JPS6144810A - Enteric soft capsule - Google Patents
Enteric soft capsuleInfo
- Publication number
- JPS6144810A JPS6144810A JP59166916A JP16691684A JPS6144810A JP S6144810 A JPS6144810 A JP S6144810A JP 59166916 A JP59166916 A JP 59166916A JP 16691684 A JP16691684 A JP 16691684A JP S6144810 A JPS6144810 A JP S6144810A
- Authority
- JP
- Japan
- Prior art keywords
- enteric
- soft capsule
- outer film
- crosslinkable polysaccharide
- base
- 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
- 239000007901 soft capsule Substances 0.000 title claims abstract description 49
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 19
- 239000005017 polysaccharide Substances 0.000 claims abstract description 19
- 150000001768 cations Chemical class 0.000 claims abstract description 12
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 11
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 11
- 239000000661 sodium alginate Substances 0.000 claims abstract description 11
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 11
- 150000005846 sugar alcohols Polymers 0.000 claims abstract description 7
- 229910001424 calcium ion Inorganic materials 0.000 claims abstract description 4
- 150000004676 glycans Chemical class 0.000 claims abstract 7
- 239000012752 auxiliary agent Substances 0.000 claims description 11
- PYMYPHUHKUWMLA-UHFFFAOYSA-N 2,3,4,5-tetrahydroxypentanal Chemical compound OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 claims description 6
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 13
- 230000032050 esterification Effects 0.000 abstract description 2
- 238000005886 esterification reaction Methods 0.000 abstract description 2
- 238000010348 incorporation Methods 0.000 abstract 1
- 239000013067 intermediate product Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 26
- 239000003921 oil Substances 0.000 description 21
- 235000019198 oils Nutrition 0.000 description 21
- 239000011162 core material Substances 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 15
- 235000011187 glycerol Nutrition 0.000 description 12
- 150000004804 polysaccharides Chemical class 0.000 description 12
- 239000008213 purified water Substances 0.000 description 12
- 238000004132 cross linking Methods 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- 239000000463 material Substances 0.000 description 11
- 239000011824 nuclear material Substances 0.000 description 10
- 108010010803 Gelatin Proteins 0.000 description 9
- 239000002775 capsule Substances 0.000 description 9
- 229920000159 gelatin Polymers 0.000 description 9
- 239000008273 gelatin Substances 0.000 description 9
- 235000019322 gelatine Nutrition 0.000 description 9
- 235000011852 gelatine desserts Nutrition 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- -1 alginic acid salts Chemical class 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 6
- 239000000600 sorbitol Substances 0.000 description 6
- 239000003549 soybean oil Substances 0.000 description 6
- 235000012424 soybean oil Nutrition 0.000 description 6
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 5
- 235000010356 sorbitol Nutrition 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
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 4
- 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 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000001110 calcium chloride Substances 0.000 description 3
- 229910001628 calcium chloride Inorganic materials 0.000 description 3
- 235000011148 calcium chloride Nutrition 0.000 description 3
- 239000007765 cera alba Substances 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 235000007682 pyridoxal 5'-phosphate Nutrition 0.000 description 3
- 239000011589 pyridoxal 5'-phosphate Substances 0.000 description 3
- 229960001327 pyridoxal phosphate Drugs 0.000 description 3
- 229940042585 tocopherol acetate Drugs 0.000 description 3
- 239000001993 wax Substances 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 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- BALXUFOVQVENIU-GNAZCLTHSA-N Ephedrine hydrochloride Chemical compound Cl.CN[C@@H](C)[C@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-GNAZCLTHSA-N 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 235000019484 Rapeseed oil Nutrition 0.000 description 2
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 235000013871 bee wax Nutrition 0.000 description 2
- 239000012166 beeswax Substances 0.000 description 2
- 239000004203 carnauba wax Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229960002534 ephedrine hydrochloride Drugs 0.000 description 2
- 229960002061 ergocalciferol Drugs 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- 229960003276 erythromycin Drugs 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 2
- 229960004172 pyridoxine hydrochloride Drugs 0.000 description 2
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 2
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 2
- 229960000342 retinol acetate Drugs 0.000 description 2
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 2
- 235000019173 retinyl acetate Nutrition 0.000 description 2
- 239000011770 retinyl acetate Substances 0.000 description 2
- 229960002477 riboflavin Drugs 0.000 description 2
- 235000019192 riboflavin Nutrition 0.000 description 2
- 239000002151 riboflavin Substances 0.000 description 2
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 2
- 229960000344 thiamine hydrochloride Drugs 0.000 description 2
- 235000019190 thiamine hydrochloride Nutrition 0.000 description 2
- 239000011747 thiamine hydrochloride Substances 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 2
- 235000001892 vitamin D2 Nutrition 0.000 description 2
- 239000011653 vitamin D2 Substances 0.000 description 2
- NNRXCKZMQLFUPL-WBMZRJHASA-N (3r,4s,5s,6r,7r,9r,11r,12r,13s,14r)-6-[(2s,3r,4s,6r)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2r,4r,5s,6s)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione;(2r,3 Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O.O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 NNRXCKZMQLFUPL-WBMZRJHASA-N 0.000 description 1
- SKDGGFHGLZBNBC-YZPBMOCRSA-N (3r,4s,5s,6r,7r,9r,11r,12r,13s,14r)-6-[(2s,3r,4s,6r)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2r,4r,5s,6s)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione;dodec Chemical compound CCCCCCCCCCCCOS(O)(=O)=O.O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 SKDGGFHGLZBNBC-YZPBMOCRSA-N 0.000 description 1
- KMZHZAAOEWVPSE-UHFFFAOYSA-N 2,3-dihydroxypropyl acetate Chemical compound CC(=O)OCC(O)CO KMZHZAAOEWVPSE-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- AEMOLEFTQBMNLQ-DTEWXJGMSA-N D-Galacturonic acid Natural products O[C@@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-DTEWXJGMSA-N 0.000 description 1
