CN101601663A - Multi-unit sustained-release preparation of levetiracetam and preparation method thereof - Google Patents
Multi-unit sustained-release preparation of levetiracetam and preparation method thereof Download PDFInfo
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- CN101601663A CN101601663A CNA2009101189560A CN200910118956A CN101601663A CN 101601663 A CN101601663 A CN 101601663A CN A2009101189560 A CNA2009101189560 A CN A2009101189560A CN 200910118956 A CN200910118956 A CN 200910118956A CN 101601663 A CN101601663 A CN 101601663A
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Abstract
The invention discloses multi-unit sustained-release preparation of a kind of levetiracetam and preparation method thereof, said preparation is to be incapsulated by a plurality of slow release cell cubes that independently have pharmacologically active to be made.Described slow release cell cube is made up of the medicine carrying core body that contains the levetiracetam active component and its outer coatings of parcel, and this slow release cell cube or in the medicine carrying core body, add delay the retardance material of drug release or in coatings adding prolong drug release time the functional coatings material or adopt the combination of above-mentioned dual mode.The multi-unit sustained-release preparation of levetiracetam of the present invention because of the prescription of its uniqueness and manufacture method in vivo slowly, stable, discharge equably, and there is not the prominent phenomenon of releasing of medicine, also unable to take food thing influence, make blood drug level more steady, the time that medicine plays a role is longer, untoward reaction obviously alleviates, and patient's compliance is greatly improved, and is a kind of novel, antiepileptic preparation efficiently.
Description
Technical field
The present invention relates to the levetiracetam preparation, more specifically, is a kind of multi-unit sustained-release preparation that contains levetiracetam and preparation method thereof.
Background technology
Levetiracetam (LEV) is the left-handed ethyl piracetam in the piracetam derivant, its chemical name is (S)-alpha-ethyl-2-oxo-1-pyrrolidine acetamide, action target spot has been proved to be synaptic vesicle albumen 2 (SV2) A of nervus centralis, has brand-new epilepsy mechanism.Levetiracetam have onset rapidly, the influence of unable to take food thing, bioavailability near 100%, protein binding rate＜10%, no drug drug interaction, untoward reaction gently, characteristics such as better tolerance, be unique antiepileptic of report at present with special performance of prevention epilepsy, clinically with it as the wide spectrum antiepileptic.
But the levetiracetam preparation of listing mostly is multiple dosing every day at present, though oral long-acting novel KEPPRA XR prolongs drug treating time to some extent, but still have the prominent shortcomings such as phenomenon, blood drug level change greatly, curative effect of medication instability of releasing of medicine, its inborn epilepsy advantage is not given full play of in actual applications.
Summary of the invention
Multi-unit sustained-release preparation that provides a kind of levetiracetam slow in vivo, stable, that evenly discharge and preparation method thereof is provided the object of the invention, said preparation has long, advantage such as untoward reaction is light of prominent time of releasing that phenomenon, the influence of unable to take food thing, blood drug level are stable, medicine plays a role of no medicine, when improving curative effect, obviously reduce the medication number of times, improve patient's compliance.
The multi-unit sustained-release preparation of levetiracetam of the present invention comprises two or more slow release cell cubes that independently has pharmacologically active, these independently the slow release cell cube can have different rate of releasing drug, and can make various ways such as micropill, granule, microsphere, microcapsule, small pieces.Described slow release cell cube is by the medicine carrying core body that contains the levetiracetam active component and wrap up its outer coatings and forms, and this cell cube or in the medicine carrying core body, add delay the retardance material of drug release or in coatings adding prolong drug release time the functional coatings material or adopt the combination of above-mentioned dual mode.
One, medicine carrying core body:
Can contain the levetiracetam of following component: 40-90%, the forming agent of 0-40%, the disintegrating agent of 0-15% and the retardance material of 0-40% according to percentage by weight in the medicine carrying core body of described slow release cell cube.
Described forming agent is selected from but is not limited to one or more combination of microcrystalline Cellulose, starch, lactose, sucrose etc.
