CN102188756A - Preparation method of medicated slow-release degradable bone scaffold - Google Patents
Preparation method of medicated slow-release degradable bone scaffold Download PDFInfo
- Publication number
- CN102188756A CN102188756A CN2011101201235A CN201110120123A CN102188756A CN 102188756 A CN102188756 A CN 102188756A CN 2011101201235 A CN2011101201235 A CN 2011101201235A CN 201110120123 A CN201110120123 A CN 201110120123A CN 102188756 A CN102188756 A CN 102188756A
- Authority
- CN
- China
- Prior art keywords
- plga
- rifampicin
- preparation
- isoniazid
- release
- 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.)
- Pending
Links
Images
Abstract
The invention discloses a preparation method of a medicated slow-release degradable bone scaffold, which comprises the following steps: preparing a biological degradable polyester material (such as PLGA (poly(lactic-co-glycolic acid)) and a loaded antitubercular medicament (such as rifampicin or isoniazide) into PLGA microspheres containing the rifampicin or isoniazide, respectively mixing the PLGA microspheres containing the rifampicin or isoniazide with a biological medical adhesive, and molding with a mold, thus obtaining the medicated slow-release degradable bone scaffold. Having a certain porosity, the medicated slow-release degradable bone scaffold prepared by the preparation method is beneficial to the transportation and exchange of body water, inorganic salt and other nutrient substances and cell metabolism products, thereby being more beneficial to the normal growth and physiologic metabolism of bone cells, and providing an ideal place for the growth of bone tissues; and accompanied by the degradation of the PLGA, the medicament can be continuously released in the focal position and can be kept at a certain concentration, thereby inhibiting the growth of tubercle bacillus, and ultimately degrading the PLGA into carbon dioxide and water which are removed from the body through body metabolism.
Description
Technical field
The present invention relates to medical technical field, relate in particular to a kind of preparation method of pastille slow-release degraded bone support.
Background technology
Bone tuberculosis is the outer tuberculosis of common Secondary cases lung, accounts for all lungyly about 3%, and wherein about half involves spinal column, as delays the diagnosis and treatment and can cause patient's lifelong disability, even death.Spinal tuberculosis is as the most common form of bone tuberculosis, and is also in rising trend with increase lungy in recent years.Medicines such as Rimactazid can penetrate the inside and outside tubercule bacillus of the interior pair cell of cell and have powerful killing and inhibitory action the tubercule bacillus sensitivity.A large amount of oral various untoward reaction that tend to cause cause the infringement of organs such as Liver and kidney.How to solve damaged, the local tuberculose focus abscess recurrence of bone of the bulk of focal cleaning postoperative, and how to shorten problems such as course of treatment of antituberculotics or administering mode, making and do not damage other organs again by the drug level of remaining valid in the tuberculose focus position, is problem anxious to be solved.
Summary of the invention
The present invention adopts biodegradable polyesters family macromolecule material and complex thereof, as being carrier with polylactide glycolide copolymer (poly (lactic-co-glycolic acid) PLGA), bag carries antituberculotics such as Rimactazid etc., makes a kind of preparation method of newtype drug slow release bone support.
A kind of preparation method of pastille slow-release degraded bone support, comprise and utilize polyester such as PLGA load antituberculotics such as rifampicin or isoniazid, obtain containing the PLGA microsphere of rifampicin or isoniazid, the PLGA microsphere that will contain rifampicin and/or isoniazid mixes with the bio-medical binding agent by mould molding, obtains described pastille slow-release degraded bone support.
Described PLGA forms by lactide (LA) and Acetic acid, hydroxy-, bimol. cyclic ester (GA) fusion ring-opening polymerisation, and wherein lactide and Acetic acid, hydroxy-, bimol. cyclic ester mol ratio are 1～9: 1, and preferred 5～9: 1.
Also can select the PLGA of different proportion according to the required pharmaceutical release time of clinical practice.
The PLGA weight average molecular weight is 20～700,000, selects according to pharmaceutical release time.
When carrying medicament rifampicin or isoniazid, with the dichloromethane solution of PLGA as oil phase, double steaming solution with rifampicin or isoniazid is interior water, with polyvinyl alcohol water solution is outer water, make W/O/W type emulsion, isolate dichloromethane microsphere is solidified, solidified microsphere obtains containing the PLGA microsphere of rifampicin or isoniazid after washing and lyophilization.
