JP3734360B2 - Formulation containing a salt of copper chlorophyllin - Google Patents
Formulation containing a salt of copper chlorophyllin Download PDFInfo
- Publication number
- JP3734360B2 JP3734360B2 JP06821398A JP6821398A JP3734360B2 JP 3734360 B2 JP3734360 B2 JP 3734360B2 JP 06821398 A JP06821398 A JP 06821398A JP 6821398 A JP6821398 A JP 6821398A JP 3734360 B2 JP3734360 B2 JP 3734360B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- copper chlorophyllin
- salt
- preparation
- internal use
- 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 - Fee Related
Links
- 229940099898 chlorophyllin Drugs 0.000 title claims description 31
- 235000019805 chlorophyllin Nutrition 0.000 title claims description 31
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 title claims description 30
- 229910052802 copper Inorganic materials 0.000 title claims description 29
- 239000010949 copper Substances 0.000 title claims description 29
- 150000003839 salts Chemical class 0.000 title claims description 29
- 238000009472 formulation Methods 0.000 title description 3
- 239000000203 mixture Substances 0.000 title description 3
- 239000002253 acid Substances 0.000 claims description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
- 239000007787 solid Substances 0.000 claims description 13
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 8
- 229910052700 potassium Inorganic materials 0.000 claims description 8
- 239000011591 potassium Substances 0.000 claims description 8
- 238000004040 coloring Methods 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 150000001413 amino acids Chemical class 0.000 claims description 4
- 235000015165 citric acid Nutrition 0.000 claims description 4
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- JVOGSHDZLOJKKR-MXFMKSRJSA-I [Na+].[Na+].[Na+].[Mg++].CCc1c(C)c2cc3[n-]c(c(C)c3C=C)c(C)c3nc(C[C@H]3CCC([O-])=O)c(CC([O-])=O)c3[n-]c(cc1n2)c(C)c3C([O-])=O Chemical compound [Na+].[Na+].[Na+].[Mg++].CCc1c(C)c2cc3[n-]c(c(C)c3C=C)c(C)c3nc(C[C@H]3CCC([O-])=O)c(CC([O-])=O)c3[n-]c(cc1n2)c(C)c3C([O-])=O JVOGSHDZLOJKKR-MXFMKSRJSA-I 0.000 claims 1
- 229940093915 gynecological organic acid Drugs 0.000 claims 1
- 235000011167 hydrochloric acid Nutrition 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 235000005985 organic acids Nutrition 0.000 claims 1
- 235000011007 phosphoric acid Nutrition 0.000 claims 1
- 210000000214 mouth Anatomy 0.000 description 9
- 239000007910 chewable tablet Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 239000008187 granular material Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 229940068682 chewable tablet Drugs 0.000 description 3