- HEBKCHPVOIAQTA-QWWZWVQMSA-N D-arabinitol Chemical compound OC[C@@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-QWWZWVQMSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 239000004348 Glyceryl diacetate Substances 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
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- BRZANEXCSZCZCI-UHFFFAOYSA-N Nifenazone Chemical compound O=C1N(C=2C=CC=CC=2)N(C)C(C)=C1NC(=O)C1=CC=CN=C1 BRZANEXCSZCZCI-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 1
- IDIDJDIHTAOVLG-VKHMYHEASA-N S-methylcysteine Chemical compound CSC[C@H](N)C(O)=O IDIDJDIHTAOVLG-VKHMYHEASA-N 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- 108010038346 Seaprose S Proteins 0.000 description 1
- YTGJWQPHMWSCST-UHFFFAOYSA-N Tiopronin Chemical compound CC(S)C(=O)NCC(O)=O YTGJWQPHMWSCST-UHFFFAOYSA-N 0.000 description 1
- 108010058907 Tiopronin Proteins 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 229920001284 acidic polysaccharide Polymers 0.000 description 1
- 150000004805 acidic polysaccharides Chemical class 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 235000010407 ammonium alginate Nutrition 0.000 description 1
- 239000000728 ammonium alginate Substances 0.000 description 1
- KPGABFJTMYCRHJ-YZOKENDUSA-N ammonium alginate Chemical compound [NH4+].[NH4+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O KPGABFJTMYCRHJ-YZOKENDUSA-N 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- AEMOLEFTQBMNLQ-UHFFFAOYSA-N beta-D-galactopyranuronic acid Natural products OC1OC(C(O)=O)C(O)C(O)C1O AEMOLEFTQBMNLQ-UHFFFAOYSA-N 0.000 description 1
- XSEUMFJMFFMCIU-UHFFFAOYSA-N buformin Chemical compound CCCC\N=C(/N)N=C(N)N XSEUMFJMFFMCIU-UHFFFAOYSA-N 0.000 description 1
- 229960004111 buformin Drugs 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 1
- 239000001639 calcium acetate Substances 0.000 description 1
- 235000011092 calcium acetate Nutrition 0.000 description 1
- 229960005147 calcium acetate Drugs 0.000 description 1
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 235000011116 calcium hydroxide Nutrition 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 235000013869 carnauba wax Nutrition 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000000110 cooling liquid Substances 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 229940099371 diacetylated monoglycerides Drugs 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
- IKALZAKZWHFNIC-JIZZDEOASA-L dipotassium;(2s)-2-aminobutanedioate Chemical compound [K+].[K+].[O-]C(=O)[C@@H](N)CC([O-])=O IKALZAKZWHFNIC-JIZZDEOASA-L 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 229960000741 erythromycin ethylsuccinate Drugs 0.000 description 1
- NSYZCCDSJNWWJL-YXOIYICCSA-N erythromycin ethylsuccinate Chemical compound O1[C@H](C)C[C@H](N(C)C)[C@@H](OC(=O)CCC(=O)OCC)[C@@H]1O[C@H]1[C@@](O)(C)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@](C)(O)[C@@H](CC)OC(=O)[C@H](C)[C@@H](O[C@@H]2O[C@@H](C)[C@H](O)[C@](C)(OC)C2)[C@@H]1C NSYZCCDSJNWWJL-YXOIYICCSA-N 0.000 description 1
- 229960004213 erythromycin lactobionate Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- PGBHMTALBVVCIT-VCIWKGPPSA-N framycetin Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VCIWKGPPSA-N 0.000 description 1
- 235000019443 glyceryl diacetate Nutrition 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- UXNFIJPHRQEWRQ-UHFFFAOYSA-N hexamethylenetetramine mandelate salt Chemical compound C1N(C2)CN3CN1CN2C3.OC(=O)C(O)C1=CC=CC=C1 UXNFIJPHRQEWRQ-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229960001913 mecysteine Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 235000019691 monocalcium phosphate Nutrition 0.000 description 1
- 229910000150 monocalcium phosphate Inorganic materials 0.000 description 1
- 239000012170 montan wax Substances 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- NXFQHRVNIOXGAQ-YCRREMRBSA-N nitrofurantoin Chemical compound O1C([N+](=O)[O-])=CC=C1\C=N\N1C(=O)NC(=O)C1 NXFQHRVNIOXGAQ-YCRREMRBSA-N 0.000 description 1
- 229960000564 nitrofurantoin Drugs 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 229960001476 pentoxifylline Drugs 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical class OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 235000010408 potassium alginate Nutrition 0.000 description 1
- 239000000737 potassium alginate Substances 0.000 description 1
- MZYRDLHIWXQJCQ-YZOKENDUSA-L potassium alginate Chemical compound [K+].[K+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O MZYRDLHIWXQJCQ-YZOKENDUSA-L 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- 229940028870 thiola Drugs 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 150000005691 triesters Chemical group 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Landscapes
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
【発明の詳細な説明】
産業上の利用分野
本発明は、腸溶性軟カプセルに関し、更に詳しくは非ゼ
ラチン系腸溶性軟カプセルに関する。DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to enteric-coated soft capsules, and more particularly to non-gelatin enteric-coated soft capsules.
従来の技術
従来、腸溶性軟カプセルとしては、ゼラチン基剤の軟カ
プセルをホルマリン処理するか腸溶性物質でコーティン
グしたもの、または腸溶性高分子化合物を基剤として軟
カプセル化したものなどがあるが、その作業性または外
皮膜の性状は満足すべきものではなかった′。Conventional technology Conventionally, enteric-coated soft capsules include gelatin-based soft capsules treated with formalin or coated with enteric substances, or soft capsules made of enteric-coated polymer compounds as a base. However, the workability and properties of the outer coating were not satisfactory.
これらの腸溶性軟カプセルの欠点を改善するものとして
、ゼラチンと水溶性多価アルコールまたは、′その誘導
体からなる基剤に低メトキシルペクチンまたはアルギン
酸ナトリウムを配合し、シームレスカプセル死後２価以
上の陽イオンで硬化させた腸溶性軟カプセルが開示され
た（特開昭５８−１７２３１３）。 ″
発明が解決しようとする問題点
しかし々がら、この腸溶性軟カプセルは、基剤にゼラチ
ンを使用しているため、低メトキシルペクチンまたはア
ルギン酸ナトリウムと、ゼラチンとの配合比に厳しい制
約があって、その制約の範囲外では作業性が悪くなった
り、あるいは外皮膜の腸溶性を損ない、保存安定性を低
下させるなどの支障がある。まだ、その製造工程におい
て、二重液滴法を利用して核物質をシームレス・カプセ
ルに封入するには基剤の加温融解が必要となる。In order to improve the shortcomings of these enteric-coated soft capsules, low methoxyl pectin or sodium alginate is blended into a base consisting of gelatin and water-soluble polyhydric alcohol or its derivatives, and after death the seamless capsule contains divalent or higher cations. An enteric-coated soft capsule cured with 100% was disclosed (Japanese Patent Application Laid-Open No. 58-172313). ``Problems to be Solved by the Invention However, since these enteric-coated soft capsules use gelatin as the base material, there are severe restrictions on the blending ratio of low methoxyl pectin or sodium alginate to gelatin. However, outside these constraints, there are problems such as poor workability, loss of enteric properties of the outer coating, and decreased storage stability. In order to encapsulate nuclear material into seamless capsules, heating and melting of the base material is required.
