JPH01135720A - Nerve fiber regenerating agent - Google Patents
Nerve fiber regenerating agentInfo
- Publication number
- JPH01135720A JPH01135720A JP29178387A JP29178387A JPH01135720A JP H01135720 A JPH01135720 A JP H01135720A JP 29178387 A JP29178387 A JP 29178387A JP 29178387 A JP29178387 A JP 29178387A JP H01135720 A JPH01135720 A JP H01135720A
- Authority
- JP
- Japan
- Prior art keywords
- regenerating agent
- disease
- phosphatidylcholine
- nerve fiber
- effective
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 210000004126 nerve fiber Anatomy 0.000 title claims abstract description 16
- 230000001172 regenerating effect Effects 0.000 title claims abstract description 13
- 239000003795 chemical substances by application Substances 0.000 title claims abstract description 11
- 150000003905 phosphatidylinositols Chemical class 0.000 claims abstract description 13
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims abstract description 11
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 claims abstract description 10
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 claims abstract description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 5
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 5
- 208000006011 Stroke Diseases 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims abstract description 4
- 239000004480 active ingredient Substances 0.000 claims abstract 5
- 239000003814 drug Substances 0.000 claims description 4
- 239000000839 emulsion Substances 0.000 claims description 4
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 3
- 239000002502 liposome Substances 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 239000012492 regenerant Substances 0.000 claims 2
- 239000008187 granular material Substances 0.000 claims 1
- 241001465754 Metazoa Species 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 230000002490 cerebral effect Effects 0.000 abstract 2
- 206010008190 Cerebrovascular accident Diseases 0.000 abstract 1
- 230000007850 degeneration Effects 0.000 abstract 1
- 208000014674 injury Diseases 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 230000008733 trauma Effects 0.000 abstract 1
- 150000003904 phospholipids Chemical class 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000003943 catecholamines Chemical class 0.000 description 2
- 210000005056 cell body Anatomy 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 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 2
- 239000002609 medium Substances 0.000 description 2
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 description 1
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- FZWBNHMXJMCXLU-UHFFFAOYSA-N 2,3,4,5-tetrahydroxy-6-[3,4,5-trihydroxy-6-[[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxyhexanal Chemical compound OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OCC(O)C(O)C(O)C(O)C=O)O1 FZWBNHMXJMCXLU-UHFFFAOYSA-N 0.000 description 1
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 1
- 101001011741 Bos taurus Insulin Proteins 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 235000019743 Choline chloride Nutrition 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 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
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 101000766306 Homo sapiens Serotransferrin Proteins 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 102000015336 Nerve Growth Factor Human genes 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 239000004105 Penicillin G potassium Substances 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 108091000117 Tyrosine 3-Monooxygenase Proteins 0.000 description 1
- 102000048218 Tyrosine 3-monooxygenases Human genes 0.000 description 1
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229940000635 beta-alanine 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
- IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- XXWCODXIQWIHQN-UHFFFAOYSA-N butane-1,4-diamine;hydron;dichloride Chemical compound Cl.Cl.NCCCCN XXWCODXIQWIHQN-UHFFFAOYSA-N 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 229960003178 choline chloride Drugs 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229940119743 dextran 70 Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- BVTBRVFYZUCAKH-UHFFFAOYSA-L disodium selenite Chemical compound [Na+].[Na+].[O-][Se]([O-])=O BVTBRVFYZUCAKH-UHFFFAOYSA-L 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
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- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
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- 238000001990 intravenous administration Methods 0.000 description 1
- 239000002960 lipid emulsion Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 235000019136 lipoic acid Nutrition 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
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- 210000005036 nerve Anatomy 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
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- 210000002241 neurite Anatomy 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
童栗上■科里光互
本発明は神経線維再生剤に関する。更に詳しくは、本発
明は天然及び合成のホスファチジルイノシトール、ホス
ファチジルコリン、ホスファチジルセリン及びスフィン
ゴミエリンを単独又は任意選択混合して含有する製剤に
関するものであって、種々の神経疾患を処置するための
新規有用な医療用途を有する医薬を提供するものである
。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a nerve fiber regenerating agent. More particularly, the present invention relates to formulations containing natural and synthetic phosphatidylinositol, phosphatidylcholine, phosphatidylserine and sphingomyelin, alone or optionally in combination, which are novel and useful agents for treating various neurological diseases. The present invention provides pharmaceuticals with medical uses.