- 229930002875 chlorophyll Natural products 0.000 description 3
- 235000019804 chlorophyll Nutrition 0.000 description 3
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 3
- 229960004106 citric acid Drugs 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- -1 hydrohalides Chemical class 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229960004543 anhydrous citric acid Drugs 0.000 description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 2
- 239000000605 aspartame Substances 0.000 description 2
- 235000010357 aspartame Nutrition 0.000 description 2
- 229960003438 aspartame Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 2
- 239000000347 magnesium hydroxide Substances 0.000 description 2
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 229940088417 precipitated calcium carbonate Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- WQNHWIYLCRZRLR-UHFFFAOYSA-N 2-(3-hydroxy-2,5-dioxooxolan-3-yl)acetic acid Chemical compound OC(=O)CC1(O)CC(=O)OC1=O WQNHWIYLCRZRLR-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- BMFMQGXDDJALKQ-BYPYZUCNSA-N Argininic acid Chemical compound NC(N)=NCCC[C@H](O)C(O)=O BMFMQGXDDJALKQ-BYPYZUCNSA-N 0.000 description 1
- 206010006326 Breath odour Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000003907 antipyretic analgesic agent Substances 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical class C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229940124568 digestive agent Drugs 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000004503 fine granule Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- DKXULEFCEORBJK-UHFFFAOYSA-N magnesium;octadecanoic acid Chemical compound [Mg].CCCCCCCCCCCCCCCCCC(O)=O DKXULEFCEORBJK-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229940023488 pill Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【０００１】
【発明の属する技術分野】
本発明は、銅クロロフィリンの塩及び酸を含有してなる製剤に関する。さらに詳しくは、服用しても口腔内に着色が起きない銅クロロフィリンの塩及び酸を含有する製剤に関する。
【０００２】
【従来の技術】
植物等の葉緑素として天然に常在するクロロフィルは、分子内にマグネシウム原子１原子を保持したポルフィリン系色素で、独特な濃緑色を有することが知られる。クロロフィルは脂溶性物質であるが、アルカリで加水分解することにより水溶性のクロロフィリンに変換することができる。銅クロロフィリンとは、上記クロロフィリンの分子中にあるマグネシウム原子を銅原子に置き換えることにより得られる化合物である。クロロフィリンは、医薬品としては口臭予防や創傷治療に効果的で、従来から多くの製品に配合されてきた。また、粘膜保護作用に基づく胃潰瘍、十二指腸潰瘍、胃炎の予防・治療剤として有用なことでも知られ、極めて身近な医薬品成分である。このため、通常は、例えば銅クロロフィリンカリウム等、塩の形で配合されて、散剤、顆粒剤、錠剤等、手軽にすぐ服用できる剤形とされる。
【０００３】
【発明が解決しようとする課題】
しかし、一方で、銅クロロフィリンカリウムをはじめとする銅クロロフィリンの塩は濃緑色を呈する物質であるために、それらを含有する製剤を服用後に口中で溶解した場合には、口腔内、舌までもが濃緑色に着色するという問題があった。かかる着色は丸一日もの間舌等に残るほど強力であるため、服用法は口腔内で溶解しない錠剤等に限られていた。しかし、消費者のニーズの多様化等から、銅クロロフィリンの塩を含有した錠剤等を、口中で溶解して服用するチュアブル錠のような剤形が望まれてきた。本発明の目的は、かかる着色を防止し、かつ服用感に優れた、銅クロロフィリンの塩を含有してなる製剤を提供することである。
【０００４】
【課題を解決するための手段】
