WO2002034254A1 - Preparations contenant du nateglinide - Google Patents
Preparations contenant du nateglinide Download PDFInfo
- Publication number
- WO2002034254A1 WO2002034254A1 PCT/JP2001/009291 JP0109291W WO0234254A1 WO 2002034254 A1 WO2002034254 A1 WO 2002034254A1 JP 0109291 W JP0109291 W JP 0109291W WO 0234254 A1 WO0234254 A1 WO 0234254A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- nateglinide
- water
- pharmaceutical preparation
- amorphous
- preparation according
- Prior art date
Links
- 229960000698 nateglinide Drugs 0.000 title claims abstract description 129
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 title claims abstract description 129
- 238000002360 preparation method Methods 0.000 title claims abstract description 38
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 46
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 39
- 239000002904 solvent Substances 0.000 claims description 29
- 239000013078 crystal Substances 0.000 claims description 28
- 229920003169 water-soluble polymer Polymers 0.000 claims description 22
- 238000004519 manufacturing process Methods 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 229920000642 polymer Polymers 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 15
- 239000007788 liquid Substances 0.000 claims description 14
- 239000002775 capsule Substances 0.000 claims description 12
- 239000008187 granular material Substances 0.000 claims description 12
- 150000005846 sugar alcohols Chemical class 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- -1 polyoxyethylene Polymers 0.000 claims description 9
- 239000004094 surface-active agent Substances 0.000 claims description 9
- 238000005469 granulation Methods 0.000 claims description 7
- 230000003179 granulation Effects 0.000 claims description 7
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 6
- 238000000576 coating method Methods 0.000 claims description 6
- 150000004676 glycans Chemical class 0.000 claims description 6
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 6
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 6
- 229920001282 polysaccharide Polymers 0.000 claims description 6
- 239000005017 polysaccharide Substances 0.000 claims description 6
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 6
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical group C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 5
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 5
- 150000001298 alcohols Chemical class 0.000 claims description 5
- 229960000913 crospovidone Drugs 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 5
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 229920002125 Sokalan® Polymers 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- 238000007909 melt granulation Methods 0.000 claims description 4
- 229920000609 methyl cellulose Polymers 0.000 claims description 4
- 239000001923 methylcellulose Substances 0.000 claims description 4
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 4
- 239000004584 polyacrylic acid Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 239000004626 polylactic acid Substances 0.000 claims description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 3
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 3
- 238000009775 high-speed stirring Methods 0.000 claims description 3
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 3
- 239000000600 sorbitol Substances 0.000 claims description 3
- 235000010356 sorbitol Nutrition 0.000 claims description 3
- 238000001694 spray drying Methods 0.000 claims description 3
- 239000000811 xylitol Substances 0.000 claims description 3
- 235000010447 xylitol Nutrition 0.000 claims description 3
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 3
- 229960002675 xylitol Drugs 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims 1
- 238000004898 kneading Methods 0.000 claims 1
- 238000010298 pulverizing process Methods 0.000 claims 1
- 150000004043 trisaccharides Chemical class 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 29
- 229940079593 drug Drugs 0.000 abstract description 28
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 4
- 238000004090 dissolution Methods 0.000 description 17
- 238000003860 storage Methods 0.000 description 14
- 239000008186 active pharmaceutical agent Substances 0.000 description 11
- 229940088679 drug related substance Drugs 0.000 description 11
- 230000000052 comparative effect Effects 0.000 description 9
- 230000007704 transition Effects 0.000 description 7
- 238000009472 formulation Methods 0.000 description 6
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 5
- 229910052782 aluminium Inorganic materials 0.000 description 5
- 238000005280 amorphization Methods 0.000 description 5
- 229940126534 drug product Drugs 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 238000011049 filling Methods 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 235000012054 meals Nutrition 0.000 description 3
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 3
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 229960003511 macrogol Drugs 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 239000002689 soil Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- SPBWHPXCWJLQRU-FITJORAGSA-N 4-amino-8-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C12=NC=NC(N)=C2C(=O)C(C(=O)N)=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O SPBWHPXCWJLQRU-FITJORAGSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 101100120289 Drosophila melanogaster Flo1 gene Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical class C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 229940126904 hypoglycaemic agent Drugs 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 238000009492 tablet coating Methods 0.000 description 1
- 239000002700 tablet coating Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
Definitions
- the present invention relates to a formulation of nateglinide useful as a diabetic, and more particularly to an immediate release formulation of nateglinide.
