JPS6322014A - Long-acting capsule drug floating in stomach - Google Patents
Long-acting capsule drug floating in stomachInfo
- Publication number
- JPS6322014A JPS6322014A JP5078786A JP5078786A JPS6322014A JP S6322014 A JPS6322014 A JP S6322014A JP 5078786 A JP5078786 A JP 5078786A JP 5078786 A JP5078786 A JP 5078786A JP S6322014 A JPS6322014 A JP S6322014A
- Authority
- JP
- Japan
- Prior art keywords
- capsule
- gastroinsoluble
- cap
- stomach
- active ingredient
- 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
- 239000002775 capsule Substances 0.000 title claims abstract description 79
- 210000002784 stomach Anatomy 0.000 title claims abstract description 15
- 239000003814 drug Substances 0.000 title abstract description 28
- 229940079593 drug Drugs 0.000 title abstract description 25
- 239000000203 mixture Substances 0.000 claims abstract description 52
- 239000007902 hard capsule Substances 0.000 claims abstract description 23
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 22
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims abstract description 18
- 235000021355 Stearic acid Nutrition 0.000 claims abstract description 17
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000008117 stearic acid Substances 0.000 claims abstract description 17
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229940106164 cephalexin Drugs 0.000 claims abstract description 6
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 claims abstract description 6
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 claims abstract description 5
- 229960003022 amoxicillin Drugs 0.000 claims abstract description 5
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229960000541 cetyl alcohol Drugs 0.000 claims abstract description 4
- 238000002844 melting Methods 0.000 claims abstract 5
- 230000008018 melting Effects 0.000 claims abstract 5
- 229940126701 oral medication Drugs 0.000 claims abstract 3
- QYIYFLOTGYLRGG-GPCCPHFNSA-N cefaclor Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 QYIYFLOTGYLRGG-GPCCPHFNSA-N 0.000 claims description 16
- 229960005361 cefaclor Drugs 0.000 claims description 16
- 229960004274 stearic acid Drugs 0.000 claims description 16
- 239000004480 active ingredient Substances 0.000 claims description 14
- 239000003925 fat Substances 0.000 claims description 14
- 235000019197 fats Nutrition 0.000 claims description 14
- 239000003921 oil Substances 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 239000007903 gelatin capsule Substances 0.000 claims description 10
- 230000002496 gastric effect Effects 0.000 claims description 7
- 230000002459 sustained effect Effects 0.000 claims description 6
- 235000019868 cocoa butter Nutrition 0.000 claims description 5
- 229940110456 cocoa butter Drugs 0.000 claims description 5
- 230000005923 long-lasting effect Effects 0.000 claims description 4
- IVVNZDGDKPTYHK-JTQLQIEISA-N 1-cyano-2-[(2s)-3,3-dimethylbutan-2-yl]-3-pyridin-4-ylguanidine Chemical compound CC(C)(C)[C@H](C)N=C(NC#N)NC1=CC=NC=C1 IVVNZDGDKPTYHK-JTQLQIEISA-N 0.000 claims description 3
- 229960001380 cimetidine Drugs 0.000 claims description 3
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 claims description 3
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims description 3
- 229960003529 diazepam Drugs 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 229960002310 pinacidil Drugs 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 abstract description 11
- 244000299461 Theobroma cacao Species 0.000 abstract description 3
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 abstract description 3
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 abstract description 3
- 235000001046 cacaotero Nutrition 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract 1
- 230000002035 prolonged effect Effects 0.000 abstract 1
- 238000000034 method Methods 0.000 description 13
- 239000004615 ingredient Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 230000005484 gravity Effects 0.000 description 8
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 6
- -1 aliphatic alcohols Chemical class 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 6
- 229940093430 polyethylene glycol 1500 Drugs 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 229920003134 Eudragit® polymer Polymers 0.000 description 5
- 239000004359 castor oil Substances 0.000 description 5
- 235000019438 castor oil Nutrition 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 4
- 239000007963 capsule composition Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 3
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 3
- 239000001856 Ethyl cellulose Substances 0.000 description 3
- 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 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 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 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 238000007922 dissolution test Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 229920001249 ethyl cellulose Polymers 0.000 description 3
- 235000019325 ethyl cellulose Nutrition 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 3
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 3
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 description 3
- 229960002508 pindolol Drugs 0.000 description 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 229940088417 precipitated calcium carbonate Drugs 0.000 description 3
- 239000002151 riboflavin Substances 0.000 description 3
- 235000019192 riboflavin Nutrition 0.000 description 3
- 229960002477 riboflavin Drugs 0.000 description 3
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 239000011247 coating layer Substances 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- GUBNMFJOJGDCEL-UHFFFAOYSA-N dicyclomine hydrochloride Chemical compound [Cl-].C1CCCCC1C1(C(=O)OCC[NH+](CC)CC)CCCCC1 GUBNMFJOJGDCEL-UHFFFAOYSA-N 0.000 description 2
- 229940110321 dicyclomine hydrochloride Drugs 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 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
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 235000014593 oils and fats Nutrition 0.000 description 2
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- 235000011293 Brassica napus Nutrition 0.000 description 1
- 240000008100 Brassica rapa Species 0.000 description 1
- 235000000540 Brassica rapa subsp rapa Nutrition 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 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 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- YLCXGBZIZBEVPZ-UHFFFAOYSA-N Medazepam Chemical compound C12=CC(Cl)=CC=C2N(C)CCN=C1C1=CC=CC=C1 YLCXGBZIZBEVPZ-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 241001310793 Podium Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
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- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000013869 carnauba wax Nutrition 0.000 description 1
- 239000004203 carnauba wax Substances 0.000 description 1
- 229960004841 cefadroxil Drugs 0.000 description 1
- NBFNMSULHIODTC-CYJZLJNKSA-N cefadroxil monohydrate Chemical compound O.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=C(O)C=C1 NBFNMSULHIODTC-CYJZLJNKSA-N 0.000 description 1
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- 230000003111 delayed effect Effects 0.000 description 1
- SWXVUIWOUIDPGS-UHFFFAOYSA-N diacetone alcohol Natural products CC(=O)CC(C)(C)O SWXVUIWOUIDPGS-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
【発明の詳細な説明】
１果上立■月至里
本発明は作用の持続を目的としたハードカプセル製剤の
製造に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the production of hard capsule preparations for the purpose of sustained action.