本発明者らは、上記事情に鑑みて鋭意検討を重ねた結果、銅クロロフィリンの塩に通常用いられる酸を添加した製剤は、口中で溶解しても銅クロロフィリンの塩による口腔内、舌の着色を大幅に軽減することを見出し、本発明を完成するに至った。
【０００５】
即ち、本発明は、銅クロロフィリンの塩及び酸を含むことを特徴とする内服用医薬固形製剤である。
【０００６】
本発明における銅クロロフィリンの塩とは、銅クロロフィリンが有するカルボキシル基が塩を形成していることを意味する。かかる塩とは、具体的に例えば、カリウム塩、ナトリウム塩などのアルカリ金属との塩；トリメチルアミン塩、トリエチルアミン塩、プロカイン塩、ピリジン塩、フェネチルベンジルアミン塩などのアミンとの塩；塩酸塩、臭化水素酸塩、ヨウ化水素酸塩、硫酸塩、硝酸塩、過塩素酸塩、リン酸塩、炭酸塩、重炭酸塩などの無機酸との塩；アルギニン酸塩、アスパラギン酸塩、グルタミン酸塩、などのアミノ酸との塩などを意味し、好ましくはカリウム塩、ナトリウム塩などのアルカリ金属との塩；アルギニン酸塩、アスパラギン酸塩、グルタミン酸塩、などのアミノ酸との塩であり、より好ましくはカリウム塩、ナトリウム塩などのアルカリ金属との塩である。
【０００７】
本発明における酸とは、医薬品添加物として配合可能なあらゆる酸を意味し、具体的には例えば、塩酸、臭化水素酸、ヨウ化水素酸、硫酸、硝酸、リン酸、炭酸、重炭酸などの無機酸；酢酸、リンゴ酸、クエン酸、マレイン酸、酒石酸、フマール酸、アスコルビン酸などの有機カルボン酸；メタンスルホン酸、トリフルオロメタンスルホン酸、エタンスルホン酸、ベンゼンスルホン酸、トルエンスルホン酸などの有機スルホン酸；アルギニン酸、アスパラギン酸、グルタミン酸などのアミノ酸があげられる。
【０００８】
本発明における銅クロロフィリンの塩と酸の重量比は、通常、銅クロロフィリンの塩１重量部に対して前記定義に同じ意味の酸を0.01〜1重量部であるが、好ましくは銅クロロフィリンの塩１重量部に対して前記定義に同じ意味の酸を0.05〜1重量部、より好ましくは0.05〜0.75重量部、さらに好ましくは0.1〜0.3重量部である。
【０００９】
更に、本発明にかかる製剤は、銅クロロフィリン塩に他の薬効成分を配合させて製造することもできる。当該他の薬効成分は特に限定されず、具体的に例えば、止しゃ剤、整腸剤、抗潰瘍剤、健胃消化剤、制酸剤、抗ヒスタミン剤、抗不安剤、抗てんかん剤、解熱鎮痛消炎剤、利尿剤、血圧降下剤、血管拡張剤、高脂血症用剤、気管支拡張剤、ビタミン、生薬、抗生物質、抗ウイルス剤等があげられる。
【００１０】
本発明にかかる製剤は、散剤、顆粒剤、細粒剤、丸剤、錠剤等の内服用医薬固形製剤である。とりわけチュアブル錠、トローチ錠等のように口中でかみ砕いたり溶解させるなどして服用する製剤に最適である。
【００１１】
これらの製剤化には通常用いられる種々の添加剤を配合することができる。かかる添加剤としては、内服用医薬固形製剤の場合、例えば、賦形剤、結合剤、滑沢剤、着色剤、矯味矯臭剤等があげられ、必要により、吸収促進剤、界面活性剤、抗酸化剤などを使用することもできる。
【００１２】
本発明にかかる内服用医薬固形製剤は、通常の製剤化の方法で製造することができる。例えば、銅クロロフィリンの塩及び酸を必要に応じて乳糖、マンニトール等の賦形剤を添加して混合し、ポリビニルピロリドン、ヒドロキシプロピルセルロース等の結合剤を加えて、押出し造粒、流動層造粒または噴霧乾燥式造粒等により造粒、乾燥し、顆粒剤とすることができ、その後これを通常の方法により、チュアブル錠等とすることもできる。
【００１３】
【実施例】
以下に、実施例及び試験例を示して本発明をさらに詳細に説明するが、本発明がこれらに限定されるものでないことはいうまでもない。
【００１４】
実施例１
銅クロロフィリンカリウム及びクエン酸を配合した顆粒剤
水酸化マグネシウム60g、沈降炭酸カルシウム110g、無水リン酸水素カルシウム120g、銅クロロフィリンカリウム9g、精製白糖21g、乳糖121.2g、アスパルテーム1g、ステアリン酸マグネシウム10g、無水クエン酸9gを撹拌混合し、粉状固形製剤を得た。かかる粉状固形製剤を乾燥後、1-メントール0.8gを投入して撹拌混合し、顆粒剤462gを得た。
【００１５】
実施例２
銅クロロフィリンカリウム及びクエン酸を配合したチュアブル錠
水酸化マグネシウム60g、沈降炭酸カルシウム110g、無水リン酸水素カルシウム120g、銅クロロフィリンカリウム9g、精製白糖21g、乳糖121.2g、アスパルテーム1g、無水クエン酸9gを撹拌混合し、粉状固形製剤を得た。かかる粉状固形製剤を乾燥後、ステアリン酸マグネシウム10g、1-メントール0.8gを投入して撹拌混合し、打錠成形によりチュアブル錠を得た。
【００１６】
対照例
実施例２に記載の処方から無水クエン酸を除いて、同様の方法によりチュアブル錠を製造し、対照例とした。
【００１７】
【試験例】
前記の実施例２と対照例で得られた錠剤それぞれ１錠を被験者20名が空腹時に口腔内でかみ砕かずに溶解し、溶解直後と、10分経過後の２回、被験者の舌の着色の度合いを観察した。結果を表１に示す。
【００１８】
【表１】
【発明の効果】
本発明は、銅クロロフィリンの塩と酸を含有することを特徴とする製剤であり、特に、口腔内で溶解後の銅クロロフィリンの塩による舌、口腔内の着色を効果的に防止できる点で優れている。
【００２０】
上記した効果から、本発明により、銅クロロフィリンの塩を含有し、かつ着色を気にせずいつでも気軽に服用可能な製剤を提供することができる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a preparation comprising a salt of copper chlorophyllin and an acid. More specifically, the present invention relates to a preparation containing a salt and acid of copper chlorophyllin that does not cause coloration in the oral cavity even when taken.