During the preparation oil phase, the volume ratio of PLGA weight and dichloromethane is 1: 50～100 (g/ml), and the weight of rifampicin or isoniazid and the volume ratio of oil phase are that 1～3: 100～200 units are g/ml.
Earlier interior water is added to oil phase when making W/O/W type emulsion, mixes forming the W/O colostric fluid.The W/O colostric fluid that obtains then adds outer aqueous phase, and being uniformly dispersed obtains W/O/W type emulsion.
Wherein said outer water is that mass percent concentration is 1～5% polyvinyl alcohol water solution.
The concentration of interior aqueous phase rifampicin or isoniazid is 10～60mg/ml.
Oil phase, interior water, outer water three volume ratio are 3～6: 0.5～2: 40～80.
For example can take by weighing PLGA 200mg and join in the 10ml dichloromethane, PLGA dissolves the back fully as oil phase, gets 100mg rifampicin or 100mg isoniazid again and adds 2ml distilled water, room temperature mixing.Be added in the above-mentioned oil phase.With rapid (otherwise reaction temperature too high the be difficult to balling-up) ice-bath ultrasonic 90～120 seconds (s) of above-mentioned mixed solution, form the W/O colostric fluid, wherein the ice bath temperature is general about 0 ℃.
Then the W/O colostric fluid slowly is added dropwise to mass percent concentration and is among 2% the polyvinyl alcohol water solution 150ml (outer water), stir 60～90s fast with the high speed dispersion homogenizer and promptly get W/O/W type emulsion.The emulsifying agent that can suitably add conventional amount used when the W/O colostric fluid mixes with outer water, for example 0.4%-0.5%Tween etc.
To continue to stir with 1000r/min with magnetic stirrer under the W/O/W type emulsion room temperature that obtain, make the dichloromethane volatilization, until organic facies (mainly is dichloromethane, for increasing the dissolubility of medicine, also may contain the methanol that is useful on dissolved substance, ethanol, ethyl acetate, acetone etc.) volatilization is complete gradually, microsphere is solidified at the aqueous phase precipitate, filter to isolate solidified microsphere, wash centrifugal 5～10 times with cold aseptic tri-distilled water, sub-argument goes out solidified microsphere and carries out lyophilization 48～56h (cryogenic temperature-20 ℃ to-60 ℃), makes the PLGA microsphere that contains rifampicin or isoniazid.Microsphere diameter 150-800 μ m, microsphere drug loading are 37.31% (scope is 22%～40%) (the microsphere drug loading is meant that rifampicin or isoniazid and load have the mass ratio of the PLGA microsphere of rifampicin or isoniazid).
During molding, the bio-medical binding agent of selecting for use can be selected a-alkyl cyanoacrylate or Fibrin Glue for use, and the PLGA microsphere that wherein contains rifampicin and/or isoniazid is 10: 1～0.2 with bio-medical binder wt ratio.
Get the PLGA microsphere that contains rifampicin and/or isoniazid and add the bio-medical binding agent, according to bone support shape need, suppress molding in 1～2 hour in 20～60 ℃ of moulds, the porosity of the pastille slow-release that obtains degraded bone support is 32～58%.
Can adopt the PLGA microsphere that only contains rifampicin during molding, also can only adopt the PLGA microsphere that only contains isoniazid, also can adopt the PLGA microsphere that contains rifampicin simultaneously and contain the PLGA microsphere of isoniazid, when adopting simultaneously, without limits the ratio of two kinds of PLGA microspheres.When calculating the bio-medical binder dosage, be benchmark with all PLGA microsphere gross masses.
Utilize the copolymer (PLGA) and the rifampicin of lactide and Acetic acid, hydroxy-, bimol. cyclic ester among the present invention, crude drug such as isoniazid adopt emulsion-solvent evaporation method to wrap the microsphere that carries different antituberculotics and make certain drug loading with the PLGA of different proportion lactide and Acetic acid, hydroxy-, bimol. cyclic ester respectively.With adhesive of medical a-alkyl cyanoacrylate, Fibrin Glue or polyurethane binder, with the bonding certain physical shape that is pressed into of the medicine carrying microballoons of different proportion.
