CN102512399B - Long-acting naltrexone implant and preparation method thereof - Google Patents
Long-acting naltrexone implant and preparation method thereof Download PDFInfo
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- CN102512399B CN102512399B CN 201110457641 CN201110457641A CN102512399B CN 102512399 B CN102512399 B CN 102512399B CN 201110457641 CN201110457641 CN 201110457641 CN 201110457641 A CN201110457641 A CN 201110457641A CN 102512399 B CN102512399 B CN 102512399B
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Abstract
The invention relates to a long-acting naltrexone implant and a preparation method thereof, which belong to the field of pharmaceutical preparations. The long-acting naltrexone implant comprises a polylactic acid and naltrexone, and is characterized in that the viscosity coefficient of the polylactic acid is 0.5-2.5dl/g (chloroform, 30 DEG C); the ratio of the polylactic acid to the naltrexone is 1:(0.5-1.8) in parts by weight; the composition structure of the long-acting naltrexone implant is a particle tabletted and coated structure; coated particles are slow release pellets which can be sieved by a 20-60 mesh screen in particle size; the slow release pellets comprise the polylactic acid and the naltrexone; the ratio of the polylactic acid to the naltrexone in the slow release pellets is 1:(1-2) in part by weight; and a coating layer is a DL-polylactic acid. The long-acting naltrexone implant has a good curative effect, better drug-loading rate and better drug release completeness, and has small side effect on human bodies.
Description
Technical field
The present invention relates to a kind of long-acting naltrexone implant (Naltrexone Implant) and preparation method thereof, belong to field of medicine preparations.
Technical background
The research of present biodegradable slow release drug delivery technologies is extensive, and this technology not only provides better administering mode for multi-medicament, and has reduced the untoward reaction of medicine and improved patient's compliance.Biodegradable slow release drug-loading system is take high molecular polymer as carrier, and the slow Novel Drug Delivery Systems of Stable Release medicine behind the topical has the medicine-releasing systems such as microsphere injection-type, tablet embedded type.The release behavior of medicine is except the feature (shape, particle diameter, surface nature etc.) of the character (composition, molecular weight, crystallinity, degradation speed etc.) of the characteristics that are subjected to medicine (molecular weight, molecular volume size, water solublity etc.), polylactide and its copolymer, preparation and release environmental effect are large, and content and the interaction of distribution, medicine and material and catabolite thereof etc. of medicine in preparation is also influential to release mode.Microsphere injection-type slow-released system is subject to the restriction of microsphere self size, and slow-release time is generally about one month, and is but easy to use clinically; And tablet embedded type slow-released system makes drug release slower because of by forming skeleton construction after tabletting or the extruding, can reach longer slow-release time, but need carry out the local operation heeling-in when using clinically.
Polylactic acid is a kind of have good biocompatibility and biodegradable polymer, the end product of metabolism is water and carbon dioxide in vivo, intermediate product lactic acid also is normal glycometabolic product in the body, can not assemble at vitals, is the medical auxiliary materials that the FDA approval is used.The polymer that uses in the slow release drug-loading system has PLLA, D-polylactic acid, DL-polylactic acid, polylactide glycolide copolymer (PLGA) etc., wherein PLLA and D-polylactic acid are semicrystalline polymeric, the DL-polylactic acid is the amorphism polymer, under the same molecular amount, PLLA and D-polylactic acid are slower than the degraded of DL-polylactic acid.
Drug dependence and alcohol dependence have become global social problem, have brought serious harm for country, society and family.Naltrexone is an old medicine, drugs approved by FDA was used for the treatment of drug dependence patient preventing suction again in 1984, nineteen ninety-five approval is used for the anti-multiple drink treatment of alcohol dependence patient, successively in American and Britain, add, tens clinical uses of country such as moral, meaning, west, day, only have at present peroral dosage form.The side effect of naltrexone is very little, also is a kind of very potential and effective medicine, but the Use Limitation fruit is unsatisfactory clinically, mainly is because the compliance that the addiction patient takes medicine every day is poor.Study novel naltrexone slow release drug-loading system, can greatly improve naltrexone result of use clinically, and slow release holds time longlyer, therapeutic effect is better, and market prospect is larger.