- Nateglinide [compound name: N- (trans-14-isopropylcyclohexylcarbonyl) -D-phenylalanine] shows an excellent hypoglycemic effect by oral administration and is known to be useful as a therapeutic agent for diabetes (Japanese Patent Publication No. 4-15202 21).
- nateglinide is a poorly soluble drug, and nateglinide drug substance-filled capsules or ordinary tablets do not dissolve satisfactorily when administered orally due to poor disintegration.
- the effect of lowering the blood glucose level over time (a rapid-acting short-acting hypoglycemic agent) cannot be achieved.
- a formulation was required.
- nateglinide has a polymorphism, but increasing the dissolution and increasing the dissolution rate by the above formulation method is effective for stable H-form and metastable form, but all of nateglinide are effective. Is not effective in the crystal form of
- the present invention relates to a nateglinide-containing pharmaceutical preparation containing amorphous nateglide, which has a good drug dissolution rate and does not undergo transition to a crystalline form during the manufacture or storage of the drug.
- the purpose is to provide.
- the present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, found that it is possible to improve the dissolution property by making nateglinide crystals amorphous in a preparation or the like. Completed the invention.
- a rapid-release nateglinide preparation which has a good drug dissolution rate and no crystalline form transition observed during the preparation or storage of the preparation, regardless of the crystalline polymorph of nateglinide. It is possible to provide
- the present invention basically relates to a preparation containing nateglinide as an active ingredient, in which nateglinide is made amorphous, and includes the following inventions.
- nateglinide which is amorphous is produced by a melt granulation method.
- Nateglidide-containing pharmaceutical preparation according to (1) is a melt granulation method.
- the water-soluble polymer or water-swellable polymer is selected from the group consisting of a polyvinylpyrrolidone derivative, a polysaccharide derivative, a polyacrylic acid derivative, a polylactic acid derivative, a polyoxyethylene derivative, a polyvinyl alcohol derivative, and a surfactant.
- a polyvinylpyrrolidone derivative a polysaccharide derivative
- a polyacrylic acid derivative a polylactic acid derivative
- a polyoxyethylene derivative a polyvinyl alcohol derivative
- surfactant eglidide-containing pharmaceutical preparation according to (7).
- the water-soluble polymer or surfactant that dissolves nateglinide is polyoxy Nateglidide-containing pharmaceutical preparation according to (15), which is an ethylene derivative.
- a method for producing a formulation containing nateglinide containing amorphous is a method for producing a formulation containing nateglinide containing amorphous.
- a method for producing an amorphous nateglinide-containing preparation comprising:
- nateglinide crystal with a hydrophilic base selected from the group consisting of a water-soluble polymer, a k-swellable polymer, a sugar alcohol and a salt, and
- a method for producing an amorphous nateglinide-containing preparation comprising:
- FIG. 1 is the DSC pattern of the nateglinide amorphized tablet.
- Figure 2 shows the DSC pattern of nateglinide type B drug substance.
- Figure 3 shows the DSC pattern of nateglinide H drug substance.
- Figure 4 shows the DSC pattern of nateglinide amorphized tablets after storage at 50 ° C in an aluminum pack for one week.
- Figure 5 shows the DSC powder after storage of nateglinide amorphized tablets at 40 ° C and 75% aluminum pack for one month.
- FIG. 6 is a comparison diagram of the dissolution profiles of the preparations of Examples 2-3 and Comparative Examples 1-3.
- FIG. 7 shows the change in nateglide plasma concentration when a nateglide tablet was administered to a beagle dog 5 minutes before a meal.
- Mean soil S E, n 3.
- FIG. 9 is a DSC graph of nateglinide amorphized tablets stored at 40 ° C., 75% RH, 6 months, aluminum pack.
- Nateglidide which is a raw material of amorphized nateglinide contained in the pharmaceutical preparation of the present invention, can be synthesized according to the method described in Japanese Patent Publication No. 4-152221 or the like. Yes, the crystal form is not particularly limited.
- Examples of the method of preparing nateglinide by making it amorphous include a solvent removal method, a method by applying high shear stress, a melt granulation method, and a method of dissolving in a pharmaceutically acceptable solvent.
- other methods may be used as long as nateglinide can be made amorphous.
- a solvent removal method, a method of dissolving in a pharmaceutically acceptable solvent, and the like are preferable from the viewpoint of ease of production and the like.
- the object in the case of amorphization, the object can be achieved without using a carrier.
- a hydrophilic base As a carrier for making nateglinide amorphous, a hydrophilic base is preferable.
- the hydrophilic base include a water-soluble polymer, a water-swellable polymer, a sugar alcohol, and salts.
