WO2013058450A1 - Composition médicale à base d'épérisone stabilisée, et préparation à libération prolongée contenant celle-ci - Google Patents

Composition médicale à base d'épérisone stabilisée, et préparation à libération prolongée contenant celle-ci Download PDF

Info

Publication number
WO2013058450A1
WO2013058450A1 PCT/KR2012/002288 KR2012002288W WO2013058450A1 WO 2013058450 A1 WO2013058450 A1 WO 2013058450A1 KR 2012002288 W KR2012002288 W KR 2012002288W WO 2013058450 A1 WO2013058450 A1 WO 2013058450A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
release
sustained
stabilized
eferison
Prior art date
Application number
PCT/KR2012/002288
Other languages
English (en)
Korean (ko)
Inventor
이창규
박상근
Original Assignee
주식회사 네비팜
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 주식회사 네비팜 filed Critical 주식회사 네비팜
Priority to BR112014009506A priority Critical patent/BR112014009506B1/pt
Priority to JP2014536967A priority patent/JP5948648B2/ja
Priority to MX2014004652A priority patent/MX346661B/es
Priority to CN201280051152.3A priority patent/CN103889455B/zh
Publication of WO2013058450A1 publication Critical patent/WO2013058450A1/fr

Links

Images

Classifications

    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
    • 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
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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

