JP6355689B2 - 肝線維化又は非アルコール性脂肪性肝を予防、治療する医薬組成物 - Google Patents
肝線維化又は非アルコール性脂肪性肝を予防、治療する医薬組成物 Download PDFInfo
- Publication number
- JP6355689B2 JP6355689B2 JP2016177566A JP2016177566A JP6355689B2 JP 6355689 B2 JP6355689 B2 JP 6355689B2 JP 2016177566 A JP2016177566 A JP 2016177566A JP 2016177566 A JP2016177566 A JP 2016177566A JP 6355689 B2 JP6355689 B2 JP 6355689B2
- Authority
- JP
- Japan
- Prior art keywords
- liver
- pharmaceutical composition
- present
- composition
- jaundice
- 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.)
- Active
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 20
- 208000019425 cirrhosis of liver Diseases 0.000 title claims description 17
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 title description 10
- 239000000843 powder Substances 0.000 claims description 13
- 206010023126 Jaundice Diseases 0.000 claims description 12
- 241000190633 Cordyceps Species 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 6
- 241000045403 Astragalus propinquus Species 0.000 claims description 5
- 235000006533 astragalus Nutrition 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 4
- 235000013402 health food Nutrition 0.000 claims description 4
- 241001416980 Paecilomyces hepiali Species 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 22
- 210000004185 liver Anatomy 0.000 description 21
- 230000000694 effects Effects 0.000 description 16
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 12
- 241000700159 Rattus Species 0.000 description 10
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 9
- 108010082126 Alanine transaminase Proteins 0.000 description 9
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 9
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 9
- 206010067125 Liver injury Diseases 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- 239000003963 antioxidant agent Substances 0.000 description 9
- 230000003078 antioxidant effect Effects 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 235000009200 high fat diet Nutrition 0.000 description 9
- 102000008186 Collagen Human genes 0.000 description 8
- 108010035532 Collagen Proteins 0.000 description 8
- 229920001436 collagen Polymers 0.000 description 8
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 8
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 8
- 231100000234 hepatic damage Toxicity 0.000 description 7
- 230000008818 liver damage Effects 0.000 description 7
- 230000037396 body weight Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 208000004930 Fatty Liver Diseases 0.000 description 5
- 206010019708 Hepatic steatosis Diseases 0.000 description 5
- 241001248610 Ophiocordyceps sinensis Species 0.000 description 5
- 208000010706 fatty liver disease Diseases 0.000 description 5
- 210000005228 liver tissue Anatomy 0.000 description 5
- 231100000240 steatosis hepatitis Toxicity 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 102000019197 Superoxide Dismutase Human genes 0.000 description 4
- 108010012715 Superoxide dismutase Proteins 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 210000002744 extracellular matrix Anatomy 0.000 description 4
- 229940125396 insulin Drugs 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 230000001502 supplementing effect Effects 0.000 description 4
- 102000016938 Catalase Human genes 0.000 description 3