従来■及歪
神経線維の再生は、高等動物の中枢神経においても徐々
にではあるが起こることが知られてきている（Ｊ、Ｗ、
Ｇｅｄｄｅｓ、 Ｄ、Ｔ、Ｍｏｎａｇｈａｎ、 Ｃ，Ｗ
、Ｃｏｔｍａｎ。It has been known that regeneration of conventional and strained nerve fibers occurs, albeit gradually, in the central nervous system of higher animals (J, W,
Geddes, D.T., Monaghan, C.W.
, Cotman.
［、Ｔ、ｌ、ｏｔｔ、 Ｒ，Ｃ，ＫｉｍおよびＨ，Ｃ，
Ｃｈｕｉ、 ５ｃｉｅｎｃｅ 。[,T,l,ott, R,C,Kim and H,C,
Chui, 5science.
」皿、 １１７９−１１８１（１９８５））。このこと
は、脳卒中、例えば脳梗塞、脳出血、脳外傷、例えば事
故、手術あるいはアルツハイマー病やパーキンソン氏病
などの種々の神経疾患で一部変性を受けた神経組織にお
いても、神経線維の再生により機能回復できることを意
味している。” Dish, 1179-1181 (1985)). This means that even in nerve tissue that has partially degenerated due to stroke, cerebral infarction, cerebral hemorrhage, brain trauma, accident, surgery, or various neurological diseases such as Alzheimer's disease and Parkinson's disease, the function can be improved by regenerating nerve fibers. It means that you can recover.
神経線維の再生に有効な物質として、ラミニン［Ｓ、Ｌ
、Ｒｏｇｅｒｓ、 Ｐ、Ｃ，Ｌｅｔｏｕｒｎｅａｕ、
Ｓ、Ｌ、Ｐａ１ｍ、 Ｊ。Laminin [S, L
, Rogers, P., C. Letourneau,
S, L, Pa1m, J.
ＭｃＣａｒｊｈｙ及びり、Ｔ、Ｆｕｒｃｈｔ、口ｅｖ、
Ｂｉｏ１． 、９８ 、２１２−２１０（１９８３）］
やフファイフロロネクチンＲ，門、八ｋｅｒｓ 。McCarjhy and T. Furcht, mouth ev.
Bio1. , 98, 212-210 (1983)]
and Fuphifluoronectin R, phylum, 8kers.
ＱＪ］ｏｓｈｅｒ及びＪ、Ｅ、Ｌｉ１ｉｅｎ、 Ｄｅｖ
、Ｂｉｏｌ、 、 ８６ 。QJ] osher and J, E, Li1ien, Dev
, Biol, , 86.
１７９−１８８（１９８１） ）などの細胞外基質や、
ナーブグロースファクター（Ｐ、Ｃａ１ｉｓｓａｎｏ
、 Ａ、Ｃａｔｔａｎｅｏ ＋Ｓ、Ｂｉｏｃｃａ、 Ｌ
、八ｌｏｅ、 ＤｏＭｅｒｃａｎｔｉ及びＲ，Ｌｅｖｉ
−。179-188 (1981)),
Nerve Growth Factor (P, Calissano
, A., Cattaneo +S., Biocca, L.
, 8 loe, DoMercanti and R, Levi.
−.
Ｍ：＋ｎｔａｌｉｃｉｎｉ、Ｅｘｐ、Ｃｅ１ｌ Ｒｅ
３−＋ １５４ 、１−９（１９８４） ） ＋塩基
性ファイプロプラストグロースファクター（Ｐ、Ｗａｌ
ｉｃｋｅ 、 Ｗ、Ｍ、Ｃｏｗａｎ 、 Ｎ、ＬＩｅｎ
ｏ、 Ａ、Ｂａ１ｒｄ及びＲ，Ｇｕｉｌｌｅｍｉｎ 、
Ｐ、Ｎ、Ａ、Ｓ、（Ｕ、Ｓ、Ａ、）、 ８３．３０１
２−３０１６ （１９８６） ）や５１００ β（Ｄ、
に１ｉｇｍａｎ及びり、Ｒ。M: +ntalicini, Exp, Ce1l Re
3-+ 154, 1-9 (1984)) + basic phyproplast growth factor (P, Wal
icke, W., M., Cowan, N., LIen.
o, A, Ba1rd and R, Guillemin,
P, N, A, S, (U, S, A,), 83.301
2-3016 (1986)) and 5100 β (D,
1igman and R.