Described disintegrating agent is selected from but is not limited to one or more combination of polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium, the low hydroxypropyl cellulose that replaces etc.
Described retardance material is selected from but is not limited to one or more combination of hydroxypropyl methylcellulose, carbopol, hydroxypropyl cellulose, alginate, pectin, agar, chitosan, chitin, gala acid mannan, sodium carboxymethyl cellulose, carboxymethyl starch sodium, methylcellulose, hydroxyethyl-cellulose, polyvinyl alcohol, polyvinyl acetate, ethyl cellulose, stearic acid, hexadecanol, octadecanol, acrylic resin etc.In the medicine carrying core body, add and block the release that material can delay medicine, the action time of prolong drug, thus reduce the medication number of times.
Further, can also contain adhesive and wetting agent in the medicine carrying core body of the multi-unit sustained-release preparation slow release cell cube of levetiracetam of the present invention.Wherein adhesive is selected from but is not limited to polyvinylpyrrolidone, hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, carboxymethyl starch sodium, methylcellulose, starch, pregelatinized Starch, modified corn starch, gelatin, alginate, chitin, ethyl cellulose, the combination of one or more of acrylic resin etc.Wetting agent is selected from but is not limited to water, ethanol and the mixture that both form with any proportioning.
Two, coatings:
The coatings of described slow release cell cube is medicine carrying core body weightening finish 0-60%, preferred 20%-40%.Coatings comprise can prolong drug release time functional coatings and/or do not possess the non-functional coating of prolong drug function release time, wherein functional coatings is medicine carrying core body weightening finish 0-50%, the non-functional coating is medicine carrying core body weightening finish 0-10%.
Described functional coatings is dissolved in appropriate solvent or the disperse medium by the functional coatings material to be made, the functional coatings material is selected from but is not limited to acrylic resin, ethyl cellulose, acetyl cellulose, polyvinyl acetate, polyvinyl alcohol, methacrylic resin, and commercial obtainable slow controlled release filmogen
NE 30D,
RS 30D, Eudragit RS PO,
RL 30D,
SR 30D,
ETHOCEL etc. can be above-mentioned one or more combination.
Described non-functional coating is dissolved in appropriate solvent or the disperse medium by the non-functional coating material to be made, and the non-functional coating material is selected from but is not limited to hyprolose, Polyethylene Glycol, titanium dioxide, and commercial obtainable
Deng thin film coating material and premix powder thereof, can be above-mentioned one or more combination.
Further, for adjusting the performance of coatings, all can add plasticizer and porogen in functional coatings and the non-functional coating, the two accounts for the 0-60% and the 0.01%-10% of polymeric material dry weight in the coatings respectively.Preferred plasticizer and porogen account for the 0-20% and the 1%-6% of polymeric material dry weight in the coatings respectively.
Described plasticizer is selected from but is not limited to triethyl citrate, acetyl triethyl citrate, tributyl 2-acetylcitrate, dibutyl sebacate, Dibutyl phthalate, glycerol, triacetin, monoacetin, cochin oil, Polyethylene Glycol, propylene glycol, diethyl phthalate, Tween-80, Semen Ricini wet goods, can be above-mentioned one or more combination.
Described porogen is selected from but is not limited to sodium lauryl sulphate, Polyethylene Glycol, hydroxypropyl methylcellulose, polyvidone etc., can be above-mentioned one or more combination.
Again further, in order to prevent to bond mutually between the slow release cell cube in the coating process, can also in coatings, add antiplastering aid, antiplastering aid is selected from but is not limited to Pulvis Talci, glyceryl monostearate, micropowder silica gel, high mountain range scholar, magnesium trisilicate, magnesium stearate etc., can be above-mentioned one or more combination.Preferably talc powder wherein.