- the carrier is capable of amorphizing nateglinide and rapidly dissolving in water. Anything that can be solved or Ji Peng Jun can be used. As the amount of addition,
- 0.1 times by weight or more it is preferable to add 0.1 times by weight or more. Desirably, 0.1 to 100 times the weight of nateglinide is preferable, and 0.1 to 50 times the weight of nateglinide is more preferable.
- the solvent for dissolving nateglinide is preferably pharmaceutically acceptable and liquid at around 37 ° C.
- a solvent include a water-soluble polymer and a surfactant.
- the solvent is preferably added in an amount of 0.1 times or more the weight of the drug. Desirably, the weight is 0.1 to 100 times the weight of nateglinide, more preferably 0.1 to 100 times the weight.
- the weight of the carrier for amorphizing nateglinide is preferably from 0 to 100 times, more preferably from 0 to 50 times.
- the solvent removal method for obtaining amorphous nadeglide used in the pharmaceutical preparation of the present invention is to dissolve a drug and a carrier for amorphization in a solvent, and then remove the solvent.
- This is a method for making a drug amorphous.
- the solvent may be any of an aqueous solvent, an organic solvent solvent, and a mixture thereof as long as the drug and the carrier can be dissolved. Specific examples include alcohols such as methanol, ethanol and isopropyl alcohol, ketones such as acetone and methyl ethyl ketone, cyclic ethers such as dioxane and tetrahydrofuran, and acetonitrile. Of these, ethanol is preferred.
- a solution obtained by dissolving a drug and a carrier for amorphizing nateglide such as a water-soluble polymer in a solvent such as ethanol is subjected to vacuum drying and evaporation.
- the conditions for removing the solvent are not particularly limited as long as amorphous nategnate can be stably present.
- nateglinide and the solvent The above operation may be performed using.
- Amorphous nateglinide granules are obtained by subjecting the amorphous nateglinide thus obtained to a fluidized bed granulation method, a high-speed stirring granulation method, a spray drying method, a coating method and the like.
- a fluidized bed granulation method a high-speed stirring granulation method, a spray drying method, a coating method and the like.
- nateglinide and a carrier for amorphizing nateglinide are dissolved in a solvent without removing the solvent from the solution.
- the product may be directly subjected to a method or the like to directly obtain a granular nateglinide-containing preparation.
- Conditions such as a fluidized bed granulation method are not particularly limited as long as the amorphous nateglinide can be stably present.
- the above operation may be performed using nateglinide alone.
- the granules can be used as they are as granules, but they can also be made into tablets by further tableting, and the dosage form of the nateglinide-containing preparation of the present invention is not particularly limited.
- the method of producing a preparation by applying a high shear stress is a method of making a drug amorphous by applying a high shear stress to a mixture of a drug and a carrier for amorphization by an appropriate method.
- the shear stress to be applied is not particularly limited as long as the amorphous nateglinide can be stably present. Further, the above operation may be performed by nateglinide alone.
- a drug and a water-soluble polymer are mixed, and then mixed and pulverized by an ultracentrifugal mill, or subjected to a process of applying a high shear stress using an extruder or the like, and the drug becomes amorphous.
- the melt granulation method is a method in which a mixture of a drug and a carrier for amorphization is heated and melted, and then cooled and solidified to amorphize the drug.
- a drug and a water-soluble polymer are put into a universal mixing stirrer that can be heated, heated and kneaded, and then cooled and pulverized to obtain amorphous granules of the drug.
- This granule is
- the dosage form of the nateglinide-containing preparation of the present invention is not particularly limited as long as it remains in an amorphous state, as long as it remains in an amorphous state. The above operation may be performed with nateglinide alone.
- the method of dissolving in a pharmaceutically acceptable liquid excipient is a method of dissolving the drug in a pharmaceutically acceptable liquid excipient to render the drug amorphous.
- a solution by dissolving a drug in a water-soluble polymer that is liquid at 37 ° C.
- This solution can be filled into hard capsules or soft capsules to give a liquid filling capsule.
- the amorphous nateglinide-containing preparation of the present invention may further contain a hydrophilic base.
- a hydrophilic base examples include water-soluble polymers, water-swellable polymers, sugar alcohols and salts.
- the same carrier as described above for amorphizing nateglinide can be used, or a different one can be used.
- water-soluble polymer or the water-swellable polymer examples include a polyvinylpyrrolidone derivative, a polysaccharide derivative, a polyacrylic acid derivative, a polylactic acid derivative, a polyoxyethylene derivative, a polyvinyl alcohol derivative, and a surfactant.
- polyvinylpyrrolidone derivative examples include cross-linked polyvinylpyrrolidone, more specifically, crospovidone (Coridone CL-M, BASF).
