OA12121A - Matrix tablet for prolonged release of trimetazidine after oral administration. - Google Patents
Matrix tablet for prolonged release of trimetazidine after oral administration. Download PDFInfo
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- OA12121A OA12121A OA1200200181A OA1200200181A OA12121A OA 12121 A OA12121 A OA 12121A OA 1200200181 A OA1200200181 A OA 1200200181A OA 1200200181 A OA1200200181 A OA 1200200181A OA 12121 A OA12121 A OA 12121A
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- matrix tablet
- tablet according
- trimetazidine
- matrix
- total mass
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Pulmonology (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention concerns a matrix object for prolonged release of trimetazidine or one of its additive salts to a pharmaceutically acceptable acid after oral administration, characterised in that the prolonged release is controlled by the use of a polymer derived from cellulose.
Description
12121 - 1 -
The présent invention relates to a matrix tablet enabling the prolongée! release oftrimetazidine, or an addition sait thereof with a pharmaceutically acceptable acid, afteradministration by the oral route.
Trimetazidine, or l-(2,3,4-trimethoxybenzyl)piperazine, is a compound which, by5 maintaining the energy metabolism of a cell exposed to hypoxia or ischaemia, avoids thecollapse of the intracellular level of adenosine triphosphate (ATP). It thus ensuresfunctioning of the ion pumps, and sodium-potassium transmembrane flows and maintains cellular homeostasis.
Trimetazidine dihydrochloride is currently used therapeutically for the prophylactic 10 treatment of angina pectoris crisis, in chorioretinal attacks and for the treatment of vertigoof vascular origin (Ménière's vertigo, tinnitus).
Trimetazidine dihydrochloride has, until now, been administered by the oral route at dosesof from 40 to 60 mg/day, in the form of tablets containing 20 mg of active ingrédient or adrinkable solution containing 20 mg of active ingrédient per ml. Those two forms are 15 immediate-release forms. Patent FR 2 490 963 describes the immediate-release tablet form.Trimetazidine dihydrochloride is rapidly absorbed and eliminated by the body, its plasmahalf-life being less than 6 hours, which means that administration of the active ingrédienthas to be split into 2 or 3 administrations per day in order to ensure sufficient plasmalevels. The dosage regimen most frequently required during treatments is three tablets per 20 day. Multiple daily administrations bear the risk of being forgotten both by patients leadingan active life and by elderly patients already taking a number of médications.
Because of the rapid absorption and the 6-hour half-life, such immediate-release formsresuit in low levels in the blood by the time of the next administration. It is known to beimportant to maintain effective myocardial protection throughout the 24-hour period and 25 especially in the early moming when the conséquences of ischaemia are most serious.Because complété coverage of the day is not achieved with the immediate-release form, theApplicant has developed a prolonged-release form enabling perfect 24-hour coverage,ensuring a sufficient level in the blood between two administrations whilst retaining a large 1 2121 - 2 - plasma peak after each administration so as to maintain the efficacy of the trimetazidine,maintaining the energy metabolism of a cell exposed to hypoxia or ischaemia and avoidingthe lowering of the intracellular level of ATP.
It also allows peripheral vasodilator effects to be avoided, while stabilising blood flow5 rates and tensional effects.
The new formulation according to the invention accordingly allows the positivecharacteristics of the formulation described in patent FR 2 490 963 to be retained whileenabling better coverage of the day, which leads to better compliance and permanentprotection. 10 The présent invention relates more especially to a matrix tablet which enables theprolonged release of trimetazidine, or a pharmaceutically acceptable sait thereof, afteradministration by the oral route and which is composed of a hydrophilic matrixcharacterised in that the prolonged release is controlled by the use of a cellulose dérivativepolymer. 15 This matrix tablet, administrable preferably twice a day, enables prolonged activeingrédient release to be obtained whilst retaining a large plasma peak on eachadministration. It allows plasma levels greater than 70 pg/l to be obtained in humans aftereach administration and a plasma level greater than or equal to 40 pg/l to be maintaineduntil the next administration, which was not the case with the tablet described in patent 20 FR 2 490 963 when administered 3 times per day.
Among the cellulose dérivatives used in the matrix according to the invention, there maybe mentioned, more especially, cellulose ethers such as hydroxypropylcellulose,hydroxyethylcellulose, hydroxymethylcellulose, methylcellulose and hydroxypropylmethylcellulose. 25 The cellulose dérivative is preferably hydroxypropyl methylcellulose. The percentage ofcellulose dérivative polymer is from 25 to 50 % of the total mass of the tablet. -3- 12121
Hydroxypropyl methylcelluloses that hâve a viscosity of from 100 cP to 100 000 cP maybe used. The preferred viscosity is 4 000 cP.