The preparation method of the multi-unit sustained-release preparation of levetiracetam of the present invention comprises following four steps:
(1) preparation medicine carrying core body: levetiracetam is a principal agent, selectivity adds suitable forming agent, disintegrating agent, retardance material, wetting agent, binding agent etc. as required, mix homogeneously is made the medicine carrying core body of forms such as micropill, granule, microsphere, microcapsule, small pieces, drying;
(2) prepare coating solution: coating material is dissolved in makes coating solution in appropriate solvent/disperse medium, can add filming performance and/or viscosity that plasticizer, porogen, antiplastering aid etc. are adjusted coating solutions;
(3) preparation slow release cell cube: the medicine carrying core body that step (1) is obtained places in fluid bed or other coating equipment, limit spray coating solution, the limit blowing hot-air, if multiple coating solution is arranged, then spray earlier have the non-functional coating solution of buffer action, again spray functional coatings liquid, spray other non-functional coating solutions at last, promptly obtain the slow release cell cube;
(4) preparation multi-unit sustained-release preparation: two or more above-mentioned slow release cell cubes are incapsulated, promptly make the multi-unit sustained-release preparation of levetiracetam.The multi-unit sustained-release preparation of levetiracetam of the present invention also can be pressed into tablet or other dosage form by a plurality of slow release cell cubes are equipped with suitable adjuvant.
Preferably, above-mentioned steps (1) can adopt either party's legal system of extruding spheronization, centrifugal lamination method, spherocrystal comminution granulation, emulsion process, oscillating drop method for making to be equipped with the medicine carrying core body, and the medicine carrying core body that makes is the entity micropill of outward appearance globulate or almost spherical.
Another optimal way, either party's legal system that above-mentioned steps (1) can adopt swing granulation, rotary granulation, high-speed stirred granulation, boiling granulating, wet-mixed granulation, melt extruded to granulate is equipped with the medicine carrying core body, and the medicine carrying core body that makes is the irregular entity granule of outward appearance.
Above-mentioned steps (1) can also adopt emulsifying dispersion method, coacervation, polymerization etc. that the medicine carrying core body is prepared into microsphere, perhaps adopt coacervation, multiple emulsion encapsulation, air suspension etc. that the medicine carrying core body is prepared into microcapsule, perhaps adopt methods such as tablet machine that the medicine carrying core body is prepared into small pieces.
The multi-unit sustained-release preparation of levetiracetam of the present invention because or in the medicine carrying core body, add the retardance material or in coatings, add the functional coatings material or adopt the combination of above-mentioned dual mode, drug release rate has greatly slowed down, prolong drug treating time, improved therapeutic effect.On the other hand, the multi-unit sustained-release preparation of levetiracetam of the present invention comprises two or more slow release cell cubes that independently has pharmacologically active, each slow release cell cube can both play a role separately again, so also have following advantage: (1) is owing to be a plurality of administrations unit, even the effect that medicine " prominent release " in the individual elements body also can obviously not influence medicine integral body occurs, " all or none " phenomenon that has often occurred when having avoided a unit administration; (2) medicine can be evenly dispersed in the body, thereby the difference that discharges in Different Individual, absorbs is very little, and it is wide to be suitable for the crowd; (3) dispersed and distributed of medicine has also obviously reduced a certain partial stimulation, and untoward reaction obviously alleviates; (4) can contain the cell cube of different rate of releasing drug in the medicine, combine to take and to reach effective treatment concentration fast and can keep this concentration for a long time again.Be the multi-unit sustained-release preparation of levetiracetam of the present invention, the drug effect performance is fast and can continue the long period, and administration number of times reduces, and has improved epileptic's compliance, and therapeutic effect is fairly obvious.
Description of drawings
With embodiment the present invention is described in further detail with reference to the accompanying drawings below.
Fig. 1 is the accumulation drug release percentage amounts of levetiracetam slow release pellet in 24 hours of embodiment 1;
Fig. 2 is the accumulation drug release percentage amounts of levetiracetam slow release pellet in 24 hours of embodiment 2;
Fig. 3 is the accumulation drug release percentage amounts of levetiracetam slow release granule in 24 hours of embodiment 3;
Fig. 4 is the accumulation drug release percentage amounts of levetiracetam slow release pellet in 24 hours of embodiment 4.