Definitions

  • the present invention relates to a stabilized epherizone pharmaceutical composition and a sustained release formulation containing the same, and more specifically, it is composed of the active ingredient eferison salt and an acidifying agent, which is active during storage of the finished product as well as while the drug stays in the patient's body.
  • a stabilized ephericone pharmaceutical composition for maintaining the chemical stability of the component, and a stabilized ephericone-containing sustained-release preparation containing a release delaying agent in addition to the eferison and the acidifying agent, which exhibits a fast release and sustained release dual release properties will be.
  • Eperisone is a drug used for the treatment of stiff paralysis caused by neurological diseases including painful muscle spasms associated with musculoskeletal diseases for a long time, the chemical structure is represented by the following formula (1).
  • the drug has chemically very unstable properties such as easy decomposition into piperidine ring in alkaline environment.
  • decomposition of the active ingredient starts immediately after preparation, and there is a problem in that the impurity content increases by 1 to 2% within 1 and 2 months after the start of product storage.
  • the drug has a short half-life and a short time in the blood, so the method of administration is mainly three times a day.
  • NSAIDs nonsteroidal anti-inflammatory drugs
  • eferison a drug for sustained release eperisone that can be taken twice daily.
  • eperisone is mainly absorbed in the upper part of the intestine, it is necessary to improve stability in the intestinal alkali environment in order to develop a sustained release formulation which stays in this absorption site for a long time and slowly releases the drug.
  • the problem to be solved by the present invention is to provide a stabilized eferison pharmaceutical composition that keeps the active ingredient chemically stable during storage of the finished product, as well as in the alkaline environment of the human intestinal tract after the patient takes the drug.
  • Another problem to be solved by the present invention is to provide a sustained release formulation containing eferisone having a dual release property to express a useful therapeutic effect even when taken once or twice daily.
  • the stabilized eferison pharmaceutical composition according to the present invention comprises an eferison salt and an acidifying agent, wherein the acidity of the 0.5% (W / V) aqueous solution is pH 0.5 to pH 5.6, and the acidifying agent is an acidic pH adjusting agent, Or an excipient which exhibits a pH of 5.0 or lower when suspended, dissolved, swelled or miscible in water.
  • the active ingredient eferison includes all pharmaceutically acceptable salt forms, but the preferred salt is hydrochloride, and the effective amount of eferison hydrochloride is 150-300 mg / day.
  • the acidifying agent when the acidifying agent is prepared in 0.5% (W / V) aqueous solution of the pharmaceutical composition of the present invention functions to adjust the pH so that the pH 0.5 ⁇ 5.6, the active ingredient eferison under such an acidic environment It has chemical stability during storage of the finished product and in the intestinal alkaline environment after taking it. Therefore, the content of the acidifying agent includes an amount in which the 0.5% (W / V) aqueous solution of the pharmaceutical composition has an acidity of pH 0.5 to 5.6.
  • the acidity of the 0.5% (W / V) aqueous solution of the eferrizone pharmaceutical composition according to the present invention is less than pH 0.5, it is not preferable because the acid property of the efferison can damage the oral cavity and esophageal mucosa of the patient when taken.
  • the acidity is alkalinized above pH 5.6, the stability of the active ingredient is remarkably degraded, and in particular, the problem of preventing the decomposition of the active ingredient in the alkaline environment inside the intestine after taking the drug occurs.
  • the acidifying agent may be an acidic pH adjusting agent or an excipient exhibiting a pH of 5.0 or less when suspended, dissolved, swelled or miscible in water.
  • the acidic pH adjusting agent may include alginic acid, acetic acid, formic acid, adipic acid, edetic acid, fumaric acid, and lactic acid.
  • the excipient may be any excipient having a pH of 5.0 or less when suspended, dissolved, swelled, or miscible in water, and more specifically, carbomer, polycarbophil, polydextrose. It is preferable to use one or more selected from (Polydextrose).
  • the release rate of the active ingredient is too low than the target dissolution rate at the initial time after taking the drug, the patient cannot obtain the fast drug.
  • the target dissolution rate is exceeded, the blood concentration in the body is excessively increased due to problems such as initial dose dosing. This may cause problems for the patient.
  • the release rate at the intermediate or final time point is too fast for the target dissolution rate, the effective blood concentration of the drug cannot be maintained until the next dose, so that an effective therapeutic effect cannot be expected.
  • the release rate is too late for the target dissolution rate, the continuous blood concentration is maintained.
  • the next dose may further increase the body's concentration of the drug, causing side effects. Therefore, controlling the release content over time after taking the drug is a very important factor in achieving the desired therapeutic purpose.