Various excipients are added to the hydrophilic matrix, for example binders, diluents,lubricants and ilow agents. Among the binders, polyvidone is preferably used. The 5 percentage of polyvidone is from 3 to 12 % of the total mass of the tablet. Among thediluents, calcium hydrogen phosphate dihydrate is preferably used, which provides betterfluidity and better compressibility than other diluents such as lactose monohydrate. Thepercentage of calcium hydrogen phosphate is from 25 to 75 % of the total mass of thetablet. 10 Among the lubricants, there may be mentioned, without implying any limitation,magnésium stéarate, stearic acid, glycerol behenate and sodium benzoate. The preferredlubricant is magnésium stéarate. Finally, colloïdal silica is preferably used as flow agent.
The trimetazidine used in the matrix tablets according to the invention is preferably in thedihydrochloride form. 15 The percentage of trimetazidine dihydrochloride is from 15 to 30 % of the total mass of thetablet, preferably from 15 to 18 %.
The person skilled in the art will generally consider the release kinetics of matrix tablets tobe dépendent on the nature and amount of the basic component of the matrix - in this case,namely, the cellulose dérivative. 20 It now appears, surprisingly, that the release kinetics of the matrix tablet according to theinvention are influenced neither by the amount nor by the grade of the cellulose dérivativeused.
Various formulations produced using, on the one hand, hydroxypropyl methylcelluloses ofdifferent viscosities and, on the other hand, variable amounts of the same grade of 12121 -4- hydroxypropyl methylcellulose hâve exhibited équivalent release kinetics, which impliesthat there exists a spécifie synergy between the cellulose dérivative and the trimetazidine.
The présent invention relates also to a process for the préparation of the matrix tablet. Thematrix tablet may be prepared by wet granulation followed by compression, by dry 5 granulation followed by compression, or by direct compression. The préparation process ispreferably wet granulation followed by compression.
The wet granulation is performed by mixing the trimetazidine, the polyvidone and thediluent, and then wetting that mixture. That first step enables a hydrophilic environment tobe created around the active ingrédient, which is bénéficiai for its dissolution, and also 10 enables a unit dose that is as uniform as possible to be obtained.
In a second step, the previously obtained granulate is mixed with the cellulose dérivative.The lubricant and the flow agent are then added to the mixture. The third step iscompression of the lubricated mixture previously obtained.
The tablets thus formed are then, if desired, coated according to a conventional coating15 technique.
The following Examples illustrate the invention but do not limit it in any way. The matrixtablets described in the Examples were prepared in the following manner : - Step A : Mixture of trimetazidine, polyvidone and calcium hydrogen phosphate dihydrate,then wetting of the mixture using a sufficient amount of purified water, granulation and 20 then drying of the granulate. ' B : Mixture of the granulate obtained in Step A with hydroxypropyl methylcellulose. " Imbrication of the mixture obtained in Step B with magnésium stéarate and colloïdal silica. 12121 - 5 - - Step D : Compression of the lubricated mixture obtained in Step C on a rotary tabletmachine so as to obtain tablets having a hardness of about from 40 to 160 N, measured bybreaking across a diameter. EXAMPLE 1 : Formulations of different matrix tablets containing various amounts5 of trimetazidine
Table 1 : Unitary formulae for 3 types of tablet
Compound Amount (mg) Fi f2 f3 Trimetazidine dihydrochloride 60 30 35 Hydroxypropyl methylcellulose 112 74 74 Polyvidone 13.3 8.7 8.7 Calcium hydrogen phosphate dihydrate 92 85.9 80.9 Magnésium stéarate 2.2 1 1 Anhydrous colloïdal silica 0.5 0.4 0.4 Total mass of the tablet 280 200 200 EXAMPLE 2 :
Example 2 shows that different amounts of hydroxypropyl methylcellulose do not hâve an10 influence on the dissolution kinetics of the tablet.
Table 2 : Unitary formulae / variable amounts ofHPMC
Compound Amount (mg) f4 f5 Trimetazidine dihydrochloride 35 35 Hydroxypropyl methylcellulose 54 94 Polyvidone 10.1 7.3 Calcium hydrogen phosphate dihydrate 99.5 62.3 Magnésium stéarate 1 1 Anhydrous colloïdal silica 0.4 0.4 Total mass of the tablet 200 200 12121 -6-
Table 3 shows the percentages of compound released as a function of time for theformulations F4 and F5.
