JP6946029B2 - Oral pharmaceutical composition - Google Patents
Oral pharmaceutical composition Download PDFInfo
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- JP6946029B2 JP6946029B2 JP2017054120A JP2017054120A JP6946029B2 JP 6946029 B2 JP6946029 B2 JP 6946029B2 JP 2017054120 A JP2017054120 A JP 2017054120A JP 2017054120 A JP2017054120 A JP 2017054120A JP 6946029 B2 JP6946029 B2 JP 6946029B2
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- scopolamine bromide
- butyl scopolamine
- aminoalkyl methacrylate
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- 239000008203 oral pharmaceutical composition Substances 0.000 title claims description 14
- HOZOZZFCZRXYEK-GSWUYBTGSA-M butylscopolamine bromide Chemical compound [Br-].C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)CCCC)=CC=CC=C1 HOZOZZFCZRXYEK-GSWUYBTGSA-M 0.000 claims description 62
- 229950009846 scopolamine butylbromide Drugs 0.000 claims description 62
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 38
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 claims description 34
- 239000000378 calcium silicate Substances 0.000 claims description 33
- 229910052918 calcium silicate Inorganic materials 0.000 claims description 33
- 235000019658 bitter taste Nutrition 0.000 claims description 30
- 229920003144 amino alkyl methacrylate copolymer Polymers 0.000 claims description 28
- 239000000654 additive Substances 0.000 claims description 25
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 21
- 239000001095 magnesium carbonate Substances 0.000 claims description 21
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 21
- 235000012239 silicon dioxide Nutrition 0.000 claims description 20
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims description 18
- 230000000996 additive effect Effects 0.000 claims description 17
- 239000000395 magnesium oxide Substances 0.000 claims description 17
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 17
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 17
- 239000000377 silicon dioxide Substances 0.000 claims description 17
- 239000003610 charcoal Substances 0.000 claims description 11
- 229920002125 Sokalan® Polymers 0.000 claims description 10
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 claims description 9
- 239000001263 FEMA 3042 Substances 0.000 claims description 9
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 claims description 9
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 claims description 9
- 229940033123 tannic acid Drugs 0.000 claims description 9
- 235000015523 tannic acid Nutrition 0.000 claims description 9
- 229920002258 tannic acid Polymers 0.000 claims description 9
- 229960003080 taurine Drugs 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 229940105082 medicinal charcoal Drugs 0.000 claims description 8
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims description 8
- 229940117841 methacrylic acid copolymer Drugs 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 229940068988 potassium aspartate Drugs 0.000 claims description 7
- -1 aminoalkyl methacrylate Chemical compound 0.000 claims description 3
- 229920000642 polymer Polymers 0.000 claims description 2
- SWHAQEYMVUEVNF-UHFFFAOYSA-N magnesium potassium Chemical compound [Mg].[K] SWHAQEYMVUEVNF-UHFFFAOYSA-N 0.000 claims 2
- 239000008187 granular material Substances 0.000 description 57
- 239000000203 mixture Substances 0.000 description 47
- 239000007787 solid Substances 0.000 description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
- 238000009472 formulation Methods 0.000 description 25
- 238000002360 preparation method Methods 0.000 description 18
- 229920003119 EUDRAGIT E PO Polymers 0.000 description 16
- 239000000243 solution Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000007788 liquid Substances 0.000 description 12
- WUKWITHWXAAZEY-UHFFFAOYSA-L calcium difluoride Chemical compound [F-].[F-].[Ca+2] WUKWITHWXAAZEY-UHFFFAOYSA-L 0.000 description 11
- 239000010436 fluorite Substances 0.000 description 11
- 239000008213 purified water Substances 0.000 description 9
- 238000009775 high-speed stirring Methods 0.000 description 8
- 238000004898 kneading Methods 0.000 description 8
- 230000000873 masking effect Effects 0.000 description 8
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 7
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 7
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 7
- 229920002678 cellulose Polymers 0.000 description 6
- 239000001913 cellulose Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229960001983 magnesium aspartate Drugs 0.000 description 6
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- YKZPPPNXRZHVGX-PXYKVGKMSA-L dipotassium;(2s)-2-aminobutanedioate;hydron;hydrate Chemical compound [H+].[H+].O.[K+].[K+].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O YKZPPPNXRZHVGX-PXYKVGKMSA-L 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 229910052749 magnesium Inorganic materials 0.000 description 5
- 208000004998 Abdominal Pain Diseases 0.000 description 4
- 206010007027 Calculus urinary Diseases 0.000 description 4
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 4
- 206010012735 Diarrhoea Diseases 0.000 description 4
- 208000005171 Dysmenorrhea Diseases 0.000 description 4
- 206010013935 Dysmenorrhoea Diseases 0.000 description 4
- 208000007882 Gastritis Diseases 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 208000003167 cholangitis Diseases 0.000 description 4
- 201000001883 cholelithiasis Diseases 0.000 description 4
- 208000001130 gallstones Diseases 0.000 description 4
- 238000005469 granulation Methods 0.000 description 4
- 230000003179 granulation Effects 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 208000008281 urolithiasis Diseases 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000004083 gastrointestinal agent Substances 0.000 description 2
- 229940127227 gastrointestinal drug Drugs 0.000 description 2
- 239000012088 reference solution Substances 0.000 description 2
- 238000007493 shaping process Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- 229920003138 Eudragit® L 30 D-55 Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 description 1
- 239000004503 fine granule Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229940086059 magnesium aspartate / potassium aspartate Drugs 0.000 description 1
- RXMQCXCANMAVIO-CEOVSRFSSA-L magnesium;(2s)-2-amino-4-hydroxy-4-oxobutanoate Chemical compound [H+].[H+].[Mg+2].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O RXMQCXCANMAVIO-CEOVSRFSSA-L 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、ブチルスコポラミン臭化物の服用時の苦味をマスキングした製剤技術に関する。 The present invention relates to a formulation technique that masks the bitterness of butyl scopolamine bromide when taken.