  • Eperisone-containing sustained-release preparation according to the present invention has a dual release property that exhibits both fast-acting for obtaining rapid muscle relaxation and analgesic effect at the beginning of the administration, and sustained release that can be taken once or twice a day.
  • the sustained-release preparation of the present invention is 0.05 to 3 parts by weight, preferably 0.1 to 2.5 parts by weight, with respect to 1 part by weight of the eferison salt in addition to the active ingredient eferison salt and an acidifying agent. Includes the first.
  • the delayed release agent is a cellulose derivative, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose;
  • Hydrophilic polymers include polysaccharides, polyacrylates, hydrogels, polyvinyl alcohols, polyvinylpyrrolidones, carbopol, polyethylene oxides, magnesium aluminum silicates, starch derivatives, or mixtures thereof;
  • Hydrophobic polymers include copolymers of acrylic acid and methacrylic acid esters, polyethylene, polyamides, polyvinylchloride, polyvinylacetate, polyvinyl alcohol, or mixtures thereof;
  • As the water-insoluble polymer any one or more selected from polyacrylic acid, acrylic resin, acrylic latex dispersion, cellulose acetate phthalate, polyvinylacetate phthalate, and hydroxypropylmethylcellulose phthalate can be used.
  • the delayed release agent may adjust the amount used according to the initial release rate or the duration of effect expression.
  • the delayed-release agent may be used alone or mixed, hydroxypropyl methyl cellulose is preferred when used alone, polyvinylpyrrolidone and polyvinylacetate as a mixture of hydrophilic polymer and hydrophobic polymer when used alone It is preferable that 2: 8 weight part mixed.
  • the ephericone-containing sustained-release preparation includes a first sustained-release preparation that can be taken once a day and a second sustained-release preparation that can be taken twice a day.
  • the first sustained-release preparation has the property of eluting 30 to 50% by weight of the active ingredient content within 60 minutes of initial dissolution, 55 to 75% by weight within 6 hours, and 85% by weight or more within 24 hours.
  • the second sustained-release preparation has a characteristic of eluting 15 to 55% by weight of the active ingredient content within 15 minutes of the initial dissolution, 55 to 75% by weight within 1 hour, and 85% by weight or more within 3 hours.
  • the first sustained-release preparation and the second sustained-release preparation can be prepared by appropriately adjusting the contents of the active ingredient and the release delaying agent as necessary.
  • the active ingredient In order to achieve the same pharmacological effect as the three doses of eferison containing sustained-release preparation of the present invention only once or twice daily, the active ingredient must be continuously released in the gastrointestinal tract.
  • Eperisone is very unstable to alkali, which is an intestinal environment, and since the absorption site of the drug is mainly located in the upper gastrointestinal tract, it is necessary to stay for a long time in an acidic environment if possible. Therefore, it is preferable to use a conventional intragastric retention system such as a floating system, a gastric adhesion system, a swelling system, and in particular, it is preferable to adjust the specific gravity of the entire formulation to a range similar to or lower than that of the gastric juice.
  • the specific gravity of the sustained release formulation is in the range of 0.5 to 1.2 g / ml in an aqueous solution of pH 1 using an excipient exhibiting a low density such as polypropylene form powder (Accurel) or porous calcium silicate (Florite). Because if the specific gravity of the sustained-release preparation exceeds 1.2 g / ml, the specific gravity is higher than the gastric juice to sink to the lower part of the stomach, which will not achieve the purpose of continuing to release the drug while staying in the stomach .
  • the specific gravity of the sustained-release preparation is lower than 0.5 g / ml, there is a problem in handling during manufacture and distribution because it does not maintain its shape as a solid and easily breaks into a powder or granular form.
  • the specific specific gravity range of the sustained release formulation is 0.8 to 1.2 g / ml.
  • the eferison containing sustained release formulations of the present invention may include all known gas generants, including sodium bicarbonate, in the formulation as a conventional intragastric retention system.
  • the gas generating agent is preferably placed in a separate outer layer to avoid contact with the active ingredient in order not to adversely affect the stability of the active ingredient, in particular, such as tablets so as not to inhibit the double release characteristics It is preferable to contact only one side.
  • the pH of the sustained-release preparation needs to be adjusted so that the pH of only the drug layer except for the layer containing the gas generator is 0.5 to 5.6.
  • the eferisone-containing sustained-release preparation according to the present invention may additionally include nonsteroidal anti-inflammatory drugs (NSAIDs), specifically, aceclofenac, diclofenac, meloxycamp, naproxen, ibuprofen, dexibuprofen, and roxofol. It may include any one or more selected from lofen, zaltoprofen, felbinac, ketoprofen, etodolak, nabumetone, celecoxib, nimesulide.
  • NSAIDs nonsteroidal anti-inflammatory drugs
  • the sustained-release preparation contains a nonsteroidal anti-inflammatory drug
  • the anti-inflammatory effect and the analgesic effect can be obtained together through the synergistic effect between the two drugs, thus enhancing the convenience of taking patients to improve medication compliance. It can be increased.
