JPH09268127A - Solid preparation composition containing vitamin b1 derivative - Google Patents
Solid preparation composition containing vitamin b1 derivativeInfo
- Publication number
- JPH09268127A JPH09268127A JP8078909A JP7890996A JPH09268127A JP H09268127 A JPH09268127 A JP H09268127A JP 8078909 A JP8078909 A JP 8078909A JP 7890996 A JP7890996 A JP 7890996A JP H09268127 A JPH09268127 A JP H09268127A
- Authority
- JP
- Japan
- Prior art keywords
- derivative
- vitamin
- starch
- solid preparation
- preparation composition
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 150000003544 thiamines Chemical class 0.000 title claims abstract description 25
- 239000007787 solid Substances 0.000 title claims abstract description 21
- 239000000203 mixture Substances 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 229920002472 Starch Polymers 0.000 claims abstract description 14
- 235000019698 starch Nutrition 0.000 claims abstract description 14
- 239000008107 starch Substances 0.000 claims abstract description 13
- 239000003381 stabilizer Substances 0.000 claims abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 9
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 9
- 229920002261 Corn starch Polymers 0.000 abstract description 4
- 239000008120 corn starch Substances 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 229920001592 potato starch Polymers 0.000 abstract description 3
- GFEGEDUIIYDMOX-BMJUYKDLSA-N n-[(4-amino-2-methylpyrimidin-5-yl)methyl]-n-[(z)-3-[[(z)-2-[(4-amino-2-methylpyrimidin-5-yl)methyl-formylamino]-5-hydroxypent-2-en-3-yl]disulfanyl]-5-hydroxypent-2-en-2-yl]formamide Chemical compound C=1N=C(C)N=C(N)C=1CN(C=O)C(\C)=C(CCO)/SSC(/CCO)=C(/C)N(C=O)CC1=CN=C(C)N=C1N GFEGEDUIIYDMOX-BMJUYKDLSA-N 0.000 abstract description 2
- 229960001385 thiamine disulfide Drugs 0.000 abstract description 2
- IWXAZSAGYJHXPX-BCEWYCLDSA-N Bisbentiamine Chemical compound C=1C=CC=CC=1C(=O)OCC/C(SS\C(CCOC(=O)C=1C=CC=CC=1)=C(/C)N(CC=1C(=NC(C)=NC=1)N)C=O)=C(/C)N(C=O)CC1=CN=C(C)N=C1N IWXAZSAGYJHXPX-BCEWYCLDSA-N 0.000 abstract 2
- 229950009892 bisbentiamine Drugs 0.000 abstract 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract 1
- 229910052791 calcium Inorganic materials 0.000 abstract 1
- 239000011575 calcium Substances 0.000 abstract 1
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 abstract 1
- 229910000389 calcium phosphate Inorganic materials 0.000 abstract 1
- 230000015556 catabolic process Effects 0.000 abstract 1
- 238000013329 compounding Methods 0.000 abstract 1
- 238000006731 degradation reaction Methods 0.000 abstract 1
- 235000019691 monocalcium phosphate Nutrition 0.000 abstract 1
- 239000006076 specific stabilizer Substances 0.000 abstract 1
- 230000006641 stabilisation Effects 0.000 abstract 1
- 238000011105 stabilization Methods 0.000 abstract 1
- CKHJPWQVLKHBIH-ZDSKVHJSSA-N sulbutiamine Chemical compound C=1N=C(C)N=C(N)C=1CN(C=O)C(/C)=C(/CCOC(=O)C(C)C)SS\C(CCOC(=O)C(C)C)=C(\C)N(C=O)CC1=CN=C(C)N=C1N CKHJPWQVLKHBIH-ZDSKVHJSSA-N 0.000 abstract 1
- 239000000126 substance Substances 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 229920002678 cellulose Polymers 0.000 description 6
- 239000001913 cellulose Substances 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 229930003451 Vitamin B1 Natural products 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- JAUGGEIKQIHSMF-UHFFFAOYSA-N dialuminum;dimagnesium;dioxido(oxo)silane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O JAUGGEIKQIHSMF-UHFFFAOYSA-N 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 229960003495 thiamine Drugs 0.000 description 3