ブチルスコポラミン臭化物（Ｃ２１Ｈ３０ＢｒＮＯ４）は胃炎や下痢、胆管炎、胆石などによる腹痛や、尿路結石症や月経困難症に処方される薬剤であり、大変有用であるが、苦味がきついことが知られている。 Butylscopolamine bromide (C 21 H 30 BrNO 4 ) is a drug prescribed for abdominal pain caused by gastritis, diarrhea, cholangitis, gallstones, urolithiasis and dysmenorrhea, and is very useful but has a strong bitter taste. It is known.
このブチルスコポラミン臭化物の苦味をマスキングするための技術としては、例えば、ステビアで胃腸薬成分の苦味をマスキングする技術が報告されている（特許文献１）。 As a technique for masking the bitterness of this butyl scopolamine bromide, for example, a technique for masking the bitterness of a gastrointestinal drug component with stevia has been reported (Patent Document 1).
しかしながら、上記報告では苦味を有する胃腸薬成分としてブチルスコポラミン臭化物が挙げられているものの、実施例はなく、実際にブチルスコポラミン臭化物の服用時の苦味をマスキングできる技術であるか不明であった。 However, although butyl scopolamine bromide is mentioned as a gastrointestinal drug component having a bitter taste in the above report, there is no example, and it is unclear whether the technique can actually mask the bitter taste when taking butyl scopolamine bromide.
従って、本発明の課題は、ブチルスコポラミン臭化物の服用時の苦味をマスキングできる技術を提供することである。 Therefore, an object of the present invention is to provide a technique capable of masking the bitter taste when taking butyl scopolamine bromide.
本発明者らは、上記課題を解決するために鋭意研究した結果、特定の添加剤を用いることにより、ブチルスコポラミン臭化物の苦味をマスキングできることを見出し、本発明を完成させた。 As a result of diligent research to solve the above problems, the present inventors have found that the bitterness of butyl scopolamine bromide can be masked by using a specific additive, and have completed the present invention.
すなわち、本発明は、ブチルスコポラミン臭化物と、ケイ酸カルシウム、二酸化ケイ素、炭酸マグネシウム、酸化マグネシウム、薬用炭、カルボキシビニルポリマー、クエン酸水和物、アスパラギン酸マグネシウム・カリウム、タウリン、タンニン酸、プルラン、アミノアルキルメタクリレートコポリマーＥおよびメタクリル酸コポリマーＬＤからなる群から選ばれる添加剤の少なくとも１種を含有することを特徴とする経口用医薬組成物である。 That is, the present invention comprises butyl scopolamine bromide, calcium silicate, silicon dioxide, magnesium carbonate, magnesium oxide, medicinal charcoal, carboxyvinyl polymer, citrate hydrate, magnesium aspartate / potassium, taurine, tannic acid, purulan, An oral pharmaceutical composition comprising at least one additive selected from the group consisting of aminoalkyl methacrylate polymer E and methacrylic acid copolymer LD.
また、本発明は、ブチルスコポラミン臭化物と、ケイ酸カルシウム、二酸化ケイ素、炭酸マグネシウムおよび酸化マグネシウムから選ばれる添加剤の少なくとも１種を含有することを特徴とする経口用医薬組成物である。 The present invention is also an oral pharmaceutical composition comprising butyl scopolamine bromide and at least one additive selected from calcium silicate, silicon dioxide, magnesium carbonate and magnesium oxide.
更に、本発明は、ブチルスコポラミン臭化物を含有する経口用医薬組成物に、ケイ酸カルシウム、二酸化ケイ素、炭酸マグネシウム、酸化マグネシウム、薬用炭、カルボキシビニルポリマー、クエン酸水和物、アスパラギン酸マグネシウム・カリウム、タウリン、タンニン酸、プルラン、アミノアルキルメタクリレートコポリマーＥおよびメタクリル酸コポリマーＬＤからなる群から選ばれる添加剤の少なくとも１種を配合することを特徴とするブチルスコポラミン臭化物を含有する経口用医薬組成物の苦味抑制方法である。 Furthermore, the present invention comprises an oral pharmaceutical composition containing a butyl scopolamine bromide, calcium silicate, silicon dioxide, magnesium carbonate, magnesium oxide, medicinal charcoal, carboxyvinyl polymer, citric acid hydrate, magnesium aspartate / potassium aspartate. , Taurine, tannic acid, purulan, aminoalkyl methacrylate copolymer E and methacrylic acid copolymer LD. This is a method for suppressing bitterness.
本発明の経口用医薬組成物は、ブチルスコポラミン臭化物を含有していながらも服用時の苦味がマスキングされているため服用が容易である。 The oral pharmaceutical composition of the present invention is easy to take because it contains butyl scopolamine bromide but the bitterness at the time of administration is masked.
そのため、本発明の経口用医薬組成物は、胃炎や下痢、胆管炎、胆石などによる腹痛や、尿路結石症や月経困難症の治療に好適である。 Therefore, the oral pharmaceutical composition of the present invention is suitable for the treatment of abdominal pain caused by gastritis, diarrhea, cholangitis, gallstones, urolithiasis, and dysmenorrhea.
本発明の経口用医薬組成物（以下、「本発明組成物」という）におけるブチルスコポラミン臭化物の含有量は特に限定されないが、固形製剤の場合、例えば、０．３〜１０質量％、好ましくは２〜５質量％である。内服液剤の場合、例えば、０.０１〜０.２質量％、好ましくは０.０２〜０.５質量％である。 The content of the butyl scopolamine bromide in the oral pharmaceutical composition of the present invention (hereinafter referred to as "the composition of the present invention") is not particularly limited, but in the case of a solid preparation, for example, 0.3 to 10% by mass, preferably 2. ~ 5% by mass. In the case of an internal liquid preparation, for example, it is 0.01 to 0.2% by mass, preferably 0.02 to 0.5% by mass.