製造しだてのシームレス・カプセルは、その外皮膜が粘
稠、軟弱でこのままでは水の作用を受けやすいので、直
ちに架橋硬化液により外皮膜を架橋硬化して、シームレ
ス・カプセルを腸溶化させることができない。従って、
このシームレス・カプセルを油性冷却液中に投じて外皮
膜を冷却硬化さぜ、これを一旦系外に取り出した後でな
ければ、次の架橋硬化（腸溶化）の工程に移行できない
。The outer shell of a freshly manufactured seamless capsule is viscous and soft, and is susceptible to the action of water if left as is. Therefore, the outer shell should be immediately cross-linked and hardened with a cross-linking curing liquid to entericize the seamless capsule. I can't. Therefore,
This seamless capsule is poured into an oil-based cooling liquid to cool and harden the outer coating, and must be taken out of the system before it can proceed to the next step of crosslinking and hardening (entericization).
すなわち、との腸溶性軟カプセルの製造においては、作
業の中断を伴い、−貫して連続作業を行なうことかでき
ないので、製造コストの増矢を招くという欠点がある。That is, in the production of enteric-coated soft capsules, the process is interrupted and the process cannot be carried out continuously, resulting in an increase in production costs.
問題点を解決するための手段
本発明者は、との腸溶性軟カプセルの欠点を解消すべく
鋭意研究の結果、配合上支障を招きやすいゼラチンを全
く使用せず、２価以上の陽イオンにより架橋硬化する架
橋性多糖類またはこれと助剤よりなる基剤を用いること
により、作業を中断することなく性状がすぐれた腸溶性
軟カプセルを製造できることを見出だし、本発明を完成
した。Means for Solving the Problems As a result of intensive research in order to resolve the drawbacks of enteric-coated soft capsules, the present inventor did not use gelatin at all, which tends to cause problems when blending, and instead created capsules containing divalent or higher cations. The present invention has been completed based on the discovery that enteric-coated soft capsules with excellent properties can be produced without interrupting work by using a crosslinkable polysaccharide that cures by crosslinking or a base consisting of this and an auxiliary agent.
本発明の軟カプセルは、架橋性多糖類またはこれと助剤
からなる非ゼラチン系基剤により形成したシームレス外
皮膜を２価以上の陽イオンにより硬化させた腸溶性軟カ
プセルである。The soft capsules of the present invention are enteric-coated soft capsules in which a seamless outer shell film formed from a non-gelatinous base consisting of a crosslinkable polysaccharide or this and an auxiliary agent is hardened with divalent or higher cations.
本発明において、架橋性多糖類とは、後記の２価以上の
陽イオンによって架橋されて硬化する水溶性の多糖類を
いう。たとえば、細胞間粘質多糖類、Ｄ−ガラクツロン
酸のα１→４結合からなる酸性多糖類など、または、こ
れらの塩や誘導体を挙げることができるが、好ましくは
アルギン酸ナトリウム、カルンウム含有アルギン酸ナト
リウム。In the present invention, the crosslinkable polysaccharide refers to a water-soluble polysaccharide that is crosslinked and hardened by divalent or higher cations described below. Examples include intercellular mucilage polysaccharides, acidic polysaccharides consisting of α1→4 bonds of D-galacturonic acid, and salts and derivatives thereof, but sodium alginate and carunium-containing sodium alginate are preferred.
アルギン酸カリウム、アルギン酸アンモニウムなどのア
ルギン酸水溶性塩；エステル化度２０〜４５％の低メト
キシルペクチンなどである。Water-soluble alginic acid salts such as potassium alginate and ammonium alginate; low methoxyl pectin with a degree of esterification of 20 to 45%, and the like.
助剤とは、カプセル外皮膜の性状を改善するだめの添加
剤をいい、外皮膜に可塑性を付与し、また腸溶速度をコ
ントロールする。たとえば、水溶性多価アルコール類、
グリ七ロール脂肪酸エステル類、アセチル化モノグリセ
ライド類、フタル酸エステル類、クエン酸エステル類な
どを挙げることができるが、好ましくは、グリセロール
、エリスリトール、アラビトール、ソルビトール、プロ
ピレングリコール、ポリプロピレングリコール。Auxiliary agents refer to additives that improve the properties of the outer shell of the capsule, impart plasticity to the outer shell, and control the rate of enteric dissolution. For example, water-soluble polyhydric alcohols,
Examples include glycerol fatty acid esters, acetylated monoglycerides, phthalate esters, citric acid esters, etc., but preferred are glycerol, erythritol, arabitol, sorbitol, propylene glycol, and polypropylene glycol.
エチレングリコール、ポリエチレングリコールなどの２
〜６価の多価アルコール：アセチン、ジアセチン、トリ
アセチンなどのグリセロール脂肪酸エステルなどである
。2 such as ethylene glycol and polyethylene glycol
- Hexavalent polyhydric alcohol: glycerol fatty acid esters such as acetin, diacetin, and triacetin.
非ゼラチン系基剤とはゼラチンを全く含くまない基剤を
いう。基剤は前記架橋性多糖類の水溶液捷たはこれに助
剤を加えたものをいう。必要に応じて更に常用の着色剤
、充填剤、滑剤、矯味矯臭剤などを加えることができる
。核物質をシームレスに被覆してシームレス軟カプセル
の外皮膜を形成し、後記２価以上の陽イオンによって架
橋されて硬化し、腸溶性皮膜に変る。A non-gelatin base is a base that does not contain any gelatin. The base refers to an aqueous solution of the crosslinkable polysaccharide mentioned above, or a solution to which an auxiliary agent is added. If necessary, conventional coloring agents, fillers, lubricants, flavoring agents, etc. can be added. The core substance is seamlessly coated to form an outer shell of a seamless soft capsule, which is crosslinked and hardened by divalent or higher cations described below, turning into an enteric coat.
２価以上の陽イオンとは、生理学的に許容することがで
きる金属のイオンであって、たとえば、マグネシウム、
カルシウム、ストロンチウム、バリウム、鉄、アルミニ
ウムなどを使用できるが、カルシウム・イオンが最も好
ましい。Divalent or higher cations are physiologically acceptable metal ions, such as magnesium,
Calcium, strontium, barium, iron, aluminum, etc. can be used, but calcium ions are most preferred.
カルシウム・イオンを賦与する化合物としては塩化カル
シウム、酢酸カルシウム、水酸化カルシウム、第一リン
酸カルシウム、第ニリン酸カルシウム、第三リン酸カル
シウム、乳酸カルシウムなどの水溶性カルシウム塩があ
るが、好捷しくけ塩化カルシウムである。Compounds that provide calcium ions include water-soluble calcium salts such as calcium chloride, calcium acetate, calcium hydroxide, monocalcium phosphate, dibasic calcium phosphate, tribasic calcium phosphate, and calcium lactate. be.
