JP2016196412A - 末梢神経障害誘発感覚異常の改善剤 - Google Patents
末梢神経障害誘発感覚異常の改善剤 Download PDFInfo
- Publication number
- JP2016196412A JP2016196412A JP2015075668A JP2015075668A JP2016196412A JP 2016196412 A JP2016196412 A JP 2016196412A JP 2015075668 A JP2015075668 A JP 2015075668A JP 2015075668 A JP2015075668 A JP 2015075668A JP 2016196412 A JP2016196412 A JP 2016196412A
- Authority
- JP
- Japan
- Prior art keywords
- aucubin
- peripheral neuropathy
- induced
- paclitaxel
- aucbin
- 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.)
- Granted
Links
- 208000033808 peripheral neuropathy Diseases 0.000 title claims abstract description 14
- 208000035824 paresthesia Diseases 0.000 title abstract 3
- RJWJHRPNHPHBRN-FKVJWERZSA-N aucubin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@@H]2C(CO)=C[C@@H](O)[C@@H]2C=CO1 RJWJHRPNHPHBRN-FKVJWERZSA-N 0.000 claims abstract description 20
- UTDFQMAXCUGNJR-UHFFFAOYSA-N aucubin Natural products OCC1OC(Oc2ccoc2C3C(O)CCC3O)C(O)C(O)C1O UTDFQMAXCUGNJR-UHFFFAOYSA-N 0.000 claims abstract description 18
- 206010040021 Sensory abnormalities Diseases 0.000 claims description 12
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 claims description 6
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 claims description 6
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 2
- DKVBOUDTNWVDEP-NJCHZNEYSA-N teicoplanin aglycone Chemical compound N([C@H](C(N[C@@H](C1=CC(O)=CC(O)=C1C=1C(O)=CC=C2C=1)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)OC=1C=C3C=C(C=1O)OC1=CC=C(C=C1Cl)C[C@H](C(=O)N1)NC([C@H](N)C=4C=C(O5)C(O)=CC=4)=O)C(=O)[C@@H]2NC(=O)[C@@H]3NC(=O)[C@@H]1C1=CC5=CC(O)=C1 DKVBOUDTNWVDEP-NJCHZNEYSA-N 0.000 claims 1
- 208000002193 Pain Diseases 0.000 abstract description 15
- 239000002246 antineoplastic agent Substances 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 11
- 238000002360 preparation method Methods 0.000 abstract description 6
- 238000011282 treatment Methods 0.000 abstract description 6
- 231100000862 numbness Toxicity 0.000 abstract description 4
- 230000002265 prevention Effects 0.000 abstract description 3
- 241001127637 Plantago Species 0.000 abstract 1
- 229930012538 Paclitaxel Natural products 0.000 description 18
- 229960001592 paclitaxel Drugs 0.000 description 18
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 11
- 229940041181 antineoplastic drug Drugs 0.000 description 9
- 230000004044 response Effects 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 210000003141 lower extremity Anatomy 0.000 description 6
- 208000004454 Hyperalgesia Diseases 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000010153 Šidák test Methods 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000003414 extremity Anatomy 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 229960001756 oxaliplatin Drugs 0.000 description 3
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- IBFYXTRXDNAPMM-BVTMAQQCSA-N Geniposide Chemical compound O([C@@H]1OC=C([C@@H]2[C@H]1C(=CC2)CO)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O IBFYXTRXDNAPMM-BVTMAQQCSA-N 0.000 description 2