本発明組成物には、ケイ酸カルシウム、二酸化ケイ素（軽質無水ケイ酸、含水二酸化ケイ素等）、炭酸マグネシウム、酸化マグネシウム、薬用炭、カルボキシビニルポリマー、クエン酸水和物、アスパラギン酸マグネシウム・カリウム、タウリン、タンニン酸、プルラン、アミノアルキルメタクリレートコポリマーＥおよびメタクリル酸コポリマーＬＤからなる群から選ばれる添加剤の少なくとも１種を含有させればよい。これら添加剤の中でもケイ酸カルシウム、炭酸マグネシウム、酸化マグネシウム、薬用炭、カルボキシビニルポリマー、クエン酸水和物、アミノアルキルメタクリレートコポリマーＥの少なくとも１種が好ましく、ケイ酸カルシウム、二酸化ケイ素、炭酸マグネシウムおよび酸化マグネシウムの少なくとも１種がより好ましく、ケイ酸カルシウムおよび炭酸マグネシウムの少なくとも１種が特に好ましい。なお、添加剤として、ケイ酸カルシウム、二酸化ケイ素、炭酸マグネシウムおよび酸化マグネシウムの少なくとも１種、あるいは、ケイ酸カルシウムおよび炭酸マグネシウムの少なくとも１種を用いる場合には、更に、アミノアルキルメタクリレートコポリマーＥと組み合わせることが苦味のマスキングの点から好ましい。 The compositions of the present invention include calcium silicate, silicon dioxide (light anhydrous silicic acid, hydrous silicon dioxide, etc.), magnesium carbonate, magnesium oxide, medicated charcoal, carboxyvinyl polymer, citrate hydrate, magnesium / potassium aspartate, etc. It may contain at least one additive selected from the group consisting of taurine, tannic acid, purulan, aminoalkyl methacrylate copolymer E and methacrylic acid copolymer LD. Among these additives, at least one of calcium silicate, magnesium carbonate, magnesium oxide, medicinal charcoal, carboxyvinyl polymer, citrate hydrate, and aminoalkyl methacrylate copolymer E is preferable, and calcium silicate, silicon dioxide, magnesium carbonate and At least one of magnesium oxide is more preferable, and at least one of calcium silicate and magnesium carbonate is particularly preferable. When at least one of calcium silicate, silicon dioxide, magnesium carbonate and magnesium oxide, or at least one of calcium silicate and magnesium carbonate is used as an additive, it is further combined with aminoalkyl methacrylate copolymer E. This is preferable from the viewpoint of masking the bitter taste.
本発明組成物において、上記添加剤の含有量は剤形に応じて適宜設定すればよく、特に限定されないが、例えば、０.０１〜７５質量％、好ましくは５〜５０質量％である。 In the composition of the present invention, the content of the additive may be appropriately set according to the dosage form and is not particularly limited, but is, for example, 0.01 to 75% by mass, preferably 5 to 50% by mass.
また、本発明組成物において、ブチルスコポラミン臭化物と、上記添加剤との質量比は特に限定されないが、例えば、１：０.０１〜５０、好ましくは１：０.５〜１０である。 Further, in the composition of the present invention, the mass ratio of the butyl scopolamine bromide to the additive is not particularly limited, but is, for example, 1: 0.01 to 50, preferably 1: 0.5 to 10.
本発明組成物には、更に、通常の経口用医薬組成物に含有させることのできる、溶解補助剤、賦形剤、結合剤、崩壊剤、矯味剤、界面活性剤、滑沢剤、香料等を含有させてもよい。 The compositions of the present invention further include solubilizing agents, excipients, binders, disintegrants, flavoring agents, surfactants, lubricants, fragrances and the like that can be contained in ordinary oral pharmaceutical compositions. May be contained.
本発明組成物は、錠剤、顆粒剤、散剤、細粒剤等の固形製剤、液剤、シロップ剤、ゼリー剤等の液剤等の経口用の剤形とすることができる。これらの剤形の中でも固形製剤が好ましく、錠剤、顆粒剤がより好ましい。 The composition of the present invention can be in the form of a solid preparation such as tablets, granules, powders and fine granules, and an oral dosage form such as a liquid preparation such as a liquid preparation, a syrup preparation and a jelly preparation. Among these dosage forms, solid formulations are preferable, and tablets and granules are more preferable.
本発明組成物を固形製剤とした場合の好ましい組成の一例としては以下のものが挙げられる。
ブチルスコポラミン臭化物 ２〜５質量％
ケイ酸カルシウム ０.３〜５０質量％
炭酸マグネシウム ０.３〜５０質量％
Examples of preferable compositions when the composition of the present invention is a solid preparation include the following.
Butyl scopolamine bromide 2-5% by mass
Calcium silicate 0.3-50% by mass
Magnesium carbonate 0.3-50% by mass
本発明組成物を固形製剤とした場合の好ましい組成の別の一例としては以下のものが挙げられる。
ブチルスコポラミン臭化物 ２〜１０質量％
ケイ酸カルシウム ０.３〜５０質量％
アミノアルキルメタクリレートコポリマーＥ ０.３〜５０質量％
The following is another example of a preferable composition when the composition of the present invention is made into a solid preparation.