The present invention is a model drug with isoniazid and rifampicin, and isoniazid has high selectivity to mycobacterium tuberculosis, and antibacterial action is strong, and in vitro the concentration of 0.025～0.05mg/L all can be antibacterial, higher concentration 10mg/L to idiophase antibacterial bactericidal action is arranged.The isoniazid list is with easily producing drug resistance, and drug combination can delay drug resistance and produce, and heightens the effect of a treatment.Isoniazid and other antitubercular agents do not have cross resistance.Rifampicin is semi-synthetic wide-spectrum bactericide, with the b subunit strong bonded of the RNA polymerase that relies on DNA, suppresses the synthetic of bacteria RNA, prevents that this enzyme is connected with DNA, thus blocking-up rna transcription process.Mycobacterium tuberculosis, gram positive bacteria and part gram negative bacteria all there is antibacterial or bactericidal action.Be mainly used in drug resistance tuberculosis and plant the infection of bacterium and drug-resistant staphylococcus aureus.
PLGA poly (d, l-lactic-co-glycolic acid) is the copolymer that is polymerized by a certain percentage by lactic acid and hydroxyacetic acid, more easily obtains than natural biodegradable polymer such as ossein, gelatin, and harmless to body.With PLGA is the effect that injections such as the microsphere that makes of material, nanocapsule, gel can play protection medicine, solubilising, raising bioavailability, reaches slow release, the controlled release purpose of long period.Be that material becomes medication preparation microparticulate systems such as microemulsion, microsphere, nanocapsule, nanoparticle by the emulsifying encapsulation five equilibrium technology of loosing with the PLGA polymer in recent years, but mainly once as slow release, controlled release injection a few days even several months injection, significantly reduce the medication number of times, strengthen the safety and the effectiveness of medicine, improve patient's compliance.The medicine that the PLGA micro-balloon injection is suitable for mainly contains protein, polypeptide, amcinonide, human growth hormone, cancer vaccine, anticarcinogen, immunosuppressant.Making cmposite artificial bone with PLGA bag year different antituberculotics does not appear in the newspapers both at home and abroad at present.
PLGA molecular weight, lactide one Acetic acid, hydroxy-, bimol. cyclic ester mol ratio, optical activity, chain end structure difference may influence drug release.PLGA can the ratio of lactic acid LA and hydroxyacetic acid GA changes the physicochemical properties of copolymer material PLGA at an easy rate thereby can control its degradation rate in self copolymer by changing. and make its degradation time satisfy the requirement of institute's embedding medicinal.
(R=H: Acetic acid, hydroxy-, bimol. cyclic ester, R=CH3: lactide)
The present invention controls rate of release, the PLGA molecular weight of Rimactazid in the medicine carrying microballoons artificial bone according to the ratio of PLGA third friendship fat and glycolide.The mechanical strength of control medicine carrying microballoons bone supports such as the method for employing biological adhesive, briquetting pressure; And drug loading and rate of release decision therapeutic effect.
The assay method of carrying drug ratio: take by weighing a certain amount of microsphere and place PBS buffer solution. stir and ultrasonicly make contained medicine fully discharge the centrifugalize of dissolving back, get the supernatant, survey its absorbance. calculate drug level according to the concentration standard regression curve, following formula calculates carrying drug ratio and envelop rate:
The pastille slow-release degraded bone support that preparation method of the present invention obtains, owing to have certain porosity, help the transportation and the exchange of moisture, inorganic salt and other nutrient substance and products of cellular metabolism, thereby more help the normal growth and the physiological metabolism of osteocyte, for the osseous tissue growth provides ideal place, follow the degraded medicine of PLGA constantly to disengage the certain drug level of lesions position maintenance, suppressed the growth of tubercule bacillus.Along with the final PLGA of the growth of osseous tissue is degraded into carbon dioxide and water and is excreted.
Description of drawings
Fig. 1 is the external accumulative total of an isoniazid release profiles in the artificial bone scaffold PLGA microsphere;
Fig. 2 is the external accumulative total of a rifampicin release profiles in the artificial bone scaffold PLGA microsphere.
The specific embodiment
(1) 2gPLGA (lactide and Acetic acid, hydroxy-, bimol. cyclic ester mol ratio are 50: 50) is dissolved in the 100mL dichloromethane, forms oil phase.
(2) the 1g rifampicin is dissolved in the 20ml distilled water, forms the 0.05g/ml drug solution.
(3) the preparation mass percent concentration is that 1.5% polyvinyl alcohol water solution 1200ml is outer water.
(4) in the oil phase with the drug solution step of falling people (1) of step (2), mix ultrasonic 3min under 0 ℃ of ice bath, emulsifying evenly obtains the W/O colostric fluid.