本発明の軟カプセルにおいては、基剤は架橋性多糖類の
適宜の濃度の水溶液またはこれと適宜の量の助剤からな
る。たとえば、アルギン酸ナトリウムならば基剤の１〜
１０重量％、好ましくけ２〜６重量％；低メトキシルペ
クチンならば基剤の１〜２０重量％、好ましくは１０〜
１５重量％用いる。助剤を用いる場合は、基剤の１０重
量％以下で、架橋性多糖類の０８５〜５重量倍用いる。In the soft capsule of the present invention, the base consists of an aqueous solution of a crosslinkable polysaccharide at an appropriate concentration or an appropriate amount of an auxiliary agent. For example, in the case of sodium alginate, the base 1 to
10% by weight, preferably 2-6% by weight; 1-20% by weight, preferably 10-20% by weight of the base for low methoxyl pectin
Use 15% by weight. When using an auxiliary agent, it is used in an amount of 10% by weight or less of the base, and 0.85 to 5 times the weight of the crosslinkable polysaccharide.
基剤は前記の２価以上の陽イオンを含む架橋硬化剤によ
って架橋されて硬化し、腸溶性の皮膜となる。The base is crosslinked and hardened by the crosslinking curing agent containing the above divalent or higher cation, forming an enteric coating.
架橋硬化剤として、前記２価以上の陽イオンを賦与する
化合物を１〜３０％、好ましくは５〜１０％を含む水溶
液を用いる。As the crosslinking curing agent, an aqueous solution containing 1 to 30%, preferably 5 to 10%, of the compound imparting divalent or higher cations is used.
架橋性多糖類のみからなる基剤は作業性が良好で、得ら
れた外皮膜の耐水性がきわめて大である。A base consisting only of crosslinkable polysaccharides has good workability, and the resulting outer film has extremely high water resistance.
従って、基剤の濃度を適宜増減することによって外皮膜
の厚さを加減し、腸における溶解時間を調整することが
できる。Therefore, by appropriately increasing or decreasing the concentration of the base agent, the thickness of the outer coat can be adjusted and the dissolution time in the intestine can be adjusted.
まだ、架橋性多糖類と助剤からなる基剤は、外皮膜の耐
水性が架橋性多糖類のみからなるものよりも小さくなる
。従って、助剤の添加量を適宜増減することによって、
腸における溶解時間を調整することができる。However, a base consisting of a crosslinkable polysaccharide and an auxiliary agent has a lower water resistance of the outer film than one consisting only of a crosslinkable polysaccharide. Therefore, by appropriately increasing or decreasing the amount of auxiliary agent added,
Dissolution time in the intestine can be adjusted.
本発明の軟カプセルは油性または水性の核物質を内蔵す
ることができる。The soft capsules of the present invention can contain oily or aqueous core materials.
油性の核物質は、油性薬物（たとえば、エリスロマイシ
ン、エリスロマイシンエチルサクシネート、エリスｂマ
イシンラクトビオネートペロピノイル、エリスロマイシ
ンラウリルサルフェート。Oily core substances are oily drugs such as erythromycin, erythromycin ethyl succinate, erythromycin lactobionate peropinoyl, erythromycin lauryl sulfate.
ペントキシフィリン、ニトロフラントイン、ニコチノイ
ルアンチピリン、アスピリン、リン酸ピリドキサール、
ビタミンＡ油、酢酸レチノール、エルゴカルシフェロー
ル、酢酸トコフェロール、リボフラビン、ニフェジピン
など）を油脂類（たとえば、ゴマ油、トウモロコシ油、
大豆油、ナタネ油、オリーブ油、ヤシ油、落花生油、硬
化油などの植物油；魚油、牛脂、豚脂、羊油などの動物
油）。Pentoxifylline, nitrofurantoin, nicotinoylantipyrine, aspirin, pyridoxal phosphate,
Vitamin A oil, retinol acetate, ergocalciferol, tocopherol acetate, riboflavin, nifedipine, etc.) and fats and oils (e.g., sesame oil, corn oil,
vegetable oils such as soybean oil, rapeseed oil, olive oil, coconut oil, peanut oil, and hydrogenated oils; animal oils such as fish oil, beef tallow, lard, and sheep oil).
ロウ類（たとえば、カーナバロウ、パームロウ。Waxes (e.g. carnauba wax, palm wax).
さとうきびロウ、ミツロウ、サラシミツロウ、羊毛脂、
モンタンロウなど）、グリセロール中鎖脂肪酸エステル
したとえば、サンソフ）Ｎα７００Ｆ−２（商品名、モ
ノエステル体、太陽化学■製）、パナセー）８１０（商
品名、トリエステル体１日本油脂■製〕などの単独また
は２種以上の混合物と混融することにより調製する。Sugar cane wax, beeswax, white beeswax, wool fat,
montan wax, etc.), glycerol medium chain fatty acid esters such as Sansof) Nα700F-2 (trade name, monoester form, manufactured by Taiyo Kagaku ■), Panase) 810 (trade name, triester form 1 manufactured by NOF ■), etc. Alternatively, it is prepared by mixing and melting two or more kinds of mixtures.
水性の核物質は、水性薬物（たとえば、塩化カリウム、
チオラ、Ｌ−アスパラギン酸カリウム。The aqueous core material is a water-based drug (e.g., potassium chloride,
Thiola, potassium L-aspartate.
メチルシスティン、マンデル酸へキサミン、フロトポル
フィリンナトリウム、ブホルミン、フラジオマイシン、
キモトリプシン、セアプローゼＳ。Methylcysteine, hexamine mandelate, flotoporphyrin sodium, buformin, fradiomycin,
Chymotrypsin, Seaprose S.
プロメライン、 Ａ Ｔ Ｐ −２Ｎａ、 ＦＤＡ
、塩酸エフェドリン、アスコルビン酸、塩酸チアミン、
リン酸ピリドキサール、塩酸ピリドキシンなど）を水溶
性多価アルコール（たとえば、グリセロール、エリスリ
トール、ソルビトール、ポリエチレングリコールなど）
、水溶性セルロース誘導体（たとえば、ヒドロキシプロ
ピルセルロース、カルボキシメチルセルロースなど）な
どの水溶液に混溶することにより調製する。Promeline, ATP-2Na, FDA
, ephedrine hydrochloride, ascorbic acid, thiamine hydrochloride,
Pyridoxal phosphate, pyridoxine hydrochloride, etc.) and water-soluble polyhydric alcohols (e.g., glycerol, erythritol, sorbitol, polyethylene glycol, etc.)
It is prepared by mixing in an aqueous solution of a water-soluble cellulose derivative (eg, hydroxypropyl cellulose, carboxymethyl cellulose, etc.).
本発明の軟カプセルは、たとえば次の方法で製造するこ
とができる。The soft capsule of the present invention can be manufactured, for example, by the following method.