The specific embodiment
Below describe several preferred implementation of the present invention, but be not in order to limit the present invention.
Embodiment 1: levetiracetam slow release pellet (loading 1000 capsules parts)
Get the raw materials ready according to following prescription, pulverize crude drug and various pharmaceutic adjuvant, cross 100 mesh sieves.
Levetiracetam (active constituents of medicine) 500g
Microcrystalline Cellulose (forming agent) 125g
Lactose (forming agent) 25g
Crosslinked carboxymethyl fecula sodium (disintegrating agent) 25g
Water (wetting agent) is an amount of
Eudragit NE 30D (functional coatings material) 450g
Pulvis Talci (antiplastering aid) 135g
Opadry (non-functional coating material) 20g
Water (solvent/disperse medium) complements to 225g
With levetiracetam, microcrystalline Cellulose, lactose, the crosslinked carboxymethyl fecula sodium uniform mixing of recipe quantity, to do wetting agent with suitable quantity of water and prepare soft material, extruder is extruded, and round as a ball preparation is also dry, obtains the medicine carrying core body of micropill form; Opadry is carried out decentralized system with suitable water get the non-functional coating solution; Eudragit NE 30D is dispersed in the suitable quantity of water,, supplies the prescription water gaging, stir, make functional coatings liquid to wherein slowly adding the Pulvis Talci of homogenize in water; The medicine carrying micropill for preparing is placed in fluid bed or other coating equipment, and spray Eudragit NE 30D functional coatings liquid sprays Opadry non-functional coating solution more earlier, limit spray coating solution, and the limit blowing hot-air promptly obtains levetiracetam slow release pellet.
The accumulation drug release percentage amounts of the levetiracetam slow release pellet of present embodiment in 24 hours as shown in Figure 1.
Embodiment 2: levetiracetam slow release pellet (loading 1000 capsules parts)
Get the raw materials ready according to following prescription, pulverize crude drug and various pharmaceutic adjuvant, cross 100 mesh sieves.
Levetiracetam (active constituents of medicine) 500g
Microcrystalline Cellulose (forming agent) 125g
Lactose (forming agent) 25g
Crosslinked carboxymethyl fecula sodium (disintegrating agent) 25g
Water (wetting agent) is an amount of
Hydroxypropyl methylcellulose (non-functional coating material) 13.5g
Pulvis Talci (antiplastering aid) 8.1g
95% ethanol (solvent/disperse medium) is an amount of
Eudragit NE 30D (functional coatings material) 337.5g
Pulvis Talci (antiplastering aid) 112.5g
Opadry (non-functional coating material) 20g
Water (solvent/disperse medium) complements to 225g
With levetiracetam, microcrystalline Cellulose, lactose, the crosslinked carboxymethyl fecula sodium mix homogeneously of recipe quantity, do wetting agent with suitable quantity of water and be mixed with soft material, extruder is extruded then, and round as a ball preparation is also dry, obtains the medicine carrying core body of micropill form; The hydroxypropyl methylcellulose of recipe quantity and Pulvis Talci be dissolved in make non-functional coating solution in an amount of 95% ethanol with buffer action; Opadry is carried out decentralized system with suitable water get the non-functional coating solution; Eudragit NE 30D is dispersed in the suitable quantity of water,, supplies the prescription water gaging, stir, make functional coatings liquid to wherein slowly adding the Pulvis Talci of homogenize in water; The medicine carrying micropill for preparing is placed in fluid bed or other coating equipment, spray the quick coating of hydroxypropyl methylcellulose alcohol-water solution earlier, spray Eudragit NE 30D functional coatings liquid again, spray Opadry non-functional coating solution at last, limit spray coating solution, the limit blowing hot-air promptly arrives levetiracetam slow release pellet.
The accumulation drug release percentage amounts of the levetiracetam slow release pellet of present embodiment in 24 hours as shown in Figure 2.
Embodiment 3: levetiracetam slow release granule (loading 1000 capsules parts)
Get the raw materials ready according to following prescription, pulverize crude drug and various pharmaceutic adjuvant, cross 100 mesh sieves.