Table 3 : Release kinetics
Time (h) Percentage of compound released(%) F4 Fs 1 41 38 2 59 59 3 80 i 77 4 97 ! 96 EXAMPLE 3 :
Example 3 shows that different grades of hydroxypropyl methylcellulose do not hâve aninfluence on the dissolution kinetics of the tablet.
Table 4 : Formulations /variable grades ofHPMC
Compound Amount (mg) f3 f6 f7 Trimetazidine dihydrochloride 35 35 35 Hydroxypropyl methylcellulose 4000 cP 74 - - Hydroxypropyl methylcellulose 100 cP - - 74 Hydroxypropyl methylcellulose 100 000 cP - 74 - Polyvidone 8.7 8.7 8.7 Calcium hydrogen phosphate dihydrate 80.9 80.9 80.9 Magnésium stéarate 1 1 1 Anhydrous colloïdal silica 0.4 0.4 0.4 10
Table 5 shows the percentages of compound released as a function of time for theformulations F3, F6 and F7.
Table 5 : Release kinetics
Time (h) Percentage of compound released (%) f3 f6 f7 1 43 41 40 2 62 59 60 3 . 86 83 83 4 105 102 100 12121 EXAMPLE 4 : Plasma kinetics study
The plasma kinetics were studied after administration of the matrix tablet of formulation F3described in Example 1 to 12 healthy volunteers. 5 Administration was carried out for 4 days at the rate of two tablets per day.
The plasma kinetics of the tablet of formula F3 were compared to those of an immediate-release (IR) tablet administered for 4 days at the rate of three tablets per day.
The unitary formulation of the immediate-release (IR) tablet is as follows :Trimetazidine dihydrochloride................................................................................20 mg 10 Maize starch............................................................................................................26 mg
Mannitol..................................................................................................................34 mg
Polyvidone.................................................................................................................4 mg
Magnésium stéarate...................................................................................................1 mg
Talc............................................................................................................................5 mg 15 The average plasma concentration is given in Figure 1. 1 2121
Figure 1 : Plasma kinetics of trimetazidine
Average plasma concentrations of trimetazidine (in μg/l) after oral administration of the F} form and an IR form to 12 healthy volunteers
Plasma
Time (h) 5 This curve clearly shows that the F3 form enables prolonged release of trimetazidine to beobtained while retaining a large plasma peak on each administration.
The plasma level observed after each administration is close to 90 pg/l and hardly differentfrom that obtained with the IR form. At the end of 24 hours the plasma level is greater than40 pg/l whereas, with the immediate-release formulation, it is only about 25 pg/l.
Claims (17)
1- Matrix tablet for the prolongée! release of trimetazidine or a pharmaceutically acceptablesait thereof, characterised in that the prolonged release is controlled by the use of acellulose dérivative polymer.
2- Matrix tablet according to claim 1, characterised in that the cellulose dérivative polymer is a hydroxypropyl methylcellulose.
3- Matrix tablet according to either claim 1 or claim 2, characterised in that the percentageof cellulose dérivative is from .25 to 50 % of the total mass of the tablet.
4- Matrix tablet according to claim 1, characterised in that it also comprises a binder, a10 diluent, a lubricant and a flow agent.
5- Matrix tablet according to claim 4, characterised in that the binder is polyvidone.
6- Matrix tablet according to claim 5, characterised in that the percentage of polyvidone isfrom 3 to 12 % of the total mass of the tablet.
7- Matrix tablet according to any one of daims 4, 5 or 6, characterised in that the diluent is15 calcium hydrogen phosphate dihydrate.
8- Matrix tablet according to claim 7, characterised in that the percentage of calciumhydrogen phosphate dihydrate is from 25 to 75 % of the total mass of the tablet.
9- Matrix tablet according to any one of daims 4, 5, 6, 7 or 8, characterised in that thelubricant is magnésium stéarate and the flow agent is anhydrous colloïdal silica. - 10- 12121
-9- 12121 CLAIMS
10- Matrix tablet according to claim 1, characterised in that the trimetazidine is in the * dihydrochloride forrn.
11- Matrix tablet according to claim 10, characterised in that the percentage oftrimetazidine dihydrochloride is from 15 to 30 % of the total mass of the tablet.