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 3
- 239000011691 vitamin B1 Substances 0.000 description 3
- 235000010374 vitamin B1 Nutrition 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- -1 bisbenchamine Chemical compound 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000314 lubricant Substances 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
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 238000010298 pulverizing process Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000035404 Autolysis Diseases 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 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 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- YMEBNAABDXLAJE-GPAWKIAZSA-N [(e)-4-[(4-amino-2-methylpyrimidin-5-yl)methyl-formylamino]-3-[[(e)-2-[(4-amino-2-methylpyrimidin-5-yl)methyl-formylamino]-5-butanoyloxypent-2-en-3-yl]disulfanyl]pent-3-enyl] butanoate Chemical compound C=1N=C(C)N=C(N)C=1CN(C=O)C(\C)=C(/CCOC(=O)CCC)SS\C(CCOC(=O)CCC)=C(/C)N(C=O)CC1=CN=C(C)N=C1N YMEBNAABDXLAJE-GPAWKIAZSA-N 0.000 description 1
- HKQKYZRQBYBWSZ-BMJUYKDLSA-N [(z)-4-[(4-amino-2-methylpyrimidin-5-yl)methyl-formylamino]-3-[[(z)-2-[(4-amino-2-methylpyrimidin-5-yl)methyl-formylamino]-5-phosphonooxypent-2-en-3-yl]disulfanyl]pent-3-enyl] dihydrogen phosphate Chemical compound C=1N=C(C)N=C(N)C=1CN(C=O)C(\C)=C(CCOP(O)(O)=O)/SSC(/CCOP(O)(O)=O)=C(/C)N(C=O)CC1=CN=C(C)N=C1N HKQKYZRQBYBWSZ-BMJUYKDLSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 230000002925 chemical effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 229960001545 hydrotalcite Drugs 0.000 description 1
- 229910001701 hydrotalcite Inorganic materials 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 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 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229940088417 precipitated calcium carbonate Drugs 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 230000028043 self proteolysis Effects 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、ビタミンＢ１誘導
体を含有する固形製剤組成物に関する。TECHNICAL FIELD The present invention relates to a solid pharmaceutical composition containing a vitamin B1 derivative.
【０００２】更に詳しくは、安定剤としてにデンプン及
びリン酸水素カルシウムを配合することを特徴とするビ
タミンＢ１誘導体を含有する固形製剤組成物に関する。More specifically, it relates to a solid pharmaceutical composition containing a vitamin B1 derivative, characterized in that starch and calcium hydrogen phosphate are added as stabilizers.
【０００３】[0003]
【発明が解決しようとする課題】ジスルフィド結合を有
するビタミンＢ１誘導体は，配合禁忌である酸性物質や
経時的に発生する酸性分解物と共存することにより経時
的に分解が起こる。The vitamin B1 derivative having a disulfide bond is decomposed with time when it coexists with an acidic substance which is incompatible with the compound or an acidic decomposition product which is generated over time.
【０００４】また、水分の影響を受け急激に分解が起こ
る。Further, it is rapidly decomposed under the influence of water.
【０００５】[0005]
【課題を解決するための手段】本発明は、ビタミンＢ１
誘導体の経時的な成分の分解を防ぐことを目的とし、種
々検討した。The present invention provides vitamin B1.
Various studies were conducted for the purpose of preventing decomposition of the components of the derivative with time.
【０００６】すなわち、塩基性物質であるビタミンＢ１
誘導体は，配合禁忌である酸性物質の共存により経時的
に分解し、さらに自己分解で発生する酸性物質により分
解は促進されることを見いだした。That is, vitamin B1 which is a basic substance
It was found that the derivative decomposes over time due to the coexistence of an acidic substance, which is a contraindication, and that the decomposition is accelerated by the acidic substance generated by autolysis.
