JPH0460971B2 - - Google Patents
Info
- Publication number
- JPH0460971B2 JPH0460971B2 JP15793583A JP15793583A JPH0460971B2 JP H0460971 B2 JPH0460971 B2 JP H0460971B2 JP 15793583 A JP15793583 A JP 15793583A JP 15793583 A JP15793583 A JP 15793583A JP H0460971 B2 JPH0460971 B2 JP H0460971B2
- Authority
- JP
- Japan
- Prior art keywords
- water
- general formula
- group
- och
- enteric coating
- 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.)
- Expired
Links
- 229920002678 cellulose Polymers 0.000 claims description 29
- 239000001913 cellulose Substances 0.000 claims description 28
- 239000006185 dispersion Substances 0.000 claims description 25
- 239000007788 liquid Substances 0.000 claims description 25
- 239000002702 enteric coating Substances 0.000 claims description 19
- 238000009505 enteric coating Methods 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 16
- 239000000843 powder Substances 0.000 claims description 13
- 239000011248 coating agent Substances 0.000 claims description 10
- 238000000576 coating method Methods 0.000 claims description 10
- 239000002245 particle Substances 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 239000002612 dispersion medium Substances 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 6
- 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 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 claims description 5
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000004185 ester group Chemical group 0.000 claims description 5
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical group O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 claims description 4
- 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 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 150000001491 aromatic compounds Chemical class 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 229920000609 methyl cellulose Polymers 0.000 claims description 3
- 235000010981 methylcellulose Nutrition 0.000 claims description 3
- 239000001923 methylcellulose Substances 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 235000010413 sodium alginate Nutrition 0.000 claims description 3
- 239000000661 sodium alginate Substances 0.000 claims description 3
- 229940005550 sodium alginate Drugs 0.000 claims description 3
- 244000215068 Acacia senegal Species 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 229920002907 Guar gum Polymers 0.000 claims description 2
- 229920000084 Gum arabic Polymers 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- 239000000205 acacia gum Substances 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 235000010418 carrageenan Nutrition 0.000 claims description 2
- 239000000679 carrageenan Substances 0.000 claims description 2
- 229920001525 carrageenan Polymers 0.000 claims description 2
- 229940113118 carrageenan Drugs 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 229940014259 gelatin Drugs 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 235000010417 guar gum Nutrition 0.000 claims description 2
- 239000000665 guar gum Substances 0.000 claims description 2
- 229960002154 guar gum Drugs 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 claims description 2
- 235000010493 xanthan gum Nutrition 0.000 claims description 2
- 239000000230 xanthan gum Substances 0.000 claims description 2
- 229920001285 xanthan gum Polymers 0.000 claims description 2
- 229940082509 xanthan gum Drugs 0.000 claims description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 229920001206 natural gum Polymers 0.000 claims 1
- -1 carboxyalkyl ether Chemical compound 0.000 description 17
- 238000000034 method Methods 0.000 description 14
- 239000000463 material Substances 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 7
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 6
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 6
- 235000012141 vanillin Nutrition 0.000 description 6
- 150000002170 ethers Chemical class 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 150000002148 esters Chemical group 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000004014 plasticizer Substances 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229920003086 cellulose ether Polymers 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 125000001033 ether group Chemical group 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 2
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 238000010298 pulverizing process Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 241000489523 Veratrum Species 0.000 description 1
- IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229920003065 carboxyethylmethyl cellulose Polymers 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000010556 emulsion polymerization method Methods 0.000 description 1
- 238000007720 emulsion polymerization reaction Methods 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 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 1
- 239000008187 granular material Substances 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000020094 liqueur Nutrition 0.000 description 1
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 1
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 1
- 150000005573 methoxybenzenes Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 235000019645 odor Nutrition 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- SATCULPHIDQDRE-UHFFFAOYSA-N piperonal Chemical compound O=CC1=CC=C2OCOC2=C1 SATCULPHIDQDRE-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000003505 polymerization initiator Substances 0.000 description 1
- 150000003151 propanoic acid esters Chemical class 0.000 description 1
- YQUVCSBJEUQKSH-UHFFFAOYSA-N protochatechuic acid Natural products OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000015067 sauces Nutrition 0.000 description 1
- 125000001424 substituent group Chemical class 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 description 1
- TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 description 1
- WJUFSDZVCOTFON-UHFFFAOYSA-N veratraldehyde Chemical compound COC1=CC=C(C=O)C=C1OC WJUFSDZVCOTFON-UHFFFAOYSA-N 0.000 description 1
- 229940057613 veratrum Drugs 0.000 description 1
Description