  • the ephericone-containing sustained-release preparation of the present invention may be prepared by mixing the active ingredient, the eferison salt, the acidifying agent and the delayed-release agent together, and then using a conventional direct method, a wet method, a dry method, granules, It includes all types of controlled release preparations, such as beads, pellets, tablets or capsules containing two or more phases, capsules, multilayers, coatings, nucleus, matrix, etc., as well as sustained release from the stomach or upper gastrointestinal tract.
  • the stabilized eferrizone pharmaceutical composition according to the present invention has an acidifying agent that maintains the atmosphere around the active ingredient in a pH range of 5.6 or less, so that even during storage of the finished product, even in the alkaline environment of the intestinal tract after the patient has taken the drug. Compared with conventional commercial formulations, there is an effect of improving the chemical stability of the active ingredient 20 times or more.
  • the stabilized sustained-release preparation containing eferisone of the present invention contains an active ingredient, an acidifying agent and a release delaying agent, which has dual release properties of fast-acting and sustained release, and can be taken once or twice a day. Because it is effective to improve patient compliance.
  • 1 is a graph showing the hourly dissolution rate for the first sustained release formulation of the present invention (taken once daily),
  • Figure 2 is a graph showing the dissolution rate over time for the second sustained release formulation of the present invention (taken twice daily),
  • FIG 3 is a graph showing the dissolution rate according to time measured according to the rotational sample method for the second sustained-release preparation of the present invention (taken twice a day);
  • Figure 4 is a graph comparing the blood concentration of the sustained release formulation of the present invention and the conventional commercial formulation.
  • the collidone SL is a trade name of BASF, which is a release retardant in which polyvinyl pyrrolidone and polyvinyl acetate are mixed in an amount of 2: 8 parts by weight.
  • the granules were dried in an oven at 50 ° C. for 2 hours, and then ground and granulated using an oscillator (Oscillator, ERWEKA AR-402) using 20 mesh (standard standard KSA5101-1) to prepare granules.
  • oscillator Oscillator, ERWEKA AR-402
  • 20 mesh standard standard KSA5101-1
  • Tablets were prepared in the same manner as in Example 3, except that 16.0 g of alginic acid was used instead of 16.0 g of citric acid in Example 3.
  • Tablets were prepared in the same manner as in Example 3, except that 16.0 g of tartaric acid was used instead of 16.0 g of citric acid in Example 3.
  • Eudragit is a copolymer of acrylic acid and methacrylic acid ester under EVONIK Industries.
  • ethanol was added to rotate the agitator 100rpm, microwave 1500rpm to rotate for 3 minutes to form a granule.
  • the granules were dried in an oven at 50 ° C. for 1 hour, and then ground and granulated using an oscillator (Oscillator, ERWEKA AR-402) using 20 mesh (standard standard KSA5101-1) to prepare granules.
  • magnesium stearate was weighed and appled into a 50 mesh sieve, and then mixed and mixed in a plastic bag for 3 minutes, and the mixture was compressed in a tableting machine to prepare 380 mg tablets containing 150 mg of eferisone hydrochloride per tablet.
  • microcrystalline cellulose 22.8 g of microcrystalline cellulose, 80.0 g of collidone SL, 6.0 g of capper, 5.0 g of citric acid, and 15.0 g of sodium bicarbonate were added to a plastic bag, mixed for 10 minutes, and 1.2 g of magnesium stearate was weighed and appled in a 50 mesh sieve. After the addition and mixing for 3 minutes to prepare a floating layer mixture.
  • the drug layer mixture 320 mg and the floating layer mixture 130 mg were tableted with a bilayer tablet press so as to be included in each layer, thereby preparing a 450 mg bilayer tablet containing 150 mg of eferison hydrochloride per tablet.
  • the mixture was compressed in a tablet press to prepare 200 mg tablets containing 75 mg of eferison hydrochloride per tablet.
  • eferison hydrochloride 300.0 g of eferison hydrochloride, 429.0 g of microcrystalline cellulose, and 24.0 g of Eudragit RS PO were added to a speed mixer (KM-5, KM-5), and the mixture was spun at 100 rpm and mixed for 3 minutes. Further ethanol was added to rotate the agitator at 100rpm, microwave 1500rpm to rotate for 3 minutes to prepare a granule.
  • the granules were dried in an oven at 50 ° C. for 1 hour, and then ground and granulated using an oscillator (Oscillator, ERWEKA AR-402) using 20 mesh (standard standard KSA5101-1) to prepare granules.
  • 7.0g of magnesium stearate was weighed, appled into a 50 mesh sieve, and then mixed and mixed in a plastic bag for 3 minutes. The mixture was compressed in a tablet press to prepare 380 mg tablets containing 150 mg of eferison hydrochloride per tablet.
  • the pH of the 0.5% aqueous solution was all 5.6 or less except Example 7.
  • all of the comparative examples without addition of the acidifying agent showed pH 6.0 or higher.
  • Example 7 the pH of the whole tablet was found to be about 6.69 high, but this was due to the sodium bicarbonate contained in the floating layer.
  • the pH of the drug layer was measured without the floating layer, the pH was determined to be 4.38.