- polysaccharide derivative as the hydrophilic base examples include a cellulose derivative.
- a cellulose derivative For example, methylcellulose, hydroxypropylcellulose, carboxymethylcell mouth and the like can be mentioned. More specifically, there may be mentioned methylcellulose SM-4, hydroxypropylcellulose SL and hydroxypropylcellulose SSL.
- Polyacrylic acid derivatives include Methacrylic acid copolymer L, Methacrylic acid copolymer Polymer S, Methacrylic acid copolymer LD (Rohm), and the like.
- Examples of the polylactic acid derivative include a lactic acid-glycolic acid copolymer (1: 1) having a molecular weight of 17,000 to 24,000.
- polyethylene glycol is preferable.
- polyethylene glycol having a molecular weight of 200 to 20000, more preferably 200 to 6000 is preferred.
- Polyvinyl alcohol derivatives include polyvinyl alcohol (completely saponified)
- surfactant examples include polysorbate 80, sodium lauryl sulfate and the like.
- Crospovidone (Coridone CL-M) is preferred as the water-swellable polymer.
- Sugar alcohols include sorbitol, xylitol and mannitol. Of these, mannitol is preferred.
- Salts include sodium chloride, phosphate, citrate and the like.
- Nateglinide type B crystal (4 g) and polyvinylpyrrolidone (32 g) were dissolved in ethanol, and the ethanol was removed by evaporation (60 ° C), followed by vacuum drying at 60 ° C for at least 3 hours.
- the obtained solid was crushed in a mortar to obtain 36 g of a nateglinide solid dispersion.
- Example 2 Production of amorphized tablet Nateglinide (B-type crystal) 60 g, hydroxypropylcellulose 4 g, and clospovidone (Corydon CL-M, BASF) 60 g were dissolved and suspended in ethanol 160 g to obtain a binding solution. Add 180 g of crospovidone (Kolydone CL-M, BASF) and 96 g of crystalline cellulose to a fluidized bed granulator (FLO-1 type, Freund Sangyo), mix, spray, and mix and spray the above-mentioned binding solution (B and air temperature: 80. C, spray speed: 4.9 g / min, spray pressure: 1.8 kgf / cm 2 ).
- hydroxypropyl methylcellulose 15 g of Macrogol 6000, 24 g of talc and 5 g of titanium oxide were dissolved and suspended in 876 g of water to prepare a coating solution.
- 300 g of the uncoated tablets are charged into a tablet coating machine ("Hyco Ichiichi Mini", Freund Sangyo), and coated with a coating of 2.54 mg of hydroxypropylmethylcellulose per uncoated tablet. 303.8 g were obtained.
- nateglinide 1456 mg of macrogol 400, and 1456 mg of polysorbate 80 were mixed at room temperature until dissolved in a stirrer to prepare a clear nateglinide solution.
- the obtained drug solution 50 Omg
- Comparative Example 1 Production of API 1 Nateglinide drug substance (B-type crystal) 30 Omg was filled in a gelatin capsule (No. 2) to obtain a capsule filled with nateglinide B-type drug substance.
- Nateglinide drug substance (H type crystal) 3 Omg was filled into a gelatin capsule (No. 2) to obtain a capsule filled with nateglinide H type drug substance.
- nateglinide H-type crystal
- an uncoated tablet weight 120 mg
- nateglinide H-type was further coated.
- a crystal-containing coating tablet was obtained.
- Example 2 The tablets produced in Example 2 were crushed in an agate mortar, about 1 Omg of the powder was placed in a silver pan and sealed with a silver lid, and then 25 ° using an 811 03 ° measuring device (type). The results of DSC measurement (Figure 1) from C to 250 ° C at a heating rate of 5 ° C / min are shown. The measurement results for nateglinide type B drug substance ( Figure 2) and the measurement of nateglinide H type drug substance are shown. The results (Fig. 3) were compared. As is clear from FIGS. 1 to 3, it is confirmed that the tablet manufactured in Example 2 does not show absorption specific to nateglinide crystals and is amorphous. The DSC charts (Fig. 4) and (Fig. 5) obtained were the same as before the storage test, and nate glinide was not crystallized and was amorphous. No) was confirmed.
- Example 5 Measurement of dissolution rate
- the preparations prepared in Examples 2 and 3 were prepared using the Japanese Pharmacopoeia (hereinafter, abbreviated to be "Abbreviated”) paddle method (50 rpm).
- the dissolution property in L was evaluated.
- Figure 6 shows the results.
