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WO2015012365A1 - Préparation pharmaceutique - Google Patents

Préparation pharmaceutique Download PDF

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Publication number
WO2015012365A1
WO2015012365A1 PCT/JP2014/069599 JP2014069599W WO2015012365A1 WO 2015012365 A1 WO2015012365 A1 WO 2015012365A1 JP 2014069599 W JP2014069599 W JP 2014069599W WO 2015012365 A1 WO2015012365 A1 WO 2015012365A1
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WO
WIPO (PCT)
Prior art keywords
metformin
salt
inhibitor
dpp
pharmaceutical preparation
Prior art date
Application number
PCT/JP2014/069599
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English (en)
Japanese (ja)
Inventor
直也 落合
Original Assignee
株式会社 三和化学研究所
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 株式会社 三和化学研究所 filed Critical 株式会社 三和化学研究所
Priority to JP2015528341A priority Critical patent/JP5922310B2/ja
Publication of WO2015012365A1 publication Critical patent/WO2015012365A1/fr

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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
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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 pharmaceutical preparation containing a DPP-IV inhibitor and metformin, wherein the DPP-IV inhibitor in the preparation is chemically stabilized, and a preparation method thereof.
  • DPP-IV inhibitor and metformin are effective compounds for the treatment of diabetes, especially type 2 diabetes, and both are currently used in clinical practice and are often administered in combination.
  • a combination preparation containing a DPP-IV inhibitor and metformin as active ingredients has been developed, and an oral solid preparation has been adopted as the dosage form from the viewpoint of ingestion.
  • a method of producing a DPP-IV inhibitor-containing granule granulated with a solvent such as ethanol or isopropanol and a metformin-containing granule as a multilayer tablet is disclosed.
  • Patent Document 2 discloses a method of adding BHT or BHA as an antioxidant in order to ensure chemical stability when a DPP-IV inhibitor, which is an active ingredient, and metformin are blended. Has been. Further, in Patent Document 3, in order to ensure chemical stability when a DPP-IV inhibitor as an active ingredient and metformin are blended, a granule containing only each active ingredient is produced and then physically mixed. A method for reducing physical contact between both active ingredients by compression molding is disclosed. Furthermore, Patent Document 4 discloses a nucleophilic and / or basic drug as a stabilizer in order to ensure chemical stability when a DPP-IV inhibitor which is an active ingredient and metformin are blended. A method of adding L-arginine is disclosed.
  • cyclodextrin is often used as a stabilizer, but usually exhibits an effect by inclusion of a drug to be stabilized, and the molar ratio with the drug to be stabilized is 1: 1. In order to make it to the extent, there is a problem that the usage amount increases.
  • An example of the use of such cyclodextrin as a stabilizer is not for a DPP-IV inhibitor, but is disclosed in Patent Document 5, for example.
  • an object of the present invention is to provide a new chemical stabilization method for a DPP-IV inhibitor in a pharmaceutical preparation containing the DPP-IV inhibitor and metformin.
  • the main configuration of the present invention is as follows.
  • a DPP-IV inhibitor and metformin or a salt thereof as active ingredients, further containing a cyclic oligosaccharide, and the metformin or a salt thereof is granulated are A pharmaceutical preparation characterized in that it is mixed and granulated separately from the cyclic oligosaccharide).
  • the chemical stability of the pharmaceutical preparation is indicated by a maximum yield of a DPP-IV inhibitor degradation product of 0.2% or less after storage for 21 days at a temperature of 60 ° C. (1 ) To (13). (15) The pharmaceutical preparation according to any one of (1) to (14), wherein the DPP-IV inhibitor is anagliptin or a salt thereof.
  • a pharmaceutical preparation comprising a DPP-IV inhibitor and metformin or a salt thereof, in which the chemical stability of the DPP-IV inhibitor is ensured, can be provided.