[0002]
[Prior art]
Chlorophyll, which is naturally present as chlorophyll in plants and the like, is a porphyrin-based pigment having one magnesium atom in its molecule and is known to have a unique dark green color. Chlorophyll is a fat-soluble substance, but can be converted to water-soluble chlorophyllin by hydrolysis with alkali. Copper chlorophyllin is a compound obtained by replacing the magnesium atom in the chlorophyllin molecule with a copper atom. As a pharmaceutical, chlorophyllin is effective in preventing bad breath and treating wounds, and has been conventionally incorporated into many products. In addition, it is known to be useful as a prophylactic / therapeutic agent for gastric ulcer, duodenal ulcer and gastritis based on mucosal protective action, and is an extremely familiar pharmaceutical ingredient. For this reason, it is usually formulated in the form of a salt such as copper chlorophyllin potassium, and the dosage form can be easily taken immediately such as powder, granule, tablet and the like.
[0003]
[Problems to be solved by the invention]
However, since copper chlorophyllin salts, such as copper chlorophyllin potassium, are substances that exhibit a dark green color, when the preparations containing them are dissolved in the mouth after taking them, the oral cavity and even the tongue may be damaged. There was a problem of coloring in dark green. Since such coloring is so strong that it remains on the tongue and the like for a whole day, the dosage method has been limited to tablets that do not dissolve in the oral cavity. However, due to diversification of consumer needs and the like, a dosage form such as a chewable tablet in which a tablet containing a salt of copper chlorophyllin is dissolved and taken in the mouth has been desired. An object of the present invention is to provide a preparation containing a salt of copper chlorophyllin, which prevents such coloring and is excellent in taking feeling.
[0004]
[Means for Solving the Problems]
As a result of intensive investigations in view of the above circumstances, the inventors of the present invention added a commonly used acid to a salt of copper chlorophyllin. As a result, the present invention has been completed.
[0005]
That is, the present invention is a solid pharmaceutical preparation for internal use comprising a salt of copper chlorophyllin and an acid.
[0006]
The salt of copper chlorophyllin in the present invention means that the carboxyl group possessed by copper chlorophyllin forms a salt. Specific examples of such salts include salts with alkali metals such as potassium salts and sodium salts; salts with amines such as trimethylamine salts, triethylamine salts, procaine salts, pyridine salts, and phenethylbenzylamine salts; Salts with inorganic acids such as hydrohalides, hydroiodates, sulfates, nitrates, perchlorates, phosphates, carbonates, bicarbonates; arginates, aspartates, glutamates, Salts with amino acids such as potassium salts and sodium salts; salts with amino acids such as arginate, aspartate and glutamate, more preferably potassium It is a salt with an alkali metal such as a salt or a sodium salt.
[0007]
The acid in the present invention means any acid that can be blended as a pharmaceutical additive, specifically, for example, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, carbonic acid, bicarbonate, etc. Inorganic acids such as: acetic acid, malic acid, citric acid, maleic acid, tartaric acid, fumaric acid, ascorbic acid and other organic carboxylic acids; methanesulfonic acid, trifluoromethanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, etc. Organic sulfonic acids; amino acids such as arginic acid, aspartic acid and glutamic acid.
[0008]
The weight ratio of the copper chlorophyllin salt to the acid in the present invention is usually 0.01 to 1 part by weight of the acid having the same meaning as defined above with respect to 1 part by weight of the copper chlorophyllin salt. The acid having the same meaning as defined above with respect to parts by weight is 0.05 to 1 part by weight, more preferably 0.05 to 0.75 part by weight, and still more preferably 0.1 to 0.3 part by weight.
[0009]
Furthermore, the preparation according to the present invention can also be produced by adding other medicinal ingredients to copper chlorophyllin salt. The other medicinal ingredients are not particularly limited, and specifically include, for example, antistagnation agents, intestinal regulating agents, anti-ulcer agents, gastric digestive agents, antacids, antihistamines, anxiolytic agents, antiepileptic agents, antipyretic analgesic / antiinflammatory agents, diuresis Agents, antihypertensive agents, vasodilators, hyperlipidemia agents, bronchodilators, vitamins, herbal medicines, antibiotics, antiviral agents and the like.