従］ヱ１１生
胃内で製剤を浮遊させることにより胃内の滞留時間を延
長許せて、かつ、内包される薬物を徐々に放出きせる事
により、作用の持続化を試みる技術はいくつか見られる
０例えば、カプセルの如き中空物質の表面かまたはそれ
自身浮力を有する発泡物質を適当な紋型としてその表面
に薬物をコーチングする方法（特公昭５５−１２４１１
）が開示されている。この方法による浮遊性製剤は、見
掛比重が１未満となり、浮遊性製剤として好ましい特徴
を備えてはいるが、いくつかの欠点も伴なっている６例
えば製造工程が煩雑である点である。カプセルや、発泡
物質の成型物の様に大きな紋型を有する核に、薬物を均
一にコーチングするためには、数層にわたって何回もコ
ーチングする作業が必要であり、この様なコーチングに
は長時間を要する。一方、抗生物質のように１回の投与
量が多い薬物の場合、製剤中の薬物含量が多くなる結果
、製剤が嵩高くなったり、薬物の物性の影響が大きくな
り、薬物を含有するコーチング層の付着性が悪くなった
りする。また、薬物の種類によって溶解度等が異なるた
め、この様なコーチング層としての形状で薬物の放出速
度をコントロールするのが難しく、一定品質の製剤を得
るには非常に困難が伴う、また、でき上がった製剤が脆
いなどの欠点もある。11) There are several techniques that attempt to extend the residence time in the stomach by suspending the drug in the raw stomach, and also to gradually release the drug contained therein, thereby attempting to prolong the action. 0 For example, a method of coating a drug on the surface of a hollow substance such as a capsule or a foamed substance which itself has buoyancy as a suitable pattern (Japanese Patent Publication No. 12411/1983)
) are disclosed. Although the floating preparation produced by this method has an apparent specific gravity of less than 1 and has desirable characteristics as a floating preparation, it also has some drawbacks, such as the complicated manufacturing process. In order to uniformly coat a drug into a core with a large pattern, such as a capsule or a molded product of foamed material, it is necessary to coat the drug many times over several layers, and such coating takes a long time. It takes time. On the other hand, in the case of drugs such as antibiotics that require large doses at one time, the drug content in the formulation increases, resulting in the formulation becoming bulky, and the physical properties of the drug being affected by the coating layer containing the drug. adhesion may deteriorate. In addition, because the solubility and other factors differ depending on the type of drug, it is difficult to control the release rate of the drug in the form of a coating layer, making it extremely difficult to obtain a drug product of constant quality. There are also disadvantages such as the fragility of the formulation.
その他の技術に、硬カプセル内にゲル形成高分子物質、
薬物および比重の小さい物質を充填する方法（特開昭５
ｌ−１１５９１０）が挙げられる。この方法によれば、
カプセル剤内部のゲル形成高分子は胃内において、カプ
セル壁を通過した水分を吸収してゲル状皮膜を形成し、
硬カプセルにとってかわり、ゲル状カプセルを形成する
と説明されている。この様にして胃内で形成されたゲル
状カプセルは比重の小さい物質で浮力を得、徐々に薬物
を放出するのであるが、この様なゲル状カプセルは胃内
における強度の点で問題が有り、食後の胃消化運動中に
破壊されやすいものと予想きれる。Other techniques include gel-forming polymeric materials within hard capsules;
Method for filling drugs and substances with low specific gravity (Unexamined Japanese Patent Publication No. 5
l-115910). According to this method,
In the stomach, the gel-forming polymer inside the capsule absorbs water that has passed through the capsule wall and forms a gel-like film.
It is explained that it forms a gel-like capsule instead of a hard capsule. The gel capsules formed in the stomach in this way gain buoyancy due to the low specific gravity and gradually release the drug, but such gel capsules have problems in terms of strength in the stomach. It can be expected that it is easily destroyed during the gastric digestive movement after meals.
明が解決しようとする問題点
前述した如く、製造が簡単であり、充分な浮力及び強度
を保ち、かつ薬物の放出速度がコントロールされた胃内
浮遊性製剤の開発は困難であつた。Problems to be Solved by Ming As mentioned above, it has been difficult to develop a gastric suspension preparation that is easy to manufacture, maintains sufficient buoyancy and strength, and has a controlled drug release rate.
以上の点に鑑み、本発明者らは鋭意研究を重ねた結果、
製造が簡単であり、充分な浮力及び強度を保ち、薬物の
放出速度をフントロールし易い浮遊性持続型製剤の製造
に成功し、本発明を完成した０本発明製剤は太ききもコ
ンパクトであり、服用しやすいものである。In view of the above points, the inventors of the present invention have conducted extensive research, and as a result,
The present invention has been completed by successfully producing a floating, long-lasting preparation that is easy to manufacture, maintains sufficient buoyancy and strength, and can easily control the drug release rate.The present invention is compact in size. , easy to take.
−侭を 決するための 段
本発明は、医薬活性成分を含むポリエチレングリコール
類および／または油脂類の溶融物を胃溶性硬質カプセル
ボデー部に充填し、次いで胃不溶性硬質カプセルキャッ
プを装着させるものである。この際、医薬活性成分はポ
リエチレングリコール類および／または油脂類とともに
溶融されていてもよいし、ポリエチレングリコール類お
よび／または油脂類の溶融物に医薬活性成分を混合した
ものであっても良い。- Steps for Deciding the Problem The present invention is a method in which a gastroinsoluble hard capsule body is filled with a melt of polyethylene glycols and/or fats and oils containing a pharmaceutically active ingredient, and then a gastroinsoluble hard capsule cap is attached. . At this time, the pharmaceutically active ingredient may be melted together with polyethylene glycols and/or fats and oils, or the pharmaceutically active ingredient may be mixed into a melt of polyethylene glycols and/or fats and oils.
胃不溶性硬質カプセルキャップ部分は、腸溶性基剤また
は胃不溶性基剤で製造した硬質カプセルキャップであっ
ても良いし、該基剤を通常のゼラチン硬質カプセルキャ
ップにコーチングした硬質カプセルキャップであっても
良い、二の除行なうコーチングは、スプレー、パンコー
チングなどの常法に従って行なえば良い。The stomach-insoluble hard capsule cap portion may be a hard capsule cap made of an enteric base or a stomach-insoluble base, or it may be a hard capsule cap made by coating a normal gelatin hard capsule cap with the base. Coaching can be done using conventional methods such as spray or pan coaching.