Butyl scopolamine bromide 2-10% by mass
Calcium silicate 0.3-50% by mass
Aminoalkyl Methacrylate Copolymer E 0.3-50% by mass
また、本発明組成物の内服液剤とした場合の好ましい組成の一例としては以下のものが挙げられる。
ブチルスコポラミン臭化物 ０.０２〜０.５質量％
ケイ酸カルシウム ０.０１〜５質量％
炭酸マグネシウム ０.０１〜５質量％
In addition, the following are examples of preferable compositions when the composition of the present invention is used as an internal liquid preparation.
Butyl scopolamine bromide 0.02 to 0.5% by mass
Calcium silicate 0.01-5% by mass
Magnesium carbonate 0.01-5% by mass
本発明組成物の内服液剤とした場合の好ましい組成の別の一例としては以下のものが挙げられる。
ブチルスコポラミン臭化物 ０.０２〜０.５質量％
ケイ酸カルシウム ０.０１〜５質量％
アミノアルキルメタクリレートコポリマーＥ ０.０１〜５質量％
The following is another example of a preferable composition when the composition of the present invention is used as an internal liquid preparation.
Butyl scopolamine bromide 0.02 to 0.5% by mass
Calcium silicate 0.01-5% by mass
Aminoalkyl Methacrylate Copolymer E 0.01-5% by mass
本発明組成物は、上記成分を用いる以外は、上記剤形の公知の調製法に基づいて調製することができる。なお、上記添加剤のうち、カルボキシビニルポリマー、プルラン、アミノアルキルメタクリレートコポリマーＥおよびメタクリル酸コポリマーＬＤは、結合剤やコーティング基剤と呼ばれるものであるため、公知の調製法において、結合剤やコーティング基剤としてこれらを用いればよい。また、上記添加剤のうち、ケイ酸カルシウム、二酸化ケイ素、炭酸マグネシウム、酸化マグネシウム、薬用炭、クエン酸水和物、アスパラギン酸マグネシウム・カリウム、タウリンおよびタンニン酸は、賦型剤と呼ばれるものであるため、公知の調製法において、賦型剤としてこれらを用いればよい。 The composition of the present invention can be prepared based on a known preparation method of the above dosage form, except that the above components are used. Among the above additives, carboxyvinyl polymer, pullulan, aminoalkyl methacrylate copolymer E and methacrylic acid copolymer LD are called binders and coating bases. Therefore, in known preparation methods, binders and coating groups are used. These may be used as an agent. Among the above additives, calcium silicate, silicon dioxide, magnesium carbonate, magnesium oxide, medicinal charcoal, citrate hydrate, magnesium / potassium aspartate, taurine and tannic acid are called typeants. Therefore, these may be used as a type-forming agent in a known preparation method.
なお、本発明組成物を顆粒剤、散剤、細粒剤等の固形製剤とする場合、通常賦型剤として用いられるケイ酸カルシウム、二酸化ケイ素、炭酸マグネシウム、酸化マグネシウム、薬用炭、クエン酸水和物、アスパラギン酸マグネシウム・カリウム、タウリンおよびタンニン酸は、顆粒剤、散剤、細粒剤中に含まれていてもよく、前記賦型剤以外の成分を用いて顆粒剤、散剤、細粒剤を調製した後、別途、ケイ酸カルシウム、二酸化ケイ素、炭酸マグネシウム、酸化マグネシウム、薬用炭、クエン酸水和物、アスパラギン酸マグネシウム・カリウム、タウリンおよびタンニン酸と混合した状態で含まれていてもよい。 When the composition of the present invention is made into a solid preparation such as a granule, a powder, or a fine granule, calcium silicate, silicon dioxide, magnesium carbonate, magnesium oxide, medicated charcoal, and citric acid hydration, which are usually used as shaping agents, are used. The substance, magnesium / potassium aspartate, taurine and tannic acid may be contained in the granules, powders and fine granules, and the granules, powders and fine granules may be prepared by using components other than the above-mentioned shaping agent. After preparation, it may be separately contained in a state of being mixed with calcium silicate, silicon dioxide, magnesium carbonate, magnesium oxide, medicinal charcoal, citric acid hydrate, magnesium / potassium aspartate, taurine and tannic acid.
また、本発明組成物が固形製剤の場合、固形製剤とした後、更に、公知の糖衣やフィルムでコーティングしてもよい。 When the composition of the present invention is a solid preparation, it may be further coated with a known sugar coating or film after the solid preparation.
斯くして得られる本発明組成物は、ブチルスコポラミン臭化物の服用時の苦味がマスキングされたものであり、例えば、胃炎や下痢、胆管炎、胆石などによる腹痛や、尿路結石症や月経困難症の治療に好適に用いることができる。 The composition of the present invention thus obtained masks the bitterness of butyl scopolamine bromide when taken, and includes, for example, abdominal pain due to gastritis, diarrhea, cholangitis, gallstones, urolithiasis, and dysmenorrhea. Can be suitably used for the treatment of.
なお、本発明組成物において、ブチルスコポラミン臭化物の服用時の苦味がマスキングされているとは、本発明組成物を服用した際に苦味が低減されることをいう。 In the composition of the present invention, the fact that the bitterness when taking the butyl scopolamine bromide is masked means that the bitterness is reduced when the composition of the present invention is taken.
以下、本発明を実施例を挙げて詳細に説明するが、本発明はこれら実施例に何ら限定されるものではない。 Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples.
実 施 例 １
添加剤の種類とマスキング効果の関係（１）：
ブチルスコポラミン臭化物１質量部に対し、表１に記載の各添加剤１０質量部（分散液等の場合は固形分）を添加した後、精製水に溶解もしくは分散してブチルスコポラミン臭化物の濃度が５０μｇ／ｍｌの水溶液を調製した。これらの水溶液について以下の評価方法に基づいて苦みを評価した。この結果も表１に記載した。
Example 1
Relationship between types of additives and masking effect (1):
After adding 10 parts by mass (solid content in the case of a dispersion) of each additive shown in Table 1 to 1 part by mass of butyl scopolamine bromide, the concentration of butyl scopolamine bromide is 50 μg by dissolving or dispersing in purified water. A / ml aqueous solution was prepared. The bitterness of these aqueous solutions was evaluated based on the following evaluation methods. This result is also shown in Table 1.