Levetiracetam (active constituents of medicine) 500g
Stearic acid (retardance material) 125g
Ethyl cellulose (retardance material) 25g
Polyvinylpyrrolidone aqueous solution (adhesive) is an amount of
Eudragit NE 30D (functional coatings material) 337.5g
Pulvis Talci (antiplastering aid) 112.5g
Opadry (non-functional coating material) 20g
Water (solvent/disperse medium) complements to 225g
With levetiracetam, stearic acid, the ethyl cellulose uniform mixing of recipe quantity, to make adhesive with the polyvinylpyrrolidone aqueous solution and prepare soft material, wet mixing pelletizer is granulated and is dry, obtains the medicine carrying core body of particle form; Opadry is carried out decentralized system with suitable water get the non-functional coating solution; Eudragit NE 30D is dispersed in the suitable quantity of water,, supplies the prescription water gaging, stir, make functional coatings liquid to wherein slowly adding the Pulvis Talci of homogenize in water; The medicine carrying granule for preparing is placed in fluid bed or other coating equipment, and spray Eudragit NE 30D functional coatings liquid sprays Opadry non-functional coating solution more earlier, limit spray coating solution, and the limit blowing hot-air promptly obtains the levetiracetam slow release granule.
The accumulation drug release percentage amounts of the levetiracetam slow release pellet of present embodiment in 24 hours as shown in Figure 3.
Embodiment 4: levetiracetam slow release pellet (loading 1000 capsules parts)
Get the raw materials ready according to following prescription, pulverize crude drug and various pharmaceutic adjuvant, cross 100 mesh sieves.
Levetiracetam (active constituents of medicine) 500g
Ethyl cellulose (retardance material) 43.75g
Stearic acid (retardance material) 43.75g
Microcrystalline Cellulose (forming agent) 37.5g
Water (wetting agent) is an amount of
Hydroxypropyl methylcellulose (non-functional coating material) 13.5g
Pulvis Talci (antiplastering aid) 8.1g
95% ethanol (wetting agent) is an amount of
Eudragit NE 30D (functional coatings material) 337.5g
Pulvis Talci (antiplastering aid) 112.5g
Opadry (non-functional coating material) 20g
Water (solvent/disperse medium) complements to 225g
With levetiracetam, ethyl cellulose, stearic acid, the microcrystalline Cellulose mix homogeneously of recipe quantity, do wetting agent with suitable quantity of water and be mixed with soft material, extruder is extruded then, and round as a ball preparation is also dry, obtains the medicine carrying core body of micropill form; Hydroxypropyl methylcellulose and Pulvis Talci be dissolved in make non-functional coating solution in an amount of 95% ethanol with buffer action; Opadry is carried out decentralized system with suitable water get the non-functional coating solution; Eudragit NE 30D is dispersed in the suitable quantity of water,, supplies the prescription water gaging, stir, make functional coatings liquid to wherein slowly adding the Pulvis Talci of homogenize in water; The medicine carrying micropill for preparing is placed in fluid bed or other coating equipment, spray the quick coating of hydroxypropyl methylcellulose alcohol-water solution earlier, spray Eudragit NE 30D functional coatings liquid again, spray Opadry non-functional coating solution at last, limit spray coating solution, the limit blowing hot-air promptly arrives levetiracetam slow release pellet.
The accumulation drug release percentage amounts of the levetiracetam slow release pellet of present embodiment in 24 hours as shown in Figure 4.
Embodiment 5: levetiracetam multi-unit sustained-release capsule
During the levetiracetam slow release pellet that makes among the embodiment 1～4 or levetiracetam slow release granule incapsulated, promptly make levetiracetam multi-unit sustained-release capsule.
Facts have proved, levetiracetam multi-unit sustained-release preparation of the present invention do not have prominent time of releasing that phenomenon, the influence of unable to take food thing, blood drug level are stable, medicine plays a role long, untoward reaction is light, when improving curative effect, obviously reduce the medication number of times, improved patient's compliance.