  • the chemical stability of the DPP-IV inhibitor can be secured without using an organic solvent or an antioxidant harmful to the human body, which is advantageous from the viewpoint of safety.
  • the product of the present invention does not require a complicated manufacturing process, it is advantageous in manufacturing.
  • the DPP-IV inhibitor used in the present invention is not particularly limited, but anagliptin or a salt thereof, linagliptin or a salt thereof, vildagliptin or a salt thereof, sitagliptin or a salt thereof, teneligliptin or a salt thereof, alogliptin or a salt thereof And saxagliptin or a salt thereof.
  • anagliptin or a salt thereof, sitagliptin or a salt thereof, teneligliptin or a salt thereof, alogliptin or a salt thereof are preferable, and anagliptin or a salt thereof is particularly preferable.
  • anagliptin is expressed as “N- [2-( ⁇ 2-[(2S) -2-cyanopyrrolidin-1-yl] -2-oxoethyl ⁇ amino) -2-methylpropyl] -2-methylpyrazolo [1,5 -a] pyrimidine-6-carboxamide ", which can be produced with reference to Examples 1 and 2 of WO2004 / 067509.
  • linagliptin or a salt thereof in WO2004 / 018468 vildagliptin or a salt thereof in WO00 / 34241, sitagliptin or a salt thereof in WO2003 / 004498, teneligliptin or a salt thereof in WO02 / 14271, alogliptin or a salt thereof in JP2005263780, Saxagliptin or a salt thereof is described in WO01 / 068603, respectively.
  • metformin or a salt thereof is an antidiabetic drug that has been often used as a biguanide, and is preferably in the form of a pharmaceutically acceptable salt.
  • the compounding amount of the DPP-IV inhibitor in the pharmaceutical preparation of the present invention is usually 2 to 30% by mass, preferably 5 to 30% by mass, and more preferably 5 to 15% by mass with respect to the whole preparation. This is 12.5 mg to 200 mg, preferably 25 mg to 200 mg, more preferably 50 mg to 100 mg, when expressed in terms of the content in a single pharmaceutical preparation.
  • the amount of metformin or a salt thereof in a pharmaceutical preparation is usually 30 to 90% by mass, preferably 40 to 90% by mass, and more preferably 50 to 80% by mass of the entire preparation. This is 125 mg to 1,000 mg, preferably 250 mg to 500 mg, when expressed in the content of a single pharmaceutical preparation.
  • the blending ratio of the DPP-IV inhibitor and metformin or a salt thereof in a pharmaceutical preparation is usually 1:11 to 1: 1, preferably 1: 6 to 1: 2.
  • the compounding ratio of anagliptin or a salt thereof and metformin or a salt thereof in a pharmaceutical preparation is usually 1:10, 1: 5, or 2: 5. Become.
  • the cyclic oligosaccharide used in the present invention is a cyclic oligosaccharide having a cyclic structure in which D-glucose is bonded by an ⁇ 1-4 glucoside bond, that is, a cyclodextrin having 6 to 8 glucose bonded. It is.
  • a cyclic oligosaccharide ⁇ -cyclodextrin, ⁇ -cyclodextrin, and ⁇ -cyclodextrin are preferable.
  • the cyclic oligosaccharide includes a cyclic oligosaccharide derivative.
  • Cyclic oligosaccharide derivatives include hydroxypropyl ⁇ -cyclodextrin, acetylated ⁇ -cyclodextrin, methylated ⁇ -cyclodextrin, monochlorotriazinylated ⁇ -cyclodextrin, dimethyl ⁇ -cyclodextrin, 2-hydroxyethyl ⁇ -cyclodextrin Examples include dextrin, 3-hydroxypropyl ⁇ -cyclodextrin, and trimethyl ⁇ -cyclodextrin.
  • the content rate of the cyclic oligosaccharide is low, and is usually 0.1% by mass or more and 25% by mass or less, preferably 0.2% by mass or more and 20% by mass or less, based on the total amount of active ingredients. Preferably they are 1 mass% or more and 15 mass% or less. If it is less than 0.1% by mass, the chemical stability of the DPP-IV inhibitor in the pharmaceutical preparation may be impaired. If it exceeds 25% by mass, the mass of the preparation increases and the size of the preparation increases. Inconvenience such as the above occurs, which is not preferable for commercialization.
  • metformin or a salt thereof it is usually 0.1% by mass to 35% by mass and preferably 0.2% by mass to 25% by mass.
  • metformin or a salt thereof it is usually 0.1% by mass to 35% by mass and preferably 0.2% by mass to 25% by mass.