＜評価方法＞
５０μｇ／ｍＬでブチルスコポラミン臭化物のみを含む水溶液（基準液）の苦味を評点「４」とした。この基準液に対し、添加剤を加えた各液を０.５ｍｌ服用し、苦味の度合を５名のパネラーが下記基準にてスコアリングした。
＜評価基準＞
評点：苦味の程度
０：全くなし
１：僅かにあり
２：少しあり
３：あり
４：非常にあり
<Evaluation method>
The bitterness of the aqueous solution (reference solution) containing only butyl scopolamine bromide at 50 μg / mL was given a score of “4”. To this reference solution, 0.5 ml of each solution to which the additive was added was taken, and the degree of bitterness was scored by 5 panelists according to the following criteria.
<Evaluation criteria>
Score: Degree of bitterness 0: None 1: Slightly 2: Slightly 3: Yes 4: Very
以上の結果から、添加剤としてケイ酸カルシウム、炭酸マグネシウム、酸化マグネシウム、薬用炭、カルボキシビニルポリマー、クエン酸水和物、アスパラギン酸マグネシウム・カリウム、タウリン、タンニン酸、プルランおよびメタクリル酸コポリマーＬＤを用いた場合に、ブチルスコポラミン臭化物の苦味を抑制できることが分かった。特に添加剤として、ケイ酸カルシウム、炭酸マグネシウム、酸化マグネシウムおよび薬用炭を用いた場合に、ブチルスコポラミン臭化物の苦味をかなり抑制できることが分かった。 Based on the above results, calcium silicate, magnesium carbonate, magnesium oxide, medicated charcoal, carboxyvinyl polymer, citric acid hydrate, magnesium / potassium aspartate, taurine, tannic acid, purulan and methacrylic acid copolymer LD are used as additives. It was found that the bitterness of butyl scopolamine bromide could be suppressed when it was present. In particular, it was found that the bitterness of butyl scopolamine bromide can be considerably suppressed when calcium silicate, magnesium carbonate, magnesium oxide and medicinal charcoal are used as additives.
実 施 例 ２
添加剤の添加量とマスキング効果の関係：
ブチルスコポラミン臭化物１質量部に対し、表２に記載の各添加剤を０.０１〜１０質量部を添加した後、精製水に溶解もしくは分散してブチルスコポラミン臭化物の濃度が５０μｇ／ｍｌの水溶液を調製した。これらの水溶液について実施例１と同様にして評価した。この結果も表２に記載した。
Example 2
Relationship between the amount of additive added and the masking effect:
After adding 0.01 to 10 parts by mass of each additive shown in Table 2 to 1 part by mass of butyl scopolamine bromide, an aqueous solution having a concentration of 50 μg / ml of butyl scopolamine bromide is dissolved or dispersed in purified water. Prepared. These aqueous solutions were evaluated in the same manner as in Example 1. This result is also shown in Table 2.
以上の結果から、ブチルスコポラミン臭化物と添加剤の質量比により、苦味の抑制の度合いが変化することが分かった。特に、ブチルスコポラミン臭化物と添加剤の質量比が、１：０.５〜１０の時に苦味の抑制効果が高いことが分かった。 From the above results, it was found that the degree of suppression of bitterness changes depending on the mass ratio of butyl scopolamine bromide and the additive. In particular, it was found that when the mass ratio of the butyl scopolamine bromide to the additive was 1: 0.5 to 10, the effect of suppressing bitterness was high.
実 施 例 ３
添加剤の種類とマスキング効果の関係（２）：
ブチルスコポラミン臭化物１質量部と、カルボキシビニルポリマー（カーボポール ９７４ＰＮＦ：ＣＢＣ製）２質量部とを混合後、錠剤成型器で圧縮した。これを乳鉢で粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Actual example 3
Relationship between the type of additive and the masking effect (2):
After mixing 1 part by mass of butyl scopolamine bromide and 2 parts by mass of a carboxyvinyl polymer (Carbopol 974PNF: manufactured by CBC), the mixture was compressed with a tablet molding machine. This was pulverized in a mortar and fractionated with a sieve of 42 to 100 mesh to obtain granules.
この顆粒を水に分散し、塩酸塩苦味を検知するセンサーを備えた味覚センサー（インテリジェントセンサーテクノロジー製）で簡易評価したところ、試験に用いた顆粒に含まれるブチルスコポラミン臭化物と同量のブチルスコポラミン臭化物を水に溶解した時よりも、苦味がマスキングされていたことを確認できた。 When these granules were dispersed in water and evaluated simply by a taste sensor (manufactured by Intelligent Sensor Technology) equipped with a sensor that detects the bitterness of hydrochloride, the same amount of butyl scopolamine bromide as that contained in the granules used in the test was obtained. It was confirmed that the bitterness was masked more than when it was dissolved in water.
実 施 例 ４
添加剤の種類とマスキング効果の関係（３）：
ブチルスコポラミン臭化物５質量部と、メタクリル酸コポリマーＬＤ（オイドラギットＬ３０Ｄ-５５：エボニック製）２.５質量部（固形分として）および結晶セルロース４２．５質量部を高速撹拌造粒機で混合後、精製水を練合液として練合した。得られた造粒物を箱型乾燥機により乾燥し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 4
Relationship between types of additives and masking effect (3):
5 parts by mass of butyl scopolamine bromide, 2.5 parts by mass of methacrylic acid copolymer LD (Eudragit L30D-55: manufactured by Ebonic) (as solid content) and 42.5 parts by mass of crystalline cellulose are mixed by a high-speed stirring granulator and then purified. Water was kneaded as a kneading liquid. The obtained granules were dried by a box dryer and fractionated with a sieve of 42 to 100 mesh to obtain granules.