- IBFYXTRXDNAPMM-FZEIBHLUSA-N Geniposide Natural products COC(=O)C1=CO[C@@H](O[C@H]2O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]2O)[C@H]2[C@@H]1CC=C2CO IBFYXTRXDNAPMM-FZEIBHLUSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229940123237 Taxane Drugs 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- VGLLGNISLBPZNL-RBUKDIBWSA-N arborescoside Natural products O=C(OC)C=1[C@@H]2C([C@H](O[C@H]3[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O3)OC=1)=C(CO)CC2 VGLLGNISLBPZNL-RBUKDIBWSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 241000411851 herbal medicine Species 0.000 description 2
- 230000009610 hypersensitivity Effects 0.000 description 2
- 210000003127 knee Anatomy 0.000 description 2
- 210000002414 leg Anatomy 0.000 description 2
- 239000009989 mao-bushi-saishin-to Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- HPPZDIWRKXHSGN-UHFFFAOYSA-N monodeoxyaucubin Natural products C12C(C)=CC(O)C2C=COC1OC1OC(CO)C(O)C(O)C1O HPPZDIWRKXHSGN-UHFFFAOYSA-N 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000002981 neuropathic effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- BACWCXKATFIVFS-JQCXWYLXSA-N (1r,4ar,5s,7as)-7-(hydroxymethyl)-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-1,5-diol Chemical compound C1=CO[C@@H](O)[C@@H]2C(CO)=C[C@@H](O)[C@@H]21 BACWCXKATFIVFS-JQCXWYLXSA-N 0.000 description 1
- FXVNPWQOVKBTRF-UHFFFAOYSA-N 10-O-caffeoylaucubin Natural products OCC1OC(OC2OC=CC3C(O)C=C(COC(=O)C=Cc4ccc(O)c(O)c4)C23)C(O)C(O)C1O FXVNPWQOVKBTRF-UHFFFAOYSA-N 0.000 description 1
- OANONBNMFPNJOA-UHFFFAOYSA-N 2'-O-benzoylaucubin Natural products OCC1OC(OC2OC=CC3C(O)C=C(CO)C23)C(OC(=O)c4ccccc4)C(O)C1O OANONBNMFPNJOA-UHFFFAOYSA-N 0.000 description 1
- OOJZWXCTDBXCJY-UHFFFAOYSA-N 2-[[5-hydroxy-7-(hydroxymethyl)-1,3,4,4a,5,7a-hexahydrocyclopenta[c]pyran-1-yl]oxy]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OC1C(O)C(O)C(CO)OC1OC1C2C(CO)=CC(O)C2CCO1 OOJZWXCTDBXCJY-UHFFFAOYSA-N 0.000 description 1
- FLXYYVTUDYLYMR-UHFFFAOYSA-N 6-O-beta-D-xylosylaucubin Natural products OCC1OC(OC2OC=CC3C(OC4OCC(O)C(O)C4O)C=C(CO)C23)C(O)C(O)C1O FLXYYVTUDYLYMR-UHFFFAOYSA-N 0.000 description 1
- BACWCXKATFIVFS-UHFFFAOYSA-N Aucubigenin Natural products C1=COC(O)C2C(CO)=CC(O)C21 BACWCXKATFIVFS-UHFFFAOYSA-N 0.000 description 1
- QIIDATRCGITYRZ-UHFFFAOYSA-N Catalpol Natural products OCC1OC(OC2OC=CC3C(O)C(=C(CO)C23)O)C(O)C(O)C1O QIIDATRCGITYRZ-UHFFFAOYSA-N 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 241000208688 Eucommia Species 0.000 description 1
- 206010016326 Feeling cold Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 235000003805 Musa ABB Group Nutrition 0.000 description 1
- 240000008790 Musa x paradisiaca Species 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 description 1
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 description 1
- 208000010886 Peripheral nerve injury Diseases 0.000 description 1
- 235000015266 Plantago major Nutrition 0.000 description 1
- 244000134552 Plantago ovata Species 0.000 description 1
- 235000003421 Plantago ovata Nutrition 0.000 description 1
- 239000009223 Psyllium Substances 0.000 description 1
- 102000003141 Tachykinin Human genes 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 206010053552 allodynia Diseases 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- LHDWRKICQLTVDL-PZYDOOQISA-N catalpol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@@H]2[C@@]3(CO)O[C@H]3[C@@H](O)[C@@H]2C=CO1 LHDWRKICQLTVDL-PZYDOOQISA-N 0.000 description 1