Ｍａｒｓｈａｋ 、 Ｐ、Ｎ、Ａ、Ｓ、（Ｕ、Ｓ、Ａ、
）、 ８２．７１３６−７１３９（１９８５） ）が、
現在までのところ報告されている。Marshak, P, N, A, S, (U, S, A,
), 82.7136-7139 (1985)),
reported so far.
一方、アルツハイマー病の患者の脳では同年令の対照に
比し、ホスファチジルイノシトールが有意に減少してい
ることが報告された（ＣＪ、５ｔｏｋｅｓ及びＪ、Ｎ、
Ｈａｗｔｈｏｒｎｅ 、 Ｊ、Ｎｅｕｒｏｃｈｅｍ 、
４８ ＋１０１８−１０２１ （１９８７） ）。ま
た、パーキンソン氏病においては、ドーパミンやノルエ
ピネフリンなどのカテコールアミン含有神経が障害され
ているが、そのカテコールアミンの生合成酵素であり律
速酵素であるチロシン水酸化酵素の活性化にホスファチ
ジルセリンが有効であることが報告されている１’Ｇ、
Ｔｏｒｆ’ａｎＯａｎｄＬ、Ｂａｔｔｉｓｔ＋ｉｎ、
Ｎｅｕｒｏｃｈｅｍｉｓｔｒｙ及びＣ１１ｎｉｃａｌ
Ｎｅｕｒｏｌｏｇｙ、 Ａｌａｎ Ｒ，Ｌｉ５ｓ 、
Ｉｎｃ、、 ＮｅｗＹｏｒｋ、 ｐｐ、２０５−２１
４（１９８０） ） 、これらのことは、リン脂質が神
経系の機能に重要な役割を果していることを示唆してい
る。しかしながら、リン脂質が神経線維の再生に有効で
あるという報告は全くない。On the other hand, it was reported that phosphatidylinositol was significantly decreased in the brains of Alzheimer's disease patients compared to age-matched controls (CJ, 5tokes and J,N,
Hawthorne, J., Neurochem.
48 +1018-1021 (1987)). In addition, in Parkinson's disease, nerves containing catecholamines such as dopamine and norepinephrine are damaged, and phosphatidylserine is effective in activating tyrosine hydroxylase, which is the rate-limiting enzyme that biosynthesizes catecholamines. 1'G has been reported,
Torf'anOandL, Battist+in,
Neurochemistry and C11nical
Neurology, Alan R, Li5s,
Inc., New York, pp. 205-21.
4 (1980)), these findings suggest that phospholipids play an important role in the function of the nervous system. However, there are no reports that phospholipids are effective in regenerating nerve fibers.
■が７″シよ゛とする課
本発明の目的は、神経線維の再生を促進させる製剤を提
供するものである。本発明は、リン脂質が神経線維の再
生に有効であるという発見に基づく。Section (2) is 7'' An object of the present invention is to provide a preparation that promotes the regeneration of nerve fibers.The present invention is based on the discovery that phospholipids are effective in regenerating nerve fibers.
課０を”ンするための 段
リン脂質には、ホスファチジルコリン、ホスファチジル
エタノールアミン、ホスファチジン酸、ホスファチジル
セリン、ホスファチジルイノシトール、ホスファチジル
グリセロール、カルシオリピン、スフィンゴミエリン及
びこれらのリゾ体がある。このうち特に有効と認められ
たのはホスファチジルイノシトール、ホスファチジルコ
リン、ホスファチジルセリン及びスフィンゴミエリンで
ある。これら４種のリン脂質は、単独又は混合して神経
線維再生剤となることができ、したがって、脳卒中、脳
外傷、アルツハイマー病、パーキンソン氏病のいづれか
の治療剤とすることができる。Examples of phospholipids include phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, calciolipin, sphingomyelin, and their lyso forms. These four phospholipids are phosphatidylinositol, phosphatidylcholine, phosphatidylserine, and sphingomyelin.These four phospholipids can be used alone or in combination as nerve fiber regenerating agents, and are therefore effective against stroke, brain trauma, Alzheimer's disease, It can be used as a therapeutic agent for any of Parkinson's disease.