- the preparations produced in Comparative Examples 1 to 3 were measured in the same manner as described above.
- Figure 6 shows the results.
- the dissolution rates of the tablets and liquid filling force tablets obtained by amorphizing nateglide produced in Example 2 and Example 3 were produced in Comparative Example 1 and Comparative Example 2. It can be seen that it is improved as compared with the drug substance-filled capsule.
- the average dissolution rate at each time point of the amorphous tablet and the liquid filling force capsule exhibited the same dissolution property as the nateglinide tablet (tablet using H-type crystal) of Comparative Example 3.
- Example 2 the dissolution properties of the drug product prepared in Example 2 and the drug product subjected to the preservation test were determined by the Japanese Pharmacopoeia Disintegration Test Method using the pharmacopeia first and third bureau paddle method (50 revolutions per minute, after 30 minutes) Table 1 shows the results of the evaluation in 50 O mL of the second liquid. As is clear from Table 1, no change was observed in the dissolution rate before and after storage.
- Table 1 Example 6: Evaluation of Oral Absorbability Using Beagle Dog The nateglidide amorphized tablet obtained in Example 2 and the nateglinide H-type crystal tablet obtained in Comparative Example 3 were administered to a Beagle dog 5 minutes before eating.
- nateglinide plasma concentration transition The results are shown in Figures 7 and 8, and Table 2. It was clarified that the nateglinide amorphized tablet exhibited oral absorption and drug efficacy equal to or higher than that of nateglinide H-type crystal tablet.
- the nateglinide amorphous tablet obtained in Example 2 was packaged in an aluminum pack and stored at 40 ° C. and 75% RH for 6 months.
- the dissolution properties were evaluated in 50 OmL of the second solution of the local disintegration test method using the pharmacopeia first-third-station paddle method (50 revolutions per minute, after 30 minutes).
- Figure 9 shows the chart.
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Description
Claims
Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2001295999A AU2001295999A1 (en) | 2000-10-24 | 2001-10-23 | Nateglinide-containing preparations |
CA2426263A CA2426263C (en) | 2000-10-24 | 2001-10-23 | Nateglinide-containing preparation |
KR1020037005634A KR100869039B1 (ko) | 2000-10-24 | 2001-10-23 | 나테글리니드 함유 제제 |
BR0114896-6A BR0114896A (pt) | 2000-10-24 | 2001-10-23 | Preparação contendo nateglinida, e, método para produzir a mesma |
DE60135674T DE60135674D1 (de) | 2000-10-24 | 2001-10-23 | Nateglinid enthaltende präparate |
JP2002537308A JP4501054B2 (ja) | 2000-10-24 | 2001-10-23 | ナテグリニド含有製剤 |
EP01976817A EP1334720B1 (en) | 2000-10-24 | 2001-10-23 | Nateglinide-containing preparations |
DK01976817T DK1334720T3 (da) | 2000-10-24 | 2001-10-23 | Nateglinid-indeholdende fremstillinger |
MXPA03003685A MXPA03003685A (es) | 2000-10-24 | 2001-10-23 | Preparaciones que contienen nateglinida. |
US10/421,898 US7605180B2 (en) | 2000-10-24 | 2003-04-24 | Nateglinide-containing preparation |
US12/424,958 US20090203791A1 (en) | 2000-10-24 | 2009-04-16 | Nateglinide-containing preparation |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000-324373 | 2000-10-24 | ||
JP2000324373 | 2000-10-24 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/421,898 Continuation US7605180B2 (en) | 2000-10-24 | 2003-04-24 | Nateglinide-containing preparation |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2002034254A1 true WO2002034254A1 (fr) | 2002-05-02 |