（１）基剤の調製
架橋性多糖類またはこれと助剤を所定量秤取し、湯浴上
で加温しながらこれに精製水を少量ずつ添加しながら溶
解し、所定濃度に達したら室温まで冷却し、必要があれ
ばその他の添加剤を加えて透明粘稠な基剤を調製する。(1) Preparation of the base Weigh out a predetermined amount of the crosslinkable polysaccharide or it and the auxiliary agent, and dissolve it while heating it on a hot water bath while adding purified water little by little. When the predetermined concentration is reached, it will be at room temperature. Cool to a temperature and add other additives if necessary to prepare a transparent viscous base.
（２）核物質の調製
■油性核物質の調製
油脂類、ロウ類、グリセロール中鎖脂肪酸エステル類な
どを所定量秤取し、湯浴上で加温しながら溶解し、室温
近くまで冷却してから所定量の油性薬物を添加して均一
に混合または溶解し、油性核物質を調製する。(2) Preparation of nuclear material ■ Preparation of oily nuclear material Weigh out a specified amount of oils and fats, waxes, glycerol medium chain fatty acid esters, etc., dissolve while heating on a hot water bath, and cool to near room temperature. A predetermined amount of oily drug is added and uniformly mixed or dissolved to prepare an oily core substance.
■水性核物質の調製
水溶性多価アルコール、水溶性セルロース誘導体などを
所定量秤取し、湯浴上で加温しながら精製水の必要量の
％を少量ずつ添加して溶解し、生成した粘稠液を室温ま
で放冷する。これに所定量の水性薬物を添加して均一に
混合または溶解し、精製水の残量を加えて水性核物質を
調製する。■Preparation of aqueous nuclear material A predetermined amount of water-soluble polyhydric alcohol, water-soluble cellulose derivative, etc. was weighed out, and while heating it on a hot water bath, % of the required amount of purified water was added little by little to dissolve it. Allow the viscous liquid to cool to room temperature. A predetermined amount of the aqueous drug is added thereto, mixed or dissolved uniformly, and the remaining amount of purified water is added to prepare an aqueous core material.
（３）軟カプセルの製造
■同軸二重ノズルを備えたシーム【／ス軟カプセル製造
機（たとえば、グローペックス社製シームレス軟カプセ
ル製造機ＭａｒｋＩＩ など）を使用する。(3) Manufacture of soft capsules ■ A Seam soft capsule manufacturing machine equipped with a coaxial double nozzle (for example, Seamless soft capsule manufacturing machine Mark II manufactured by Growpex) is used.
同軸二重ノズルの外側ノズルには基剤を通し、内側ノズ
ルに核物質を通し、下方の油性キャリヤー（たとえば、
大豆油、ナタネ油、トウモロコシ油力どの植物油：流動
パラフィン類；パナセート８１０、サンソフトＮα７０
０Ｆ−２などのグリセロール中鎖脂肪酸エステル類など
）と架橋硬化剤とが重なった二層に向って基剤と核物質
を同時に押し出す。油性キャリヤーと架橋硬化剤は常温
に保ってあればよく、冷却しておく必要はない。The outer nozzle of the coaxial dual nozzle passes the base material, the inner nozzle passes the core material, and the lower oil carrier (e.g.
Vegetable oils such as soybean oil, rapeseed oil, and corn oil: Liquid paraffins; Panacet 810, Sunsoft Nα70
The base material and the core material are simultaneously extruded toward two overlapping layers of a glycerol medium chain fatty acid ester such as 0F-2) and a crosslinking curing agent. The oil-based carrier and crosslinking curing agent need only be kept at room temperature and do not need to be cooled.
■基剤が低粘度の場合には、前記二重ノズルの先端を油
性キャリヤーの上方に保ち、基剤と核物質を前記二重の
ノズルの先端から滴々と空中に滴下させる。(2) When the base has a low viscosity, the tip of the double nozzle is kept above the oil carrier, and the base and the core material are dripped into the air from the tip of the double nozzle.
空中で生成した二重液滴は空中を落下する間にほぼ球状
となり、油性キャリヤーの中を落下する間に更にその形
状を整える。油性キャリヤーの下層の架橋硬化剤をかな
シ強く攪拌すると、油性キャリヤーと架橋硬化剤との界
面においては、油性キャリヤーが逆さの円錐状となって
架橋硬化剤にくいこむ。すなわち、中央部では油性キャ
リヤーが渦巻いて垂れ下り、周囲では架橋硬化剤が盛シ
上って来る。二重液滴は落下の勢いと中央部の渦巻きの
吸引力とによって、油性キャリヤーの界面を突き抜けて
架橋硬化剤中に容易に移行する。The double droplets formed in the air become approximately spherical while falling through the air, and further refine their shape while falling through the oil carrier. When the cross-linked curing agent in the lower layer of the oil-based carrier is vigorously stirred, the oil-based carrier forms an inverted conical shape at the interface between the oil-based carrier and the cross-linked curing agent and embeds the cross-linked curing agent. That is, the oil-based carrier swirls and hangs down in the center, and the crosslinked curing agent rises up around the periphery. The double droplet easily penetrates the interface of the oily carrier and transfers into the crosslinked curing agent due to the force of the fall and the suction force of the central swirl.
（気中落下方式）
■基剤が高粘度の場合には、前記二重ノズルの先端を油
性キャリヤーの中に浸し、油性キャリヤーを下方に向け
て環流しながら前記二重ノズルの先端から基剤と核物質
を同時に油性キャリヤー中に送り出す。この二重液は油
性キャリヤーの流れによって引き伸ばされた後、切断さ
れて二重液滴が生成し、油性キャリヤー中を移動して行
く途中で球状に整形される。下層の架橋剤を軽く攪拌す
ると、■と同様の現象が生じ、二重液滴は送り出しの勢
いと中央部の渦巻きの吸引力とによって油性キャリヤー
の界面を突き抜けて架橋硬化剤中に移行する。（液中落
下方式）
■前項■まだは■で架橋硬化剤に移行した二重液滴を１
〜６０分間そのままに保ち、その外皮膜を架橋して硬化
する。これを取シ出して水洗いし、変形を防ぐため比較
的低温（２０〜４０℃で、１〜３日間、好ましくは２日
間乾燥して本発明の腸溶性軟カプセルを同軸二重ノズル
の径を変化させるか、または基剤や核物質の粘性を変化
させることにより任意の径、好ましくは０．５〜１１圏
の径の腸溶性軟カプセルを製造することができる。(Air drop method) ■If the base material has a high viscosity, dip the tip of the double nozzle into the oil-based carrier, and while the oil-based carrier is refluxed downward, pour the base material from the tip of the double nozzle. and nuclear material simultaneously into an oil-based carrier. This double liquid is stretched by the flow of the oil carrier and then cut to form double droplets, which are shaped into a spherical shape while traveling through the oil carrier. When the cross-linking agent in the lower layer is lightly stirred, a phenomenon similar to that described in (2) occurs, and the double droplets penetrate the interface of the oil carrier and migrate into the cross-linked curing agent due to the force of the sending out and the suction force of the swirl in the center. (Drop in liquid method) ■Double droplets transferred to the crosslinked curing agent in the previous section■Madaha■
Hold for ~60 minutes to crosslink and cure the outer film. The capsules are taken out, washed with water, and dried at a relatively low temperature (20 to 40°C for 1 to 3 days, preferably 2 days to prevent deformation). Enteric-coated soft capsules of any diameter, preferably in the range of 0.5 to 11, can be produced by changing the viscosity of the base material or core substance.