- UXSACQOOWZMGSE-UHFFFAOYSA-N catalposide Natural products OC1C(O)C(O)C(CO)OC1OC1C2C3(CO)OC3C(OC(=O)C=3C=CC(O)=CC=3)C2C=CO1 UXSACQOOWZMGSE-UHFFFAOYSA-N 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- -1 dehydroaucubin Natural products 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 210000001061 forehead Anatomy 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 239000009896 gosha-jinki-gan Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 229930182489 iridoid glycoside Natural products 0.000 description 1
- 150000008145 iridoid glycosides Chemical class 0.000 description 1
- 239000003410 keratolytic agent Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- LHDWRKICQLTVDL-UHFFFAOYSA-N methyl iridoid glycoside Natural products OC1C(O)C(O)C(CO)OC1OC1C2C3(CO)OC3C(O)C2C=CO1 LHDWRKICQLTVDL-UHFFFAOYSA-N 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229940070687 psyllium Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 1
- 239000009181 shakuyaku-kanzoh-toh Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 108060008037 tachykinin Proteins 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
イリドイドの配糖体は多くの薬用植物で見出されており、例えば、アウクビンは、オオバコ、アオキ、トチュウなどに含まれており、B型肝炎治療薬(特許文献1)、脳神経障害に対する治療薬(特許文献2)などの用途が知られている。
その結果、単回投与では、パクリタキセルおよびビンクリスチン誘発性疼痛に対して、使用したすべての漢方方剤では抑制効果が認められなかった。一方,オキサリプラチン誘発性疼痛反応に対して,牛車腎気丸,八味地黄丸及び六味丸が抑制効果を示した。しかし、麻黄附子細辛湯は,疼痛抑制効果を示さなかった。
本発明者らは、さらに有効成分の探索を進めた結果、車前子に含まれる成分の一つであるアウクビンがパクリタキセル誘発性疼痛反応を抑制することを見出し、本発明を完成させた。
以下に本発明を詳細に説明する。
それらを用いて常法に従って製造することができる。
なお、感覚異常の指標としてvon Freyフィラメントを用いた感覚の過過敏症(アロディニア)の評価を用いた。
<実験動物>
C57 BL/6NCr系6週齢の雄性マウス16匹を用いた。
<用いる試薬及び投与方法>
(a)5mg/kgになるように調製したパクリタキセル(SIGMA/SLBB4755V)あるいは溶媒をマウスの体重10gあたり0.1mL腹腔内投与した。
(b)パクリタキセルの溶媒組成は100% ethanol:CremophorEL(Fluka/1048604):saline(大塚製薬/M2J98)を1:1:8で混合したものを用いた。
(c)アウクビンは1匹あたり1mg腹腔内投与(1mg×8匹×1群×13日)した。また、アウクビンの溶媒は生理食塩水とし、0.1mL/体重10gを投与した。
<群の分類>
A群:パクリタキセル+アウクビン投与群
B群:パクリタキセル+アウクビンの溶媒投与群
<疼痛発生の指標>
0.69 mNのvFFを後肢足蹠に3秒押し当てた時のマウスの反応を以下のように分類し集計する。この操作は1匹につき片足3回ずつ計6回行う。
0point:反応なし/足を水平に動かす
1point:後肢を持ち上げる
2point:後肢を振る/後肢を舐める
<慣らし操作>
マウスを観察容器内の環境に慣れさせるため、実験を行う前に観察容器内に入れ30分放置。
結果を図1に示す。
<実験動物>
C57 BL/6NCr系6週齢の雄性マウス16匹を用いた。
<用いる試薬及び投与方法>
(a)5mg/kgになるように調製したパクリタキセル(SIGMA/SLBB4755V)あるいは溶媒をマウスの体重10gあたり0.1mL腹腔内投与した。
(b)パクリタキセルの溶媒組成は100% ethanol:CremophorEL(Fluka/1048604):saline(大塚製薬/M2J98)を1:1:8で混合したものを用いた。
(c)2.8mLの100%エタノールに28mgのアウクビンを溶解させ、 1匹あたり20μL塗布した。塗布は右足に行った(後述のvFF刺激は両足に行った)。また、調製した溶液はアルミホイルに包んで遮光・冷蔵保存した。
<群の分類>
A群:パクリタキセル+アウクビン塗布群
B群:パクリタキセル+アウクビンの溶媒塗布群
<疼痛発生の指標>
0.69 mNのvFFを後肢足蹠に3秒押し当てた時のマウスの反応を以下のように分類し集計する。この操作は1匹につき片足6回ずつ計12回行う。
0point:反応なし/足を水平に動かす
1point:後肢を持ち上げる
2point:後肢を振る/後肢を舐める
<慣らし操作>
マウスを観察容器内の環境に慣れさせるため、実験を行う前に観察容器内に入れ30分放置。
結果を図2に示す。
アウクビンの代わりに、ゲニポシド酸およびカタルポールを用い、実施例1と同様の方法で試験した。結果を図3および図4に示す。
Claims (2)
- アウクビン、アウクビンのアナログまたはそれらのアグリコンから選ばれる一つ以上の化合物を有効成分とする末梢神経障害で誘発される感覚異常改善剤。
- 化合物が、アウクビンまたはそのアグリコンである請求項1に記載の末梢神経障害で誘発される感覚異常改善剤。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2015075668A JP6537064B2 (ja) | 2015-04-02 | 2015-04-02 | 末梢神経障害誘発感覚異常の改善剤 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2015075668A JP6537064B2 (ja) | 2015-04-02 | 2015-04-02 | 末梢神経障害誘発感覚異常の改善剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2016196412A true JP2016196412A (ja) | 2016-11-24 |
JP6537064B2 JP6537064B2 (ja) | 2019-07-03 |
Family
ID=57357437