12-Matrix tablet according to either claim 10 or claim 11, characterised in that the percentage of trimetazidine dihydrochloride is 17.5 % ofthe total mass of the tablet.
13- Matrix tablet according to any one of daims 1 to 12, characterised in that it contains35 mg of trimetazidine dihydrochloride, 74 mg of hydroxypropyl methylcellulose, 8.7 mgof polyvidone, 80.9 mg of calcium hydrogen phosphate dihydrate, 1 mg of magnésium 10 stéarate and 0.4 mg of anhydrous colloïdal silica.
14- Matrix tablet according to claim 13, characterised in that it is administered twice perday.
15- Matrix tablet according to claim 1, characterised in that it enables plasma levels greaterthan 70 pg/l to be obtained in humans afîer each administration and a plasma level greater 15 than or equal to 40 pg/l to be maintained until the next administration.
16- Process for the préparation of a matrix tablet according to any one of daims 1 to 13,characterised in that : - wet granulation is carried out by mixing trimetazidine, polyvidone and the diluent andthen wetting that mixture, 20 - the granulate thus obtained is mixed with the cellulose dérivative, - the lubricant and the flow agent are then added, - the previous mixture is then compressed.
. 17-Matrix tablet according to any one of daims 1 to 15 for use in the prophylactic treatment of angina pectoris, in chorioretinal attacks and in the treatment of vertigo of 25 vascular origin.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9915960A FR2802424B1 (en) | 1999-12-17 | 1999-12-17 | MATRIX TABLET FOR THE EXTENDED RELEASE OF TRIMETAZIDINE AFTER ORAL ADMINISTRATION |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA12121A true OA12121A (en) | 2003-10-20 |
Family
ID=9553398
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| OA1200200181A OA12121A (en) | 1999-12-17 | 2000-12-15 | Matrix tablet for prolonged release of trimetazidine after oral administration. |
Country Status (33)
| Country | Link |
|---|---|
| EP (1) | EP1108424B2 (en) |
| JP (2) | JP2001172181A (en) |
| KR (1) | KR100456933B1 (en) |
| CN (1) | CN1166408C (en) |
| AR (1) | AR026968A1 (en) |
| AT (1) | ATE296622T1 (en) |
| AU (1) | AU780011B2 (en) |
| BG (1) | BG65773B1 (en) |
| BR (1) | BR0005915A (en) |
| CY (1) | CY2347B1 (en) |
| CZ (1) | CZ299461B6 (en) |
| DE (1) | DE60020501T3 (en) |
| DK (1) | DK1108424T4 (en) |
| EA (2) | EA008223B1 (en) |
| ES (2) | ES2176106B1 (en) |
| FR (1) | FR2802424B1 (en) |
| GE (1) | GEP20053540B (en) |
| GR (1) | GR1003658B (en) |
| HK (1) | HK1036937A1 (en) |
| HU (1) | HU226956B1 (en) |
| IE (1) | IE20001017A1 (en) |
| IT (1) | IT1317075B1 (en) |
| LU (1) | LU90700B1 (en) |
| MX (1) | MXPA00012462A (en) |
| NZ (1) | NZ508912A (en) |
| OA (1) | OA12121A (en) |
| PL (1) | PL206994B1 (en) |
| PT (2) | PT1108424E (en) |
| SI (1) | SI1108424T2 (en) |
| SK (1) | SK286752B6 (en) |
| UA (1) | UA80087C2 (en) |
| WO (1) | WO2001043747A1 (en) |
| ZA (1) | ZA200007548B (en) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1195160E (en) * | 2000-10-05 | 2009-12-07 | Usv Ltd | Sustained release trimetazidine pharmaceutical compositions and a method of their preparation |
| CA2532714C (en) | 2003-08-04 | 2010-11-16 | Kyorin Pharmaceutical Co., Ltd. | Oral sustained-release tablet comprising 4-(2-methyl-1-imidazolyl)-2,2-diphenylbutylamide |
| SG126792A1 (en) * | 2005-04-27 | 2006-11-29 | Servier Lab | Matrix tablet enabling the prolonged release of trimetazidine after administration by the oral route |