たとえば、同軸二重ノズルを使用する場合には、内側ノ
ズルの径を０５〜８匍、外側ノズルの径を１〜１７ヴに
することにより径０５〜１４喘の腸溶性軟カプセルを得
ることができる。For example, when using a coaxial double nozzle, enteric-coated soft capsules with a diameter of 05 to 14 mm can be obtained by setting the diameter of the inner nozzle to 0.5 to 8 mm and the diameter of the outer nozzle to 1 to 17 mm. can.
作 用
本発明の軟カプセルは水および局方第１液には溶解せず
、局方第２液にのみ溶解する性質を有する。Function The soft capsule of the present invention has a property that it does not dissolve in water or the first liquid of the pharmacopoeia, but dissolves only in the second liquid of the pharmacopoeia.
、以下、試験例を挙げて本発明の作用を具体的に説明す
る。Hereinafter, the effects of the present invention will be specifically explained with reference to test examples.
試験例
基剤と核物質は下記処方とし、内径２〜８ｍ＋ｎの内側
ノズルと内径７〜１７咽の外側ノズルとからなる同軸二
重ノズルを用い、実施例１または実施例２に準じて試料
の軟カプセルを調製し、これについて第１０改正日本薬
局方の崩壊試験を行なった。Test sample The base material and nuclear material have the following formulation, and a coaxial double nozzle consisting of an inner nozzle with an inner diameter of 2 to 8 m+n and an outer nozzle with an inner diameter of 7 to 17 mm is used to form a sample according to Example 1 or 2. Soft capsules were prepared and subjected to a disintegration test according to the 10th edition of the Japanese Pharmacopoeia.
その結果を次表に示す。The results are shown in the table below.
処 方
崩壊試験（分）
（註）
一：２時間溶解せず
本発明の効果
本発明の軟カプセルは、局方第１液には２時間以内に溶
解することなく、局方筒■液には短時間で溶解するとい
うすぐれた腸溶性を有するばかシか、油性核物質も水性
核物質も内蔵することができるという汎用性を有する。Prescription disintegration test (minutes) (Note) 1: Effect of the present invention without dissolving in 2 hours The soft capsules of the present invention do not dissolve in the first liquid of the pharmacopoeia within 2 hours, but do not dissolve in the first liquid of the pharmacopoeia. It has excellent enteric properties that allow it to dissolve in a short time, and it has the versatility of being able to contain both oily and aqueous nuclear substances.
また、基剤にゼラチンを全く含まないため、その外皮膜
は耐湿性がすぐれていて長期の保存が可能であり、製造
上は配合の制約が少なく、作業性が良好で、しかも中間
製品を途中で系外に取出すことなく製品の仕上りまで一
貫した連続作業を行なうことが可能であるから、製造コ
ストを著しく低減させることができる。In addition, since the base does not contain gelatin at all, the outer film has excellent moisture resistance and can be stored for a long period of time.There are fewer restrictions on formulation during manufacturing, and workability is good. Since it is possible to carry out consistent continuous work up to the finished product without taking it out of the system, manufacturing costs can be significantly reduced.
従って、本発明の軟カプセルは腸溶性軟カプセルとして
利用することができる。Therefore, the soft capsule of the present invention can be used as an enteric-coated soft capsule.
実施例 以下、実施例を挙げて本発明を具体的に説明する。Example The present invention will be specifically described below with reference to Examples.
実施例 １
（１） アルギン酸す） ＩＪウム５１を湯浴上で加
温しながら精製水９５１を少しずつ添加して溶解し、室
温まで冷却して基剤を調製した。Example 1 (1) Alginic acid While heating IJum 51 on a hot water bath, purified water 951 was added little by little to dissolve it, and the mixture was cooled to room temperature to prepare a base.
（２）パナセート８１０ １７ｆ、サンソフト尚７００
Ｐ−２４０ｆ、サラシミッロウ６ｆを湯浴上で加温溶解
し、これを室温近くまで冷却してからエリスロマイシン
４０２を添加して油性核物質を調製した。(2) Panacet 810 17f, Sunsoft Nao 700
P-240f and Sarashimiro 6f were heated and dissolved on a hot water bath, and after cooling to near room temperature, erythromycin 402 was added to prepare an oily core material.
（３）前項（す、（２）で得た基剤と油性核物質を用い
、内径１朋の内Ｉ１１ノズルと内径１．５唄の外側ノズ
ルからなる同軸二重ノズルを備えたグローペックス社製
シームレス軟カプセル製造機ＭａｒＦｌを使用し、油性
キャリヤーは、２０℃の大豆油、架橋硬化剤は２０℃の
５％塩化カルシウム水溶液を用い、架橋硬化時間を５分
として気中落下方式でシームレス軟カプセルを製造した
。(3) Using the base material and oily core material obtained in the previous section (2), Gropex Co., Ltd. is equipped with a coaxial double nozzle consisting of an inner nozzle with an inner diameter of 1 mm and an outer nozzle with an inner diameter of 1.5 mm. Seamless soft capsule manufacturing machine MarFl, made by M. Co., Ltd., was used.The oil-based carrier was soybean oil at 20°C, the crosslinking hardening agent was a 5% calcium chloride aqueous solution at 20°C, and the crosslinking hardening time was 5 minutes. produced capsules.
硬化した軟カプセルを取出して流水で水洗いし、２０℃
で３日間乾燥して径１ｍｍの軟カプセルを得た。Take out the hardened soft capsules, wash them with running water, and store them at 20°C.
After drying for 3 days, soft capsules with a diameter of 1 mm were obtained.
実施例 ２
（１） アルギン酸ナトリウム２５ｆ、グリセリン５
ｖおよびソルビトール５２を均一に混合し、湯浴上で加
温しながら精製水８Ｚ５２を少しずつ添加して溶解し、
室温まで冷却して基剤を調製した。Example 2 (1) Sodium alginate 25f, glycerin 5
V and Sorbitol 52 are mixed uniformly, and purified water 8Z52 is added little by little while heating on a hot water bath to dissolve.
The base was prepared by cooling to room temperature.
（２）大豆油８０２．ブラシミツロウ２０２．リン酸ピ
リドキサール１０２を用い、実施例１（２）に準じて油
性核物質を調製した。(2) Soybean oil 802. Brush beeswax 202. An oily core material was prepared using pyridoxal phosphate 102 according to Example 1 (2).