Family
ID=18801918
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2001/009291 WO2002034254A1 (fr) | 2000-10-24 | 2001-10-23 | Preparations contenant du nateglinide |
Country Status (17)
Country | Link |
---|---|
US (2) | US7605180B2 (ja) |
EP (1) | EP1334720B1 (ja) |
JP (3) | JP4501054B2 (ja) |
KR (1) | KR100869039B1 (ja) |
CN (1) | CN100352432C (ja) |
AT (1) | ATE406885T1 (ja) |
AU (1) | AU2001295999A1 (ja) |
BR (1) | BR0114896A (ja) |
CA (1) | CA2426263C (ja) |
DE (1) | DE60135674D1 (ja) |
DK (1) | DK1334720T3 (ja) |
ES (1) | ES2307653T3 (ja) |
MX (1) | MXPA03003685A (ja) |
PT (1) | PT1334720E (ja) |
RU (1) | RU2271805C2 (ja) |
TW (1) | TWI283573B (ja) |
WO (1) | WO2002034254A1 (ja) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003160474A (ja) * | 2001-11-28 | 2003-06-03 | Taisho Pharmaceut Co Ltd | 難溶性薬物含有固形製剤の製造方法 |
WO2005013964A1 (ja) * | 2003-08-08 | 2005-02-17 | Ajinomoto Co., Inc. | ナテグリニド含有製剤 |
US6861553B2 (en) | 2002-07-03 | 2005-03-01 | Teva Pharmaceuticals Industries Ltd. | Process for preparing nateglinide and intermediates thereof |
WO2005094812A1 (ja) * | 2004-04-01 | 2005-10-13 | Ajinomoto Co., Inc. | ナテグリニド含有製剤 |
WO2006016602A1 (ja) * | 2004-08-10 | 2006-02-16 | Ajinomoto Co., Inc. | 苦味の低減したナテグリニド含有製剤 |
US7148376B2 (en) | 2002-07-18 | 2006-12-12 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
US7358390B2 (en) | 2002-07-18 | 2008-04-15 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
US7420084B2 (en) | 2002-07-18 | 2008-09-02 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
JP2009510138A (ja) * | 2005-10-04 | 2009-03-12 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | 経口投与でき、かつ活性成分の迅速な放出を有する固形医薬投与形態 |
US7534913B2 (en) | 2002-07-18 | 2009-05-19 | Teva Pharmaceutica Industries Ltd. | Crystalline form of nateglinide |
JP2017081894A (ja) * | 2015-10-30 | 2017-05-18 | 株式会社ファンケル | 徐放性顆粒剤 |
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EP1258249B1 (en) * | 1999-12-28 | 2005-11-23 | Ajinomoto Co., Inc. | Oral preparations for diabetes |
BR0109336A (pt) * | 2000-03-17 | 2003-06-24 | Ajinomoto C0 Inc | Medicamento para a prevenção, melhora e/ou tratamento de uma complicação diabética, droga medicinal adequada ou utilizável como o mesmo, método para prevenir, melhorar e/ou tratar a complicação diabética, e a neuropatia, e, usos de um agente redutor do açúcar no sangue pós-prandial e pelo menos um agente selecionado de um agente anti-hipertensivo, um agente vasodilatador e um agente anti-hiperlipidêmico |
MXPA03003483A (es) * | 2000-10-18 | 2003-07-14 | Ajinomoto Kk | Procedimiento para la preparacion de acilfenilalaninas. |
RU2273629C2 (ru) * | 2000-10-18 | 2006-04-10 | Адзиномото Ко., Инк. | Способы получения кристаллов натеглинида |
DK1334964T3 (da) * | 2000-10-24 | 2007-09-24 | Ajinomoto Kk | Fremgangsmåde til fremstilling af nateglinidkrystaller med B form |
MXPA03003686A (es) * | 2000-10-24 | 2004-01-26 | Ajinomoto Kk | Preparaciones hidrofilas de farmaco que contienen nateglinida. |
ATE406885T1 (de) * | 2000-10-24 | 2008-09-15 | Ajinomoto Kk | Nateglinid enthaltende präparate |
WO2005020979A1 (en) * | 2003-09-03 | 2005-03-10 | Ranbaxy Laboratories Limited | A process for the preparation of pharmaceutical compositions of nateglinide |
US20070219250A1 (en) * | 2003-11-28 | 2007-09-20 | Romi Singh | Pharmaceutical Compositions of Nateglinide |
EP1891971A4 (en) * | 2005-01-31 | 2010-02-03 | Ajinomoto Kk | MEDICAL COMPOSITION USING HYPERGLY CRAB MEDICAMENT TO TREAT OR TREAT GLUCOSE-INTOLERANCE, BORDERLINE DIABETES, INSULIN RESISTANCE AND HYPERINSULINEMIA |