(5) getting the 1200mL mass percent concentration is 1.5% polyvinyl alcohol water solution. evenly the W/O colostric fluid that step (4) is obtained is poured into wherein. add 3 emulsifying agent Tween80 again.High-speed stirred, emulsifying is even, obtains W/O/W type emulsion.
(6) will be under the W/O/W type emulsion room temperature stir 24 hours volatilization organic solvents, up to there being microsphere to separate out and harden.
(7) centrifugal sucking filtration gets microsphere, wash three times, and-38 ℃ of lyophilization 24h, the PLGA microsphere that obtains containing rifampicin is standby.
Repeating step (1)～(7) only change rifampicin into isoniazid, obtain containing the PLGA microsphere of isoniazid.
The PLGA microsphere that contains rifampicin that (8) will prepare respectively mixes by quality with the PLGA microsphere that contains isoniazid at 1: 1, add 2% bio-medical binding agent a-alkyl cyanoacrylate, compacting molding in 1 hour in 35 ℃ of moulds obtains pastille slow-release degraded bone support through the Co-60 sterilization.
Embodiment 2
(1) 1gPLGA (lactide and Acetic acid, hydroxy-, bimol. cyclic ester mol ratio are 75: 25) is dissolved in the 70mL dichloromethane, forms oil phase.
(2) the 0.7g isoniazid is dissolved in the 10ml distilled water, forms the 0.07g/ml drug solution.
(3) the preparation mass percent concentration is that 2% polyvinyl alcohol water solution 600ml is outer water.
(4) in the oil phase with the drug solution step of falling people (1) of step (2), mix ultrasonic 3min under 0 ℃ of ice bath, emulsifying evenly obtains the W/O colostric fluid.
(5) getting the 600mL mass percent concentration is 2% polyvinyl alcohol water solution. evenly the W/O colostric fluid that step (4) is obtained is poured into wherein. add 3 emulsifying agent Tween80 again.High-speed stirred, emulsifying is even, obtains W/O/W type emulsion.
(6) will be under the W/O/W type emulsion room temperature stir 24 hours volatilization organic solvents, up to there being microsphere to separate out and harden.
(7) centrifugal sucking filtration gets microsphere, wash three times, and-38 ℃ of lyophilization 24h, the PLGA microsphere that obtains containing rifampicin is standby.
Repeating step (1)～(7) only change isoniazid into rifampicin, obtain containing the PLGA microsphere of rifampicin.
The PLGA microsphere that contains rifampicin that (8) will prepare respectively mixes by quality with the PLGA microsphere that contains isoniazid at 3: 2, adds 3% bio-medical adhesive fiber albumin glue and mixes, compacting molding in 1.5 hours in 25 ℃ of moulds.Compacting molding in 1 hour in 30 ℃ of moulds, the oxirane disinfection sterilization is standby.
Performance Detection
Get the pastille slow-release degraded bone support of embodiment 1 preparation, be put in 50ml, in the phosphate buffer of PH 7.4, place again the vibration of water bath constant speed constant temperature (37 ℃, 30r/min).From timing sampling the 1st day every day (getting the solvent that the back replenishes equal volume), sampling and measuring every other day after 1 month, cycle is 90d altogether, the liquid of taking a sample filter the back and measure peak area by pharmacopeia regulation chromatographic condition sample introduction, respectively with the cumulative release rate in isoniazid and the rifampicin main peak area calculating pastille slow-release degraded bone support, with accumulative total release rate and time match drug release equation, analyze the drug release test result according to the drug release equation.
Claims (9)
1. the preparation method of pastille slow-release degraded bone support, it is characterized in that, utilize PLGA load rifampicin or isoniazid, obtain containing the PLGA microsphere of rifampicin or isoniazid, the PLGA microsphere that will contain rifampicin and/or isoniazid mixes with the bio-medical binding agent by mould molding, obtains described pastille slow-release degraded bone support.
2. the preparation method of pastille slow-release degraded bone support as claimed in claim 1 is characterized in that described PLGA forms by lactide and Acetic acid, hydroxy-, bimol. cyclic ester fusion ring-opening polymerisation, and wherein lactide and Acetic acid, hydroxy-, bimol. cyclic ester mol ratio are 1～9: 1.