胃溶性カプセルボデーは、胃内可溶性基剤からなるもの
であれば全て使用可能であり、通常のゼラチンカプセル
ボデーが好ましく用いられる。Any gastric soluble capsule body can be used as long as it is composed of a gastric soluble base, and a typical gelatin capsule body is preferably used.
カプセルに充填する溶融混合物の量は、最終のカプセル
剤の見掛比重が１未満になる程度に用いれば良い、胃内
で食物の影響を受けにくい好ましい浮遊性を持たせる為
には、見掛比重を約０．５〜約０．９にする事が好まし
い、最終のカプセル中に残されるべき空間は、充填する
溶融混合物の比重によって変わるので、−概に言えない
が、−般には、カプセルの全内容積に対して約５〜約４
０％になる様にするのが好ましい、勿論、残された空間
が上記範囲以上であっても良いが、いずれの場合にも胃
不溶性のカプセルキャップが、その空間より大きい内容
積を持っていなければならない、さもなければ胃内でカ
プセルボデーが溶解する結果、浮力を持たせるべき空間
が保持されなくなる。The amount of the molten mixture to be filled into the capsules should be such that the apparent specific gravity of the final capsule is less than 1. It is preferred that the specific gravity be between about 0.5 and about 0.9, since the space to be left in the final capsule will vary depending on the specific gravity of the molten mixture to be filled, and therefore - in general - although not generally speaking. About 5 to about 4 for the total internal volume of the capsule
It is preferable that the remaining space be 0%.Of course, the remaining space may be greater than the above range, but in any case, the gastroinsoluble capsule cap must have an internal volume larger than that space. Otherwise, the capsule body will dissolve in the stomach and the buoyant space will no longer be retained.
この様にして製造した本発明カプセル製剤は溶融物が固
化し、カプセル内部では移動しなくなっているので、空
間がカプセルキャップ部分に固定される結果、丁度、浮
きの様に一定方向を保ちつつ胃内を浮遊し、胃液と接す
るカプセルボデー部分から徐々に薬物が放出きれること
となる。In the capsule formulation of the present invention manufactured in this way, the melt solidifies and does not move inside the capsule, so the space is fixed to the capsule cap part, and as a result, the stomach maintains a fixed direction just like a float. The drug floats inside the capsule and is gradually released from the part of the capsule body that comes into contact with gastric juice.
本発明において、腸溶性基剤とは、フタル酸セルロース
アセテート、ヒＦロキシブロビルメチルセルロースフタ
レート、ポリビニルアルコールフタレート、カルボキシ
メチルエチルセルローススチレン・マレイン酸共重合体
、メタアクリル酸・メタアクリル酸エステル共重合体、
およびヒドロキシプロピルメチルセルロースアセテート
フタレートなどが例示される．胃不溶性基剤としてはエ
チルセルロース等が例示きれる。In the present invention, enteric bases include cellulose phthalate acetate, hydroxybrobyl methylcellulose phthalate, polyvinyl alcohol phthalate, carboxymethylethylcellulose styrene/maleic acid copolymer, methacrylic acid/methacrylate ester copolymer. ,
and hydroxypropyl methyl cellulose acetate phthalate. Examples of gastric insoluble bases include ethyl cellulose.
ポリエチレングリコールは、その重合度によって、様々
なグレードが有るが、本発明は通常、医薬に使用を認め
られている全ての種類が適用可能であり、単独または混
合物で使用する。There are various grades of polyethylene glycol depending on the degree of polymerization, but the present invention is generally applicable to all types of polyethylene glycol that are approved for use in medicine, and can be used alone or in mixtures.
油脂類とはカカオ脂、ミツロウ及びカルナウバロウ等の
ワックス類、ステアリン酸、バルミチン酸等の脂肪酸類
、セチルアルコール、ステアリルアルコール等の長鎖脂
肪族アルコール類、脂肪酸または水素添加脂肪酸のグリ
セリンエステルの如きグリセリド、例えばグリセリルモ
ノステアレート、グリセリルジステアレート、水素添加
ヒマシ油のグリセリンエステル等が例示される．これら
は単独または混合物で使用する。Fats and oils include cocoa butter, waxes such as beeswax and carnauba wax, fatty acids such as stearic acid and balmitic acid, long-chain aliphatic alcohols such as cetyl alcohol and stearyl alcohol, and glycerides such as glycerin esters of fatty acids or hydrogenated fatty acids. Examples include glyceryl monostearate, glyceryl distearate, and glycerin ester of hydrogenated castor oil. These may be used alone or in mixtures.
本発明に於ては、通常の保存状態及び体内で概溶融混合
物が固化している事が必要であり、通常、約５０〜約７
０℃で溶融し、約４０℃以下で固化する様なポリエチレ
ングリコール類および／または油脂類を選択する。In the present invention, it is necessary that the almost molten mixture be solidified under normal storage conditions and in the body, and usually about 50 to about 7
Select polyethylene glycols and/or fats and oils that melt at 0°C and solidify at about 40°C or below.
これらポリエチレングリコール類と油脂類の添加比率を
変える事により薬物の放出速度を調節することができる
．一般には油脂類の添加比率が高くなれば薬物の放出速
度が遅くなる．用いる医薬活性成分の溶解度によっては
、ポリエチレングリコール類単独または油脂類単独で適
用することも可能である。By changing the ratio of these polyethylene glycols and fats and oils added, the drug release rate can be adjusted. Generally, the higher the ratio of fats and oils added, the slower the drug release rate. Depending on the solubility of the pharmaceutical active ingredient used, it is also possible to apply polyethylene glycols alone or oils and fats alone.
医薬活性成分の放出速度をコントロールする為に、前記
添加物以外に、ポリオキシエチレン［１６０］ポリオキ
シプロピレン［３０］グリフール、ポリビニルピロリド
ン、ヒドロキシプロピルセルロース、乳糖、ブドウ糖、
アスコルビン酸等の水溶性物質を適宜使用しても良い。In order to control the release rate of pharmaceutically active ingredients, in addition to the above additives, polyoxyethylene [160] polyoxypropylene [30] glyfur, polyvinylpyrrolidone, hydroxypropylcellulose, lactose, glucose,
Water-soluble substances such as ascorbic acid may be used as appropriate.