この顆粒を水に分散し、実施例３と同様にして簡易評価したところ、試験に用いた顆粒に含まれるブチルスコポラミン臭化物と同量のブチルスコポラミン臭化物を水に溶解した時よりも、苦味がマスキングされていたことを確認できた。 When these granules were dispersed in water and simply evaluated in the same manner as in Example 3, the bitterness was masked as compared with the case where the same amount of butyl scopolamine bromide as the butyl scopolamine bromide contained in the granules used in the test was dissolved in water. I was able to confirm that it had been done.
実 施 例 ５
固形製剤（１）：
ブチルスコポラミン臭化物１０質量部と、ケイ酸カルシウム（フローライトＲＥ：富田製薬製）１００質量部、ヒドロキシプロピルセルロース５質量部および乳糖水和物６５質量部を高速撹拌造粒機で混合後、精製水を練合液として練合した。得られた造粒物を箱型乾燥機により乾燥し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 5
Solid formulation (1):
Purified water after mixing 10 parts by mass of butyl scopolamine bromide, 100 parts by mass of calcium silicate (Florite RE: manufactured by Tomita Pharmaceutical Co., Ltd.), 5 parts by mass of hydroxypropyl cellulose and 65 parts by mass of lactose hydrate with a high-speed stirring granulator. Was kneaded as a kneading solution. The obtained granules were dried by a box dryer and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 ６
固形製剤（２）：
ブチルスコポラミン臭化物１０質量部と、炭酸マグネシウム１００質量部、ヒドロキシプロピルセルロース５質量部および乳糖水和物６５質量部を高速撹拌造粒機で混合後、精製水を練合液として練合した。得られた造粒物を箱型乾燥機により乾燥し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 6
Solid formulation (2):
After mixing 10 parts by mass of butyl scopolamine bromide, 100 parts by mass of magnesium carbonate, 5 parts by mass of hydroxypropyl cellulose and 65 parts by mass of lactose hydrate with a high-speed stirring granulator, purified water was kneaded as a kneading solution. The obtained granules were dried by a box dryer and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 ７
固形製剤（３）：
ブチルスコポラミン臭化物１０質量部と、酸化マグネシウム１００質量部、ヒドロキシプロピルセルロース５質量部および乳糖水和物６５質量部を高速撹拌造粒機で混合後、精製水を練合液として練合した。得られた造粒物を箱型乾燥機により乾燥し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 7
Solid formulation (3):
After mixing 10 parts by mass of butyl scopolamine bromide, 100 parts by mass of magnesium oxide, 5 parts by mass of hydroxypropyl cellulose and 65 parts by mass of lactose hydrate with a high-speed stirring granulator, purified water was kneaded as a kneading solution. The obtained granules were dried by a box dryer and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 ８
固形製剤（４）：
ブチルスコポラミン臭化物１０質量部と、結晶セルロース８５質量部、ヒドロキシプロピルセルロース５質量部を高速撹拌造粒機により混合後、精製水を加えて練合・造粒した。得られた造粒物を箱型乾燥機により乾燥し、４２〜１００メッシュの篩にて分画して、顆粒を得た。この顆粒１００質量部に対しケイ酸カルシウム（フローライトＲＥ：富田製薬製）５０質量部を加えて混合し顆粒剤を得た。
Example 8
Solid formulation (4):
10 parts by mass of butyl scopolamine bromide, 85 parts by mass of crystalline cellulose, and 5 parts by mass of hydroxypropyl cellulose were mixed by a high-speed stirring granulator, and then purified water was added for kneading and granulation. The obtained granules were dried by a box dryer and fractionated with a sieve of 42 to 100 mesh to obtain granules. To 100 parts by mass of these granules, 50 parts by mass of calcium silicate (Fluorite RE: manufactured by Tomita Pharmaceutical Co., Ltd.) was added and mixed to obtain granules.
実 施 例 ９
固形製剤（５）：
ブチルスコポラミン臭化物１０質量部と、結晶セルロース８５質量部、ヒドロキシプロピルセルロース５質量部を高速撹拌造粒機により混合後、精製水を加えて練合・造粒した。得られた造粒物を箱型乾燥機により乾燥し、４２〜１００メッシュの篩にて分画して、顆粒を得た。この顆粒１００質量部に対し炭酸マグネシウム５０質量部を加えて混合し顆粒剤を得た。
Example 9
Solid formulation (5):
10 parts by mass of butyl scopolamine bromide, 85 parts by mass of crystalline cellulose, and 5 parts by mass of hydroxypropyl cellulose were mixed by a high-speed stirring granulator, and then purified water was added for kneading and granulation. The obtained granules were dried by a box dryer and fractionated with a sieve of 42 to 100 mesh to obtain granules. 50 parts by mass of magnesium carbonate was added to 100 parts by mass of the granules and mixed to obtain a granule.
実 施 例 １０
固形製剤（６）：
ブチルスコポラミン臭化物１０質量部と、結晶セルロース８５質量部、ヒドロキシプロピルセルロース５質量部を高速撹拌造粒機により混合後、精製水を加えて練合・造粒した。得られた造粒物を箱型乾燥機により乾燥し、４２〜１００メッシュの篩にて分画して、顆粒を得た。この顆粒１００質量部に対し酸化マグネシウム５０質量部を加えて混合し顆粒剤を得た。
Example 10
Solid formulation (6):
10 parts by mass of butyl scopolamine bromide, 85 parts by mass of crystalline cellulose, and 5 parts by mass of hydroxypropyl cellulose were mixed by a high-speed stirring granulator, and then purified water was added for kneading and granulation. The obtained granules were dried by a box dryer and fractionated with a sieve of 42 to 100 mesh to obtain granules. 50 parts by mass of magnesium oxide was added to 100 parts by mass of the granules and mixed to obtain a granule.