【０００７】そこで、塩基性物質を添加することにより
安定化できることを類推し、メタケイ酸アルミン酸マグ
ネシウム，炭酸ナトリウム，合成ヒドロタルサイト等の
種々の塩基性物質を用いて検討たが、充分な安定化効果
は得られなかった。[0007] Therefore, by analogy with the fact that it can be stabilized by adding a basic substance, various basic substances such as magnesium aluminometasilicate, sodium carbonate, synthetic hydrotalcite, etc. were investigated, but sufficient stability was obtained. The chemical effect was not obtained.
【０００８】ところが、ビタミンＢ１誘導体であるビス
イブチアミンは、リン酸水素カルシウムを添加すること
により、経時的に安定化することを見いだし、さらにデ
ンプンをも配合すると安定化することを見いだし、その
知見に基づき、本発明を完成したものである。[0008] However, it was found that the vitamin B1 derivative, bis-butyamine, was stabilized with the addition of calcium hydrogen phosphate over time, and that it was also stabilized by the addition of starch. The present invention has been completed based on the above.
【０００９】すなわち、本発明は、ビタミンＢ１誘導体
にデンプンおよびリン酸水素カルシウムを添加して得ら
れる安定なビタミンＢ１誘導体含有固形製剤組成物であ
る。Specifically, the present invention is a stable vitamin B1 derivative-containing solid pharmaceutical composition obtained by adding starch and calcium hydrogen phosphate to a vitamin B1 derivative.
【００１０】本発明において、ビタミンＢ１誘導体は、
ジスルフィド結合を有するビタミンＢ１誘導体であり、
例えば、ビスイブチアミン，チアミンジスルフィド，ビ
スベンチアミン，ビスブチチアミン，チアミンモノフォ
スフェイトジスルフィドである。特に安定化効果の著し
いものは、ビスイブチアミンである。In the present invention, the vitamin B1 derivative is
A vitamin B1 derivative having a disulfide bond,
For example, bis-butyamine, thiamine disulfide, bisbenchamine, bisbutytiamine, thiamine monophosphate disulfide. Especially, a compound having a remarkable stabilizing effect is bis-butyamine.
【００１１】ビタミンＢ１誘導体とリン酸水素カルシウ
ムとの配合比は，ビタミンＢ１誘導体１重量部に対し
て、０．０１〜１０重量部であり、，好ましくは０．０
２〜５重量部である。The blending ratio of the vitamin B1 derivative and calcium hydrogen phosphate is 0.01 to 10 parts by weight, preferably 0.0
2 to 5 parts by weight.
【００１２】また、デンプンは、その種類は問わない
が、コーンスターチもしくはバレイショデンプンが好ま
しい。デンプンの配合比は、ビタミンＢ１誘導体１重量
部に対して、０．０１〜１０重量部であり、好ましくは
０．０２〜５重量部である。The starch may be of any kind, but corn starch or potato starch is preferred. The blending ratio of starch is 0.01 to 10 parts by weight, preferably 0.02 to 5 parts by weight, relative to 1 part by weight of the vitamin B1 derivative.
【００１３】本発明の固形製剤組成物は、ビタミンＢ１
誘導体に塩基性物質を混合，粉砕するか、混合，粉砕し
た混合物を更に造粒することにより、調製することがで
きる。The solid pharmaceutical composition of the present invention comprises vitamin B1.
The derivative can be prepared by mixing and pulverizing a basic substance, or by further granulating the mixture obtained by mixing and pulverizing.