これら４種のリン脂質は動物、植物、酵母などの天然由
来のものであるか、または合成により製造したものであ
るかを問わない。また、脂肪酸銀の長さや、飽和・不飽
和であるかを問わない。These four types of phospholipids may be naturally derived from animals, plants, yeast, etc., or may be synthetically produced. In addition, the length of the fatty acid silver and whether it is saturated or unsaturated does not matter.
前記の医薬は経口、非経口及び直腸投与に適した剤型を
含めて種々の製薬上許容しうる形で製造できる。The aforementioned medicaments can be manufactured in a variety of pharmaceutically acceptable forms, including dosage forms suitable for oral, parenteral and rectal administration.
経口投与に適した形態は、錠剤、眩粒、粉末、カプセル
懸濁液及び乳化液である。Forms suitable for oral administration are tablets, tablets, powders, capsule suspensions and emulsions.
非経口投与に適した形態は、アンプル、点滴瓶又は注射
器の中に入れた注射可能な懸濁液、乳化液又はリポソー
ム製剤である。Forms suitable for parenteral administration are injectable suspensions, emulsions or liposomal preparations in ampoules, dropper bottles or syringes.
直腸投与に適当な形態には生薬又は直腸カプセルがある
。Forms suitable for rectal administration include herbal medicines or rectal capsules.
本発明によるホスファチジルイノシトール、ホスファチ
ジルコリン、ホスファチジルセリン及ヒスフィンゴミエ
リンの新規な医療用途を次の実施例により説明する。た
だし、本発明はこれらに限定されるものではない。The novel medical uses of phosphatidylinositol, phosphatidylcholine, phosphatidylserine and hisphingomyelin according to the present invention are illustrated by the following examples. However, the present invention is not limited to these.
災施炎上 点滴用注射剤。disaster blaze Injection for intravenous drip.
１バイアル５００ ｍｌホスファチジルコリン含有卵黄
リン脂質６ｇ、精製大豆油５０ｇ、注射用グリセリン１
２．５ｇを含有する脂肪乳剤。1 vial 500 ml 6 g of phosphatidylcholine-containing egg yolk phospholipid, 50 g of purified soybean oil, 1 glycerin for injection
Fat emulsion containing 2.5 g.
尖旌桝ｌ 注射剤。Chimcheongbo l Injection.
１アンプル２５ｄ中、豚肝臓ホスファチジルイノシトー
ル０．０５ｇ、精製ゴマ油５ｇ、Ｄ−ソルビトール２ｇ
、デキストラン７０ １．２５ｇを含有する乳化液。In 1 ampoule 25d, pig liver phosphatidylinositol 0.05g, refined sesame oil 5g, D-sorbitol 2g
, an emulsion containing 1.25 g of Dextran 70.
炎施班ｌ 注射剤。Flame control group Injection.
ホスファチジルコリン含有の卵黄レシチン５００ｍｇ、
パン酵母ホスファチジルイノシトール５０＋ｎｇより調
製したリポソーム製剤。500mg of egg yolk lecithin containing phosphatidylcholine,
A liposome preparation prepared from 50+ng of baker's yeast phosphatidylinositol.
実画Ｌｌｌ 経口剤。Actual picture Lll Oral preparation.
パン酵母ホスファチジルイノシトール０．２ｇ、大豆レ
シチン０．２ ｇ、カカオ脂２ｇを含有する粒粉製剤。A grain powder preparation containing 0.2 g of baker's yeast phosphatidylinositol, 0.2 g of soybean lecithin, and 2 g of cacao butter.
尖膳班Ｖ
薬理活性の研究
リン脂質特にホスファチジルイノシトール、ホスファチ
ジルコリン、ホスファチジルセリン及びスフィンゴミエ
リンの神経線維の生成を促進させる能力は種々の試験に
より、特に以下に記載したラット脳中隔野神経細胞の突
起形成促進試験により証明された。Research on the pharmacological activity of phospholipids, particularly phosphatidylinositol, phosphatidylcholine, phosphatidylserine, and sphingomyelin, have been shown through various tests to promote the production of nerve fibers, especially the protrusions of rat septal cortex neurons described below. Proven by formation acceleration test.