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The present invention relates to enteric coating fluids. More specifically, the present invention relates to an aqueous enteric coating liquid. Conventionally, the method of producing enteric coating liquids is to dissolve a polymeric substance that does not dissolve in water or gastric fluid but dissolves in intestinal fluid in an organic solvent, and then add plasticizers, colorants, etc. to this as necessary. There is. However, this method requires a large amount of organic solvent to produce the coating liquid, and it is difficult to recover the organic solvent, which is economically disadvantageous. In addition, there were problems with safety for workers during production and formulation due to the use of large amounts of organic solvents, risk of ignition, and safety for users due to residual solvent in the drug. From this point of view, there has recently been an increasing recognition of the need for a water-based enteric coating solution, that is, a method using water as a dispersion medium, and various methods have been proposed. However, enteric coating materials are generally polymeric compounds with carboxyl groups, and their characteristic is that they can only be solubilized by forming salts in alkaline water, so they cannot simply be made into an aqueous solution. That is the reality. Therefore, although various methods have been proposed for producing water-based enteric coating liquids using polymeric substances having carboxyl groups, almost no methods have been put into practical use. The only practical method is to use methyl methacrylate/methacrylic acid copolymer in the form of an aqueous emulsion obtained by emulsion polymerization; Because it relies on the emulsion polymerization method, there are concerns about the residual presence of polymerization initiators, monomers, etc., which poses safety issues when applied to pharmaceuticals. In order to solve the problems of the prior art, the present inventors have conducted intensive studies on an economical and favorable method for producing a water-based enteric coating liquid. It is not enough to simply reduce the particle size of the dry base powder; it is important to overplasticize the enteric base powder, which is essentially insoluble in water, and to adhesively bond the plasticized particles together. From this point of view, the key point is the selection of the plasticizer and binder, while from the perspective of the characteristics of the enteric base material, the conclusion is that the affinity of the base material particles for the dispersion medium in an aqueous dispersion system is an extremely important factor. This has led to the completion of the present invention. That is, the present invention is prepared by dissolving or dispersing an aromatic compound and a water-soluble gummy substance of the general formula (1) as essential components in water or an aqueous alcohol solution containing 20% by weight or less of a lower alcohol having 1 to 3 carbon atoms. This invention relates to an enteric coating liquid whose main feature is to disperse in the liquid a water-insoluble oxycarboxylic acid type cellulose derivative powder represented by the general formula (2) with a particle size of 100 ÎŒm or less. General formula (1)
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ã³ã°è©Šéšã«äŸããããšã¯ã§ããªããã®ã§ãã€ãã[Formula] (R 1 and R 2 are H, OCH 3 , OCH 2 CH 3 , OH, or
R 1 R 2 together represent OCH 2 O, R 3 represents CHO, CO 2 H) General formula (2) (In the formula, Gul represents an anhydroglucose unit skeleton of cellulose consisting of C 6 H 7 O 2 , R 1 is hydrogen or a carboxyalkyl group having 1 to 5 carbon atoms, R 2 and R 3 are
When R 1 is hydrogen, at least one of them represents the same or different ester group or ether group having a carboxyl group, and when R 1 is a carboxyalkyl group having 1 to 5 carbon atoms, at least one of them has a hydroxyl group. Indicates the same or different ether or ester groups. ) The oxycarboxylic acid type cellulose derivatives represented by the general formula (2) include those belonging to cellulose ethers, cellulose esters, and cellulose ether esters. The degree of substitution of substituents is determined depending on the purpose. In the above general formula (2), R 2 ,
The ester group or ether group represented by R 3 means an atomic group introduced into cellulose through an ester or ether bond. Examples of esters include acetate, propionate, butyrate, succinate, phthalate, and higher fatty acid. Examples of the ether include carboxyalkyl ether, alkyl ether, and hydroxyalkyl ether having 1 to 5 carbon atoms. Therefore, examples of the oxycarboxylic acid type cellulose derivatives represented by the above general formula (2) include carboxyalkylalkylcellulose mixed ethers such as carboxymethylethylcellulose, carboxyethylmethylcellulose, and carboxypropylmethylcellulose, hydroxypropylmethylcellulose succinate, and hydroxypropylcellulose. Cellulose mixed ether esters such as methylcellulose phthalate, acidic succinoyl and acidic phthaloyl mixed esters of hydroxypropylmethylcellulose, acidic succinoyl and propionic acid esters of hydroxypropylmethylcellulose, cellulose acetate phthalate,
Includes cellulose mixed esters such as cellulose acetate succinate. As mentioned above, the oxycarboxylic acid type cellulose derivative represented by general formula (2) is required to be a powder of 100Ό or less, but there are no particular restrictions on the method for preparing such powder, and mechanical It can be adjusted by any method among methods such as a pulverization method and a physicochemical pulverization method. Furthermore, the purpose of the present invention is to provide an aqueous enteric coating solution, and the selection of the enteric coating material itself is also an important factor. That is, the following can be the selection criteria. (1) It is advantageous for the enteric coating material itself to be highly hydrophilic to the extent that it does not impair the enteric function. (2) Adjust the coating liquid using an aqueous system,
In addition, since it is used for coating, it is more practical if the enteric coating material itself is highly resistant to hydrolysis. As a result of various studies from the above point of view, we found that the enteric coating material to be used is an oxycarboxylic acid type cellulose derivative represented by the general formula (2).