JP4463875B2 (ja) | 2007-03-29 | 2010-05-19 | 第一三共株式会社 | 医薬組成物 |
TR200801178A2 (tr) * | 2008-02-22 | 2009-09-23 | Bi̇li̇m İlaç Sanayi̇ Ti̇caret A.Ş. | Nateglinid ve surfaktan-ph ayarlayıcı sistemi içeren oral tablet kompozisyonları |
CN101590063A (zh) * | 2008-05-26 | 2009-12-02 | 中国科学院上海生命科学研究院 | 丹参酮iia在制备治疗肥胖及胰岛素抵抗的药物中的应用 |
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WO2011157986A1 (en) | 2010-06-14 | 2011-12-22 | Cipla Limited | A process for the preparation of nateglinide |
BR112014002397B1 (pt) | 2011-08-10 | 2021-08-03 | Daiichi Sankyo Company, Limited | Formulação sólida na forma de tablete ou cápsula contendo derivado de diamida |
CN102813636B (zh) * | 2012-08-28 | 2014-04-16 | 西南药业股份有限公司 | 那格列奈片及其制备方法 |
CA2918570A1 (en) * | 2013-07-22 | 2015-01-29 | Sandoz Ag | Formulations containing amorphous dapagliflozin |
KR20240025990A (ko) * | 2022-08-19 | 2024-02-27 | 주식회사 스카이테라퓨틱스 | 무정형 수니티닙, 그 제조방법 및 이를 포함한 의약 조성물 |
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EP0965339A1 (en) * | 1996-11-15 | 1999-12-22 | Ajinomoto Co., Inc. | Tabletted preparation |
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JPS56110612A (en) * | 1980-02-08 | 1981-09-01 | Yamanouchi Pharmaceut Co Ltd | Readily disintegrable and absorbable compression molded article of slightly soluble drug |
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EP1258249B1 (en) | 1999-12-28 | 2005-11-23 | Ajinomoto Co., Inc. | Oral preparations for diabetes |
BR0109336A (pt) | 2000-03-17 | 2003-06-24 | Ajinomoto C0 Inc | Medicamento para a prevenção, melhora e/ou tratamento de uma complicação diabética, droga medicinal adequada ou utilizável como o mesmo, método para prevenir, melhorar e/ou tratar a complicação diabética, e a neuropatia, e, usos de um agente redutor do açúcar no sangue pós-prandial e pelo menos um agente selecionado de um agente anti-hipertensivo, um agente vasodilatador e um agente anti-hiperlipidêmico |
RU2273629C2 (ru) | 2000-10-18 | 2006-04-10 | Адзиномото Ко., Инк. | Способы получения кристаллов натеглинида |
MXPA03003483A (es) | 2000-10-18 | 2003-07-14 | Ajinomoto Kk | Procedimiento para la preparacion de acilfenilalaninas. |
DK1334964T3 (da) | 2000-10-24 | 2007-09-24 | Ajinomoto Kk | Fremgangsmåde til fremstilling af nateglinidkrystaller med B form |
ATE406885T1 (de) * | 2000-10-24 | 2008-09-15 | Ajinomoto Kk | Nateglinid enthaltende präparate |
MXPA03003686A (es) | 2000-10-24 | 2004-01-26 | Ajinomoto Kk | Preparaciones hidrofilas de farmaco que contienen nateglinida. |
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-
2001
- 2001-10-23 AT AT01976817T patent/ATE406885T1/de active
- 2001-10-23 DK DK01976817T patent/DK1334720T3/da active
- 2001-10-23 PT PT01976817T patent/PT1334720E/pt unknown
- 2001-10-23 EP EP01976817A patent/EP1334720B1/en not_active Expired - Lifetime
- 2001-10-23 ES ES01976817T patent/ES2307653T3/es not_active Expired - Lifetime
- 2001-10-23 CA CA2426263A patent/CA2426263C/en not_active Expired - Fee Related
- 2001-10-23 BR BR0114896-6A patent/BR0114896A/pt not_active IP Right Cessation
- 2001-10-23 DE DE60135674T patent/DE60135674D1/de not_active Expired - Lifetime
- 2001-10-23 JP JP2002537308A patent/JP4501054B2/ja not_active Expired - Fee Related
- 2001-10-23 CN CNB018212174A patent/CN100352432C/zh not_active Expired - Fee Related
- 2001-10-23 KR KR1020037005634A patent/KR100869039B1/ko not_active IP Right Cessation
- 2001-10-23 WO PCT/JP2001/009291 patent/WO2002034254A1/ja active IP Right Grant
- 2001-10-23 RU RU2003111950/04A patent/RU2271805C2/ru not_active IP Right Cessation
- 2001-10-23 AU AU2001295999A patent/AU2001295999A1/en not_active Abandoned