- 108010053835 Catalase Proteins 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 206010016654 Fibrosis Diseases 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 230000004761 fibrosis Effects 0.000 description 3
- 229960003180 glutathione Drugs 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- SEBFKMXJBCUCAI-UHFFFAOYSA-N NSC 227190 Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-UHFFFAOYSA-N 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 241001149964 Tolypocladium Species 0.000 description 2
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 description 2
- 240000008866 Ziziphus nummularia Species 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 230000007882 cirrhosis Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 231100000753 hepatic injury Toxicity 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 235000021590 normal diet Nutrition 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical compound C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-HKTJVKLFSA-N 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 229960004245 silymarin Drugs 0.000 description 2
- 235000017700 silymarin Nutrition 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 229960000306 zinc gluconate Drugs 0.000 description 2
- 235000011478 zinc gluconate Nutrition 0.000 description 2
- 239000011670 zinc gluconate Substances 0.000 description 2
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 1
- -1 CAT Proteins 0.000 description 1
- 241000123346 Chrysosporium Species 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 108010063907 Glutathione Reductase Proteins 0.000 description 1
- 102000006587 Glutathione peroxidase Human genes 0.000 description 1
- 108700016172 Glutathione peroxidases Proteins 0.000 description 1
- 102100036442 Glutathione reductase, mitochondrial Human genes 0.000 description 1
- 241000143459 Hirsutella Species 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 241000422921 Polycephalomyces sinensis Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 241001626366 Sporothrix insectorum Species 0.000 description 1
- 241001574328 Stachybotrys sp. Species 0.000 description 1
- GLEVLJDDWXEYCO-UHFFFAOYSA-N Trolox Chemical compound O1C(C)(C(O)=O)CCC2=C1C(C)=C(C)C(O)=C2C GLEVLJDDWXEYCO-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000004500 stellate cell Anatomy 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/481—Astragalus (milkvetch)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/062—Ascomycota
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/062—Ascomycota
- A61K36/066—Clavicipitaceae
- A61K36/068—Cordyceps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Description
本発明のある好ましい具体例に用いた冬虫夏草菌糸体は、ペシロマイセスヘピアリ菌糸体粉末である。当該ペシロマイセスヘピアリ菌糸体粉末の製造は、図1のフロー図に示され、当該ペシロマイセスヘピアリ菌糸体は、培養及び発酵を経て、更に、得られた菌糸体を冷凍又は熱乾燥、磨砕及び濾過し、粉末にしたものである。また、黄耆は、ナイモウ黄耆又はキバナ黄耆から選ばれる、乾燥した根から作られた市販の黄耆濃縮粉末を用いた。また、本発明の医薬組成物は、ナツメ濃縮粉末及び薬理学的に許容できる賦形剤を更に含み、当該賦形剤は、リン酸カルシウム、グルコン酸亜鉛、ステアリン酸マグネシウム、二酸化ケイ素及びでん粉のうちの1つ又は複数の組み合せから選ばれる。上記組成物は、カプセル剤型に製造されることが好ましく、その中に含まれる各成分及び含有量は、下記に示す。
図2A及び図2Bに示すように、TAA処理は、血液脂質(トリグリセリド(TG)及びコレステロール(TC))の低下をもたらしたが、TAAのみで処理した個体と比較して、本発明の組成物を補充した個体の血清においてTG及びTCのいずれも著しく高い値を示しており、TCは対照群の水準までに回復可能である。肝臓の脂質分析結果では、本発明の組成物を補充することにより、肝臓脂肪の蓄積を有効に低減することができると示された(表1に示す)。
各群の抗酸化成分及び酵素活性を測定し、その結果を表2に示す。