Claims (10)
1. the multi-unit sustained-release preparation of a levetiracetam is characterized in that containing in the said preparation slow release cell cube that two or more independently have pharmacologically active.
2. the multi-unit sustained-release preparation of levetiracetam according to claim 1, the dosage form that it is characterized in that described preparation is a capsule.
3. the multi-unit sustained-release preparation of levetiracetam according to claim 1 is characterized in that described slow release cell cube can make micropill, granule, microsphere, microcapsule or small pieces.
4. according to the multi-unit sustained-release preparation of each described levetiracetam of claim 1 to 3, it is characterized in that described slow release cell cube is made up of the medicine carrying core body that contains the levetiracetam active component and its outer coatings of parcel, and this slow release cell cube or in the medicine carrying core body, add delay the retardance material of drug release or in coatings adding prolong drug release time the functional coatings material or adopt the combination of above-mentioned dual mode.
5. the multi-unit sustained-release preparation of levetiracetam according to claim 4 is characterized in that described retardance material accounts for the 0-40% of slow release cell cube medicine carrying core body weight.
6. the multi-unit sustained-release preparation of levetiracetam according to claim 4 is characterized in that described retardance material is selected from one or more combination of hydroxypropyl methylcellulose, carbopol, hydroxypropyl cellulose, alginate, pectin, agar, chitosan, chitin, gala acid mannan, sodium carboxymethyl cellulose, carboxymethyl starch sodium, methylcellulose, hydroxyethyl-cellulose, polyvinyl alcohol, polyvinyl acetate, ethyl cellulose, stearic acid, hexadecanol, octadecanol, acrylic resin etc.
7. the multi-unit sustained-release preparation of levetiracetam according to claim 4, it is characterized in that described functional coatings material is selected from acrylic resin, ethyl cellulose, acetyl cellulose, polyvinyl acetate, polyvinyl alcohol, methacrylic resin, and commercial obtainable slow controlled release filmogen
NE 30D,
RS 30D, Eudragit RS PO,
RL 30D,
SR 30D,
ETHOCEL etc. can be above-mentioned one or more combination.
8. method for preparing the multi-unit sustained-release preparation of the described levetiracetam of claim 1 is characterized in that comprising following four steps:
(1) preparation medicine carrying core body: levetiracetam is a principal agent, selectivity adds suitable forming agent, disintegrating agent, retardance material, wetting agent, binding agent etc. as required, mix homogeneously is made the medicine carrying core body of forms such as micropill, granule, microsphere, microcapsule, small pieces, drying;
(2) prepare coating solution: coating material is dissolved in makes coating solution in appropriate solvent/disperse medium, can add filming performance and/or viscosity that plasticizer, porogen, antiplastering aid etc. are adjusted coating solutions;
(3) preparation slow release cell cube: the medicine carrying core body that step (1) is obtained places in fluid bed or other coating equipment, limit spray coating solution, the limit blowing hot-air, if multiple coating solution is arranged, then spray earlier have the non-functional coating solution of buffer action, again spray functional coatings liquid, spray other non-functional coating solutions at last, promptly obtain the slow release cell cube;
(4) preparation multi-unit sustained-release preparation: two or more above-mentioned slow release cell cubes are incapsulated the multi-unit sustained-release preparation of promptly making levetiracetam of the present invention.
9. the preparation method of the multi-unit sustained-release preparation of levetiracetam according to claim 8, it is characterized in that described step (1) adopts arbitrary method of extruding spheronization, centrifugal lamination method, spherocrystal comminution granulation, emulsion process, oscillating drop method for making, makes the medicine carrying core body entity micropill of outward appearance globulate or almost spherical.
10. the preparation method of the multi-unit sustained-release preparation of levetiracetam according to claim 8, it is characterized in that arbitrary method that described step (1) adopts swing granulation, rotary granulation, high-speed stirred granulation, boiling granulating, wet-mixed granulation, melt extruded to granulate, the medicine carrying core body is made the irregular entity granule of outward appearance.