（３）前項（１）、 （２）で得た基剤と油性核物質を
用い、内径２簡の内側ノズルと内径８咽の外側ノズルか
らなる同軸二重ノズルを備えたシームレス軟カプセル製
造機Ｍａｒｋ ｌを使用し、油性キャリヤーは２０℃の
流動性パラフィン、架橋硬化剤は２０℃の５％塩化カル
シウム水溶液を用い、架橋硬化時間を１０分として液中
落下方式でアームレス軟カプセルを製造した。(3) Seamless soft capsule manufacturing machine using the base material and oily core material obtained in the previous sections (1) and (2) and equipped with a coaxial double nozzle consisting of an inner nozzle with an inner diameter of 2 and an outer nozzle with an inner diameter of 8. Armless soft capsules were produced using Mark 1, liquid paraffin at 20° C. as an oil carrier, 5% calcium chloride aqueous solution at 20° C. as a crosslinking hardening agent, and a crosslinking hardening time of 10 minutes using a drop-in-liquid method.
硬化した軟カプセルを取出して流水で水洗いし、２０℃
で３日間乾燥して径５咽の軟カプセルを得た。Take out the hardened soft capsules, wash them with running water, and store them at 20°C.
After drying for 3 days, soft capsules with a diameter of 5 pharynges were obtained.
実施例 ６
（基 剤）
アルギン酸ナトリウム ２ｖグリセリ
ン ６．５２ソルビトール
４を精製水 ９０５ｖ
（油性核物質）
酢酸トコフェロール ５を大豆油
４０ ｒ
サラシミツロウ １０ を酢酸レ
チロール １．０００．０００ 工Ｕ前記組
成の基剤と油性核物質を用い、実施例２に準じて処理し
、径５ｍの軟カプセルを得た。Example 6 (Base) Sodium alginate 2v Glycerin 6.52 Sorbitol
4 is purified water 905v (oily nuclear material) tocopherol acetate 5 is soybean oil
40 ml of white beeswax was treated with 1.000.000 ml of retylol acetate using a base having the above composition and an oily core material according to Example 2 to obtain soft capsules with a diameter of 5 m.
実施例 ４ （１）（基 剤） アルギン酸ナトリウム ３ｖ グリセリン ３２ ソルビトール ５２ 精製水 ９１ｆ 実施例２（１）に準じて基剤を調製した。Example 4 (1) (base agent) Sodium alginate 3v Glycerin 32 Sorbitol 52 Purified water 91f A base was prepared according to Example 2 (1).
（２） ヒドロキシグロピルセルロース５１とグリセ
リン２Ｏｒを湯浴上で加温しながら精製水５６Ｖを少し
ずつ添加して溶解し、室温まで放冷して粘稠液を得た。(2) Hydroxyglopylcellulose 51 and glycerin 2Or were heated on a hot water bath, and purified water 56V was added little by little to dissolve them, and the mixture was allowed to cool to room temperature to obtain a viscous liquid.
これに塩酸エフェドリン５０■を添加し、精製水１４２
を加えて水性核物質を調製した。Add 50μ of ephedrine hydrochloride to this, and add 142μ of purified water.
was added to prepare aqueous nuclear material.
（３）前項（１）、 （２）で得た基剤と水性核物質を
用い、内径２咽の内側ノズルと内径７ｍの外側ノズルか
らなる同軸二重ノズルを備えたシームレス軟カプセル製
造機Ｍａｒｋ ＩＩを使用し、実施例２（３）に準じて
処理し、径４胴の軟カプセルを得た。(3) Seamless soft capsule manufacturing machine Mark equipped with a coaxial double nozzle consisting of an inner nozzle with two inner diameters and an outer nozzle with an inner diameter of 7 m, using the base material and aqueous core material obtained in the previous sections (1) and (2). II and processed according to Example 2 (3) to obtain soft capsules with a diameter of 4.
実施例 ５
（基 剤）
アルギン酸ナトリウム ３タグリセリ
ン ２２ソルビトール
５２精製水 ８０２
（水性核物質）
アスコルビン酸 １０２塩酸チアミ
ン ２グ塩酸ピリドキシン
０．５ ｔグリセリン
２０１ヒドロキシプロピルセルロース ２
２精製水 ３０２
前記組成の基剤と水性核物質を用い、内径０．５叫の内
側ノズルと内径 １／ｗ・ｉの外側ノズルからなる同軸
二重ノズルを備えたシームレス軟カプセル製造機Ｍａｒ
ｋＩＩを使用し、実施例２（３）に準じて処理し、径０
５Ｉ＋ＩＩ＋ｌの軟カプセルを得た。Example 5 (Base) Sodium alginate 3-taglycerin 22-sorbitol
52 Purified water 802 (Aqueous nuclear material) Ascorbic acid 102 Thiamine hydrochloride 2g Pyridoxine hydrochloride
0.5t glycerin
201 Hydroxypropylcellulose 2
2 Purified water 302 Seamless soft capsule manufacturing machine using a base of the above composition and an aqueous core substance and equipped with a coaxial double nozzle consisting of an inner nozzle with an inner diameter of 0.5 mm and an outer nozzle with an inner diameter of 1/w.i.
kII and treated according to Example 2 (3) to obtain a diameter of 0.
Soft capsules of 5I+II+l were obtained.
実施例 ６
（基 剤）
低メトキシルペクチン １０ グンルビ
トール ６２精製水
８４ Ｆ
（油性核物質）
エルゴカルシフェロール ５０，０００ 工Ｕ
酢酸トコフェロール ０．５ ｒ酢
酸レチノール ｉ、 ０００．０００
工Ｕリボフラビン １２大
豆油 ３０１
サラシミツロウ １０２前記組成
の基剤と油性核物質を用い、内径１０朔の内側ノズルと
内径１７調の外側ノズルからなる同軸二重ノズルを備え
たシームレス軟カプセル製造機Ｍａｒｋ ＩＩを使用し
、実施例２（３）に準じて処理し、径１４謹の軟カプセ
ルを得た。Example 6 (Base) Low methoxyl pectin 10 Gunrbitol 62 Purified water
84 F (oil-based nuclear material) Ergocalciferol 50,000 engineering U
Tocopherol acetate 0.5 r Retinol acetate i, 000.000
U Riboflavin 12 Soybean oil 301 White beeswax 102 Seamless soft capsule manufacturing machine Mark equipped with a coaxial double nozzle consisting of an inner nozzle with an inner diameter of 10 mm and an outer nozzle with an inner diameter of 17 mm, using the base of the above composition and an oily core substance. II and treated according to Example 2 (3) to obtain soft capsules with a diameter of 14 mm.
Claims (5)
ン系基剤により形成したシームレス外皮膜を２価以上の
陽イオンにより硬化させた腸溶性軟カプセル。(1) Enteric-coated soft capsules in which a seamless outer shell film formed from a non-gelatinous base consisting of a crosslinkable polysaccharide or this and an auxiliary agent is hardened with divalent or higher cations.