| FR2885807B1 (en) * | 2005-05-18 | 2008-05-16 | Mg Pharma | SOLID PHARMACEUTICAL COMPOSITION WITH PROLONGED RELEASE OF 1- (2,3,4-TRIMETHOXYBENZYL) PIPERAZINE, AND PREPARATION METHOD |
| CZ300307B6 (en) * | 2006-01-04 | 2009-04-15 | Zentiva, A. S. | Modified release tablet containing trimetazidine or pharmacologically acceptable salts thereof |
| EA009776B1 (en) * | 2006-07-18 | 2008-04-28 | Мераб Ревазович Кокеладзе | Method for preparing tablets of dihydrochloride trimethazine and composition thereof |
| EA009810B1 (en) * | 2006-12-26 | 2008-04-28 | Закрытое Акционерное Общество "Канонфарма Продакшн" | Matrix for manufacturing tableted dosage form and method of treatment |
| EP2200591A2 (en) * | 2007-09-11 | 2010-06-30 | Ranbaxy Laboratories Limited | Controlled release pharmaceutical dosage forms of trimetazidine |
| JP2012515757A (en) | 2009-01-20 | 2012-07-12 | マイクロ ラブス リミテッド | Trimetazidine controlled release solid pharmaceutical composition and method for producing the same |
| HUE027498T2 (en) * | 2009-01-30 | 2016-10-28 | Lupin Ltd | Pharmaceutical compositions of trimetazidine |
| TR201001902A2 (en) | 2010-03-12 | 2011-04-21 | Ali̇ Rai̇f İlaç Sanayi̇ Ve Ti̇caret A.Ş. | Trimetazidine tablets with extended release |
| RU2445958C2 (en) * | 2010-04-20 | 2012-03-27 | Общество с ограниченной ответственностью "Озон" (ООО "Озон") | Matrix tablet with trimetazidine prolonged-release base and method for preparing it |
| ES2508490T3 (en) | 2010-05-04 | 2014-10-16 | Sanovel Ilaç Sanayi Ve Ticaret Anonim Sirketi | Formulation of trimetazidine with different release profiles |
| EP2386302A1 (en) | 2010-05-11 | 2011-11-16 | Ranbaxy Laboratories Limited | A controlled release pharmaceutical dosage form of trimetazidine and processes for the preparation thereof |
| EP2491930A1 (en) | 2011-02-25 | 2012-08-29 | Deva Holding Anonim Sirketi | Pharmaceutical combination of betahistine and trimetazidine |
| FR2978916B1 (en) * | 2011-08-10 | 2013-07-26 | Servier Lab | SOLID PHARMACEUTICAL COMPOSITION FOR BUCCAL ADMINISTRATION OF AGOMELATIN |
| FR2986431B1 (en) * | 2012-02-03 | 2017-03-17 | Servier Lab | PROLONGED RELEASE OF TRIMETAZIDINE PHARMACEUTICAL COMPOSITION, PROCESS FOR THE PRODUCTION THEREOF AND USE IN THERAPEUTIC TREATMENTS |
| CN102824644B (en) * | 2012-09-13 | 2013-12-25 | 浙江诚意药业有限公司 | High-stability sustained-release tablet prepared by using hydroxy propyl cellulose |
| KR20160118733A (en) | 2015-04-03 | 2016-10-12 | 이인현 | Hose guide apparatus for hose winder and hose winder |
| CN109316455B (en) * | 2017-07-31 | 2021-05-25 | 北京福元医药股份有限公司 | Trimetazidine hydrochloride sustained release tablet |
| CN109908096A (en) * | 2017-12-12 | 2019-06-21 | 武汉武药科技有限公司 | A kind of trimetazidine hydrochloride sustained-release tablets and preparation method thereof |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4226849A (en) * | 1979-06-14 | 1980-10-07 | Forest Laboratories Inc. | Sustained release therapeutic compositions |
| FR2490963B1 (en) * | 1980-09-30 | 1986-04-18 | Science Union & Cie | NOVEL THERAPEUTIC COMPOSITION WITH ANTI-ISCHEMIC ACTION CONTAINING TRIMETHOXY 2, 3, 4-BENZYL 1-PIPERAZINE |
| KR850006132A (en) * | 1984-02-29 | 1985-10-02 | 진 크라메르, 한스 루돌프 하우스 | Bromocriptine Composition |
| JPS61293931A (en) * | 1985-06-24 | 1986-12-24 | Teijin Ltd | Slow-releasing pharmaceutical composition |
| JPH0625055B2 (en) * | 1985-03-18 | 1994-04-06 | 日本ケミフア株式会社 | Persistent tablets |
| EP0207638B1 (en) † | 1985-06-04 | 1990-12-19 | Teijin Limited | Sustained-release pharmaceutical preparation |
| SE455836B (en) * | 1985-10-11 | 1988-08-15 | Haessle Ab | PREPARATION WITH CONTROLLED RELEASE CONTAINING A SALT OF METOPROLOL AND METHOD FOR PREPARING THIS PREPARATION |