  • the pharmaceutical preparation of the present invention is a preparation in which part or all of the ingredients are granulated by a dry processing method or a wet processing method. That is, at least metformin or a salt thereof is granulated. In this granulation, it is preferable to granulate metformin or a salt thereof separately from the DPP-IV inhibitor. That is, it is preferable that the DPP-IV inhibitor is not granulated or that metformin or a salt thereof and the DPP-IV inhibitor are granulated separately. Further, in the granulation of metformin or a salt thereof, it is preferable to granulate with the cyclic oligosaccharide.
  • Embodiments of granulating active ingredients are (1) mixing and granulating two active ingredients, (2) granulating metformin or a salt thereof and not granulating a DPP-IV inhibitor, (3 ) It is divided into three embodiments of granulating the DPP-IV inhibitor and metformin or a salt thereof separately. These can be further divided according to whether or not granulation is performed together with the cyclic oligosaccharide in each granulation. In the embodiment in which the two active ingredients of (1) are mixed and granulated, the cyclic oligosaccharide must be granulated together with the cyclic oligosaccharide in a situation where mixing and granulation tend to be unstable.
  • the subject of the present invention is to improve the chemical stability of the active ingredient DPP-IV inhibitor, but instead of adding a cyclic oligosaccharide as a stabilizer to the DPP-IV inhibitor.
  • cyclic oligosaccharide is added to and mixed with metformin or a salt thereof and granulated, it is also a surprising effect that cannot be predicted.
  • the pharmaceutical preparation of the present invention can be in various dosage forms, for example, provided as granules, fine granules, powders, capsules, or tablets.
  • the pharmaceutical preparation of the present invention is provided as a tablet, it is provided as a multilayer tablet such as a monolayer tablet, a bilayer tablet or a trilayer tablet, a dry tablet, or a film-coated tablet thereof.
  • a tablet is generally produced by granulating a part or all of the ingredients and then compression molding.
  • the granulation method is preferably a granulation by a wet processing method, that is, a wet granulation method.
  • the chemical stability of the DPP-IV inhibitor is the amount of the maximum degradation product of the DPP-IV inhibitor after storage for 21 days at a temperature of 60 ° C. Judge by (%).
  • the value of 0.20% or less is used as the standard for good chemical stability.
  • the numerical value is preferably 0.15% or less, more preferably 0.1% or less.
  • anagliptin was used as an active ingredient DPP-IV inhibitor.
  • the stability test of the preparations obtained in the examples and comparative examples was conducted by confirming the amount of each decomposition product produced after storing each test specimen for 21 days at a temperature of 60 ° C. This was done by evaluating the chemical stability of DPP-IV inhibitors by physical quantity. By this stability test, the effectiveness of the added stabilizer was determined.
  • the maximum degradation product amount is determined by measuring the DPP-IV inhibitor (anagliptin) and all degradation products derived from the DPP-IV inhibitor with a well-known analytical method (HPLC), and all the peak area values obtained. Was calculated by calculating the amount (%) of each decomposed product as an area percentage of the peak area value of each confirmed decomposed product.
  • Test Example 1 Necessity of granulation of metformin and standard setting of chemical stability of DPP-IV inhibitor
  • all ingredients other than lubricants that were not granulated were weighed.
  • a lubricant was mixed so that the blending ratio shown in Table 1 was obtained to obtain a tableting powder.
  • the blending ratio is the same as that in Example 25 described later.
  • the tableting powder was attempted to be tableted using a tableting machine VIRG (manufactured by Kikusui Seisakusho Co., Ltd.), but due to the lack of fluidity of the tableting powder, the tableting powder was pressed from the hopper.
  • the tablet was not supplied and could not be tableted. As can be seen from the test, it is understood that granulation of metformin or a salt thereof with a high content is essential in order to produce a compounding agent of anagliptin and metformin or a salt thereof.