本発明には、はとんど全ての医薬が適用可能であり、作
用の持続化が望まれている経口投与用医薬に格別好まし
い、しいて例示すれば、アンピシリン、アモキシシリン
、シクラシリン、バカンビシリン、カルフエシリンナト
リウム等のペニシリン類、セファレキシン、セファクロ
ル、セファドロキシル、セファトリジン、セフラジン等
のセファロスポリン類、ミノマイシン等のテトラサイク
リン類等の抗生物質類、ピンドロール、ピナシジル等の
降圧剤、ジアゼパム、ニトラゼバム、メダゼパム等のベ
ンゾジアゼピン系マイナートランキライザー、シメチジ
ン、ジサイクロミン等の抗潰瘍剤、沈降炭酸カルシウム
、沈降炭酸マグネシウム等の制酸剤、リボフラビン等が
挙げられる。Almost all pharmaceuticals are applicable to the present invention, and are particularly preferable for orally administered pharmaceuticals for which sustained action is desired. Penicillins such as fecillin sodium, cephalosporins such as cephalexin, cefaclor, cefadroxil, cefatridine, and cefrazine, antibiotics such as tetracyclines such as minomycin, antihypertensive agents such as pindolol, pinacidil, diazepam, nitrazebam, medazepam, etc. Examples include benzodiazepine minor tranquilizers, anti-ulcer agents such as cimetidine and dicyclomine, antacids such as precipitated calcium carbonate and precipitated magnesium carbonate, and riboflavin.
以下に参考例、実施例及び実験例を示し、本発明を更に
詳しく説明するが、これらは何ら本発明を限定するもの
ではない。The present invention will be explained in more detail by referring to Reference Examples, Examples, and Experimental Examples below, but these are not intended to limit the present invention in any way.
（以下余白）
実験例１
セファクロルの通常カプセル製剤と本発明カプセル製剤
の溶出速度と血漿中濃度の比較（１）使用製剤
対照カプセル剤： セファクロル原末１８７゜５ｍｇ力
価宛をゼラチン２号カプセルに充填。(Leaving space below) Experimental Example 1 Comparison of dissolution rate and plasma concentration of cefaclor conventional capsule formulation and capsule formulation of the present invention (1) Control capsule formulation of used formulation: Cefaclor bulk powder 187° 5 mg titer was placed in gelatin No. 2 capsules. filling.
被検薬： 実施例１に記載の本発明カプセル剤（セファ
クロル１８７．５ｍｇ力価／カプセル含有、見掛比重０
．８４０）
■溶出試験
前記薬剤の溶出を下記の条件により測定した。Test drug: Capsules of the present invention described in Example 1 (contains cefaclor 187.5 mg potency/capsule, apparent specific gravity 0)
．． 840) (1) Dissolution test The dissolution of the above drug was measured under the following conditions.
なお、セファクロルの溶出量は２６３ｎｍにおける吸光
度をＵＶ法（Ｕｌｔｒａｖｉｏｌｅｔ ａｂｓｏｒｐｔ
ｉｏｎ ｍｅｔｈｏｄ）により測定して求めた。The elution amount of cefaclor was determined by measuring the absorbance at 263 nm using the UV method (Ultraviolet absorbance).
ion method).
装置： ビーカー法（６０ｒ、ｐ、ｍ、 ）Ｋ験遺：
ｐＨ１、２（第１０改正日本薬局方第１液）
ｐＨ２，０（０，２Ｎ塩酸１０．２Ｎ
塩化カリウム）
ｐＨ６，３（蒸留水）
試験液量： ２５０ｍ１
Ｋ菓魔皇１： ３７±０．５℃
溶出試験の結果を表１に示す。Apparatus: Beaker method (60r, p, m, )K test results:
pH 1, 2 (10th edition Japanese Pharmacopoeia 1st solution) pH 2, 0 (0, 2N hydrochloric acid 10.2N potassium chloride) pH 6, 3 (distilled water) Test liquid volume: 250ml Kakamaou 1: 37±0. Table 1 shows the results of the 5°C dissolution test.
（以下余白）
対照として用いた通常のカプセル剤が約１時間で、はぼ
１００％の溶出を示したが、本発明のカプセル剤は長時
間にわたって持続的な溶出を示すことが確認された。(The following is a blank space) The conventional capsule used as a control showed almost 100% dissolution in about 1 hour, but it was confirmed that the capsule of the present invention showed sustained dissolution over a long period of time.
０）血漿中濃度 対 および 与量 体重約１０ｋｇの雄性ピーグル犬４頭を用いた。0) Plasma concentration pair and dose Four male peagle dogs weighing approximately 10 kg were used.
４頭のうち２頭に対照薬を、残りの２頭に被検薬を投与
した。投与量はそれぞれ１カプセル宛であった。Two of the four animals received the control drug, and the remaining two received the test drug. The dosage was for one capsule each.
逸王直羞
市販のドッグフード約１００ｇを水３００ｍ１とともに
給餌後３０分に、各１カプセル宛を水１００ｍ１ととも
に投与した。なお第１回目の給餌５時間後に第２回目の
給餌を行なった。Approximately 100 g of commercially available dog food from Itsuo Naoki was administered along with 300 ml of water and 30 minutes after feeding, one capsule of each was administered along with 100 ml of water. The second feeding was performed 5 hours after the first feeding.
激皇１羞
表２に示す時間（薬剤投与後の時間）について各７回採
血を行ない、 ＨＰ Ｌ Ｃ（）ｌｉｇｈ Ｐｅｒｆｏ
ｒｍａｎｃｅＬｉｑｕｉｄ Ｃｈｒｏｍａｔｏｇｒａｐ
ｈｙ）にて血漿中のセファクロル濃度を測定した。Blood was collected 7 times each at the times shown in Table 2 (time after drug administration), and HPLC()light Perfo
rmanceLiquid Chromatograp
Cefaclor concentration in plasma was measured at hy).
尚、前記表中で用いられたＡＵＧとは曲線下面積（Ａｒ
ｅａ Ｕｕｄｅｒ ｔｈｅ Ｃｕｒｖｅ）の略称であり
、血漿中濃度−時間曲線の積分値、すなわち生物学的利
用度を表わす一つの指標である。Note that AUG used in the table above refers to the area under the curve (Ar
It is an abbreviation for "EA UDER THE CURVE" and is an index representing the integral value of the plasma concentration-time curve, that is, the degree of bioavailability.