試験はウィスタ一種ラット胎生１７日の胎児から取出し
た中隔野神経細胞について行った。中隔野神経細胞は０
．３％トリプシン処理により単離細胞とし、Ｌ−１５培
地〔へルｅｉｂｏｖｉｔｚ 、 Ａｍ、Ｊ、ｌｌｙｇ、
。The test was carried out on septal nerve cells taken from a 17-day-old Wista rat fetus. 0 septal area neurons
．． Isolated cells were treated with 3% trypsin and placed in L-15 medium [Helebovitz, Am, J.
.
邦、 １７３−１８０（１９６３） ）で洗浄し、ポリ
ーＬ−リジンで被覆した２４穴プラスチツクプレートに
１平方センチメートルあたり５０００個の細胞の密度で
まいた。培養液には以下の組成のものを使用した：
Ｌ−１５培地７８０ ｄ、β−アラニン５ｍｇ、アスパ
ラギン酸１５ｍｇ、グルタミン酸１５ｍｇ、ｐ−アミノ
安息香酸５ ｍｇ、アスコルビン酸６４ｍｇ、塩化コリ
ン１０ｍｇ、フマール酸２５■、グルタチオン３ｍｇ、
イミダゾール６ｏ１１１ｇ１」ｕ−イノシトール１０ｍ
ｇ、α−リポ酸０．５ｍｇ、ジアノコバラミン２ｍｇ、
ブドウ糖１１．３ｇ、グルタミン１．１ ｇ 、 ０．
１５Ｍ重炭酸ナトリウム２００ｄ、牛インシュリン２５
ｍｇ、ヒト・トランスフェリン１００■、塩酸プトレシ
ン９．７ｍｇ、 １００μＭプロゲステロン０．２ｄ
。173-180 (1963)) and plated at a density of 5000 cells per square centimeter in 24-well plastic plates coated with poly-L-lysine. The culture medium used had the following composition:
L-15 medium 780 d, β-alanine 5 mg, aspartic acid 15 mg, glutamic acid 15 mg, p-aminobenzoic acid 5 mg, ascorbic acid 64 mg, choline chloride 10 mg, fumaric acid 25 mg, glutathione 3 mg,
Imidazole 6o111g1” u-inositol 10m
g, α-lipoic acid 0.5 mg, dianocobalamin 2 mg,
Glucose 11.3g, Glutamine 1.1g, 0.
15M Sodium Bicarbonate 200d, Bovine Insulin 25
mg, human transferrin 100■, putrescine hydrochloride 9.7mg, 100μM progesterone 0.2d
.
１００８ｍ亜セレン酸ナトリウム０ 、３ ｍｌ、及び
ペニシリンＧカリウムｌＯ万単位。1008m sodium selenite 0.3 ml and penicillin G potassium 10,000 units.
リン脂質はクロロホルム等の溶媒で溶解し、任意の量を
ガラス試験管に入れ、窒素気流を送ってガラス器壁に付
着・乾燥させ、更に減圧下で乾燥して溶媒を完全に除去
した。この試験管内に適当量の前記の培養液を加え、プ
ローブ型超音波処理装置により均質な脂質浮遊液とし、
必要に応じて前記培養液にて希釈し試験を行った。Phospholipids were dissolved in a solvent such as chloroform, an arbitrary amount was placed in a glass test tube, and a nitrogen stream was sent to adhere and dry the solution to the glass vessel wall, followed by drying under reduced pressure to completely remove the solvent. Add an appropriate amount of the above culture solution to this test tube, make a homogeneous lipid suspension using a probe-type ultrasonic treatment device,
Tests were conducted by diluting with the above culture solution as needed.
細胞は５％炭酸ガス−９５％空気の培養器の中で３７
’Ｃ２４時間培養し、３％グルタルアルデヒド固定後、
位相差顕微鏡（倍率１００）にて１穴あたり４ケ所計測
した。活性は、明るく丸い細胞体で、かつ細胞体の長さ
の２倍以上の長さの神経突起を有する細胞の全体の細胞
数に占める割合で表した。Cells were grown in an incubator with 5% carbon dioxide and 95% air for 37 days.