At present, the pertinent literature of medicine polylactic acid microsphere slow-released system technology is more, mostly concentrate on the synthesis technique of polylactic acid and the laboratory research level of microsphere preparation, Korean minister in ancient times (Beijing University of Chemical Technology, Master degree candidate's academic dissertation, 2010) carried out adopting easy emulsifying-solvent evaporation method to prepare polylactic acid microsphere and polylactic acid/Imidacloprid, polylactic acid/pyridine worm miaow carried medicine sustained-release microsphere, studied the impact of preparation process condition on microspherulite diameter at laboratory level, and the microsphere Release Performance has been studied.The most handy dichloromethane was as organic interior decentralized photo when conclusion was the preparation polylactic acid microsphere, and polyvinyl alcohol is made emulsifying agent, and at ambient temperature, emulsification times is 2-3h.The size of polylactic acid microsphere particle diameter is subjected to the control of many factors, wherein PLA concentration, surfactant concentration and the charge ratio between them have significant impact to the size of preparation polylactic acid microsphere particle diameter, and select and investigated some influence factors wherein, screen, the sustained-release micro-spheres of making exists the significantly prominent phenomenon of releasing.
Lan Ting (Northwest University, master's research paper, 2007, the preparation of polylactic acid microsphere) carried out the preparation research of Urapidil hydrochloride PLLA (Poly-L-lactic acid) sustained-release micro-spheres, parameter is wherein carried out screening investigated, wherein solved the prominent problem of releasing of medicine with the method for Urapidil hydrochloride PLLA microsphere parcel adventitia, namely on medicine carrying microballoons, wrapped up respectively chitosan adventitia and chitosan+sodium alginate adventitia, obtain A, two kinds of microspheres of B.With A, two kinds of microspheres of B and the medicine carrying microballoons C that does not wrap up adventitia do the release in vitro performance test under the same conditions, and release is mild, do not have " prominent the releasing " of medicine.
(preparation of triptorelin microsphere and the quality control such as Long Lei, Hubei Institute For Nationalities's journal, 2011,2:28) carried out the Study on Preparation of triptorelin microsphere, adopt emulsion-liquid drying method to prepare sustained-release micro-spheres, specifically adopted aqueous gelatin solution and triptorelin mixed liquor as interior water, inject certain density PVA (using polyvinyl alcohol) solution, high-speed stirred is carried out emulsifying, then the dry sustained-release micro-spheres that obtains.
Chinese patent CN200610152903.7 discloses a kind of long-acting slow-release preparation of naltrexone, it is comprised of through compress tablet coating the microsphere that naltrexone and polylactic acid form, the mean molecule quantity of polylactic acid is between 15-35 ten thousand dalton, specifically adopted and outerly with polylactic acid the microsphere that naltrexone and polylactic acid form has been carried out coating, do not release phenomenon so that drug release has had to dash forward, obtained the effect of slow release.
Comprehensive present research and open source literature technology, be the preparation technology of laboratory level, can't carry out large-scale production, wherein investigating numerous influence factors of screening and the condition of acquisition all can not be suitable for when carrying out large-scale production, this is because the active component of microsphere parcel is different, the mode that interior phase emulsion adds foreign minister's solution is different, the composition of solution is different, the concrete adjunct ingredient that adopts is not equal, all can cause its optimum preparation process condition that the variation that is difficult to predict has occured, research need to be re-started, the desirable sustained-release micro-spheres of slow release effect and therapeutic effect could be obtained.
Summary of the invention
Deficiency and defective for present sustained release microsphere agents and the existence of preparation technology aspect thereof, the invention provides a kind of long-acting naltrexone implant and preparation method thereof, be fit to large-scale production, technology controlling and process is good, the sample of the method preparation has reached the quality standard of new drug requirements of customs declaration, the single impurity of determination of related substances all is no more than 0.5%, total impurities is no more than 1.5%, can well control the prominent of medicine and release, the stable release of control drug slow, slow-release time is 90-500 days, good effect, side effect to human body is little, has preferably drug loading, and the release completeness of medicine is also better.
Long-acting naltrexone implant provided by the invention; can large-scale production; meet the quality standard that pharmacopeia requires, the anti-multiple drink for the treatment of the preventing suction again behind the opium drug addiction patient treating narcotic addiction and alcohol dependence patient that can be comparatively desirable is treated, and solves the problem that society is badly in need of.