  • the tablets prepared in each Example and Comparative Example were put in a bottle made of HDPE, and capped, and then the degree of generation of impurities was compared for 8 weeks while being kept in a constant temperature and humidity chamber at a temperature of 40 ° C. and a relative humidity of 75%.
  • the impurity measurement was put in a 60% methanol solution containing 0.1% perchloric acid, dissolved sufficiently by sonication and then filtered through a 0.45 ⁇ m membrane filter was tested according to the liquid chromatograph method.
  • Example 1 and Comparative Example 1 were put in 100 mL of pH 6.8 solution buffer and left at 37 ° C. for 6 hours. Subsequently, 900 mL of 60% methanol solution containing 0.1% perchloric acid was added, and dissolved sufficiently by sonication, filtered through a 0.45 ⁇ m membrane filter, and tested according to a liquid chromatograph method.
  • the sustained-release preparation according to the present invention is not completely disintegrated during the time of staying in the stomach as well as the time of passing through the small intestine, and moves to the state of continuously containing the drug in the tablet. In other words, only a part of the active ingredient, epherisone, is released while staying in the stomach, and the remaining amount remains in the non-disintegrated tablet and passes slowly through the small intestine.
  • Example 1 Each tablet of the tablet of Example 1 was put in a buffer of pH 1.2 at 37 °C, the dissolution test was carried out at 50rpm conditions by the paddle method. 5 mL was collected at each time point, filtered through a membrane filter, tested by liquid chromatography, and the results are shown in FIGS. 1 and 2.
  • the average per minute up to the first hour was used.
  • the release rate is 0.77-0.84 mg, and about 50 mg of eferison hydrochloride is rapidly released in one hour.
  • the amount of release corresponds to the amount of release of one tablet three times daily, which is a conventional commercial preparation, and can be said to be an amount required for rapid effect expression.
  • the first sustained-release preparation can be confirmed that the release proceeds at an average rate of 0.17 to 0.18 mg per minute for 6 hours thereafter, indicating a stable drug release pattern for a long time.
  • the eferisone-containing sustained-release preparation according to the present invention has a dual release property with both fast and sustained release.
  • the second sustained release formulation gradually released an average of 0.13 mg of eferison hydrochloride per minute from 60 minutes to 240 minutes. Therefore, it can be seen that the second sustained release formulation also has a double release property in the same manner as the first sustained release formulation.
  • Example 8 One tablet of the sustained-release preparation of Example 8 was put in a buffer of pH 1.2 at 37 ° C., and the dissolution test was performed under a rotational sample method at 100 rpm. 5 mL was collected at each time point, filtered through a membrane filter, tested by liquid chromatography, and the results are shown graphically in FIG. 3.
  • the blood concentration analysis experiment in the beagle dog was carried out with the tablet of Example 8.
  • the beagle dog used for the test was fasted for 4 hours after dosing from 10 o'clock on the day before dosing, and 150 mg (75 mg / tablet, 2 tablets) of the sustained-release tablet of Example 8 was added to each of 6 beagle dogs as 30 ml of water.
  • the crossover test was performed by oral cross-dosing of each drug at 1 week interval, which is a sufficient discharge period.
  • the initial blood concentrations of the initial 1.5 hours were 1.205 ng / mL and 1.353 ng, respectively. / mL similar to that, but at 4 hours, 0.973 ng / mL, 0.497 ng / mL, and at 6 hours, 0.539 ng / mL and 0.271 ng / mL, respectively, about twice the blood concentration of the commercial drug. Observation could be observed. That is, when the sustained-release tablet of the present invention is taken, it can be seen that blood concentration is maintained for a longer time than the general rapid-release preparation.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Neurology (AREA)
  • Pain & Pain Management (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Rheumatology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne une composition médicale à base d'épérisone stabilisée, et une préparation à libération prolongée contenant celle-ci. Plus particulièrement, la présente invention concerne une composition médicale à base d'épérisone stabilisée comprenant, comme ingrédients efficaces, un sel d'épérisone et un oxydant, pour maintenir ainsi la stabilité chimique des principes actifs pendant le temps de séjour des médicaments dans un corps ainsi que le stockage des produits finis. L'invention concerne également une préparation à libération prolongée contenant l'épérisone stabilisée qui présente des caractéristiques de libération doubles consistant en une libération rapide et une libération lente car la préparation comprend en outre un agent retardant la libération en plus de l'épérisone et de l'oxydant.
PCT/KR2012/002288 2011-09-05 2012-03-28 Composition médicale à base d'épérisone stabilisée, et préparation à libération prolongée contenant celle-ci WO2013058450A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
BR112014009506A BR112014009506B1 (pt) 2011-10-18 2012-03-28 preparação estabilizada de liberação sustentada contendo eperisona
JP2014536967A JP5948648B2 (ja) 2011-10-18 2012-03-28 安定化されたエペリゾンを含有する徐放性製剤
MX2014004652A MX346661B (es) 2011-09-05 2012-03-28 Composicion medica de eperisona estabilizada, y preparacion de liberacion sostenida que contiene la misma.
CN201280051152.3A CN103889455B (zh) 2011-10-18 2012-03-28 稳定化乙哌立松医药组成物及含有上述组成物的缓释制剂