After culturing for 24 hours and fixing with 3% glutaraldehyde,
Measurements were made at four locations per hole using a phase contrast microscope (magnification: 100). The activity was expressed as a percentage of the total number of cells having bright, round cell bodies and neurites with a length of at least twice the length of the cell body.
４回行った実験の平均と標準誤差の結果を表１に示す。Table 1 shows the average and standard error results of the four experiments.
この表から、ホスファチジルイノシトール、ホスファチ
ジルコリン、ホスファチジルセリン及びスフィンゴミエ
リンに明白な神経線維再生作用のあることが明らかであ
る。またホスファチジルエタノールアミン及びホスファ
チジン酸にも弱いながら活性がある。また天然ばかりか
合成のリン脂質にも活性がみられている。From this table, it is clear that phosphatidylinositol, phosphatidylcholine, phosphatidylserine, and sphingomyelin have a clear nerve fiber regeneration effect. It is also weakly active against phosphatidylethanolamine and phosphatidic acid. Activity has also been observed in both natural and synthetic phospholipids.
かくして、神経線維の再生剤を堤供するという本発明の
目的は、有効に達成されることは前記の記載から明らか
である。Thus, it is clear from the above description that the object of the present invention, which is to provide a nerve fiber regenerating agent, is effectively achieved.
本発明を実施するに当り、本発明の精神を逸脱しない限
り、その範囲内で種々変更を成しうる。In carrying out the present invention, various changes may be made within the scope of the invention without departing from the spirit of the invention.
従って、前記の記載に包含される全ての事項は例示的で
あって何らこれらに限定されるものではない。Therefore, all matters included in the above description are illustrative and not limiting in any way.
Claims (1)
ノシトール、ホスファチジルコリン、ホスファチジルセ
リン及びスフィンゴミエリンを単独又は任意選択混合し
て含有して成る神経線維再生剤。 ２、再生剤が脳卒中、脳外傷、アルツハイマー病、パー
キンソン氏病のいずれかの治療剤である特許請求の範囲
第１項記載の再生剤。 ３、再生剤がリポソーム、乳化液、顆粒剤のいずれかで
ある特許請求の範囲第１項または第２項記載の再生剤。[Claims] 1. A nerve fiber regenerating agent containing natural or synthetic phosphatidylinositol, phosphatidylcholine, phosphatidylserine, and sphingomyelin as active ingredients, singly or optionally in a mixture. 2. The regenerating agent according to claim 1, wherein the regenerating agent is a therapeutic agent for any one of stroke, brain trauma, Alzheimer's disease, and Parkinson's disease. 3. The regenerant according to claim 1 or 2, wherein the regenerant is a liposome, an emulsion, or a granule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29178387A JPH01135720A (en) | 1987-11-20 | 1987-11-20 | Nerve fiber regenerating agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29178387A JPH01135720A (en) | 1987-11-20 | 1987-11-20 | Nerve fiber regenerating agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01135720A true JPH01135720A (en) | 1989-05-29 |
Family
ID=17773367
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP29178387A Pending JPH01135720A (en) | 1987-11-20 | 1987-11-20 | Nerve fiber regenerating agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01135720A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994003178A1 (en) * | 1992-08-03 | 1994-02-17 | Fidia S.P.A. | Therapeutic use of phosphoryl-l-serine-n-acyl-sphingosine |
| WO1994005319A1 (en) * | 1992-09-02 | 1994-03-17 | Taiyo Gyogyo Kabusiki Kaisya | Brain function ameliorant composition, learning capacity enhancer, mnemonic agent, dementia preventive, dementia curative, or functional food with brain function ameliorant effect |
| EP0711559A3 (en) * | 1994-11-08 | 1997-01-15 | Yakult Honsha Kk | Use of phosphatidylserines for the manufacture of a medicament for improving cerebration |
| JP2003146883A (en) * | 2001-11-07 | 2003-05-21 | Snow Brand Milk Prod Co Ltd | Preventing and treating agent for defect of memory |
| EP1500593A2 (en) | 2003-07-24 | 2005-01-26 | Shikoku Kakoki Co., Ltd. | Method for manufacturing food in container and food in container |