特許請求の範囲第１項に記載の腸溶性軟カプセル。(2) The enteric-coated soft capsule according to claim 1, wherein the crosslinkable polysaccharide is sodium alginate.
特許請求の範囲第１項に記載の腸溶性軟カプセル。(3) The enteric-coated soft capsule according to claim 1, wherein the crosslinkable polysaccharide is low methoxyl pectin.
特許請求の範囲第１項に記載の腸溶性軟カプセル。(4) The enteric-coated soft capsule according to claim 1, wherein the divalent cation is a calcium ion.
の範囲第１項に記載の腸溶性軟カプセル。(5) The enteric-coated soft capsule according to claim 1, wherein the auxiliary agent is a water-soluble polyhydric alcohol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59166916A JPS6144810A (en) | 1984-08-09 | 1984-08-09 | Enteric soft capsule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59166916A JPS6144810A (en) | 1984-08-09 | 1984-08-09 | Enteric soft capsule |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS6144810A true JPS6144810A (en) | 1986-03-04 |
Family
ID=15840019
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59166916A Pending JPS6144810A (en) | 1984-08-09 | 1984-08-09 | Enteric soft capsule |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6144810A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07318161A (en) * | 1995-05-29 | 1995-12-08 | Rinnai Corp | Bath water supplement controlling device for bath apparatus |
| KR20010063313A (en) * | 1999-12-22 | 2001-07-09 | 김상호 | Method for manufacturing an industrial soft capsule |
| WO2003084516A1 (en) * | 2002-04-04 | 2003-10-16 | Fmc Biopolymer As | Polysaccharide capsules and methods of preparation |
| JP2009502841A (en) * | 2005-07-26 | 2009-01-29 | グラクソ グループ リミテッド | Encapsulation of lipid-based formulations in enteric polymers |
| DE102007039772A1 (en) | 2007-08-22 | 2009-02-26 | Cavis Microcaps Gmbh | Microcapsule and process for its preparation |
| US7766637B2 (en) | 2006-03-03 | 2010-08-03 | Fmc Corporation | Method and apparatus for the preparation of capsules |
| DE102010027202A1 (en) | 2010-07-08 | 2012-01-12 | Uratanishoji K.K. | Marking device comprises outer shell comprising first engraving surface to be placed in cavity of injection molding device, rotatable tube comprising second engraving surface, indicator comprising head and support mechanism |
-
1984
- 1984-08-09 JP JP59166916A patent/JPS6144810A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07318161A (en) * | 1995-05-29 | 1995-12-08 | Rinnai Corp | Bath water supplement controlling device for bath apparatus |
| KR20010063313A (en) * | 1999-12-22 | 2001-07-09 | 김상호 | Method for manufacturing an industrial soft capsule |
| WO2003084516A1 (en) * | 2002-04-04 | 2003-10-16 | Fmc Biopolymer As | Polysaccharide capsules and methods of preparation |
| EP1990045A1 (en) | 2002-04-04 | 2008-11-12 | FMC Biopolymer AS | Polysaccharide capsules and methods of preparation |
| US7972620B2 (en) | 2002-04-04 | 2011-07-05 | Fmc Biopolymer As | Polysaccharide capsules and methods of preparation |
| US9017720B2 (en) | 2002-04-04 | 2015-04-28 | FMC Bioploymer AS | Polysaccharide capsules and method of preparation |
| JP2009502841A (en) * | 2005-07-26 | 2009-01-29 | グラクソ グループ リミテッド | Encapsulation of lipid-based formulations in enteric polymers |
| US7766637B2 (en) | 2006-03-03 | 2010-08-03 | Fmc Corporation | Method and apparatus for the preparation of capsules |
| US8153037B2 (en) | 2006-03-03 | 2012-04-10 | Fmc Corporation | Method and apparatus for the preparation of capsules |
| US8916192B2 (en) | 2006-03-03 | 2014-12-23 | Fmc Corporation | Method and apparatus for the preparation of capsules |
| DE102007039772A1 (en) | 2007-08-22 | 2009-02-26 | Cavis Microcaps Gmbh | Microcapsule and process for its preparation |
| DE102010027202A1 (en) | 2010-07-08 | 2012-01-12 | Uratanishoji K.K. | Marking device comprises outer shell comprising first engraving surface to be placed in cavity of injection molding device, rotatable tube comprising second engraving surface, indicator comprising head and support mechanism |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2008272135B2 (en) | Seamless capsule | |
| DE69118592T3 (en) | Process for the preparation of active ingredient granules by extrusion | |
| US4994279A (en) | Multi-layer granule | |
| US9456991B2 (en) | Gelatin/alginate delayed release capsules comprising omega-3 fatty acids, and methods and uses thereof | |
| TWI472323B (en) | Aqueous composition for enteric hard capsule, method of preparing enteric hard capsule,and enteric hard capsule prepared using the method | |
| JP2006505542A (en) | Enteric preparation | |
| US2526683A (en) | Methyl cellulose capsules and process of manufacture | |
| US5389380A (en) | Sustained release pharmaceutical preparation and process for preparing the same | |
| KR890002238A (en) | Degraded starch that does not basically contain crosslinked phosphate groups and methods for preparing the same | |
| HUT64833A (en) | Soft capsule with coating dissoluble in intestines and method for manufacturing it | |
| EP0958813B1 (en) | Sustained-release preparation utilizing thermal change and process for the production thereof | |
| RU2011110100A (en) | EXTRUSION OF HOT MELT OF MULTIPLE PARTICLES OF MODIFIED RELEASE | |
| JP6317425B2 (en) | Silk capsule | |
| JPS61260029A (en) | Composition for manufacturing microparticles for prolonged release of biologically active substance | |
| NO329728B1 (en) | Spheroids containing ± one or more active principles, with the exception of tiagabine, processes for forming the same and multiparticulates, pharmaceutical preparations containing the spheroids, and their preparation. | |
| JPH04211334A (en) | Coated vitamin c preparation for feed, production thereof and use thereof | |
| DE2146859A1 (en) | Process for coating tablets with sugar | |
| JP3672008B2 (en) | Hard capsule and method for producing the same | |
| JPS6144810A (en) | Enteric soft capsule | |
| JP2001521894A (en) | Pharmaceutical active compositions containing artemisinin and / or artemisinin derivatives | |
| DE2336807A1 (en) | INTESTINAL CAPSULES | |
| IT201700021879A1 (en) | RELEASED COMPOSITION OF PHYSIOLOGICALLY ACTIVE SUBSTANCES AND PROCESS FOR ITS PREPARATION | |
| US3149039A (en) | Thin film coating for tablets and the like and method of coating | |
| CN1960716A (en) | Oral preparations and process for production thereof | |
| JPH0725663B2 (en) | Method for producing enteric coated soft capsule |