General formula (3) with high hydrophilicity and excellent hydrolysis resistance
It has been found that the oxycarboxylic acid type cellulose mixed ethers shown below are preferable. general formula
The oxycarboxylic acid type cellulose derivatives represented by (3) include carboxymethylethyl cellulose,
Examples include carboxyethylethylcellulose, carboxybutylethylcellulose, carboxypropylmethylcellulose, and the like. General formula (3) (In the formula, Gul represents an anhydroglucose unit skeleton of cellulose consisting of C 6 H 7 O 2 , m is an integer of 1 to 5, and R 4
represents a hydroxyl group and a methoxyl group or an ethoxyl group. ) Next, vanillin, which is a representative example of the aromatic compound represented by the general formula (1), which is an essential component of the present invention, is generally used in all kinds of flavors, including ice cream, tiocholate, candy, cake, essence, liqueur, tobacco, and sauce. It is a highly safe food flavoring agent that is added to water, and is also used as a deodorizer to remove chlorine odors from water supplies and castor oil. This material has a benzene ring and is slightly soluble in water at room temperature, and is effective as a plasticizer for water dispersion systems, and the appropriate amount to be used is 30% by weight or less based on the enteric base material. In addition to vanillin, examples of methoxybenzene derivatives represented by general formula (1) that can be used in the present invention include vanillic acid, veratrumaldehyde, veratrum acid, anisaldehyde,
Heliotropin, etc. Water-soluble gums include cellulose derivatives such as methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and carboxymethylcellulose, synthetic gums such as polyvinyl alcohol, polyvinylpyrrolidone, sodium polyacrylate, polyethylene glycol, and polyethylene oxide, and carrageenan. , guar gum, xanthan gum, sodium alginate, gelatin, and gum arabic, any one or a combination of several can be selected. The amount of water-soluble gum substance is determined by the general formula (2) or (3).
Although it varies depending on the type of oxycarboxylic acid type cellulose derivative represented by and the dosage form of the product to be coated, it is generally 50% by weight or less of the oxycarboxylic acid type cellulose derivative. Although water alone is mainly used as the dispersion medium, bases with strong affinity for lower alcohols having 1 to 3 carbon atoms, such as oxycarboxylic acid type cellulose mixed ethers represented by general formula (2), are also used. In some cases, it is advantageous to improve the uniformity of the coating film by using water containing a lower alcohol having 1 to 3 carbon atoms within a range that does not cause agglomeration of base particles during dispersion. In such cases, the alcohol content is generally 20
It is preferable to adjust the amount to % by weight or less. In carrying out the present invention, the method for dispersing the oxycarboxylic acid type cellulose derivative powder in the dispersion medium referred to in the present invention is not particularly limited, and conventionally known methods are sufficient. Further, it is optional to use various emulsifiers in combination for the purpose of further improving the dispersion stability of the powder. In order to further improve the film-forming properties of the coating liquid, conventionally known plasticizers such as polyethylene glycol, propylene glycol, various phthalate esters, or various glycerin fatty acid esters are added during or after dispersion. This is optional and does not contradict the gist of the present invention. The enteric coating liquid of the present invention does not have a very high minimum film forming temperature and provides a stable continuous coating under mild drying conditions, so it can be used to coat the surface or inner layer of solid drugs, tablets, multilayer tablets, granules, capsules, etc., or to coat the inner layer of capsules. Excellent enteric-coated preparations can be obtained by blending into materials or by kneading and molding powdered drugs. Next, the present invention will be further explained with reference to Examples.