前記の溶出試験の結果から予想される如く、本発明の被
検薬剤は血漿中濃度の持続化を達成し、ＡＵＧも対照薬
のものと比べ同等以上であり、吸収量も好ましい事が確
認された。As expected from the results of the dissolution test described above, it was confirmed that the test drug of the present invention achieved a sustained plasma concentration, had an AUG equal to or higher than that of the control drug, and had a favorable absorption amount. Ta.
実験例２
本発明カプセル剤における医薬活性成分の溶出率（％）
実施例４または５で製した本発明カプセル剤について、
各カプセル剤に含有されるセファクロルの溶出率（％）
をビーカー法（６０ｒ、ｐ、ｍ、 ）により測定した。Experimental Example 2 Dissolution rate (%) of pharmaceutically active ingredients in capsules of the present invention Regarding the capsules of the present invention produced in Example 4 or 5,
Dissolution rate (%) of cefaclor contained in each capsule
was measured by the beaker method (60r, p, m, ).
試験液としては第１０改正日本薬局方第１液を用いた。The 10th revised Japanese Pharmacopoeia liquid 1 was used as the test liquid.
各カプセル剤の見掛比重を第３表に併せて示す。The apparent specific gravity of each capsule is also shown in Table 3.
（以下余白）
表３
実験例１で試験した実施例１のカプセル剤及び本実験に
おける実施例４および５のカプセル剤が第１液中で長時
間、好ましい浮遊状態を示していたのは勿論であるが、
実施例４および５の組成物では、油脂類の含量比が多い
ためセファクロルの溶出がざらに遅延された。これらの
カプセル剤は２４時間でセファクロルをほぼ１００％溶
出したが、この事実は本発明組成物が、１日１回投与を
可能にする胃内浮遊性製剤を示唆するものである。(Leaving space below) Table 3 It goes without saying that the capsules of Example 1 tested in Experimental Example 1 and the capsules of Examples 4 and 5 in this experiment exhibited a favorable floating state for a long time in the first liquid. Yes, but
In the compositions of Examples 4 and 5, the elution of cefaclor was significantly delayed because the content ratio of oils and fats was high. These capsules dissolved almost 100% of cefaclor in 24 hours, which suggests that the composition of the present invention is a gastric suspension formulation that allows for once-daily administration.
この様にポリエチレングリコール類と油脂類との混合比
を調節することにより容易に溶出速度をコントロールし
得る事が確認された。It was thus confirmed that the elution rate could be easily controlled by adjusting the mixing ratio of polyethylene glycols and fats and oils.
第１図〜第３図に本発明組成物の代表的なＭ４様を模式
的に示す。FIGS. 1 to 3 schematically show typical M4 forms of the composition of the present invention.
実施例１
成 分
ｍｇ／カプセルセファクロル １
８７ポリエチレングリコール１５４０ ２３０合
計 ４１７
ポリエチレングリコール１５４０を約５５°Ｃで溶融し
たのち、セファクロルを加えて混合し、この溶融混合物
を２号カプセルのポデーに充填し、このポデーに参考例
３で製した２号カプセルキャップをする。Example 1 Ingredients
mg/capsule cefaclor 1
87 Polyethylene glycol 1540 230 total 417 Polyethylene glycol 1540 was melted at about 55°C, cefaclor was added and mixed, and this molten mixture was filled into a No. 2 capsule pode. Put on the capsule cap.
実施例２
成 分 ｍｇ／カブや
、リボフラビン １０ポリエチ
レングリコール４０００ １９０ステアリン酸
３５カカオ脂
１７−久ユ土ユ”、ｙ ％−／ノＪコ−二
ニヒー １１−一合計 ３１０
リボフラビンにポリエチレングリコール４０００、ステ
アリン酸、カカオ脂およびグリセリンモノステアレート
を加え、約６５℃で溶融混合する。この溶融混合物を３
号カプセルのポデーに充填し、このポデーに参考例３で
製した３号カプセルキャップをする。Example 2 Ingredients mg/turnip, riboflavin 10 polyethylene glycol 4000 190 stearic acid
35 cocoa butter
17-Kuyu Toyu'', y %-/NoJ Corner 11-1 Total 310 Polyethylene glycol 4000, stearic acid, cocoa butter and glycerin monostearate are added to riboflavin and melt-mixed at about 65°C. Add this molten mixture to 3
It is filled into a No. 3 capsule pode, and the No. 3 capsule cap made in Reference Example 3 is attached to this pode.
実施例３
成 分
ｍｇ／カプセル塩酸ジサイクロミン
２０硬化ヒマシ油 １５５ステア
リン酸 ７０乳糖
８０合計 ３２５
硬化ヒマシ油にステアリン酸を加え、約７０℃で溶融し
たのち塩酸ジサイクロミンと乳糖の混合物を加えて混合
する。この溶融混合物を３号カプセルのポデーに充填し
、このポデーに参考例３で製した３号カプセルキャップ
をする。Example 3 Ingredients
mg/capsule dicyclomine hydrochloride
20 hydrogenated castor oil 155 stearic acid 70 lactose
80 Total 325 Stearic acid is added to hydrogenated castor oil and melted at about 70°C, then a mixture of dicyclomine hydrochloride and lactose is added and mixed. This molten mixture is filled into a No. 3 capsule pode, and the No. 3 capsule cap prepared in Reference Example 3 is attached to the pode.
実施例４
成 分 ｍｇハブセルセ
ファクロル １８７ポリエチレン
グリコール１５００ １５６ステアリン酸
４２合計 ３８５
セファクロルにポリエチレングリコール１５００とステ
アリン酸を加え、約６０℃で溶融混合したのちこの溶卵
混合物を２号カプセルのポデーに充填し、このポデーに
参考例１で製した２号カプセルキャップをする。Example 4 Ingredients mg hubcelcefachlor 187 polyethylene glycol 1500 156 stearic acid
42 Total 385 Add polyethylene glycol 1500 and stearic acid to cefaclor, melt and mix at about 60°C, then fill the molten egg mixture into a No. 2 capsule pode, and insert the No. 2 capsule cap made in Reference Example 1 into the pode. do.