【００１４】[0014]
【発明の実施の形態】このようにして得られる本発明の
固形製剤組成物は、そのまま，あるいは必要に応じて一
般の造粒に用いられる賦形剤，結合剤，崩壊剤，滑沢剤
等を添加して、更に各種固形製剤（例えば，散剤，顆粒
剤，カプセル剤，錠剤等）に調製することが出来る。BEST MODE FOR CARRYING OUT THE INVENTION The solid pharmaceutical composition of the present invention thus obtained is used as it is, or if necessary, as an excipient, a binder, a disintegrating agent, a lubricant and the like used for general granulation. Can be further added to prepare various solid preparations (for example, powders, granules, capsules, tablets, etc.).
【００１５】賦形剤としては，コーンスターチなどのデ
ンプン類，乳糖，白糖，マンニット，キシリットなどの
糖類，結晶セルロース，軽質無水ケイ酸，メタケイ酸ア
ルミン酸マグネシウム，炭酸マグネシウム，酸化マグネ
シウム，酸化チタン，ポリエチレングリコールなどが挙
げられる。Excipients include starches such as corn starch, sugars such as lactose, sucrose, mannitol and xylite, crystalline cellulose, light anhydrous silicic acid, magnesium aluminometasilicate, magnesium carbonate, magnesium oxide, titanium oxide, Examples thereof include polyethylene glycol.
【００１６】結合剤としては、例えば，ポリビニルピロ
リドン，ヒドロキシプロピルセルロース，ヒドロキシプ
ロピルメチルセルロース，ゼラチン，アラビアゴム，エ
チルセルロース，ポリビニルアルコール，プルランが挙
げられる。Examples of the binder include polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose, gelatin, gum arabic, ethylcellulose, polyvinyl alcohol and pullulan.
【００１７】崩壊剤としては、例えば，低置換度ヒドロ
キシプロピルセルロース，カルボキシメチルセルロー
ス，カルボキシメチルセルロースナトリウム，カルボキ
シメチルセルロースカルシウム，ヒドロキシプロピルス
ターチ，部分アルファー化デンプン，沈降炭酸カルシウ
ム，クロスカルメロースナトリウムが挙げられる．滑沢
剤としては，例えば，ステアリン酸マグネシウム，ステ
アリン酸，ステアリン酸カルシウム，タルク，硬化油，
ショ糖脂肪酸エステルが挙げられる。Examples of the disintegrant include low-substituted hydroxypropyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose sodium, carboxymethyl cellulose calcium, hydroxypropyl starch, partially pregelatinized starch, precipitated calcium carbonate and croscarmellose sodium. Examples of lubricants include magnesium stearate, stearic acid, calcium stearate, talc, hydrogenated oil,
Examples include sucrose fatty acid ester.
【００１８】また，ここに挙げたもの以外にも本発明の
効果を損なわない内服可能なものであれば，適宜加えて
も差し支えない。In addition to the above-listed substances, any substance may be added as long as it can be taken internally without impairing the effects of the present invention.
【００１９】[0019]
【発明の効果】本発明により、ビタミンＢ１誘導体が経
時的に安定化がなされた品質のよいビタミンＢ１誘導体
を含有する固形製剤組成物が提供できる。INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a solid pharmaceutical composition containing a high-quality vitamin B1 derivative in which the vitamin B1 derivative is stabilized over time.
【００２０】[0020]
【実施例】以下、実施例をあげて本発明の組成物の製造
方法，効果を具体的に説明する。[Examples] The method for producing the composition of the present invention and its effects will be specifically described below with reference to Examples.