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2009101189560A CN101601663A (en) | 2009-03-10 | 2009-03-10 | Multi-unit sustained-release preparation of levetiracetam and preparation method thereof |
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| CNA2009101189560A CN101601663A (en) | 2009-03-10 | 2009-03-10 | Multi-unit sustained-release preparation of levetiracetam and preparation method thereof |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102379857A (en) * | 2011-05-30 | 2012-03-21 | 深圳信立泰药业股份有限公司 | Levetiracetam slow release medicinal composite and preparation method thereof |
| CN102688214A (en) * | 2012-06-15 | 2012-09-26 | 孙威 | Preparation method of levetiracetam sustained release tablet |
| CN105030714A (en) * | 2015-07-06 | 2015-11-11 | 长春中医药大学 | Aniracetam sustained release tablet and preparation method thereof |
| CN106619530A (en) * | 2015-10-27 | 2017-05-10 | 重庆润泽医药有限公司 | Levorotatory oxiracetam granule and preparation method thereof |
| CN106619575A (en) * | 2017-02-27 | 2017-05-10 | 佛山市弘泰药物研发有限公司 | Levetiracetam sustained-release capsule and preparing method thereof |
| CN106511307B (en) * | 2015-09-11 | 2018-10-23 | 重庆润泽医药有限公司 | It is a kind of（S）- 2 oxo-1-pyrrolidine ethanamide spansule of -4- hydroxyls and preparation method thereof |
| CN115192572A (en) * | 2021-04-08 | 2022-10-18 | 成都同道慧宜生物医药科技有限公司 | Brivaracetam medicament, preparation method and application thereof |
| CN115501207A (en) * | 2022-07-29 | 2022-12-23 | 上海安必生制药技术有限公司 | Levetiracetam sustained release preparation and preparation method thereof |
| WO2024021050A1 (en) * | 2022-07-29 | 2024-02-01 | 上海安必生制药技术有限公司 | Levetiracetam sustained-release formulation and preparation method therefor |
-
2009
- 2009-03-10 CN CNA2009101189560A patent/CN101601663A/en active Pending
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102379857A (en) * | 2011-05-30 | 2012-03-21 | 深圳信立泰药业股份有限公司 | Levetiracetam slow release medicinal composite and preparation method thereof |
| CN102688214A (en) * | 2012-06-15 | 2012-09-26 | 孙威 | Preparation method of levetiracetam sustained release tablet |
| CN102688214B (en) * | 2012-06-15 | 2013-05-22 | 孙威 | Preparation method of levetiracetam sustained release tablet |
| CN105030714A (en) * | 2015-07-06 | 2015-11-11 | 长春中医药大学 | Aniracetam sustained release tablet and preparation method thereof |
| CN106511307B (en) * | 2015-09-11 | 2018-10-23 | 重庆润泽医药有限公司 | It is a kind of（S）- 2 oxo-1-pyrrolidine ethanamide spansule of -4- hydroxyls and preparation method thereof |
| CN106619530A (en) * | 2015-10-27 | 2017-05-10 | 重庆润泽医药有限公司 | Levorotatory oxiracetam granule and preparation method thereof |
| CN106619575A (en) * | 2017-02-27 | 2017-05-10 | 佛山市弘泰药物研发有限公司 | Levetiracetam sustained-release capsule and preparing method thereof |
| CN115192572A (en) * | 2021-04-08 | 2022-10-18 | 成都同道慧宜生物医药科技有限公司 | Brivaracetam medicament, preparation method and application thereof |
| CN115192572B (en) * | 2021-04-08 | 2023-09-19 | 成都同道慧宜生物医药科技有限公司 | Brivaracetam medicament, preparation method and application thereof |
| CN115501207A (en) * | 2022-07-29 | 2022-12-23 | 上海安必生制药技术有限公司 | Levetiracetam sustained release preparation and preparation method thereof |
| WO2024021050A1 (en) * | 2022-07-29 | 2024-02-01 | 上海安必生制药技术有限公司 | Levetiracetam sustained-release formulation and preparation method therefor |
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