Long-acting naltrexone implant provided by the invention contains polylactic acid and naltrexone, wherein, the viscosity coefficient of polylactic acid is at 0.5-2.5dl/g (chloroform, 30 ℃), the weight part ratio of polylactic acid and naltrexone is: 1: 0.5-1.8, preferably, the weight part ratio of polylactic acid and naltrexone is: 1: 0.8-1.5, it forms structure is microgranule compress tablet coating structure, the tabletting microgranule is the slow-release micro-pill that particle diameter can be crossed the 20-60 mesh sieve, slow-release micro-pill contains polylactic acid and naltrexone, and the weight part ratio of polylactic acid and naltrexone is 1 in the slow-release micro-pill: 1-2.Coatings is the DL-polylactic acid.
According to the difference that slow-release time requires, consider simultaneously the systemic speed of body, the biodegradable polymers in the naltrexone implant has been selected the DL-polylactic acid.
The viscosity coefficient of polylactic acid has obvious impact to the effect of preparation and coating, excessive or the too small slow release effect that all can affect preparation of the present invention of viscosity, the viscosity coefficient of the polylactic acid that the present invention is used is at 0.5-2.5dl/g (chloroform, 30 ℃) between better, preferred viscosity coefficient scope is 0.8-1.5dl/g (chloroform, 30 ℃).
The hardness of tabletting has certain impact to slow release effect, and the sheet hardness behind the long-acting implantation agent tabletting of the present invention is preferably 5-7KG, more preferably 5-6KG.
Long-acting naltrexone implant of the present invention, by polylactic acid and naltrexone medicine, after adopting reactor SPG (Shirasu Porous Glass) film emulsion process to prepare microsphere, be pressed into tablet with suitable pressure again, the surface is adopted polylactic acid to carry out Cotton seeds again and is made, and treats for the treatment of the preventing suction again after the opium drug addiction patient detoxification and alcohol dependence patient's anti-multiple drink.
The invention provides a kind of preparation method of long-acting naltrexone implant, the technical scheme of employing is: polylactic acid and naltrexone are dissolved in formation medicine decentralized photo (Dispersion Phase, DP) in the organic solvent in proportion; The preparation poly-vinyl alcohol solution is as continuous phase (Continuous Phase, CP); Reactor connects the SPG film, utilizes peristaltic pump to flow by continuous phase, by nitrogen decentralized photo is pressed into continuous phase from the SPG film outside; Heating, reduce pressure, it is complete to continue to be stirred to the organic solvent volatilization; Filter and collect microsphere also cleaning, drying; Dried microsphere is pressed into tablet with suitable pressure; Surface coatings; Make the naltrexone implant behind the irradiation sterilization.
Further preferred, the technique of naltrexone implant of the present invention is: polylactic acid and naltrexone in proportion 1: 0.5-1.8 is dissolved in a certain amount of organic solvent, as the DP phase; Compound concentration is the poly-vinyl alcohol solution of 0.5%-1.5%, as the CP phase; With DP from the SPG film outside be pressed into CP mutually, continue to stir; After solidifying, collects by microsphere microsphere, tabletting, and sheet footpath size is 3-10mm; Hardness is 5-7KG, surface one or more layers coating of DL-polylactic acid.
The polyethylene solution of CP of the present invention in mutually can add sucrose and carry out saturated.
Different according to decentralized photo and continuous phase kind, the SPG film can be selected hydrophilic and hydrophobic film; According to different pharmaceutical dosage form requirements, the aperture of SPG film can be selected between 10 μ m-20 μ m.The preferred hydrophobicity of SPG film, tubulose, 15-25 μ m film among the present invention, further preferred 20 μ m films.
Among the preparation technology of the present invention, DP is pressed into CP from the SPG film outside mutually preferably is: reactor connects SPG, and the peristaltic pump rotating speed is made as 150rpm-400rpm, and nitrogen pressure is made as 0-180Kpa, and agitator speed is made as 150rpm-300rpm; By nitrogen with DP from the SPG film outside be pressed into CP mutually, be heated to 37 ℃, decompression be-0.08Mpa to continue stirring to vacuum.
The method of collecting microsphere is: after microsphere solidifies, be cooled in the ice-water bath below 10 ℃, filter an amount of distilled water wash of microsphere, vacuum drying.
After collecting microsphere, the preparation technology of implant is, adds magnesium stearate 0.2%-0.8%, mixes, and crosses the 20-60 mesh sieve, and with suitable pressure tabletting, sheet directly size is 3-10mm, is preferably 5-8mm behind the mixing; The surface gets long-acting implantation agent of the present invention with DL-polylactic acid coating, and irradiation dose is between 10kGy-25kGy, after the sterilization and get final product.