3. the preparation method of pastille slow-release degraded bone support as claimed in claim 1, it is characterized in that, when carrying medicament rifampicin or isoniazid, double steaming solution with rifampicin or isoniazid is interior water, with the dichloromethane solution of PLGA as oil phase, with polyvinyl alcohol water solution is that outer water is made W/O/W type double emulsion, isolates dichloromethane again microsphere is solidified, and solidified microsphere obtains containing the PLGA microsphere of rifampicin or isoniazid after washing and lyophilization.
4. the preparation method of pastille slow-release degraded bone support as claimed in claim 3, it is characterized in that, during the preparation oil phase, the volume ratio of PLGA weight and dichloromethane is 1: 50～100, unit is g/ml, the volume ratio of the rifampicin of interior aqueous phase or the weight of isoniazid and oil phase is 1～3: 100～200, and unit is g/ml.
5. the preparation method of pastille slow-release degraded bone support as claimed in claim 4 is characterized in that, earlier interior water is added to oil phase when making W/O/W type emulsion, mixes forming the W/O colostric fluid.The W/O colostric fluid that obtains then adds outer aqueous phase, and being uniformly dispersed obtains W/O/W type emulsion;
Wherein said outer water is that mass percent concentration is 1～5% polyvinyl alcohol water solution.
6. the preparation method of pastille slow-release degraded bone support as claimed in claim 5 is characterized in that described oil phase, interior water, outer water three volume ratio are 3～6: 0.5～2: 40～80.
7. the preparation method of pastille slow-release degraded bone support as claimed in claim 6 is characterized in that described bio-medical binding agent is selected a-alkyl cyanoacrylate or Fibrin Glue for use.
8. the preparation method of pastille slow-release degraded bone support as claimed in claim 7 is characterized in that the PLGA microsphere that contains rifampicin and/or isoniazid is 10: 1～0.2 with bio-medical binder wt ratio.
9. the preparation method of pastille slow-release degraded bone support as claimed in claim 8, it is characterized in that, get the PLGA microsphere that contains rifampicin and/or isoniazid during described mould molding and add the bio-medical binding agent, in 20～60 ℃ of moulds, suppress molding in 1～2 hour, the described pastille slow-release degraded bone support that obtains.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011101201235A CN102188756A (en) | 2011-05-12 | 2011-05-12 | Preparation method of medicated slow-release degradable bone scaffold |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011101201235A CN102188756A (en) | 2011-05-12 | 2011-05-12 | Preparation method of medicated slow-release degradable bone scaffold |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102188756A true CN102188756A (en) | 2011-09-21 |
Family
ID=44598183
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011101201235A Pending CN102188756A (en) | 2011-05-12 | 2011-05-12 | Preparation method of medicated slow-release degradable bone scaffold |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102188756A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103550824A (en) * | 2013-11-01 | 2014-02-05 | 南京医科大学附属口腔医院 | Preparation method of bracket for guiding bone regeneration |
| CN105268027A (en) * | 2015-11-19 | 2016-01-27 | 天津市海河医院 | Bone tissue engineering stent and preparation method thereof |
| CN108295050A (en) * | 2018-01-29 | 2018-07-20 | 西北工业大学 | A kind of bone tuberculosis medicine controlled releasing microballoon and preparation method with Bone Defect Repari effect |
| CN110237308A (en) * | 2019-06-06 | 2019-09-17 | 中南大学湘雅二医院 | It is a kind of for repairing the artificial bone and preparation method thereof of tumprigenicity bone defect |
| CN111249533A (en) * | 2020-01-09 | 2020-06-09 | 中国人民解放军总医院 | Composite aperture electrostatic spinning bracket modified by desferrioxamine sustained-release microbubbles and preparation method thereof |
| CN113318265A (en) * | 2021-04-30 | 2021-08-31 | 南京师范大学 | Synthetic polymer antibacterial tissue adhesive and preparation method thereof |
| CN113398337A (en) * | 2021-06-23 | 2021-09-17 | 上海市肺科医院 | Spinal internal fixation device containing artificial bone carrier implanted with antituberculosis drugs in sustained release manner |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1437933A (en) * | 2003-03-28 | 2003-08-27 | 中国科学院长春应用化学研究所 | Method for preparing Rifampiciu microballs covered by degradable high-molecular material |