  • the degradation product amount (%) of anagliptin was measured and found to be 0.22%. Therefore, an anagliptin degradation product amount of 0.2% or less was set as a criterion that the chemical stability of the DPP-IV inhibitor as a preparation was particularly good.
  • Test Example 2 Identification of Stabilizer Having Anagliptin Decomposition Suppressing Effect
  • the stabilizer shown in Table 2 was used to examine the effect of DPP-IV inhibitors on chemical stability.
  • the preparations of Example 1 and Comparative Examples 1 to 6 were filled in glass bottles (about 2 g in a 20 mL bottle) immediately after preparation and sealed as follows. Such a test specimen was subjected to a stability test, and the degradation product amount (%) of anagliptin was measured. In the following tests, when the ingredients are granulated and used, the fact is clearly stated, and those without such description are used without granulation.
  • Example 1 Each component was mixed according to the blending ratio of Example 1 in Table 2, purified water was added, wet granulation was performed, and drying was performed to prepare a granular preparation.
  • Comparative Example 1 Production was carried out in the same manner as in Example 1 except for the stabilizer of Example 1.
  • Comparative Examples 2 to 6 The same procedure as in Example 1 was performed using the stabilizers described in Table 2 instead of the stabilizer in Example 1.
  • Example 3 shows the results of stability tests of Example 1 and Comparative Examples 1 to 6.
  • Example 1 using ⁇ -cyclodextrin which is a cyclic oligosaccharide as a stabilizer
  • the maximum degradation product derived from anagliptin is 0.26% or less at 0.16%
  • Comparative Example 1 containing no stabilizer the maximum degradation product derived from anagliptin was 0.42%.
  • Test Example 3 Verification of anagliptin degradation inhibitory effect when stabilizer is granulated with all active ingredients DPP-IV inhibition when granulated together with all active ingredients for cyclic oligosaccharide as a stabilizer used in the present invention The effect of suppressing the degradation of the drug was examined together with the compounding ratio of the cyclic oligosaccharide.
  • Examples 1 to 4 were prepared as follows, and immediately filled into a glass bottle (about 1 g in a 20 mL bottle) and sealed. Such a test specimen was subjected to a stability test, and the degradation product amount (%) of anagliptin was measured.
  • Example 1 Already described in Test Example 2 (Examples 2 to 4) Each component was mixed according to the blending ratio in Table 4 and manufactured in the same manner as in Example 1.
  • Test Example 4 Verification of the anagliptin degradation inhibitory effect when the stabilizer was granulated with metformin hydrochloride
  • the cyclic oligosaccharide which is a stabilizer used in the present invention, was granulated with metformin hydrochloride which is one of the active ingredients.
  • the effect of inhibiting the degradation of anagliptin in some cases was examined together with the molecular weight and blending ratio of the cyclic oligosaccharide.
  • Examples 5 to 19 were prepared as follows and immediately filled into a glass bottle (about 1 g in a 20 mL bottle) and sealed. Such a test specimen was subjected to a stability test, and the degradation product amount (%) of anagliptin was measured.
  • Example 5 Metformin hydrochloride and ⁇ -cyclodextrin, which is a cyclic oligosaccharide, were mixed according to the blending ratios shown in Table 6, purified water was added and wet granulation was performed, followed by drying to obtain a granulated product. Anagliptin was mixed with the obtained granulated product according to the blending ratio shown in Table 6 to prepare a preparation which is a granule / powder mixture. (Example 11) Purified water was added to metformin hydrochloride and wet granulation was performed, followed by drying to obtain a granulated product.
  • the resulting granulated product was mixed with cyclic oligosaccharides ⁇ -cyclodextrin and anagliptin in accordance with the blending ratios shown in Table 6 to prepare a formulation as a granule / powder mixture.
  • Metformin hydrochloride and ⁇ -cyclodextrin, which is a cyclic oligosaccharide were mixed according to the blending ratios shown in Table 7, purified water was added and wet granulation was performed, followed by drying to obtain a granulated product.