実 施 例 １１
固形製剤（７）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）５質量部を加えて溶解させる。次に、ケイ酸カルシウム（フローライトＲＥ：富田製薬製）５質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 11
Solid formulation (7):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, 5 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) is added and dissolved. Next, this solution was added to 5 parts by mass of calcium silicate (Fluorite RE: manufactured by Tomita Pharmaceutical Co., Ltd.), kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 １２
固形製剤（８）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）１０質量部を加えて溶解させる。次に、ケイ酸カルシウム（フローライトＲＥ：富田製薬製）５質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 12
Solid formulation (8):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, add 10 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) to dissolve. Next, this solution was added to 5 parts by mass of calcium silicate (Fluorite RE: manufactured by Tomita Pharmaceutical Co., Ltd.), kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 １３
固形製剤（９）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）１０質量部を加えて溶解させる。次に、ケイ酸カルシウム（フローライトＲＥ：富田製薬製）１０質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 13
Solid formulation (9):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, add 10 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) to dissolve. Next, this solution was added to 10 parts by mass of calcium silicate (Fluorite RE: manufactured by Tomita Pharmaceutical Co., Ltd.), kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 １４
固形製剤（１０）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）１０質量部を加えて溶解させる。次に、ケイ酸カルシウム（フローライトＲＥ：富田製薬製）２０質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 14
Solid formulation (10):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, add 10 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) to dissolve. Next, this solution was added to 20 parts by mass of calcium silicate (Fluorite RE: manufactured by Tomita Pharmaceutical Co., Ltd.), kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 １５
固形製剤（１１）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）１５質量部を加えて溶解させる。次に、ケイ酸カルシウム（フローライトＲＥ：富田製薬製）３質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 15
Solid formulation (11):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, 15 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) is added and dissolved. Next, this solution was added to 3 parts by mass of calcium silicate (Fluorite RE: manufactured by Tomita Pharmaceutical Co., Ltd.), kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 １６
固形製剤（１２）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）１５質量部を加えて溶解させる。次に、ケイ酸カルシウム（フローライトＲＥ：富田製薬製）５質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 16
Solid formulation (12):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, 15 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) is added and dissolved. Next, this solution was added to 5 parts by mass of calcium silicate (Fluorite RE: manufactured by Tomita Pharmaceutical Co., Ltd.), kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 １７
固形製剤（１３）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）１５質量部を加えて溶解させる。次に、ケイ酸カルシウム（フローライトＲＥ：富田製薬製）１０質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 17
Solid formulation (13):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, 15 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) is added and dissolved. Next, this solution was added to 10 parts by mass of calcium silicate (Fluorite RE: manufactured by Tomita Pharmaceutical Co., Ltd.), kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 １８
固形製剤（１４）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）２０質量部を加えて溶解させる。次に、ケイ酸カルシウム（フローライトＲＥ：富田製薬製）５質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 18
Solid formulation (14):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, 20 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) is added and dissolved. Next, this solution was added to 5 parts by mass of calcium silicate (Fluorite RE: manufactured by Tomita Pharmaceutical Co., Ltd.), kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 １９
固形製剤（１５）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）２０質量部を加えて溶解させる。次に、ケイ酸カルシウム（フローライトＲＥ：富田製薬製）２０質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 19
Solid formulation (15):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, 20 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) is added and dissolved. Next, this solution was added to 20 parts by mass of calcium silicate (Fluorite RE: manufactured by Tomita Pharmaceutical Co., Ltd.), kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 ２０
固形製剤（１６）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）２０質量部を加えて溶解させる。次に、軽質無水ケイ酸（アエロジル２００：エボニック製）２０質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 20
Solid formulation (16):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, 20 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) is added and dissolved. Next, this liquid was added to 20 parts by mass of light anhydrous silicic acid (Aerosil 200: manufactured by Evonik), kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 ２１
固形製剤（１７）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）２０質量部を加えて溶解させる。次に、軽質無水ケイ酸（アドソリダー１０１：フロイント製）２０質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 21
Solid formulation (17):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, 20 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) is added and dissolved. Next, this liquid was added to 20 parts by mass of light anhydrous silicic acid (Adsolider 101: manufactured by Freund), kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 ２２
固形製剤（１８）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）２０質量部を加えて溶解させる。次に、軽質無水ケイ酸（サイリシア３５０：富士シリシア化学製）２０質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 22
Solid formulation (18):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, 20 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) is added and dissolved. Next, this liquid was added to 20 parts by mass of light silicic anhydride (Syricia 350: manufactured by Fuji Silysia Chemical Ltd.), kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 ２３
固形製剤（１９）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）２０質量部を加えて溶解させる。次に、含水二酸化ケイ素（カープレックス６７：エボニック製）２０質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 23
Solid formulation (19):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, 20 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) is added and dissolved. Next, this liquid was added to 20 parts by mass of hydrous silicon dioxide (Carplex 67: manufactured by Evonik), kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 ２４
固形製剤（２０）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）２０質量部を加えて溶解させる。次に、乳糖水和物２０質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 24
Solid formulation (20):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, 20 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) is added and dissolved. Next, this liquid was added to 20 parts by mass of lactose hydrate, kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 ２５
固形製剤（２１）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）２０質量部を加えて溶解させる。次に、結晶セルロース（ＰＨ−１０１：旭化成製）２０質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Example 25
Solid formulation (21):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, 20 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) is added and dissolved. Next, this solution was added to 20 parts by mass of crystalline cellulose (PH-101: manufactured by Asahi Kasei), kneaded, and then dried by a box dryer. The obtained product was pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules.