| CN101121044A (en) * | 2006-08-09 | 2008-02-13 | 温州医学院 | Bone-repairing material and preparing method thereof |
-
2011
- 2011-05-12 CN CN2011101201235A patent/CN102188756A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1437933A (en) * | 2003-03-28 | 2003-08-27 | 中国科学院长春应用化学研究所 | Method for preparing Rifampiciu microballs covered by degradable high-molecular material |
| CN101121044A (en) * | 2006-08-09 | 2008-02-13 | 温州医学院 | Bone-repairing material and preparing method thereof |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103550824A (en) * | 2013-11-01 | 2014-02-05 | 南京医科大学附属口腔医院 | Preparation method of bracket for guiding bone regeneration |
| CN103550824B (en) * | 2013-11-01 | 2016-03-02 | 南京医科大学附属口腔医院 | A kind of preparation method of support of inducting osseous tissue regeneration |
| CN105268027A (en) * | 2015-11-19 | 2016-01-27 | 天津市海河医院 | Bone tissue engineering stent and preparation method thereof |
| CN108295050A (en) * | 2018-01-29 | 2018-07-20 | 西北工业大学 | A kind of bone tuberculosis medicine controlled releasing microballoon and preparation method with Bone Defect Repari effect |
| CN110237308A (en) * | 2019-06-06 | 2019-09-17 | 中南大学湘雅二医院 | It is a kind of for repairing the artificial bone and preparation method thereof of tumprigenicity bone defect |
| CN111249533A (en) * | 2020-01-09 | 2020-06-09 | 中国人民解放军总医院 | Composite aperture electrostatic spinning bracket modified by desferrioxamine sustained-release microbubbles and preparation method thereof |
| CN113318265A (en) * | 2021-04-30 | 2021-08-31 | 南京师范大学 | Synthetic polymer antibacterial tissue adhesive and preparation method thereof |
| CN113398337A (en) * | 2021-06-23 | 2021-09-17 | 上海市肺科医院 | Spinal internal fixation device containing artificial bone carrier implanted with antituberculosis drugs in sustained release manner |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Yang et al. | Reservoir-based polymer drug delivery systems | |
| CN102188756A (en) | Preparation method of medicated slow-release degradable bone scaffold | |
| JP6302983B2 (en) | Biodegradable drug delivery composition | |
| AU2008254538B2 (en) | Improved depot formulations | |
| CN103079544B (en) | The flowable composition of the injectable comprising buprenorphine | |
| CN101623256B (en) | Ivermectin nanoemulsion drug combination and preparation method thereof | |
| CA2877083A1 (en) | Biodegradable drug delivery for hydrophobic compositions | |
| CN101756908A (en) | Hydroxyapatite micro-sphere with polyester coating and preparation method thereof | |
| Wang et al. | Parenteral thermo-sensitive organogel for schizophrenia therapy, in vitro and in vivo evaluation | |
| CN110025593B (en) | Cell microcapsule, cell microcapsule loaded with anticancer drug, preparation method and application thereof | |
| Huang et al. | Rifapentine-linezolid-loaded PLGA microspheres for interventional therapy of cavitary pulmonary tuberculosis: preparation and in vitro characterization | |
| CN1939316B (en) | Microsphere containing adriamycin, its usage and preparation | |
| CN108912349A (en) | Polylactic acid microsphere and preparation method thereof and the application in medicament slow release | |
| CN102641281A (en) | Monosialotetrahexosyl ganglioside sodium for injection and preparation method thereof | |
| CN101773478B (en) | Pulmonary targeting microsphere of veterinary ceftiofur hydrochloride and preparation method thereof | |
| CN104622815A (en) | Cyclic ether side group-containing amphiphilic polymer lyophilized powder and composition thereof, and applications of composition | |
| CN101756910A (en) | Lung targeting ceftiofur microsphere and preparation method | |
| CN102724969A (en) | A human factor IX slow release dosage form | |
| CN101756909A (en) | Lung-targeting ceftiofur microsphere and preparation method thereof | |
| CN103127006A (en) | Dexlansoprazole composition for injection and preparation method thereof | |
| TW201215412A (en) | Stable pharmaceutical composition | |
| CN104825399B (en) | Contain reverse micelle-microsphere sustained-release preparation of CA-4 P and preparation method thereof | |
| CN112451475B (en) | Long-acting sustained-release gel for treating cavernous pulmonary tuberculosis | |
| Rastogi et al. | Evaluation of a perforated drug delivery system in mice for prolonged and constant release of a hydrophilic drug | |
| JP2010514679A (en) | Controlled release compositions and methods |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20110921 |