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020110106388A KR101156054B1 (ko) 2011-09-05 2011-10-18 안정한 에페리손 함유 서방성 의약조성물
KR10-2011-0106388 2011-10-18

Publications (1)

Publication Number Publication Date
WO2013058450A1 true WO2013058450A1 (fr) 2013-04-25

Family

ID=48141658

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2012/002288 WO2013058450A1 (fr) 2011-09-05 2012-03-28 Composition médicale à base d'épérisone stabilisée, et préparation à libération prolongée contenant celle-ci

Country Status (6)

Country Link
JP (1) JP5948648B2 (fr)
KR (1) KR101156054B1 (fr)
CN (1) CN103889455B (fr)
BR (1) BR112014009506B1 (fr)
MX (1) MX346661B (fr)
WO (1) WO2013058450A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9044401B2 (en) 2010-06-10 2015-06-02 Navipharm Co., Ltd. Composition for preventing or treating osteoporosis, and manufacturing method therefor

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101832842B1 (ko) * 2012-01-13 2018-02-27 한미약품 주식회사 안정성이 향상된 에페리손 또는 이의 약학적으로 허용 가능한 염 및 특정 산성화제를 포함하는 약학 조성물
KR101497354B1 (ko) * 2013-03-29 2015-03-02 초당약품공업 주식회사 활성 성분으로 에페리손을 함유하는 서방성 제제 조성물
KR20140118410A (ko) * 2013-03-29 2014-10-08 초당약품공업 주식회사 저장 및 pH 안정성이 개선된 에페리손 의약 조성물
WO2018044020A1 (fr) * 2016-08-29 2018-03-08 초당약품공업 주식회사 Procédé de préparation de microsphère à libération prolongée d'épérisone, et préparation composite de microsphère à libération prolongée d'épérisone et d'acéclofénac
KR101760278B1 (ko) 2016-08-29 2017-07-21 초당약품공업 주식회사 에페리손을 유효 성분으로 함유하는 서방성 미립구의 제조방법
KR101799321B1 (ko) 2016-08-29 2017-11-20 초당약품공업 주식회사 에페리손 서방성 미립구와 아세클로페낙 복합제제
KR102254307B1 (ko) 2019-04-03 2021-05-21 위더스제약주식회사 보관 안정성이 향상된 에페리손 약제학적 조성물
KR102444073B1 (ko) * 2020-01-06 2022-09-16 (주)휴온스 안정성이 향상된 메틸에르고메트린말레산염 함유 약제학적 제제 및 이의 제조방법

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06211696A (ja) * 1992-11-09 1994-08-02 Sekisui Chem Co Ltd エペリゾンまたはトルペリゾン経皮吸収製剤
US6692769B1 (en) * 1998-10-26 2004-02-17 Tanabe Seiyaku Co., Ltd. Sustained-release particles
WO2010103544A2 (fr) * 2009-03-09 2010-09-16 Dinesh Shantilal Patel Nouvelle composition à libération prolongée de composés choisis dans la classe des relaxants musculaires à action centrale
US20100273746A1 (en) * 2007-12-20 2010-10-28 Balazs Ottilia Pharmaceutical formulations containing tolperisone

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR0163199B1 (ko) * 1990-05-24 1998-12-01 다이도 나오가따 서방성 좌제
JP2000143510A (ja) * 1998-11-16 2000-05-23 Taisho Pharmaceut Co Ltd 外用組成物
AT500144A1 (de) * 2004-03-05 2005-11-15 Sanochemia Pharmazeutika Ag Tolperison enthaltende, pharmazeutische zubereitung mit steuerbarer wirkstofffreisetzung zur oralen verabreichung
DE102005014080B4 (de) * 2005-03-21 2007-11-22 Birds Pharma Gmbh Berolina Innovative Research & Development Services Additionssalze des Tolperison, Verfahren zu deren Herstellung, Verwendung derselben und diese enthaltende Arzneimittel
NZ572207A (en) * 2006-03-24 2012-02-24 Auxilium Int Holdings Inc Stabilized compositions containing alkaline labile drugs
AT505225A1 (de) * 2007-04-26 2008-11-15 Sanochemia Pharmazeutika Ag 0erfahren zur herstellung von hoch reinem 2,4'-dimethyl-3-piperidino-propiophenon (tolperison), dieses enthaltende pharmazeutische zusammensetzungen, sowie tolperison enthaltende wirkstoffformulierungen