実 施 例 ２６
固形製剤（２２）：
ブチルスコポラミン臭化物２質量部を日本薬局方エタノールに溶解させた後、アミノアルキルメタクリレートコポリマーＥ（オイドラギットＥＰＯ：エボニック製）２０質量部を加えて溶解させる。次に、乳糖水和物２０質量部にこの液を加えて練合した後に箱型乾燥機により乾燥した。得られたものを粉砕し、４２〜１００メッシュの篩にて分画して、顆粒を得る。この顆粒１００質量部に対しケイ酸カルシウム（フローライトＲＥ：富田製薬製）２５質量部を加えて混合し顆粒剤を得た。
Example 26
Solid formulation (22):
After dissolving 2 parts by mass of butyl scopolamine bromide in ethanol according to the Japanese Pharmacopoeia, 20 parts by mass of aminoalkyl methacrylate copolymer E (Eudragit EPO: manufactured by Ebonic) is added and dissolved. Next, this liquid was added to 20 parts by mass of lactose hydrate, kneaded, and then dried by a box dryer. The obtained product is pulverized and fractionated with a sieve of 42 to 100 mesh to obtain granules. 25 parts by mass of calcium silicate (Fluorite RE: manufactured by Tomita Pharmaceutical Co., Ltd.) was added to 100 parts by mass of these granules and mixed to obtain granules.
比 較 例 １
固形製剤（２３）：
ブチルスコポラミン臭化物１０質量部と、結晶セルロース８５質量部、ヒドロキシプロピルセルロース５質量部を高速撹拌造粒機により混合後、精製水を加えて練合・造粒した。得られた造粒物を箱型乾燥機により乾燥し、４２〜１００メッシュの篩にて分画して、顆粒を得た。
Comparison example 1
Solid formulation (23):
10 parts by mass of butyl scopolamine bromide, 85 parts by mass of crystalline cellulose, and 5 parts by mass of hydroxypropyl cellulose were mixed by a high-speed stirring granulator, and then purified water was added for kneading and granulation. The obtained granules were dried by a box dryer and fractionated with a sieve of 42 to 100 mesh to obtain granules.
試 験 例 １
苦味の評価試験：
実施例５〜２６および比較例１で調製した顆粒剤や顆粒について以下の評価方法に基づいて苦みを評価した。この結果を表３に記載した。
Trial example 1
Bitterness evaluation test:
The bitterness of the granules and granules prepared in Examples 5 to 26 and Comparative Example 1 was evaluated based on the following evaluation methods. The results are shown in Table 3.
＜評価方法＞
顆粒剤や顆粒のブチルスコポラミン臭化物１０ｍｇ相当量を口に含み、溶けだしてくる苦味の度合を５名のパネラーが下記基準にてスコアリングし、その平均を示した。
＜評価基準＞
評点：苦味の程度
０：全くなし
１：僅かにあり
２：少しあり
３：あり
４：非常にあり
<Evaluation method>
Five panelists scored the degree of bitterness that began to dissolve in the mouth containing 10 mg of butyl scopolamine bromide of granules or granules according to the following criteria, and the average was shown.
<Evaluation criteria>
Score: Degree of bitterness 0: None 1: Slightly 2: Slightly 3: Yes 4: Very
本発明組成物は、胃炎や下痢、胆管炎、胆石などによる腹痛や、尿路結石症や月経困難症の治療に利用可能である。
以 上
The composition of the present invention can be used for the treatment of abdominal pain caused by gastritis, diarrhea, cholangitis, gallstones, urolithiasis, and dysmenorrhea.
that's all
Claims (5)
Oral pharmaceutical composition containing butyl scopolamine bromide, calcium silicate, silicon dioxide, magnesium carbonate, magnesium oxide, medicinal charcoal, carboxyvinyl polymer, magnesium potassium aspartate, taurine, tannic acid, purulan, aminoalkyl methacrylate copolymer An oral pharmaceutical composition containing a butyl scopolamine bromide, which comprises at least one additive selected from the group consisting of E and a methacrylic acid copolymer LD (provided that it contains silicon dioxide and an aminoalkyl methacrylate copolymer E). Method of suppressing bitterness ( excluding those that do).
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| JP2000086537A (en) * | 1998-09-11 | 2000-03-28 | Fuji Chem Ind Co Ltd | Inorganic compound saccharide composition, vehicle, rapidly disintegrating compression molded product, and their production |
| JP5266627B2 (en) * | 2006-07-20 | 2013-08-21 | 大正製薬株式会社 | Oral composition |
| WO2008018371A1 (en) * | 2006-08-08 | 2008-02-14 | Kissei Pharmaceutical Co., Ltd. | Oral disintegrating tablet having masked bitter taste and method for production thereof |
| JP2009263298A (en) * | 2008-04-28 | 2009-11-12 | Ss Pharmaceut Co Ltd | Oral composition having masked disagreeable taste |
| JP2012025711A (en) * | 2010-07-27 | 2012-02-09 | Ohara Yakuhin Kogyo Kk | Method for producing physiologically active substance-containing particle |
| JP6088151B2 (en) * | 2012-04-11 | 2017-03-01 | ロート製薬株式会社 | Pharmaceutical composition |
| JP6549428B2 (en) * | 2014-07-23 | 2019-07-24 | エスエス製薬株式会社 | Oral composition |
| DK3257511T3 (en) * | 2015-02-10 | 2019-01-21 | Fujifilm Corp | ORAL SOLUBLE TABLE AND METHOD OF PREPARING IT |
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