実施例５
成 分 ｍ
ｇ／カブｔＬセファクロル ２５
０ポリエチレングリコール１５００ ３６７ステ
アリン酸 ３３合計 ６
４０
ポリエチレングリコール１５００にステアリン酸を加え
、約６０℃で溶融したのちセファクロルを加えて混合し
、この溶融混合物を０号カプセルのポデーに充填し、こ
のポデーに参考例４で製したＯ号カプセルキャップをす
る。Example 5 Ingredient m
g/kabutL cefaclor 25
0 Polyethylene glycol 1500 367 Stearic acid 33 Total 6
40 Stearic acid was added to polyethylene glycol 1500, melted at about 60°C, cefaclor was added and mixed, the molten mixture was filled into a No. 0 capsule pode, and the No. O capsule cap prepared in Reference Example 4 was placed in this pode. do.
実施例６
成 分
ｍｇ／カプセルセファレキシン ２
５０ポリエチレングリコール１５４０ ３５０硬
化ヒマシ油 ３０アスフルビン
４０合計 ６７０
ポリエチレングリコール１５４０に硬化ヒマシ油を加え
、約６０°Ｃで熔融したのちセファレキシンとアスコル
ビン酸の混合物を加えて混合し、この溶融混合物を０号
カプセルのボデーに充填し、このボデーに参考例２で製
した０号カプセルキャップをする。Example 6 Ingredients
mg/capsule cephalexin 2
50 Polyethylene Glycol 1540 350 Hydrogenated Castor Oil 30 Asfulvin
40 total 670 Add hydrogenated castor oil to polyethylene glycol 1540 and melt it at about 60°C, then add and mix a mixture of cephalexin and ascorbic acid, fill the body of a No. 0 capsule with this molten mixture, and use this body as a reference. Put on the No. 0 capsule cap made in Example 2.
実施例７
成 分 １
１１ｇハブセル 、アモキシシリン
２００ポリエチレングリコール６０００
１９５ステアリン酸 ５５カカオ
１００合計 ５５０
ポリエチレングリコール６０００にステアリン酸、カカ
オ脂を加え、約６５℃で溶融したのちアモキシシリンを
加え混合し、この溶融混合物を１号カプセルのボデーに
充填し、このボデーに参考例５で製した１号カプセルキ
ャップをする。Example 7 Component 1
11g hubcell, amoxicillin
200 polyethylene glycol 6000
195 Stearic acid 55 Cacao 100 Total 550 Stearic acid and cacao butter are added to polyethylene glycol 6000, melted at approximately 65°C, amoxicillin is added and mixed, this molten mixture is filled into the body of No. 1 capsule, and this body is used as a reference. Put on the No. 1 capsule cap made in Example 5.
実施例８
成 分
ｍｇ／カプセルピンドロール
１０ポリエチレングリコール１５００ ２７３
ステアリン酸 ３７合計
３２０
ポリエチレングリコール１５００にステアリン酸を加え
、約６０°Ｃで溶融混合したのちピンドロールを加えて
十分混合する。この溶融混合物を３号カプセルのボデー
に充填し、このボデーに参考例８で製した３号カプセル
キャップをする。Example 8 Ingredients
mg/capsule pindolol
10 polyethylene glycol 1500 273
Stearic acid 37 total
320 Add stearic acid to polyethylene glycol 1500, melt and mix at about 60°C, then add pindolol and mix thoroughly. This molten mixture is filled into the body of a No. 3 capsule, and the No. 3 capsule cap prepared in Reference Example 8 is attached to this body.
実施例９
成 分
ｍｇ／カプセルメグゼパム
１０ポリエチレングリコール４０００ ２９４ス
テアリン酸 １６合計
３２０
ポリエチレングリコール４０００にステアリン酸を加え
、約６０℃で溶融混合したのちメタゼパムを加えて混合
する。この溶融混合物を３号カプセルのボデーに充填し
、このボデーに参考例１で製した３号カプセルキャップ
をする。Example 9 Ingredients
mg/capsule megzepam
10 Polyethylene Glycol 4000 294 Stearic Acid 16 Total
320 Add stearic acid to polyethylene glycol 4000, melt and mix at about 60°C, then add metazepam and mix. This molten mixture is filled into the body of a No. 3 capsule, and the No. 3 capsule cap prepared in Reference Example 1 is attached to this body.
実施例１０
成 分 ｍ
ｇハシセル沈降炭酸カルシウム １６７
ポリエチレングリコール１５４０ ３６３ステア
リルアルコール ２０合計 ５５０
ポリエチレングリコール１５４０にステアリルアルコー
ルを加え、約６０℃で溶融混合したのち沈降炭酸カルシ
ウムを加えて混合する。この溶融混合物を１号カプセル
のボデーに充填し、このボデーに参考例４で製した１号
カプセルキャップをする。Example 10 Ingredient m
g Hashicell precipitated calcium carbonate 167
Polyethylene glycol 1540 363 Stearyl alcohol 20 Total 550 Add stearyl alcohol to polyethylene glycol 1540, melt and mix at about 60°C, then add precipitated calcium carbonate and mix. This molten mixture is filled into the body of a No. 1 capsule, and the No. 1 capsule cap prepared in Reference Example 4 is attached to this body.
（以下余白）
参考例１
通常の医薬用２号または３号ゼラチン硬質カプセルのキ
ャップにオイドラギット＠５５重量部、エチルアルコー
ル９５重量部からなる溶液をスプレーガンとコーチング
パンの使用によりコーチングし、キャップ１個あたりオ
イドラギット＠５４ｍｇをコーチングした。(Leaving space below) Reference Example 1 A solution consisting of 55 parts by weight of Eudragit and 95 parts by weight of ethyl alcohol was coated on the cap of a regular pharmaceutical No. 2 or No. 3 hard gelatin capsule using a spray gun and a coaching pan, and Cap 1 Eudragit@54mg was coached per person.
参考例２
通常の医薬用０号ゼラチン硬質カプセルのキャップにエ
チルセルロース３重量部、エチルアルコール９７重量部
からなる溶液を参考例１と同様にコーチングしてキャッ
プ１個あたりエチルセルロース６ｍｇをコーチングした
。Reference Example 2 A solution consisting of 3 parts by weight of ethyl cellulose and 97 parts by weight of ethyl alcohol was coated on the cap of a regular pharmaceutical No. 0 hard gelatin capsule in the same manner as in Reference Example 1, so that 6 mg of ethyl cellulose was coated per cap.