- 2001-10-23 MX MXPA03003685A patent/MXPA03003685A/es active IP Right Grant
- 2001-10-24 TW TW090126307A patent/TWI283573B/zh not_active IP Right Cessation
-
2003
- 2003-04-24 US US10/421,898 patent/US7605180B2/en not_active Expired - Fee Related
-
2009
- 2009-04-16 US US12/424,958 patent/US20090203791A1/en not_active Abandoned
-
2010
- 2010-02-05 JP JP2010024276A patent/JP2010100654A/ja active Pending
-
2012
- 2012-10-01 JP JP2012219402A patent/JP5610165B2/ja not_active Expired - Fee Related
Patent Citations (2)
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EP0526171A2 (en) * | 1991-07-30 | 1993-02-03 | Ajinomoto Co., Inc. | Crystals of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine and methods for preparing them |
EP0965339A1 (en) * | 1996-11-15 | 1999-12-22 | Ajinomoto Co., Inc. | Tabletted preparation |
Cited By (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003160474A (ja) * | 2001-11-28 | 2003-06-03 | Taisho Pharmaceut Co Ltd | 難溶性薬物含有固形製剤の製造方法 |
US6861553B2 (en) | 2002-07-03 | 2005-03-01 | Teva Pharmaceuticals Industries Ltd. | Process for preparing nateglinide and intermediates thereof |
US7534913B2 (en) | 2002-07-18 | 2009-05-19 | Teva Pharmaceutica Industries Ltd. | Crystalline form of nateglinide |
US7420084B2 (en) | 2002-07-18 | 2008-09-02 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
US7358390B2 (en) | 2002-07-18 | 2008-04-15 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
US7148376B2 (en) | 2002-07-18 | 2006-12-12 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of nateglinide |
JPWO2005013964A1 (ja) * | 2003-08-08 | 2006-09-28 | 味の素株式会社 | ナテグリニド含有製剤 |
JP2009051852A (ja) * | 2003-08-08 | 2009-03-12 | Ajinomoto Co Inc | ナテグリニド含有製剤 |
WO2005013964A1 (ja) * | 2003-08-08 | 2005-02-17 | Ajinomoto Co., Inc. | ナテグリニド含有製剤 |
US7732492B2 (en) | 2003-08-08 | 2010-06-08 | Ajinomoto Co., Inc. | Nateglinide-containing preparation |
JP4505859B2 (ja) * | 2003-08-08 | 2010-07-21 | 味の素株式会社 | ナテグリニド含有製剤 |
JP2012046534A (ja) * | 2003-08-08 | 2012-03-08 | Ajinomoto Co Inc | ナテグリニド含有製剤 |
JPWO2005094812A1 (ja) * | 2004-04-01 | 2008-02-14 | 味の素株式会社 | ナテグリニド含有製剤 |
WO2005094812A1 (ja) * | 2004-04-01 | 2005-10-13 | Ajinomoto Co., Inc. | ナテグリニド含有製剤 |
JP5168712B2 (ja) * | 2004-04-01 | 2013-03-27 | 味の素株式会社 | ナテグリニド含有製剤 |
WO2006016602A1 (ja) * | 2004-08-10 | 2006-02-16 | Ajinomoto Co., Inc. | 苦味の低減したナテグリニド含有製剤 |
JP2009510138A (ja) * | 2005-10-04 | 2009-03-12 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | 経口投与でき、かつ活性成分の迅速な放出を有する固形医薬投与形態 |
JP2017081894A (ja) * | 2015-10-30 | 2017-05-18 | 株式会社ファンケル | 徐放性顆粒剤 |
Also Published As
Publication number | Publication date |
---|---|
DE60135674D1 (de) | 2008-10-16 |
CN100352432C (zh) | 2007-12-05 |
MXPA03003685A (es) | 2004-01-26 |
KR20030042027A (ko) | 2003-05-27 |
EP1334720A4 (en) | 2004-02-04 |
AU2001295999A1 (en) | 2002-05-06 |
CA2426263C (en) | 2010-05-25 |
JP5610165B2 (ja) | 2014-10-22 |
JP2013028636A (ja) | 2013-02-07 |
ES2307653T3 (es) | 2008-12-01 |
CA2426263A1 (en) | 2003-04-23 |
US7605180B2 (en) | 2009-10-20 |
US20040014815A1 (en) | 2004-01-22 |
BR0114896A (pt) | 2003-08-12 |
PT1334720E (pt) | 2008-09-30 |
EP1334720A1 (en) | 2003-08-13 |
US20090203791A1 (en) | 2009-08-13 |
DK1334720T3 (da) | 2009-01-19 |
EP1334720B1 (en) | 2008-09-03 |
JPWO2002034254A1 (ja) | 2004-08-26 |
ATE406885T1 (de) | 2008-09-15 |
TWI283573B (en) | 2007-07-11 |
RU2271805C2 (ru) | 2006-03-20 |
KR100869039B1 (ko) | 2008-11-17 |
JP4501054B2 (ja) | 2010-07-14 |
CN1482903A (zh) | 2004-03-17 |
JP2010100654A (ja) | 2010-05-06 |
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