The present invention is not limited to the following examples unless it exceeds the spirit thereof. In addition, in the following examples, both parts and % mean parts by weight and % by weight. Example 1 A 2% aqueous solution of 0.1 part of polyoxyethylene sorbitan monooleate (trade name Tween 80, manufactured by Kao Atlas Co., Ltd.) and hydroxypropyl methyl cellulose (trade name TC-5R, manufactured by Shin-Etsu Chemical Co., Ltd.) in 165.9 parts of water. 10 parts were added to form a dispersion medium. 4 parts of vanillin was added to this dispersion medium and emulsified and dispersed using a homomixer. Next, carboxymethylethylcellulose powder (average particle size 80Ό) with carboxymethyl group DS0.52 and ethoxyl group DS1.95
20 parts were gradually added and thoroughly dispersed to obtain a white dispersion of carboxymethylethyl cellulose. The minimum film forming temperature (abbreviated as MFT) of this dispersion is
At temperatures above MFT (35°C), a transparent uniform continuous film was formed. Next, 1 kg of tablets with a diameter of 8 mm and a weight of 150 mg, mainly composed of lactose/crystalline cellulose, were placed in an automatic ban coating device FM-2 manufactured by Freund Sangyo, and the solid content was approximately 15 mg per tablet using the above dispersion.
Coated. When the coated tablet was tested according to the disintegration test method for enteric-coated preparations of the Japanese Pharmacopoeia (10th revision), there was no change in the first liquid, and 12 in the test with the second liquid.
It collapsed in ~15 minutes. Example 2 In Example 1, instead of carboxymethylethylcellulose, carboxyethyl group DS0.56,
A white dispersion of carboxyethyl ethyl cellulose was obtained in the same manner as in Example 1 except that carboxyethyl ethyl cellulose powder (average particle size 30 Όm) having an ethoxyl group DS of 1.81 was used. The MFT of this dispersion was 33°C, and a transparent uniform continuous film was formed at temperatures above the MFT. A disintegration test was conducted on tablets coated with this dispersion in the same manner as in Example 1.
There was no change in the liquid, and the test with the second liquid was 10 to 14.
It collapsed in minutes. Example 3 163.9 parts of water, 0.1 part of polyoxyethylene sorbitan monooleate (trade name Tween 80, manufactured by Kao Atlas Co., Ltd.), and 2 parts of polyvinyl alcohol (trade name) Gohsenol NL-05, manufactured by Nippon Gohsen Kagaku Kogyo Co., Ltd.) % aqueous solution was added to form a dispersion medium. 4 parts of vanillin and 2 parts of glycerin fatty acid ester (trade name: MGK, manufactured by Nisshin Oil Co., Ltd.) were added to this dispersion medium, and the mixture was emulsified and dispersed using a homomixer. Next, 20 parts of the same carboxymethylethylcellulose powder used in Example 1 was gradually added and thoroughly dispersed to obtain a white dispersion of carboxymethylethylcellulose. The MFT of this dispersion was 32°C, and a transparent uniform continuous film was formed at temperatures above the MFT. A disintegration test was conducted on tablets coated with this dispersion in the same manner as in Example 1.
There was no change in the liquid, and the test with the second liquid was 13 to 15.
It collapsed in minutes. Example 4 In Example 3, 2 of polyvinyl alcohol
Except that a 2% aqueous solution of sodium alginate was used instead of a 2% aqueous solution, and hydroxypropylmethylcellulose phthalate (trade name HP-55, manufactured by Shin-Etsu Chemical Co., Ltd.) powder (average particle size 30Ό) was used instead of carboxymethylethylcellulose. All treatments were carried out in the same manner as in Example 3 to obtain a white dispersion of hydroxypropyl methylcellulose phthalate. The MFT of this dispersion was 52°C, and a transparent uniform film was formed at temperatures above the MFT. A disintegration test was conducted on tablets coated with this dispersion in the same manner as in Example 1. There was no change in the first solution, and the test with the second solution showed 14 to
It collapsed in 16 minutes. Example 5 A white dispersion of carboxymethylethyl cellulose was obtained in the same manner as in Example 3 except that 163.9 parts of a 2% ethanol aqueous solution was used instead of 163.9 parts of water. This dispersion formed a transparent continuous film at a temperature of 30°C and above MFT. A disintegration test was conducted on tablets coated with this dispersion in the same manner as in Example 1.