参考例３
通常の医薬用２号または３号ゼラチン硬質カプセルのキ
ャップをオイドラギット＠Ｌ７重量部、エチルアルコー
ル９３重量部からなる溶液に浸漬したのち乾燥許せてキ
ャップ１個あたりオイドラギット＠Ｌ４ｍｇをコーチン
グした。Reference Example 3 Caps of ordinary pharmaceutical No. 2 or No. 3 hard gelatin capsules were immersed in a solution consisting of 7 parts by weight of Eudragit@L and 93 parts by weight of ethyl alcohol, allowed to dry, and coated with 4 mg of Eudragit@L per cap.
参考例４
通常の医薬用０号または１号ゼラチン硬質カプセルのキ
ャンプをオイドラギット＠Ｓ７重量部、ニブルアルフー
ル９３重量部からなる溶液に浸漬したのち乾燥させてキ
ャンプ１個あたり０号カプセルのキャップは５ｍｇ宛、
１号カプセルのキャップは４ｍｇ宛のオイドラギット＠
Ｓをコーチングした。Reference Example 4 A regular pharmaceutical No. 0 or No. 1 hard gelatin capsule Camp was immersed in a solution consisting of Eudragit@S7 parts by weight and Nibble Alfur 93 parts by weight, and then dried. To 5mg,
Cap of Capsule No. 1 is Eudragit @ 4 mg
I coached S.
参考例５
通常の医薬用１号ゼラチン硬質カプセルのキャンプをヒ
ドロキシプロピル、メチルセルロースフタレート６１ｉ
量部、アセトン／エチルアルコール（１：２）混合液９
４重量部からなる溶液に浸漬ｉ。Reference Example 5 The camp of ordinary pharmaceutical No. 1 gelatin hard capsules was mixed with hydroxypropyl and methylcellulose phthalate 61i.
Volume, acetone/ethyl alcohol (1:2) mixture 9
Immersion in a solution consisting of 4 parts by weight i.
たのも乾燥させてキャップ１個あたりヒドロキシプロピ
ルメチルセルロースブタレート５ｍｇをコーテングした
。The caps were dried and coated with 5 mg of hydroxypropyl methylcellulose butarate per cap.
第１．２および３図において、１．腸溶性皮膜、２．ゼ
ラチンカプセルキャップ、３、空間、４、ゼラチンカプ
セルボデー、５．溶融固化物、６６バンドシーノ呟 ７
．ロック、８１１％？ＩＦｉロツクイ寸カプセルキャッ
プ、９．ロツクイ寸ゼラチンカプセルポデーを示す。
特許出願人 塩野義製薬株式会社
第１図
ｊ
手続′Ｐ市正装置方式）
１、事件の表示
昭和６１年特許願第５０７８７号
２、発明の名称
胃内浮遊性持続型カプセル剤
３、補正をする者
事件との関係 特許出願人
住所 大阪府大阪市東区道修町３丁目１２番地塩野義製
薬株式会社 特許部
昭和６２年７月２８日（発送日）
６、補正の対象
明細書の図面の簡単な説明の欄。
７、補正の内容
明細書第２８頁第１行目と第２行目の間に以下を挿入す
る。
１第１〜第３図は本発明カプセル剤の断面図を示し、第
１図は腸溶性皮膜付カプセル剤を、第２図はバンドシー
ル付カプセル剤を、第３図はロック付カプセル剤をそれ
ぞれ示す、」
以上In Figures 1.2 and 3, 1. enteric coating, 2. Gelatin capsule cap, 3. Space, 4. Gelatin capsule body, 5. Melted and solidified material, 66 Bandsino Mutsu 7
．． Rock, 811%? IFi rotsukui size capsule cap, 9. Showing a gelatin capsule podium with a large size. Patent Applicant Shionogi & Co., Ltd. Figure 1j Procedure 'P Municipal Apparatus Method) 1. Indication of the incident Patent Application No. 50787 of 1985 2. Name of the invention Long-lasting capsules floating in the stomach 3. Amendment Relationship with the case involving the person who made the amendment Patent applicant address Shionogi & Co., Ltd. Patent Department 3-12 Doshomachi, Higashi-ku, Osaka-shi, Osaka Prefecture July 28, 1988 (shipment date) 6. Brief description of the drawings of the specification subject to amendment An explanation column. 7. Insert the following between the first and second lines of page 28 of the statement of contents of the amendment. 1. Figures 1 to 3 show cross-sectional views of capsules of the present invention. Figure 1 shows a capsule with an enteric coating, Figure 2 shows a capsule with a band seal, and Figure 3 shows a capsule with a lock. Each is shown above.
Claims (18)
を溶融したのち医薬活性成分を添加した混合物、あるい
はポリエチレングリコール類および／または油脂類と医
薬活性成分を混合溶融した混合物を、胃溶性硬質カプセ
ルボデー部に充填し、次いで胃不溶性硬質カプセルキャ
ップを該ボデー部分に、内部に空間を残す程度に被せて
製造したことを特徴とする胃内浮遊性持続型組成物。(1) A mixture obtained by melting polyethylene glycols and/or fats and oils and then adding a pharmaceutically active ingredient, or a mixture obtained by mixing and melting polyethylene glycols and/or fats and oils with a pharmaceutically active ingredient, into the body of a gastrically soluble hard capsule. 1. A long-lasting composition that floats in the stomach, characterized in that it is produced by filling the body portion with a gastroinsoluble hard capsule cap to the extent that a space is left inside.
ルアルコールまたはその混合物である特許請求の範囲第
１項に記載の組成物。(2) The composition according to claim 1, wherein the oil or fat is cocoa butter, stearic acid, cetyl alcohol, or a mixture thereof.
薬である特許請求の範囲第１項に記載の組成物。(3) The composition according to claim 1, wherein the pharmaceutically active ingredient is an oral drug that is desired to have a sustained action.
ン、セフアクロル、ピナシジル、ジアゼパムまたはシメ
チジンである特許請求の範囲第３項に記載の組成物。(4) The composition according to claim 3, wherein the pharmaceutically active ingredient is amoxicillin, cephalexin, cefaclor, pinacidil, diazepam or cimetidine.