[0010]
The preparation according to the present invention is a solid pharmaceutical preparation for internal use such as powder, granule, fine granule, pill, tablet and the like. In particular, it is most suitable for preparations such as chewable tablets, troche tablets, etc. that are taken in the mouth by being chewed or dissolved.
[0011]
These additives can be formulated with various commonly used additives. Examples of such additives include solid excipients for internal use, such as excipients, binders, lubricants, coloring agents, flavoring agents, and the like. If necessary, absorption enhancers, surfactants, An oxidizing agent or the like can also be used.
[0012]
The solid pharmaceutical preparation for internal use according to the present invention can be produced by a usual formulation method. For example, salt and acid of copper chlorophyllin are mixed by adding excipients such as lactose and mannitol as necessary, and binders such as polyvinyl pyrrolidone and hydroxypropyl cellulose are added, extrusion granulation, fluidized bed granulation Alternatively, it can be granulated and dried by spray-drying granulation or the like to obtain granules, which can then be made into chewable tablets or the like by a usual method.
[0013]
【Example】
Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples, but it goes without saying that the present invention is not limited thereto.
[0014]
Example 1
Granules containing copper chlorophyllin potassium and citric acid 60g magnesium hydroxide, precipitated calcium carbonate 110g, anhydrous calcium hydrogen phosphate 120g, copper chlorophyllin potassium 9g, purified white sugar 21g, lactose 121.2g, aspartame 1g, stearic acid Magnesium 10 g and anhydrous citric acid 9 g were mixed with stirring to obtain a powdery solid preparation. After drying the powdery solid preparation, 0.8 g of 1-menthol was added and mixed by stirring to obtain 462 g of granules.
[0015]
Example 2
Chewable tablet containing copper chlorophyllin potassium and citric acid 60g magnesium hydroxide, precipitated calcium carbonate 110g, anhydrous calcium hydrogen phosphate 120g, copper chlorophyllin potassium 9g, purified white sugar 21g, lactose 121.2g, aspartame 1g, anhydrous citric acid 9 g of acid was mixed with stirring to obtain a powdery solid preparation. After drying this powdery solid preparation, 10 g of magnesium stearate and 0.8 g of 1-menthol were added and mixed with stirring, and chewable tablets were obtained by tableting.
[0016]
Control Example A chewable tablet was produced by the same method except that citric acid anhydride was removed from the formulation described in Example 2, and used as a control example.
[0017]
[Test example]
Each of the tablets obtained in Example 2 and the control example was dissolved by 20 subjects without chewing in the oral cavity on an empty stomach, and immediately after dissolution and twice after 10 minutes, the subject's tongue was colored. The degree of was observed. The results are shown in Table 1.
[0018]
[Table 1]
【The invention's effect】
The present invention is a preparation characterized by containing a salt and an acid of copper chlorophyllin, and particularly excellent in that it can effectively prevent coloring of the tongue and oral cavity due to the salt of copper chlorophyllin after dissolution in the oral cavity. ing.
[0020]
From the effects described above, the present invention can provide a preparation that contains a salt of copper chlorophyllin and can be easily taken at any time without worrying about coloring.
Claims (6)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP06821398A JP3734360B2 (en) | 1998-03-18 | 1998-03-18 | Formulation containing a salt of copper chlorophyllin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP06821398A JP3734360B2 (en) | 1998-03-18 | 1998-03-18 | Formulation containing a salt of copper chlorophyllin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH11269073A JPH11269073A (en) | 1999-10-05 |
| JP3734360B2 true JP3734360B2 (en) | 2006-01-11 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP06821398A Expired - Fee Related JP3734360B2 (en) | 1998-03-18 | 1998-03-18 | Formulation containing a salt of copper chlorophyllin |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN117100756A (en) * | 2015-01-19 | 2023-11-24 | C·V·萨万基卡尔 | Chlorophylin compositions and uses thereof |
| WO2023190849A1 (en) * | 2022-03-31 | 2023-10-05 | 第一三共ヘルスケア株式会社 | Liquid composition for oral use |
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| JPH11269073A (en) | 1999-10-05 |
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