【００２１】実施例１ ビスイブチアミン１００ｇ，コーンスターチ６０ｇ，リ
ン酸水素カルシウム３０ｇ，結晶セルロース７０ｇを十
分に混合し，粉砕した混合物に撹拌しながらアルコール
を加えた後，乾燥し固形製剤組成物を得た。Example 1 100 g of bis-butyamine, 60 g of corn starch, 30 g of calcium hydrogen phosphate and 70 g of crystalline cellulose were thoroughly mixed, alcohol was added to the ground mixture while stirring, and the mixture was dried to obtain a solid pharmaceutical composition. It was
【００２２】実施例２ ビスイブチアミン１００ｇ，バレイショデンプン７０
ｇ，リン酸水素カルシウム３０ｇ，結晶セルロース７０
ｇを十分に混合し，粉砕した混合物に撹拌しながらアル
コールを加えた後，乾燥し固形製剤組成物を得た。Example 2 Bisbutyamine 100 g, potato starch 70
g, calcium hydrogen phosphate 30 g, crystalline cellulose 70
g was thoroughly mixed, alcohol was added to the pulverized mixture with stirring, and the mixture was dried to obtain a solid pharmaceutical composition.
【００２３】比較例１ ビスイブチアミン１００ｇ，デンプン６０ｇ，炭酸ナト
リウム３０ｇ，結晶セルロース７０ｇを十分に混合し，
固形製剤組成物を得た。Comparative Example 1 100 g of bisbutyamine, 60 g of starch, 30 g of sodium carbonate and 70 g of crystalline cellulose were thoroughly mixed,
A solid pharmaceutical composition was obtained.
【００２４】比較例２ ビスイブチアミン１００ｇ，デンプン６０ｇ，メタケイ
酸アルミン酸マグネシウム３０ｇ，結晶セルロース７０
ｇを十分に混合し，固形製剤組成物を得た。COMPARATIVE EXAMPLE 2 Bisbutyamine 100 g, starch 60 g, magnesium aluminometasilicate 30 g, crystalline cellulose 70
g was thoroughly mixed to obtain a solid pharmaceutical composition.
【００２５】比較例３ ビスイブチアミン１００ｇ，炭酸ナトリウム３０ｇ，結
晶セルロース７０ｇを十分に混合し，固形製剤組成物を
得た。Comparative Example 3 100 g of bis-butyamine, 30 g of sodium carbonate and 70 g of crystalline cellulose were thoroughly mixed to obtain a solid pharmaceutical composition.
【００２６】比較例４ 実施例１において塩基性物質を加えなかった他は実施例
と同様にして固形製剤組成物を得た。Comparative Example 4 A solid pharmaceutical composition was obtained in the same manner as in Example 1 except that the basic substance was not added.
【００２７】試験例１ 実施例１，２を試料１，２とし，比較例１，２，３，及
び４を試料３，４，５，及び６とした。Test Example 1 Examples 1 and 2 were Samples 1 and 2, and Comparative Examples 1, 2, 3, and 4 were Samples 3, 4, 5, and 6.
【００２８】試料１から６をガラス瓶に秤量し，密栓し
て４０度に保存し、６ヶ月後の残存率を測定した。Samples 1 to 6 were weighed in glass bottles, sealed tightly and stored at 40 ° C., and the residual rate after 6 months was measured.
【００２９】その結果を表１に示す。The results are shown in Table 1.
【００３０】[0030]
【表１】 [Table 1]
───────────────────────────────────────────────────── フロントページの続き (72)発明者 牧 亨 東京都豊島区高田３丁目24番１号 大正製 薬株式会社内 (72)発明者 水谷 卓 東京都豊島区高田３丁目24番１号 大正製 薬株式会社内 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Toru Maki 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. (72) Inventor Taku Mizutani 3-24-1 Takada, Toshima-ku, Tokyo Taisho Inside Pharmaceutical Co., Ltd.
Claims (5)
ン酸水素カルシウムを含有することを特徴とする固形製
剤用組成物。1. A composition for solid preparation comprising a vitamin B1 derivative, starch and calcium hydrogen phosphate.
を有するビタミンＢ１誘導体である請求項１の固形製剤
組成物。2. The solid pharmaceutical composition according to claim 1, wherein the vitamin B1 derivative is a vitamin B1 derivative having a disulfide bond.