たは胃不溶性基剤で製造されたカプセルキャップである
ことを特徴とする特許請求の範囲第１項に記載の組成物
。(5) The composition according to claim 1, wherein the gastroinsoluble hard capsule cap is a capsule cap made of an enteric base or a gastroinsoluble base.
は胃不溶性基剤でコーチングされたカプセルキャップで
あることを特徴とする特許請求の範囲第１項記載の組成
物。(6) The composition according to claim 1, wherein the gastroinsoluble hard capsule cap is coated with an enteric base or a gastroinsoluble base.
デーである特許請求の範囲第１項記載の組成物。(7) The composition according to claim 1, wherein the gastrically soluble hard capsule body is a gelatin capsule body.
ある特許請求の範囲第１項記載の組成物。(8) The composition according to claim 1, wherein the capsule is a capsule with a lock.
積に対して約５〜約４０％であることを特徴とする特許
請求の範囲第１項記載の組成物。(9) The composition according to claim 1, wherein the space left inside the capsule is about 5 to about 40% of the total internal volume of the capsule.
類を溶融したのち医薬活性成分を添加した混合物、ある
いはポリエチレングリコール類および／または油脂類と
医薬活性成分を混合溶融した混合物を、胃溶性硬質カプ
セルボデー部に充填し、次いで胃不溶性硬質カプセルキ
ャップを該ボデー部分に、内部に空間を残す程度に被せ
て製造する胃内浮遊性持続型組成物の製造法。(10) A mixture obtained by melting polyethylene glycols and/or fats and oils and then adding a pharmaceutically active ingredient, or a mixture obtained by mixing and melting polyethylene glycols and/or fats and oils and a pharmaceutically active ingredient, into the body of a gastrically soluble hard capsule. A method for producing a long-lasting composition that floats in the stomach, which comprises filling the body part with a gastric insoluble hard capsule cap to the extent that a space is left inside.
チルアルコールまたはその混合物である特許請求の範囲
第１０項に記載の製造法。(11) The production method according to claim 10, wherein the oil or fat is cocoa butter, stearic acid, cetyl alcohol, or a mixture thereof.
医薬である特許請求の範囲第１０項に記載の製造法。(12) The manufacturing method according to claim 10, wherein the pharmaceutically active ingredient is an oral drug that is desired to have a sustained action.
シン、セフアクロル、ピナシジル、ジアゼパムまたはシ
メチジンである特許請求の範囲第１０項に記載の製造法
。(13) The manufacturing method according to claim 10, wherein the pharmaceutically active ingredient is amoxicillin, cephalexin, cefaclor, pinacidil, diazepam or cimetidine.
または胃不溶性基剤で製造されたカプセルキャップであ
ることを特徴とする特許請求の範囲第１０項に記載の製
造法。(14) The manufacturing method according to claim 10, wherein the gastroinsoluble hard capsule cap is a capsule cap manufactured with an enteric base or a gastroinsoluble base.
たは胃不溶性基剤でコーチングされたカプセルキャップ
であることを特徴とする特許請求の範囲第１０項記載の
製造法。(15) The manufacturing method according to claim 10, wherein the gastroinsoluble hard capsule cap is a capsule cap coated with an enteric base or a gastroinsoluble base.
ボデーである特許請求の範囲第１０項記載の製造法。(16) The manufacturing method according to claim 10, wherein the gastrically soluble hard capsule body is a gelatin capsule body.
である特許請求の範囲第１０項記載の製造法。(17) The manufacturing method according to claim 10, wherein the capsule is a capsule with a lock.
容積に対して約５〜約４０％であることを特徴とする特
許請求の範囲第１０項記載の製造法。(18) The manufacturing method according to claim 10, wherein the space left inside the capsule is about 5 to about 40% of the total internal volume of the capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5078786A JPS6322014A (en) | 1986-03-07 | 1986-03-07 | Long-acting capsule drug floating in stomach |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5078786A JPS6322014A (en) | 1986-03-07 | 1986-03-07 | Long-acting capsule drug floating in stomach |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS6322014A true JPS6322014A (en) | 1988-01-29 |
Family
ID=12868523
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5078786A Pending JPS6322014A (en) | 1986-03-07 | 1986-03-07 | Long-acting capsule drug floating in stomach |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6322014A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6310719A (en) * | 1986-03-18 | 1988-01-18 | Dai Ichi Seiyaku Co Ltd | Slow-releasing capsule drug |
| WO2000051570A1 (en) * | 1999-02-26 | 2000-09-08 | Shionogi & Co., Ltd. | Chewable soft capsules having improved administration properties and process for producing the same |
| JP2013530200A (en) * | 2010-07-05 | 2013-07-25 | ヤゴテック アーゲー | Dosage form |
| JP2023516370A (en) * | 2020-03-02 | 2023-04-19 | クラフト ヘルス プライベート リミテッド | Oral dosage form for sustained drug release |
| WO2024019133A1 (en) * | 2022-07-22 | 2024-01-25 | クオリカプス株式会社 | Multilayered enteric rigid capsule |
-
1986
- 1986-03-07 JP JP5078786A patent/JPS6322014A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6310719A (en) * | 1986-03-18 | 1988-01-18 | Dai Ichi Seiyaku Co Ltd | Slow-releasing capsule drug |
| WO2000051570A1 (en) * | 1999-02-26 | 2000-09-08 | Shionogi & Co., Ltd. | Chewable soft capsules having improved administration properties and process for producing the same |
| US8372428B2 (en) | 1999-02-26 | 2013-02-12 | Shionogi & Co., Ltd. | Chewable soft capsule having improved ingestion property and method for producing same |
| JP2013530200A (en) * | 2010-07-05 | 2013-07-25 | ヤゴテック アーゲー | Dosage form |
| US9314430B2 (en) | 2010-07-05 | 2016-04-19 | Jagotec Ag | Floating gastric retentive dosage form |
| JP2017014257A (en) * | 2010-07-05 | 2017-01-19 | ヤゴテック アーゲー | Dosage form |
| US10076500B2 (en) | 2010-07-05 | 2018-09-18 | Jagotec Ag | Floating gastric retentive dosage form |
| JP2023516370A (en) * | 2020-03-02 | 2023-04-19 | クラフト ヘルス プライベート リミテッド | Oral dosage form for sustained drug release |
| WO2024019133A1 (en) * | 2022-07-22 | 2024-01-25 | クオリカプス株式会社 | Multilayered enteric rigid capsule |
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