| DE10352449A1 (en) * | 2003-11-07 | 2005-06-16 | Ruprecht-Karls-Universität Heidelberg | Product for preventing or treating Alzheimer's disease comprises sphingomyelin and/or an activator of endogenous sphingomyelin synthesis and/or an inhibitor of endogenous sphingomyelin degradation |
| JP2007504197A (en) * | 2003-09-04 | 2007-03-01 | ビオグルト ビオガルデ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディートゲゼルシャフト | Physiologically active composition of phosphatidylserine base |
| WO2010128807A3 (en) * | 2009-05-07 | 2011-03-31 | (주)문엔제이 | Pharmaceutical composition for preventing or treating neuronal damage and neurological diseases |
| US9186366B2 (en) | 2005-09-22 | 2015-11-17 | Megmilk Snow Brand Co., Ltd. | Medicine, food and drink or feed containing sphingomyelin |
-
1987
- 1987-11-20 JP JP29178387A patent/JPH01135720A/en active Pending
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994003178A1 (en) * | 1992-08-03 | 1994-02-17 | Fidia S.P.A. | Therapeutic use of phosphoryl-l-serine-n-acyl-sphingosine |
| WO1994005319A1 (en) * | 1992-09-02 | 1994-03-17 | Taiyo Gyogyo Kabusiki Kaisya | Brain function ameliorant composition, learning capacity enhancer, mnemonic agent, dementia preventive, dementia curative, or functional food with brain function ameliorant effect |
| EP0711559A3 (en) * | 1994-11-08 | 1997-01-15 | Yakult Honsha Kk | Use of phosphatidylserines for the manufacture of a medicament for improving cerebration |
| US5900409A (en) * | 1994-11-08 | 1999-05-04 | Kabushiki Kaisha Yakult Honsha | Cerebration improver |
| US6117853A (en) * | 1994-11-08 | 2000-09-12 | Kabushiki Kaisha Yakult Honsha | Cerebration improver |
| JP2003146883A (en) * | 2001-11-07 | 2003-05-21 | Snow Brand Milk Prod Co Ltd | Preventing and treating agent for defect of memory |
| EP1500593A2 (en) | 2003-07-24 | 2005-01-26 | Shikoku Kakoki Co., Ltd. | Method for manufacturing food in container and food in container |
| JP2007504197A (en) * | 2003-09-04 | 2007-03-01 | ビオグルト ビオガルデ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディートゲゼルシャフト | Physiologically active composition of phosphatidylserine base |
| DE10352449A1 (en) * | 2003-11-07 | 2005-06-16 | Ruprecht-Karls-Universität Heidelberg | Product for preventing or treating Alzheimer's disease comprises sphingomyelin and/or an activator of endogenous sphingomyelin synthesis and/or an inhibitor of endogenous sphingomyelin degradation |
| US9186366B2 (en) | 2005-09-22 | 2015-11-17 | Megmilk Snow Brand Co., Ltd. | Medicine, food and drink or feed containing sphingomyelin |
| WO2010128807A3 (en) * | 2009-05-07 | 2011-03-31 | (주)문엔제이 | Pharmaceutical composition for preventing or treating neuronal damage and neurological diseases |
| EP2428211A2 (en) * | 2009-05-07 | 2012-03-14 | Moon&J Inc. | Pharmaceutical composition for preventing or treating neuronal damage and neurological diseases |
| CN102421440A (en) * | 2009-05-07 | 2012-04-18 | Moon&J股份有限公司 | Pharmaceutical composition for preventing or treating neuronal damage and neurological diseases |
| JP2012526104A (en) * | 2009-05-07 | 2012-10-25 | ムーン アンド ジェイ インコーポレイテッド | Pharmaceutical composition for preventing or treating nerve damage and disease |
| EP2428211A4 (en) * | 2009-05-07 | 2013-04-03 | Moon & J Inc | Pharmaceutical composition for preventing or treating neuronal damage and neurological diseases |
| US9168282B2 (en) | 2009-05-07 | 2015-10-27 | Dongkook Pharmaceutical Co., Ltd. | Method for treating neuronal damage and neurological diseases |
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