  • Anagliptin was mixed with the obtained granulated material according to the blending ratio shown in Table 7 to prepare a preparation which is a granule / powder mixture.
  • Example 16 to 19 Metformin hydrochloride and cyclic oligosaccharide ⁇ -cyclodextrin were mixed in accordance with the blending ratios shown in Table 8, purified water was added and wet granulation was performed, followed by drying to obtain a granulated product. Anagliptin was mixed with the obtained granulated material according to the blending ratio shown in Table 8 to prepare a preparation which is a granule / powder mixture.
  • Example 5 which is an extremely low dose of ⁇ -cyclodextrin of 0.17%, the amount of the maximum degradation product derived from anagliptin is less than 0.1%, and the effect of suppressing the degradation of anagliptin is at a level that can be said to be remarkable.
  • the cyclic oligosaccharide that is a stabilizer is effective even when added without granulation, but by granulating with metformin hydrochloride, a DPPIV inhibitor It was found that the effect of inhibiting the degradation of anagliptin, which is an extremely low dose of ⁇ -cyclodextrin of 0.17%, the amount of the maximum degradation product derived from anagliptin is less than 0.1%, and the effect of suppressing the degradation of anagliptin is at a level that can be said to be remarkable.
  • the cyclic oligosaccharide that is a stabilizer is effective even when added without granulation, but by granulating with metformin hydroch
  • Test Example 5 Influence of Anagliptin and Metformin Hydrochloride on the Effect of Stabilizer Effect of Anagliptin and Metformin Hydrochloride on the Effect of Inhibiting Degradation of Anagliptin by Stabilizer ⁇ -Cyclodextrin was examined.
  • Examples 7 and 8 and Examples 20 to 24 were filled in glass bottles (about 1 g in a 20 mL bottle) immediately after preparation and sealed as follows. Such a test specimen was subjected to a stability test, and the amount (%) of an anagliptin degradation product was measured.
  • Examples 7 and 8 Already described in Test Example 4 (Examples 20 to 24)
  • metformin hydrochloride and ⁇ -cyclodextrin were mixed according to the blending ratio in Table 10, purified water was added and wet granulation was performed, followed by drying to obtain a granulated product.
  • Anagliptin was mixed with the obtained granulated material according to the blending ratio shown in Table 10 to prepare a preparation as a granule / powder mixture.
  • Test Example 6 Verification of Anagliptin Decomposition Suppressing Effect of Stabilizer in Tablet The effect of the stabilizer in the present invention to suppress the degradation of anagliptin in the tablet was verified.
  • Examples 25 and 26 were filled in glass bottles (2 tablets in a 20 mL bottle) immediately after preparation and sealed as follows. Such a test specimen was subjected to a stability test, and the amount (%) of an anagliptin degradation product was measured. (Examples 25 and 26) Metformin hydrochloride and a stabilizer were mixed according to the blending ratio shown in Table 12, purified water was added and wet granulation was performed, followed by drying to obtain a granulated product.
  • the diameter is 11.5 mm and the pressure is about 10 kN with a (R15) circular ridge. Compressed to obtain tablets containing 100 mg anagliptin and 500 mg metformin hydrochloride per tablet.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Obesity (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une préparation pharmaceutique, qui comprend un inhibiteur de DPP-IV et de la metformine, et dans laquelle l'inhibiteur de DPP-IV est stabilisé chimiquement. L'invention concerne une préparation pharmaceutique qui comprend un inhibiteur de DPP-IV et de la metformine ou un sel de cette dernière comme principes actifs et, de plus, un oligosaccharide cyclique, caractérisée en ce que la metformine mentionnée ci-dessus, ou un sel de cette dernière, est granulée (à l'exception d'un cas dans lequel l'inhibiteur de DPP-IV et la metformine ou un sel de cette dernière sont mélangés et granulés ensemble, séparément de l'oligosaccharide cyclique).
PCT/JP2014/069599 2013-07-25 2014-07-24 Préparation pharmaceutique WO2015012365A1 (fr)