アラニントランスアミナーゼ(alanine transaminase,ALT)及びアスパラギン酸トランスアミナーゼ(aspartate transaminase,AST)は、肝臓損傷の指標として用いられ、結果では、本発明の組成物が血液中のALT及びASTを有効に低減させることができることが示され(図2C及び図2Dに示す)、また、低い投与量の組成物でも、ALT及びASTを低減させる効果を示した。
六週間後、採血して、下記表4中の肝臓機能の各項目を測定した。その結果、本発明の組成物は、AST、ALT及びビリルビンを減少させ、且つ血清アルブミンの含有量を増加させた。
肝臓組織中の抗酸化分子であるグルタチオン(GSH)、グルタチオンペルオキシダーゼ(GSH-Px)、グルタチオンレダクターゼ(GSH-Rd)、スーパーオキシドディスムターゼ(SOD)及びカタラーゼ(Catalase)の活性を測定した。結果は、表5に示す。
四塩化炭素が肝損傷を引き起こし、病理切片中で肝臓表面が荒いことが観察されたが、本発明の組成物を投与したラットの肝臓組織では、線維化した現象が軽微であり、肝小葉の変形の確率が低下した。
表6
60%以上のカロリーを脂肪として含む高脂肪飼料(D12492, Research Diets, USA)で6週齢のC57BL/6のマウスを18週間飼育し、マウスの肥満を誘発した。一方、10%以上のカロリーを脂肪として含む通常の飼料(D12450B, Research Diets, USA)で、同じ週齢のC57BL/6のマウスを飼育して、対照群とした。
Claims (6)
- 50重量%〜90重量%の冬虫夏草菌糸体と10重量%〜50重量%の黄耆とを含む、非ウィルス性の肝線維化を予防、治療するための医薬組成物。
- 前記冬虫夏草菌糸体は、ペシロマイセスヘピアリ菌糸体(Paecilomyces hepiali Chen et Dai mycelia)である、請求項1に記載の医薬組成物。
- 前記冬虫夏草菌糸体は、乾燥粉末状である、請求項1に記載の医薬組成物。
- 前記黄耆は、ナイモウ黄耆(Astragalus membranaceus (Fisch.)Bge. Var. mongholicus (Bge.) Hsiao)又はキバナオウギ(Astragalus membranaceus (Fisch.) Bge.)の乾燥した根から作られる濃縮黄耆粉末から選ばれる、請求項1に記載の医薬組成物。
- 前記医薬組成物は、薬剤または保健用食品を製造するために用いられる、請求項1に記載の医薬組成物。
- 前記薬剤または保健用食品が、カプセル剤、錠剤又は散剤である経口製剤である、請求項5に記載の医薬組成物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
TW101110713A TWI554277B (zh) | 2012-03-28 | 2012-03-28 | 預防及治療非酒精性脂肪肝之醫藥組成物 |
TW101110713 | 2012-03-28 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012255844A Division JP6050099B2 (ja) | 2012-03-28 | 2012-11-22 | 肝線維化又は非アルコール性脂肪性肝を予防、治療する医薬組成物 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017031171A JP2017031171A (ja) | 2017-02-09 |
JP6355689B2 true JP6355689B2 (ja) | 2018-07-11 |
Family
ID=46851885
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012255844A Active JP6050099B2 (ja) | 2012-03-28 | 2012-11-22 | 肝線維化又は非アルコール性脂肪性肝を予防、治療する医薬組成物 |
JP2016177566A Active JP6355689B2 (ja) | 2012-03-28 | 2016-09-12 | 肝線維化又は非アルコール性脂肪性肝を予防、治療する医薬組成物 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012255844A Active JP6050099B2 (ja) | 2012-03-28 | 2012-11-22 | 肝線維化又は非アルコール性脂肪性肝を予防、治療する医薬組成物 |
Country Status (5)
Country | Link |
---|---|
US (2) | US8658181B2 (ja) |
EP (1) | EP2644201B1 (ja) |
JP (2) | JP6050099B2 (ja) |
CN (2) | CN104382985A (ja) |
TW (1) | TWI554277B (ja) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3191110A4 (en) * | 2014-08-18 | 2018-04-18 | Pharmagenesis, Inc. | Polygalacturonan rhamnogalacturonan1 (pgrg1) composition |
CN105521327B (zh) * | 2015-11-03 | 2017-02-15 | 山西大同大学 | 预防和/或治疗酒精性肝病或肝癌的药物组合物 |
IL243707A0 (en) | 2016-01-20 | 2016-05-01 | Galmed Res And Dev Ltd | Treatment to regulate the microbiota in the intestine |
US11197870B2 (en) | 2016-11-10 | 2021-12-14 | Galmed Research And Development Ltd | Treatment for hepatic fibrosis |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1127612A (zh) * | 1995-12-07 | 1996-07-31 | 汪景山 | 一种新型虫草饮料 |
CN1063655C (zh) * | 1998-07-21 | 2001-03-28 | 邢炳荣 | 治疗乙型肝炎的纯中药浓缩胶囊 |
CN1274356C (zh) * | 2002-02-07 | 2006-09-13 | 应天明 | 治疗乙肝后肝纤维化和肝硬化的中药组合物及其制造方法 |
CN1243557C (zh) * | 2003-01-21 | 2006-03-01 | 赵胜利 | 一种抗肝纤维化的药物 |
US8722056B2 (en) * | 2003-10-03 | 2014-05-13 | Tcm Biotech International Corp. | Methods for making and compositions comprising fermentation products of cordyceps sinensis |
TWI258373B (en) * | 2003-10-07 | 2006-07-21 | Tcm Biotech Internat Corp | Auxiliary agent for hepatitis C |
CN1274363C (zh) * | 2003-10-16 | 2006-09-13 | 泰宗生物科技股份有限公司 | C型肝炎辅助治疗剂 |