| SE8601624D0 (en) * | 1986-04-11 | 1986-04-11 | Haessle Ab | NEW PHARMACEUTICAL PREPARATIONS |
| FR2677886B1 (en) * | 1991-06-18 | 1995-03-31 | Adir | MATRIX TABLET FOR THE EXTENDED RELEASE OF INDAPAMIDE AFTER ORAL ADMINISTRATION. |
| FR2681324B1 (en) * | 1991-09-18 | 1993-10-29 | Adir Cie | NOVEL TRIMETAZIDINE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM. |
| KR940021051A (en) * | 1993-03-03 | 1994-10-17 | 손정삼 | 3-step drug release sustained tablet |
| RU2082400C1 (en) * | 1993-12-16 | 1997-06-27 | Акционерное общество - Фармацевтическая фирма "Ник-Фарм" | Method of nitroglycerol prolonged action preparing |
| FR2717687B1 (en) * | 1994-03-24 | 1996-06-14 | Adir | Pharmaceutical compositions for the sustained release of trimetazidine after oral administration. |
-
1999
- 1999-12-17 FR FR9915960A patent/FR2802424B1/en not_active Expired - Fee Related
-
2000
- 2000-12-11 JP JP2000375812A patent/JP2001172181A/en active Pending
- 2000-12-14 IT IT2000RM000667A patent/IT1317075B1/en active
- 2000-12-14 CY CY0000059A patent/CY2347B1/en unknown
- 2000-12-14 AU AU72285/00A patent/AU780011B2/en not_active Expired
- 2000-12-14 MX MXPA00012462A patent/MXPA00012462A/en active IP Right Grant
- 2000-12-15 PL PL344564A patent/PL206994B1/en not_active IP Right Cessation
- 2000-12-15 CZ CZ20022082A patent/CZ299461B6/en not_active IP Right Cessation
- 2000-12-15 ES ES200003018A patent/ES2176106B1/en not_active Expired - Fee Related
- 2000-12-15 SK SK863-2002A patent/SK286752B6/en not_active IP Right Cessation
- 2000-12-15 WO PCT/FR2000/003546 patent/WO2001043747A1/en active IP Right Grant
- 2000-12-15 NZ NZ508912A patent/NZ508912A/en not_active IP Right Cessation
- 2000-12-15 ES ES00403533.3T patent/ES2240033T5/en not_active Expired - Lifetime
- 2000-12-15 DK DK00403533.3T patent/DK1108424T4/en active
- 2000-12-15 HU HU0004966A patent/HU226956B1/en active IP Right Maintenance
- 2000-12-15 ZA ZA200007548A patent/ZA200007548B/en unknown
- 2000-12-15 SI SI200030704T patent/SI1108424T2/en unknown
- 2000-12-15 DE DE60020501.0T patent/DE60020501T3/en not_active Expired - Lifetime
- 2000-12-15 PT PT00403533T patent/PT1108424E/en unknown
- 2000-12-15 OA OA1200200181A patent/OA12121A/en unknown
- 2000-12-15 GE GE4838A patent/GEP20053540B/en unknown
- 2000-12-15 EP EP00403533.3A patent/EP1108424B2/en not_active Expired - Lifetime
- 2000-12-15 LU LU90700A patent/LU90700B1/en active
- 2000-12-15 CN CNB001380605A patent/CN1166408C/en not_active Expired - Lifetime
- 2000-12-15 AT AT00403533T patent/ATE296622T1/en active
- 2000-12-15 PT PT102542A patent/PT102542A/en not_active IP Right Cessation
- 2000-12-15 UA UA2002075914A patent/UA80087C2/en unknown
- 2000-12-15 IE IE20001017A patent/IE20001017A1/en not_active Application Discontinuation
- 2000-12-15 KR KR10-2000-0076962A patent/KR100456933B1/en active IP Right Review Request
- 2000-12-15 AR ARP000106662A patent/AR026968A1/en not_active Application Discontinuation
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- 2000-12-18 EA EA200001201A patent/EA008223B1/en not_active IP Right Cessation
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- 2000-12-18 BR BR0005915-3A patent/BR0005915A/en not_active Application Discontinuation
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2001
- 2001-11-12 HK HK01107928A patent/HK1036937A1/en not_active IP Right Cessation
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2002
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2007
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