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JP2013154841 2013-07-25
JP2013-154841 2013-07-25

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WO2015012365A1 true WO2015012365A1 (fr) 2015-01-29

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020208201A1 (fr) * 2019-04-11 2020-10-15 Add Advanced Drug Delivery Technologies Ltd. Procédé de production continue de granulés de principe actif
RU2742418C1 (ru) * 2017-02-03 2021-02-05 Гленмарк Фармасьютикалс Лимитед Лекарственные формы, содержащие оксалатные соли тенелиглиптина и их сольваты
CN114302711A (zh) * 2019-04-11 2022-04-08 埃德先进药物输送技术有限责任公司 连续制造有效成分颗粒的方法

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008543767A (ja) * 2005-06-10 2008-12-04 ノバルティス アクチエンゲゼルシャフト Ｄｐｐ−ｉｖ阻害剤とグリタゾンの直接圧縮製剤および方法
JP2009510068A (ja) * 2005-09-29 2009-03-12 ノバルティス アクチエンゲゼルシャフト 新規製剤
JP2009519934A (ja) * 2005-12-16 2009-05-21 メルク エンド カムパニー インコーポレーテッド ジペプチジルペプチダーゼ−４インヒビターとメトホルミンとを組み合わせた医薬組成物
JP2010533643A (ja) * 2007-07-19 2010-10-28 武田薬品工業株式会社 アログリプチンおよび塩酸メトホルミンを含有する固形製剤
JP2011510986A (ja) * 2008-02-05 2011-04-07 メルク・シャープ・エンド・ドーム・コーポレイション メトホルミン及びジペプチジルペプチダーゼ−ｉｖ阻害剤の併用医薬組成物
JP2011513408A (ja) * 2008-03-04 2011-04-28 メルク・シャープ・エンド・ドーム・コーポレイション メトホルミン及びジペプチジルペプチダーゼ−ｉｖ阻害剤の併用医薬組成物
JP2011516456A (ja) * 2008-04-03 2011-05-26 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 新規製剤、該製剤を含む錠剤、それらの使用及びそれらの調製方法
JP2013507356A (ja) * 2009-10-09 2013-03-04 ユンジン・ファーム・カンパニー・リミテッド 速効性と持続性を同時に有する薬剤学的組成物

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008543767A (ja) * 2005-06-10 2008-12-04 ノバルティス アクチエンゲゼルシャフト Ｄｐｐ−ｉｖ阻害剤とグリタゾンの直接圧縮製剤および方法
JP2009510068A (ja) * 2005-09-29 2009-03-12 ノバルティス アクチエンゲゼルシャフト 新規製剤
JP2009519934A (ja) * 2005-12-16 2009-05-21 メルク エンド カムパニー インコーポレーテッド ジペプチジルペプチダーゼ−４インヒビターとメトホルミンとを組み合わせた医薬組成物
JP2010533643A (ja) * 2007-07-19 2010-10-28 武田薬品工業株式会社 アログリプチンおよび塩酸メトホルミンを含有する固形製剤
JP2011510986A (ja) * 2008-02-05 2011-04-07 メルク・シャープ・エンド・ドーム・コーポレイション メトホルミン及びジペプチジルペプチダーゼ−ｉｖ阻害剤の併用医薬組成物
JP2011513408A (ja) * 2008-03-04 2011-04-28 メルク・シャープ・エンド・ドーム・コーポレイション メトホルミン及びジペプチジルペプチダーゼ−ｉｖ阻害剤の併用医薬組成物
JP2011516456A (ja) * 2008-04-03 2011-05-26 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 新規製剤、該製剤を含む錠剤、それらの使用及びそれらの調製方法
JP2013507356A (ja) * 2009-10-09 2013-03-04 ユンジン・ファーム・カンパニー・リミテッド 速効性と持続性を同時に有する薬剤学的組成物

Cited By (4)

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RU2742418C1 (ru) * 2017-02-03 2021-02-05 Гленмарк Фармасьютикалс Лимитед Лекарственные формы, содержащие оксалатные соли тенелиглиптина и их сольваты
WO2020208201A1 (fr) * 2019-04-11 2020-10-15 Add Advanced Drug Delivery Technologies Ltd. Procédé de production continue de granulés de principe actif
CN114126591A (zh) * 2019-04-11 2022-03-01 埃德先进药物输送技术有限责任公司 连续制造有效成分颗粒的方法
CN114302711A (zh) * 2019-04-11 2022-04-08 埃德先进药物输送技术有限责任公司 连续制造有效成分颗粒的方法

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