In the preparation of the present invention preparation, after collecting microsphere, also can be with microsphere and Polyethylene Glycol or stearic acid, or after both mixture mix, sieve again, tabletting.The amount that adds is the 0.2%-0.8% of microsphere amount.
Through many experiments and test, the best preparation technology of naltrexone implant is: DL-polylactic acid and naltrexone in proportion 1: 0.8-1.5 (W/W) is dissolved in a certain amount of dichloromethane, as the DP phase; Compound concentration is 0.5% poly-vinyl alcohol solution and saturated with 10% sucrose, as the CP phase; Reactor connects SPG, and the peristaltic pump rotating speed is made as 180rpm-220rpm, and nitrogen pressure is made as 0-20Kpa, and agitator speed is made as 180rpm-220rpm; By nitrogen with DP from the outside be pressed into CP mutually, be heated to 37 ℃, decompression be-0.08Mpa to continue stirring to vacuum; Microsphere is cooled in the ice-water bath below 10 ℃ after solidifying, and filters microsphere distilled water wash 3 times, vacuum drying 48 hours; Microsphere adds 0.5% magnesium stearate to be crossed behind the 40 mesh sieve mixings with suitable pressure tabletting, and sheet footpath size is 5-8mm; Surface DL-polylactic acid coating.
Irradiation dose is between 10kGy-25kGy, preferably at 15-20kGy.
Above-mentioned stable preparation process is reliable, and favorable reproducibility can be used for the GMP large-scale production, and the preparation determination of related substances that makes meets the pharmacopeia regulation, and single impurity all is no more than 0.5%, and total impurities is no more than 1.5%.Adopt above-mentioned technique, select the DL-polylactic acid of different viscosities coefficient and naltrexone to prepare by different proportion and can obtain slow-release time behind the microsphere from 90 days to 500 days naltrexone implant.
During clinical use, by the regional surgery minor operation with the heeling-in of naltrexone implant in the underbelly subcutaneous layer of fat of patient, be used for drug addiction and alcohol dependence patient preventing suction again or anti-multiple drink treatment, can prevent that the patient from forgetting takes medicine, the patient is under the therapeutical effect of medicine always, improves greatly the clinical therapeutic efficacy of medicine.
Description of drawings
Below, come by reference to the accompanying drawings more detailed explanation content of the present invention, wherein:
Fig. 1 is embodiment 6 described release in vitro meansigma methods curve charts
Curve chart when Fig. 2 is the interior naltrexone medicine of embodiment 7 described Beagle Canis familiaris L. bodies
The specific embodiment
Embodiment 1:
The DL-polylactic acid is selected viscosity coefficient 0.9dl/g, and mean molecule quantity is 50,000 dalton approximately.DL-polylactic acid (20g) and naltrexone (20g) are dissolved in the dichloromethane (200mL), as the DP phase; Compound concentration is 0.5% poly-vinyl alcohol solution 6000ml and saturated with 10% sucrose, as the CP phase; The peristaltic pump rotating speed is made as 180rpm, and nitrogen pressure is made as 2Kpa, and agitator speed is made as 180rpm; By nitrogen with DP from the outside be pressed into CP mutually, be heated to 37 ℃, decompression be-0.08Mpa to continue stirring to vacuum; Microsphere is cooled in the ice-water bath below 10 ℃ after solidifying, and filters microsphere distilled water wash 3 times, vacuum drying 48 hours; Merge microsphere, cross 40 mesh sieves, mixing, with suitable pressure tabletting, sheet directly size is 6.8mm; Surface DL-polylactic acid coating, every weight 300mg, hardness is 5KG, irradiation dose 15kGy makes the naltrexone implant.
Embodiment 2:
The DL-polylactic acid is selected viscosity coefficient 1.5dl/g (chloroform, 30 ℃), and DL-polylactic acid (20g) and naltrexone (30g) are dissolved in the dichloromethane (200mL), as the DP phase; Compound concentration is 1% poly-vinyl alcohol solution 6000ml and saturated with 10% sucrose, as the CP phase; The peristaltic pump rotating speed is made as 200rpm, and nitrogen pressure is made as 8Kpa, and agitator speed is made as 180rpm; By nitrogen with DP from the outside be pressed into CP mutually, be heated to 37 ℃, decompression be-0.08Mpa to continue stirring to vacuum; Microsphere is cooled in the ice-water bath below 10 ℃ after solidifying, and filters microsphere distilled water wash 3 times, vacuum drying 48 hours; Merge microsphere, cross 30 mesh sieves, mixing, with suitable pressure tabletting, sheet directly size is 8mm; Surface DL-polylactic acid coating, every weight 460mg, hardness is 6KG, irradiation dose 20kGy makes the naltrexone implant.