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06211696A (ja) * 1992-11-09 1994-08-02 Sekisui Chem Co Ltd エペリゾンまたはトルペリゾン経皮吸収製剤
US6692769B1 (en) * 1998-10-26 2004-02-17 Tanabe Seiyaku Co., Ltd. Sustained-release particles
US20100273746A1 (en) * 2007-12-20 2010-10-28 Balazs Ottilia Pharmaceutical formulations containing tolperisone
WO2010103544A2 (fr) * 2009-03-09 2010-09-16 Dinesh Shantilal Patel Nouvelle composition à libération prolongée de composés choisis dans la classe des relaxants musculaires à action centrale

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9044401B2 (en) 2010-06-10 2015-06-02 Navipharm Co., Ltd. Composition for preventing or treating osteoporosis, and manufacturing method therefor

Also Published As

Publication number Publication date
BR112014009506B1 (pt) 2020-04-07
JP5948648B2 (ja) 2016-07-06
MX346661B (es) 2017-03-28
CN103889455A (zh) 2014-06-25
KR101156054B1 (ko) 2012-06-20
CN103889455B (zh) 2017-12-05
JP2014530250A (ja) 2014-11-17
MX2014004652A (es) 2015-03-05
BR112014009506A2 (pt) 2017-05-09

Similar Documents

Publication Publication Date Title
WO2013058450A1 (fr) Composition médicale à base d'épérisone stabilisée, et préparation à libération prolongée contenant celle-ci
CA2616081C (fr) Formulations de retention gastrique et procede de fabrication de celles-ci
AU2011290614B2 (en) Nalbuphine-based formulations and uses thereof
EP2099430A2 (fr) Formulation de matrice sensible au ph
NZ582648A (en) Pharmaceutical composition containing dihydropyridine calcium channel antagonist and method for the preparation thereof
AU2018256998B2 (en) Pharmaceutical composition for oral administration comprising
EP2393486A1 (fr) Préparations médicamenteuses orales à libération contrôlée contenant de l'acéclofénac et leur procédé de fabrication
WO2016013795A1 (fr) Preparation a liberation prolongee
WO2010023690A2 (fr) Formulation à libération prolongée d'amisulpride
EP3648745A1 (fr) Composition pharmaceutique comprenant un comprimé sphéroïdal à unités multiples contenant de l'ésoméprazole et un sel de qualité pharmaceutique de celui-ci, et procédé de préparation de la composition pharmaceutique
WO2014157852A1 (fr) Composition médicinale à libération prolongée contenant de l'épérisone en tant que principe actif
WO2018143511A1 (fr) Comprimé oral triple à libération prolongée contenant de la prégabaline
KR101093781B1 (ko) ｐＨ조절제를 함유하는 목시플록사신 고형 조성물
US20070059354A1 (en) Sustained release dosage forms of oxcarbazepine
WO2013157841A1 (fr) Comprimé à libération prolongée contenant de la lévodropropizine et procédé pour préparer celui-ci
WO2013032206A1 (fr) Composition orale à libération prolongée contenant du chlorhydrate d'itopride, et procédé de préparation associé
BRPI0721049A2 (pt) Composições farmaceuticas de memantina
WO2017116031A1 (fr) Composition pharmaceutique contenant du géfitinib, pouvant être administrée à des patients présentant une intolérance au lactose, et présentant une commodité de dosage améliorée
EP3796908B1 (fr) Formulations de propivérine à libération contrôlée
WO2016137266A2 (fr) Composition pharmaceutique contenant de l'épérisone et du pélubiprofène
WO2016195377A2 (fr) Composition de préparation solide contenant du pranlukast à biodisponibilité améliorée et procédé pour sa préparation
WO2014133329A1 (fr) Formulation composite destinée au traitement de l'arthrite
WO2018043850A1 (fr) Formulation pharmaceutique de d-cyclosérine et procédé de production associé
WO2015056956A1 (fr) Composition pharmaceutique à libération contrôlée à base d'acide propionique
WO2021145625A1 (fr) Composition pharmaceutique comprenant de l'acide r-thioctique ou son sel pharmaceutiquement acceptable et substance de base d'enrobage entérique

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12842528

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: MX/A/2014/004652

Country of ref document: MX

ENP Entry into the national phase

Ref document number: 2014536967

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112014009506

Country of ref document: BR

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 22.08.2014)

122 Ep: pct application non-entry in european phase

Ref document number: 12842528

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 112014009506

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20140417