ES2400580T3 (es) * | 2006-12-20 | 2013-04-10 | Jung Sik Lee | Una composición que comprende el extracto de hierbas combinadas para prevenir y tratar enfermedades hepáticas |
JP2008201749A (ja) * | 2007-02-21 | 2008-09-04 | Okayama Univ | 肝細胞増殖因子産生誘導剤及びその医薬品組成物 |
CN101574388A (zh) * | 2009-03-26 | 2009-11-11 | 杨毅 | 虫草口服液及其制备方法 |
-
2012
- 2012-03-28 TW TW101110713A patent/TWI554277B/zh active
- 2012-09-19 EP EP12184990.5A patent/EP2644201B1/en active Active
- 2012-09-26 CN CN201410673517.7A patent/CN104382985A/zh active Pending
- 2012-09-26 CN CN2012103636397A patent/CN103356732A/zh active Pending
- 2012-10-31 US US13/664,550 patent/US8658181B2/en active Active
- 2012-11-22 JP JP2012255844A patent/JP6050099B2/ja active Active
-
2014
- 2014-01-09 US US14/151,001 patent/US8858954B2/en active Active
-
2016
- 2016-09-12 JP JP2016177566A patent/JP6355689B2/ja active Active
Also Published As
Publication number | Publication date |
---|---|
US8858954B2 (en) | 2014-10-14 |
EP2644201A1 (en) | 2013-10-02 |
EP2644201B1 (en) | 2018-12-26 |
US20140127256A1 (en) | 2014-05-08 |
CN103356732A (zh) | 2013-10-23 |
JP6050099B2 (ja) | 2016-12-21 |
US8658181B2 (en) | 2014-02-25 |
JP2017031171A (ja) | 2017-02-09 |
TWI554277B (zh) | 2016-10-21 |
CN104382985A (zh) | 2015-03-04 |
JP2013203739A (ja) | 2013-10-07 |
US20130259894A1 (en) | 2013-10-03 |
TW201338786A (zh) | 2013-10-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6355689B2 (ja) | 肝線維化又は非アルコール性脂肪性肝を予防、治療する医薬組成物 | |
CN110787233B (zh) | 保肝中药组合物及其提取物和制药用途 | |
Yen et al. | The hepatoprotective effect of Bupleurum kaoi, an endemic plant to Taiwan, against dimethylnitrosamine-induced hepatic fibrosis in rats | |
CN101856384B (zh) | 一种护肝组合物 | |
CN104436142B (zh) | 一种治疗猪流行性腹泻的中药组合物 | |
CN1230160C (zh) | 竹叶总黄酮在制备前列腺疾病防治药物中的应用 | |
CN1879845A (zh) | 一种具有预防或治疗急慢性肝病的药物组合物 | |
TWI637748B (zh) | 蓮蓬萃取物用於治療及/或預防腎臟病變之用途 | |
CN105232588B (zh) | 一种具有保护酒精性肝损伤作用的保健食品及制备方法 | |
TWI605820B (zh) | 用以改善酒精中毒之中草藥複方組合物及其用途 | |
TWI501771B (zh) | 預防及治療肝纖維化之醫藥組成物 | |
KR102192586B1 (ko) | 아위버섯의 추출물 또는 분말을 유효성분으로 함유하는 지방간 질환 치료용 약학적 조성물 및 간기능 개선용 건강기능식품 | |
CN1679658A (zh) | 一种治疗艾兹病的中药制剂及其加工方法 | |
KR101093006B1 (ko) | 미생물을 이용한 우황 청심원 원료 함유 건강식품의 제조방법 및 그 제조방법에 의해 제조된 건강식품 | |
CN108096321A (zh) | 一种防治pm2.5引起的肺损伤的中药组合物 | |
CN113101331B (zh) | 一种百里香药茶及其制备方法和应用 | |
CN103735631B (zh) | 一种治疗乙肝的药物组合物及其制备方法 | |
WO2019014040A1 (en) | METHOD OF TREATING HEPATIC STEATOSIS | |
CN112316100B (zh) | 人丹中药组合物用于防醉解酒或治疗酒精性肝损伤的新用途 | |
CN113057326B (zh) | 一种含猴头菇的组合物的制备方法及其应用 | |
Park et al. | Effects of medicinal enzyme powder on intestinal mobility, lipid level, and blood parameters of loperamide-induced constipation in rats | |
CN117815342A (zh) | 一种药食同源口服液及其制备方法 | |
CN116808156A (zh) | 一种防治动脉粥样硬化的中药组合物及其应用 | |
CN1528387A (zh) | 红景天在制备治疗或预防老年痴呆症药物中的应用 | |
CN109731016A (zh) | 一种治疗乳腺癌的中药组合物及其制备方法与药物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170718 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20171002 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20171215 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180117 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20180522 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20180612 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6355689 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |