares vagina medicine carrying Controlled Release System.
Elevated temperature is observed the sol-gel transition behavior of vagina medicine carrying Controlled Release System and is adopted static its viscosity situation of change of flow graph research.When vagina medicine carrying Controlled Release System can not be defined as gel state by mobile state when vial reverses.Fig. 1 is the vagina medicine carrying Controlled Release System rheological curve that (20,25,30,35 and 40wt%) raise with temperature under variable concentrations.Temperature corresponding when viscosity sharply increases is the sol-gel transition point.The reversibility of vagina medicine carrying Controlled Release System is very obvious, and colloidal sol forms gel when being heated, and its gel reverts back to flowable colloidal sol again when cooling.
Star poly (glycolide-lactide) (PLGA)-poly glycol monomethyl ether (mPEG) block copolymer; The lactide molar ratio is 75% in its poly (glycolide-lactide) (PLGA) block; The Acetic acid, hydroxy-, bimol. cyclic ester molar ratio is 25%; With its simulation vaginal secretion that is dissolved in 2-4 ℃ fully, being mixed with concentration is 30wt% radial copolymer solution.It is the above-mentioned radial copolymer solution of 30wt% that 2.0mg ethinylestradiol, 4.80mg gestodene and 12mg indomethacin are dissolved in 1ml concentration, prepares vagina medicine carrying Controlled Release System.
Star poly (glycolide-lactide) (PLGA)-poly glycol monomethyl ether (mPEG) block copolymer; The lactide molar ratio is 50% in its poly (glycolide-lactide) (PLGA) block; The Acetic acid, hydroxy-, bimol. cyclic ester molar ratio is 50%; With its simulation vaginal secretion that is dissolved in 2-4 ℃ fully, being mixed with concentration is 30wt% radial copolymer solution.It is the above-mentioned radial copolymer solution of 30wt% that 2.0mg ethinylestradiol, 4.80mg gestodene and 12mg indomethacin are dissolved in 1ml concentration, prepares vagina medicine carrying Controlled Release System.
Star poly (glycolide-lactide) (PLGA)-poly glycol monomethyl ether (mPEG) block copolymer; The lactide molar ratio is 50% in its poly (glycolide-lactide) (PLGA) block; The Acetic acid, hydroxy-, bimol. cyclic ester molar ratio is 50%; With its simulation vaginal secretion that is dissolved in 2-4 ℃ fully, being mixed with concentration is 30wt% radial copolymer solution.It is the above-mentioned radial copolymer solution of 30wt% that 4.0mg ethinylestradiol, 10mg gestodene and 25mg indomethacin are dissolved in 1ml concentration, prepares vagina medicine carrying Controlled Release System.
Star poly (glycolide-lactide) (PLGA)-poly glycol monomethyl ether (mPEG) block copolymer; The lactide molar ratio is 50% in its poly (glycolide-lactide) (PLGA) block; The Acetic acid, hydroxy-, bimol. cyclic ester molar ratio is 50%; With its simulation vaginal secretion that is dissolved in 2-4 ℃ fully, being mixed with concentration is 30wt% radial copolymer solution.It is the above-mentioned radial copolymer solution of 30wt% that 8.0mg ethinylestradiol, 20mg gestodene and 50mg indomethacin are dissolved in 1ml concentration, prepares vagina medicine carrying Controlled Release System.
Embodiment 6-13
Vagina medicine carrying Controlled Release System among the embodiment 3 is after 37 ℃ of following 20-30 form gel second, and the simulation vaginal secretion that adds 10 milliliters 37 ℃ is as release medium.In the particular point in time sampling, replenish fresh simulated solution simultaneously with volume, continue sampling 35 days.The sample liquid drug level adopts HPLC (HPLC) to detect.HPLC mobile phase is the mixed liquor of first alcohol and water, and Fig. 2 has confirmed that the volume ratio of mixed flow phase is 53:47, can be preferably with three kinds of medicines separately under this condition.Fig. 3 has confirmed the peak sequence of three kinds of medicines, and promptly indomethacin goes out the peak the earliest, and the time is 11.12min, and secondly the gestodene goes out the peak, and the time is 13.23min, and ethinylestradiol goes out the peak at last, and the time is 15.67min.The standard curve that three kinds of medicines detect under the variable concentrations gradient presents good linear relationship; Fig. 4 has showed the cumulative release law curve of three kinds of medicines; Curve is carried out zero level, one-level and the match of Higuchi model; Find the linear relationship (Fig. 5 is the matched curve of ethinylestradiol) that the match of Higuchi model behaves oneself best, show that the release rule of three kinds of medicines meets the Higuchi model.In the time of 35 days, the cumulative release mark of ethinylestradiol is 38%, gestodene's cumulative release mark is 84%, the cumulative release mark of indomethacin is 55%.
Vagina medicine carrying Controlled Release System among the embodiment 4 is after 37 ℃ of following 20-30 form gel second, and the simulation vaginal secretion that adds 10 milliliters 37 ℃ is as release medium.In the particular point in time sampling, replenish fresh simulated solution simultaneously with volume, continue sampling 35 days.The sample liquid drug level adopts HPLC (HPLC) to detect.The standard curve that three kinds of medicines detect under the variable concentrations gradient presents good linear relationship; Cumulative release law curve to three kinds of medicines carries out zero level, one-level and the match of Higuchi model; Find the linear relationship that the match of Higuchi model behaves oneself best, show that the release rule of three kinds of medicines meets the Higuchi model.In the time of 35 days, the cumulative release mark of ethinylestradiol is 32%, gestodene's cumulative release mark is 58%, the cumulative release mark of indomethacin is 38%.
Vagina medicine carrying Controlled Release System among the embodiment 5 is after 37 ℃ of following 20-30 form gel second, and the simulation vaginal secretion that adds 10 milliliters 37 ℃ is as release medium.In the particular point in time sampling, replenish fresh simulated solution simultaneously with volume, continue sampling 35 days.The sample liquid drug level adopts HPLC (HPLC) to detect.The standard curve that three kinds of medicines detect under the variable concentrations gradient presents good linear relationship; Cumulative release law curve to three kinds of medicines carries out zero level, one-level and the match of Higuchi model; Find the linear relationship that the match of Higuchi model behaves oneself best, show that the release rule of three kinds of medicines meets the Higuchi model.In the time of 35 days, the cumulative release mark of ethinylestradiol is 20%, gestodene's cumulative release mark is 30%, the cumulative release mark of indomethacin is 21%.
When Controlled Release System as other medicines; Adopting corresponding water body simulated solution (can be aqueous solution, simulation vaginal secretion or other simulated solution; Like PBS buffer, simulated body fluid, simulated uterine fluid); The present invention also can produce identical good technical effect, be free-pouring liquid colloidal sol in room temperature or below the room temperature, and fast transition is not free flowable medicine carrying gel under human body temperature.
Those skilled in the art will readily understand; The above is merely preferred embodiment of the present invention; Not in order to restriction the present invention, all any modifications of within spirit of the present invention and principle, being done, be equal to and replace and improvement etc., all should be included within protection scope of the present invention.
Claims (10)
1. a temperature sensitivity injectable medicine carrying Controlled Release System is characterized in that, star poly (glycolide-lactide)-poly glycol monomethyl ether block copolymer and human body simulation liquid, and the mass percentage content of said copolymer is 15-40%.
2. temperature sensitivity injectable medicine carrying Controlled Release System according to claim 1; It is characterized in that; Said human body simulation liquid is the simulation vaginal secretion, and contained medicine is the mixture of ethinylestradiol, gestodene and indomethacin, and contained medicine is the 0.01-8wt% of system's gross mass.
3. temperature sensitivity injectable medicine carrying Controlled Release System according to claim 1 and 2 is characterized in that in the said copolymer, the mass percentage content of poly (glycolide-lactide) is 55-85%, and the mass percentage content of poly glycol monomethyl ether is 15-45%.
4. temperature sensitivity injectable medicine carrying Controlled Release System according to claim 1 and 2 is characterized in that in the said copolymer, the mass percentage content of poly (glycolide-lactide) is 60-75%, and the mass percentage content of poly glycol monomethyl ether is 25-40%.
5. temperature sensitivity injectable medicine carrying Controlled Release System according to claim 1 and 2 is characterized in that in the block poly (glycolide-lactide) of said copolymer, lactide content is 0-100mol%, and surplus is an Acetic acid, hydroxy-, bimol. cyclic ester.
6. temperature sensitivity injectable medicine carrying Controlled Release System according to claim 4 is characterized in that in the block poly (glycolide-lactide) of said copolymer, lactide content is 0-100mol%, and surplus is an Acetic acid, hydroxy-, bimol. cyclic ester.
7. temperature sensitivity injectable medicine carrying Controlled Release System according to claim 1 and 2 is characterized in that in the block poly (glycolide-lactide) of said copolymer, lactide content is 50-90mol%, and surplus is an Acetic acid, hydroxy-, bimol. cyclic ester.
8. temperature sensitivity injectable medicine carrying Controlled Release System according to claim 6 is characterized in that in the block poly (glycolide-lactide) of said copolymer, lactide content is 50-90mol%, and surplus is an Acetic acid, hydroxy-, bimol. cyclic ester.
9. temperature sensitivity injectable medicine carrying Controlled Release System according to claim 1 and 2 is characterized in that the number-average molecular weight of the block poly glycol monomethyl ether of said copolymer is 350-1000, and more suitable molecular weight is 350-750.
10. temperature sensitivity injectable medicine carrying Controlled Release System according to claim 1 and 2 is characterized in that, said human body simulation liquid is aqueous solution, simulate vaginal secretion or comprise other simulated solution of PBS buffer, simulated body fluid and simulated uterine fluid.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108078911A (en) * | 2017-12-08 | 2018-05-29 | 复旦大学 | Thermotropic hydrogel sustained release veterinary drug injection for animal contraception and preparation method thereof |
| CN109575303A (en) * | 2018-12-03 | 2019-04-05 | 温州大学 | A kind of amphiphilic polymer and preparation method thereof |
| CN109908359A (en) * | 2019-04-21 | 2019-06-21 | 西北工业大学 | A kind of drug continuous controlled-release administrating system and preparation method thereof stage by stage |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1706879A (en) * | 2005-05-13 | 2005-12-14 | 沈阳药科大学 | Temperature-sensitive biodegradable block copolymer and its prepn process |
| CN101862454A (en) * | 2009-04-20 | 2010-10-20 | 复旦大学 | Physical cross-linking hydrogel composition and preparation method and application thereof |
-
2012
- 2012-06-01 CN CN2012101793872A patent/CN102755282A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1706879A (en) * | 2005-05-13 | 2005-12-14 | 沈阳药科大学 | Temperature-sensitive biodegradable block copolymer and its prepn process |
| CN101862454A (en) * | 2009-04-20 | 2010-10-20 | 复旦大学 | Physical cross-linking hydrogel composition and preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| PENG ZOU ET AL.: "Temperature-responsive biodegradable star-shaped block copolymers for vaginal gels", 《JOURNAL OF MATERIALS CHEMISTRY》, vol. 22, 21 February 2012 (2012-02-21), pages 6316 - 6326 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108078911A (en) * | 2017-12-08 | 2018-05-29 | 复旦大学 | Thermotropic hydrogel sustained release veterinary drug injection for animal contraception and preparation method thereof |
| CN109575303A (en) * | 2018-12-03 | 2019-04-05 | 温州大学 | A kind of amphiphilic polymer and preparation method thereof |
| CN109575303B (en) * | 2018-12-03 | 2021-07-13 | 温州大学 | Amphiphilic polymer and preparation method thereof |
| CN109908359A (en) * | 2019-04-21 | 2019-06-21 | 西北工业大学 | A kind of drug continuous controlled-release administrating system and preparation method thereof stage by stage |
| CN109908359B (en) * | 2019-04-21 | 2022-04-29 | 西北工业大学 | Multi-drug staged continuous controlled release drug delivery system and preparation method thereof |
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