Embodiment 3:
The DL-polylactic acid is selected viscosity coefficient 0.7dl/g, and DL-polylactic acid (25g) and naltrexone (20g) are dissolved in the dichloromethane (250mL), as the DP phase; Compound concentration is 0.8% poly-vinyl alcohol solution 6000ml and saturated with 10% sucrose, as the CP phase; The peristaltic pump rotating speed is made as 200rpm, and nitrogen pressure is made as 15Kpa, and agitator speed is made as 180rpm; By nitrogen with DP from the outside be pressed into CP mutually, be heated to 37 ℃, decompression be-0.08Mpa to continue stirring to vacuum; Microsphere is cooled in the ice-water bath below 10 ℃ after solidifying, and filters microsphere distilled water wash 3 times, vacuum drying 48 hours; Merge microsphere, cross 60 mesh sieves, mixing, with suitable pressure tabletting, sheet directly size is 5.5mm; Surface DL-polylactic acid coating, every weight 280mg, hardness is 7KG, irradiation dose 25kGy makes long-acting naltrexone implant.
Embodiment 4:
The DL-polylactic acid is selected viscosity coefficient 2.5dl/g, and DL-polylactic acid (20g) and naltrexone (20g) are dissolved in the dichloromethane (200mL), as the DP phase; Compound concentration is 1.2% poly-vinyl alcohol solution 6000ml and saturated with 10% sucrose, as the CP phase; The peristaltic pump rotating speed is made as 300rpm, and nitrogen pressure is made as 10Kpa, and agitator speed is made as 220rpm; By nitrogen with DP from the outside be pressed into CP mutually, be heated to 37 ℃, decompression be-0.08Mpa to continue stirring to vacuum; Microsphere is cooled in the ice-water bath below 10 ℃ after solidifying, and filters microsphere distilled water wash 3 times, vacuum drying 48 hours; Merge microsphere, cross 20 mesh sieves, mixing, with suitable pressure tabletting, sheet directly size is 6.8mm; Surface DL-polylactic acid coating, every weight 300mg, hardness is 5KG, irradiation dose 18kGy makes long-acting naltrexone implant.
Embodiment 5
Naltrexone implant quality standard is measured, and according to the assay method of high performance liquid chromatography (two appendix VI of Chinese Pharmacopoeia version in 2010 D), the tablet that embodiment 1 is made carries out determination of related substances, and the content of related substance is as shown in the table:
Table 1 its related substances table
| The material title | Content (%) |
| Content of dispersion | 99.00±0.4 |
| Nor-hydroxyl hydromorphone | 0.35±0.02 |
| 10-ketone group naltrexone | 0.098±0.003 |
| 2,2 '-two naltrexones | 0.16±0.02 |
Embodiment 6
Embodiment 7
The naltrexone implant that embodiment 1 makes gives the Beagle Canis familiaris L. with 3/subdermal implantations, and naltrexone blood drug level keeps the certain level sustained release after the heeling-in, still can detect naltrexone in 148 days to the heeling-in, sees Fig. 2.
The tablet that trial drug: embodiment 4 makes
Experiment condition: 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5%.
Test method: placed 12 months under the condition of 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5%, detect once every month.
Conclusion: the stability test through six months, related substance are single assorted all less than 0.5% in 6 months, total mixing less than 1.5%, and impurity content does not have significant change, and naltrexone content is greater than 98.7%.
Claims (6)
1. long-acting naltrexone implant, contain polylactic acid and naltrexone, it is characterized in that, wherein the viscosity coefficient of polylactic acid is 0.8-1.5dl/g in 30 ℃, chloroform, and the weight part ratio of polylactic acid and naltrexone is 1: 0.5-1.8, and it forms structure is microgranule compress tablet coating structure, by the diameter of particle of coating for crossing the slow-release micro-pill of 20-60 mesh sieve, slow-release micro-pill contains polylactic acid and naltrexone, and the weight part ratio of polylactic acid and naltrexone is 1 in the slow-release micro-pill: 1-2, and coatings is the DL-polylactic acid; The magnesium stearate mixed pressuring plate of slow-release micro-pill and 0.2-0.8%, and then carry out coating; The coatings of described preparation is one deck or multilamellar.