There was no change in the liquid, and in the test with the second liquid, it disintegrated in 12 to 16 minutes. Comparative Example 1 A white dispersion of carboxymethylethylcellulose was obtained in the same manner as in Example 1 except that vanillin was not added. The MFT of this dispersion was 80°C or higher, and if it was lower than 80°C, powder simply adhered and no continuous film was formed and it could not be subjected to a coating test. Comparative Example 2 A white dispersion of carboxymethylethyl cellulose was obtained in the same manner as in Example 3 except that vanillin and polyvinyl alcohol aqueous solution were not added. The MFT of this dispersion was 70°C, but even above the MFT it did not form a completely transparent film, but instead remained a semi-transparent, rough film with poor slipperiness, which could not be used in coating tests. Ta.
Claims (1)
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R1R2ããããŠOCH2OãR3ã¯CHOãCO2Hãã瀺
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ãïŒ[Scope of Claims] 1. General formula (1) in water or an aqueous alcohol solution containing 20% by weight or less of a lower alcohol having 1 to 3 carbon atoms.
A water-insoluble oxycarboxylic acid type cellulose derivative powder represented by the general formula (2) with a particle size of 100Ό or less is dispersed in a liquid obtained by dissolving or decomposing an aromatic compound and a water-soluble gummy substance as essential components. enteric coating liquid. General formula (1) [Formula] (R 1 and R 2 are H, OCH 3 , OCH 2 CH 3 , OH, or
R 1 R 2 together represent OCH 2 O, R 3 represents CHO, CO 2 H) General formula (2) (In the formula, Gul is an anhydroglucose unit skeleton of cellulose consisting of C 6 H 7 O 2, R 1 is hydrogen or a carboxyalkyl group having 1 to 5 carbon atoms, R 2 and R 3 are R 1
When is hydrogen, at least one of them is the same or different ester group or ether having a carboxyl group, and when R1 is a carboxyalkyl group having 1 to 5 carbon atoms, at least one of them is the same or different ether having a hydroxyl group. group or ester group. 2. The enteric coating liquid according to claim 1, wherein the water-insoluble oxycarboxylic acid type cellulose derivative is an oxycarboxylic acid type mixed ether represented by the general formula (3). General formula (3) (In the formula, Gul represents anhydroglucose unit skeleton of cellulose consisting of C 6 H 7 O 2 , m is an integer from 1 to 5, -
Indicates an OH group, -OCH3 group or -OC2H5 group. 3. The enteric coating liquid according to claim 1 or 2, wherein the water-soluble gummy substance is a cellulose derivative such as methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, or carboxymethylcellulose. 4 Water-soluble gums include polyvinyl alcohol, polyvinylpyrrolidone, sodium polyacrylate,
The enteric coating liquid according to claim 1 or 2, which is a synthetic gum such as polyethylene glycol or polyethylene oxide. 5 Water-soluble gums include carrageenan, guar gum,
3. The enteric coating liquid according to claim 1 or 2, which is made of a natural gum such as xanthan gum, sodium alginate, gelatin, or gum arabic. 6 Compound of general formula (1), water-soluble gum, particle size
An enteric-coated preparation in which the drug is treated with a continuous coating formed from a dispersion liquid containing oxycarboxylic acid type cellulose derivative powder of 100Ό or less as an essential ingredient and water as the main dispersion medium. General formula (1) [Formula] (R 1 and R 2 are H, OCH 3 , OCH 2 CH 3 , OH, or
R 1 R 2 together represent OCH 2 O, R 3 represents CHO, CO 2 H)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP15793583A JPS6051123A (en) | 1983-08-31 | 1983-08-31 | Enteric coating liquid |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP15793583A JPS6051123A (en) | 1983-08-31 | 1983-08-31 | Enteric coating liquid |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS6051123A JPS6051123A (en) | 1985-03-22 |
JPH0460971B2 true JPH0460971B2 (en) | 1992-09-29 |
Family
ID=15660690
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP15793583A Granted JPS6051123A (en) | 1983-08-31 | 1983-08-31 | Enteric coating liquid |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS6051123A (en) |
-
1983
- 1983-08-31 JP JP15793583A patent/JPS6051123A/en active Granted
Also Published As
Publication number | Publication date |
---|---|
JPS6051123A (en) | 1985-03-22 |
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