ミンＢ１誘導体１重量部に対して、０．０１〜１０重量
部である請求項１または請求項２の固形製剤組成物。3. The solid preparation composition according to claim 1 or 2, wherein the amount of calcium hydrogen phosphate blended is 0.01 to 10 parts by weight with respect to 1 part by weight of the vitamin B1 derivative.
量部に対して、０．０１〜１０重量部である請求項１、
請求項２または請求項３の固形製剤組成物。4. The amount of starch is 0.01 to 10 parts by weight with respect to 1 part by weight of the vitamin B1 derivative.
The solid pharmaceutical composition according to claim 2 or 3.
カルシウムを含有することを特徴とするビタミンＢ１誘
導体含有固形製剤用組成物。5. A composition for solid preparation containing a vitamin B1 derivative, which comprises starch and calcium hydrogen phosphate as stabilizers.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8078909A JPH09268127A (en) | 1996-04-01 | 1996-04-01 | Solid preparation composition containing vitamin b1 derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8078909A JPH09268127A (en) | 1996-04-01 | 1996-04-01 | Solid preparation composition containing vitamin b1 derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH09268127A true JPH09268127A (en) | 1997-10-14 |
Family
ID=13674978
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8078909A Pending JPH09268127A (en) | 1996-04-01 | 1996-04-01 | Solid preparation composition containing vitamin b1 derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH09268127A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007023001A (en) * | 2005-07-21 | 2007-02-01 | Daiichi Sankyo Healthcare Co Ltd | Method for stabilizing thiamine compounds |
-
1996
- 1996-04-01 JP JP8078909A patent/JPH09268127A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007023001A (en) * | 2005-07-21 | 2007-02-01 | Daiichi Sankyo Healthcare Co Ltd | Method for stabilizing thiamine compounds |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2142790C1 (en) | Pharmaceutical composition stabilized by basic agent | |
| JP4621326B2 (en) | Teprenone stabilized composition | |
| IE913054A1 (en) | Stabilized solid chemical compositions | |
| US5441747A (en) | Stabilized solid pharmaceutical composition containing acid addition salts of a basic drug and an alkaline stabilizer | |
| CA2637925A1 (en) | Levetiracetam formulations and methods for their manufacture | |
| AU742382B2 (en) | Pharmaceutical preparation containing levothyroxine sodium | |
| US4666919A (en) | Stabilized pharmaceutical composition containing an isocarbostyril derivative | |
| JP2000191516A (en) | Solid oral composition | |
| US5004651A (en) | Stabilizing system for solid dosage forms | |
| JP2007145758A (en) | Stabilized pharmaceutical formulation | |
| EP0394022B1 (en) | Calcium pantothenate composit | |
| EP0952823B1 (en) | Stabilized pharmaceutical compositions and process for the preparation thereof | |
| EP0159777A1 (en) | Stabilized 4-carbamoyl-imidazolium-5-olate | |
| JP2001233766A (en) | Pravastatin sodium tablet | |
| JPH09268127A (en) | Solid preparation composition containing vitamin b1 derivative | |
| KR20050052361A (en) | Solid preparation which is preventive against sublimation of drug and the process for preparing the same | |
| JP2689458B2 (en) | Granular or powdered Vitamin B composition containing lower 1 and lower 2 | |
| JP2974550B2 (en) | Solid composition for oral administration | |
| HU217810B (en) | Cytarabine ocfosfate hard capsule preparations and process for production them | |
| JPH09124480A (en) | Vitamin preparation | |
| KR100686300B1 (en) | Hydroxypropylmethylcellulose Capsule Preparation Having Teprenone Encapsulated Therein | |
| JP2001354566A (en) | Tablet of nicergoline | |
| JP2002284679A (en) | Stable solid preparation composition containing thyroid hormone | |
| JP2003160487A (en) | Pravastatin sodium-containing tablet and method for producing the same | |
| AU2003201879B2 (en) | Pharmaceutical composition comprising 2,2-Dichloro-12-(4-chlorophenyl)-dodecanoic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20060613 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060725 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20060822 |