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015075668A Active JP6537064B2 (ja) | 2015-04-02 | 2015-04-02 | 末梢神経障害誘発感覚異常の改善剤 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP6537064B2 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107137393A (zh) * | 2017-06-08 | 2017-09-08 | 中国人民解放军第四军医大学 | 一种用于治疗糖尿病神经损伤的植物单体复方制剂 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101863938A (zh) * | 2010-03-23 | 2010-10-20 | 南京泽朗农业发展有限公司 | 一种制备高纯度桃叶珊瑚苷的方法 |
-
2015
- 2015-04-02 JP JP2015075668A patent/JP6537064B2/ja active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101863938A (zh) * | 2010-03-23 | 2010-10-20 | 南京泽朗农业发展有限公司 | 一种制备高纯度桃叶珊瑚苷的方法 |
Non-Patent Citations (2)
Title |
---|
EXPERIMENTAL NEUROBIOLOGY, vol. 23, no. 3, JPN6018049909, 2014, pages 238 - 245 * |
JOURNAL OF TRADITIONAL AND COMPLEMENTARY MEDICINE, vol. 4, no. 4, JPN6018049910, 2014, pages 293 - 297 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107137393A (zh) * | 2017-06-08 | 2017-09-08 | 中国人民解放军第四军医大学 | 一种用于治疗糖尿病神经损伤的植物单体复方制剂 |
Also Published As
Publication number | Publication date |
---|---|
JP6537064B2 (ja) | 2019-07-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20190224140A1 (en) | Cannabinoids for use in the treatment of neuropathic pain | |
JP2008534666A (ja) | 抗炎症製剤 | |
CN109200046A (zh) | 大麻素类化合物在治疗神经性皮炎中的应用 | |
WO2019155337A1 (en) | Compositions comprising a cannabinoid and punicalagin and methods of use thereof | |
BR112015010703B1 (pt) | uso de uma composição farmacêutica e composição farmacêutica | |
KR20130093180A (ko) | 항암제에 의한 말초신경장애의 예방 또는 치료제 | |
US20220331287A1 (en) | Compounds comprising cannabinoids and other natural ingredients for alieving premenstrual, menstrual and menopausal symptoms | |
WO2017111069A1 (ja) | 止痒剤 | |
JP6537064B2 (ja) | 末梢神経障害誘発感覚異常の改善剤 | |
WO2009043671A1 (en) | Use of a silybum marianum extract | |
Mullaicharam | A review on evidence based practice of Ginkgo biloba in brain health | |
KR20150037890A (ko) | 암-관련 피로 치료용 조성물 | |
Sinniah et al. | The anthelmintic effects of pyrantel pamoate, oxantel-pyrantel pamoate, levamisole and mebendazole in the treatment of intestinal nematodes | |
KR101793308B1 (ko) | 5-ht3 수용체 길항제인 사인 추출물을 포함하는 구토 또는 설사의 치료용 조성물 | |
da Silva et al. | Adverse reactions after orange essential oil administration to lambs | |
Edirisinghe et al. | Effect of Sapa Vireka Choorna on Vibandha (Mala Adassiya/Chronic Constipation)–Series of case studies | |
JP2013166744A (ja) | 経口紫外線抵抗性向上剤 | |
DE2422612C3 (de) | .Verwendung von 2,6-trans-Diphenylhexamethylcyclotetrasiloxan zur Herstellung eines oral oder intravenös verabreichbaren Arzneimittels zur Erhöhung des Dopamingehalts fan Gehirn von Tieren | |
US20220105107A1 (en) | Bioidentical progesterone cream infused with nanoemulsified cbd | |
KR102274174B1 (ko) | 알파피넨을 유효성분으로 함유하는 메스암페타민 중독 예방 또는 치료용 조성물 | |
Jantwal et al. | Gynocordia odorata R. Br. | |
KR20210023872A (ko) | Rls 치료를 위한 님 | |
JP2006131571A (ja) | 月経関連症状の緩和剤 | |
JPH06183988A (ja) | 膀胱癌予防剤 | |
WO2021247447A1 (en) | Antiviral compositions |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20161208 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180327 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190104 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190207 |
|
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: 20190508 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190529 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6537064 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
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 |