2. implant as claimed in claim 1 is characterized in that, the weight part ratio of polylactic acid and naltrexone is 1: 0.8-1.5.
3. implant as claimed in claim 1 is characterized in that, is the slow-release micro-pill that can cross the 30-40 mesh sieve by the diameter of particle of coating.
4. implant as claimed in claim 1 is characterized in that, magnesium stearate can be with one or more the mixture replacing in Polyethylene Glycol and the stearic acid.
5. implant as claimed in claim 1 is characterized in that, its preparation technology is: DL-polylactic acid and naltrexone in proportion 1: 0.5-1.8 is dissolved in a certain amount of organic solvent, as decentralized photo; Compound concentration is the poly-vinyl alcohol solution of 0.5%-1.5%, as continuous phase; Decentralized photo is pressed into the continuous phase from the SPG film outside, continues to stir; After solidifying, collects by microsphere microsphere, tabletting, and sheet footpath size is 3-10mm; Hardness is 5-7KG, surface one or more layers coating of DL-polylactic acid.
6. implant as claimed in claim 5 is characterized in that, the polyethylene solution in the continuous phase adds sucrose and carries out saturated.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3340968A4 (en) * | 2015-08-24 | 2019-03-27 | Rusan Pharma Limited | Implantable naltrexone tablets |
| EP4085901A4 (en) * | 2019-12-31 | 2023-11-29 | Guangzhou DiQi Pharmaceuticals Co., Ltd. | Tertiary amine pharmaceutical composition and industrial batch preparation method therefor |
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| CN112741813A (en) * | 2021-02-08 | 2021-05-04 | 北京佗林医药科技有限公司 | Naltrexone binary subcutaneous implant and preparation method thereof |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1468090A (en) * | 2000-09-01 | 2004-01-14 | Slow release pharmaceutical preparation and method of administering same | |
| CN1973840A (en) * | 2006-09-19 | 2007-06-06 | 深圳市思沃生命科学技术有限公司 | Long acting slow releasing drug addiction eliminating prepn and its prepn process and use |
| CN101612437A (en) * | 2009-01-09 | 2009-12-30 | 清华大学 | Naltrexone microsphere-hydrogel skeleton original position heeling-in drug-supplying system |
| CN101700226A (en) * | 2009-03-26 | 2010-05-05 | 海南凤凰国际药物研究院 | Naltrexone long-acting sustained-release preparation with no need of coating and preparation method thereof |
-
2011
- 2011-12-31 CN CN 201110457641 patent/CN102512399B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1468090A (en) * | 2000-09-01 | 2004-01-14 | Slow release pharmaceutical preparation and method of administering same | |
| CN1973840A (en) * | 2006-09-19 | 2007-06-06 | 深圳市思沃生命科学技术有限公司 | Long acting slow releasing drug addiction eliminating prepn and its prepn process and use |
| CN101612437A (en) * | 2009-01-09 | 2009-12-30 | 清华大学 | Naltrexone microsphere-hydrogel skeleton original position heeling-in drug-supplying system |
| CN101700226A (en) * | 2009-03-26 | 2010-05-05 | 海南凤凰国际药物研究院 | Naltrexone long-acting sustained-release preparation with no need of coating and preparation method thereof |
Non-Patent Citations (4)
| Title |
|---|
| 纳曲酮植入剂不同动物体内的药物释放和吸收;陆兵 等;《中国药学杂志》;20000831;第35卷(第8期);第524-527页 * |
| 纳曲酮植入剂体外处方优化;陆兵 等;《中国药学杂志》;20000731;第35卷(第7期);第452-455页 * |
| 陆兵 等.纳曲酮植入剂不同动物体内的药物释放和吸收.《中国药学杂志》.2000,第35卷(第8期),第524-527页. |
| 陆兵 等.纳曲酮植入剂体外处方优化.《中国药学杂志》.2000,第35卷(第7期),第452-455页. |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3340968A4 (en) * | 2015-08-24 | 2019-03-27 | Rusan Pharma Limited | Implantable naltrexone tablets |
| EP4085901A4 (en) * | 2019-12-31 | 2023-11-29 | Guangzhou DiQi Pharmaceuticals Co., Ltd. | Tertiary amine pharmaceutical composition and industrial batch preparation method therefor |
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| Publication number | Publication date |
|---|---|
| CN102512399A (en) | 2012-06-27 |
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