JPH02250890A - New phospholipid - Google Patents
New phospholipidInfo
- Publication number
- JPH02250890A JPH02250890A JP21535089A JP21535089A JPH02250890A JP H02250890 A JPH02250890 A JP H02250890A JP 21535089 A JP21535089 A JP 21535089A JP 21535089 A JP21535089 A JP 21535089A JP H02250890 A JPH02250890 A JP H02250890A
- Authority
- JP
- Japan
- Prior art keywords
- myxobacteria
- phospholipid
- formula
- silica gel
- methanol
- 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
- 150000003904 phospholipids Chemical class 0.000 title claims abstract description 24
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims abstract description 4
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims abstract description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 6
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 abstract description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract description 4
- 239000000741 silica gel Substances 0.000 abstract description 4
- 229910002027 silica gel Inorganic materials 0.000 abstract description 4
- 238000004809 thin layer chromatography Methods 0.000 abstract description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 3
- 208000004930 Fatty Liver Diseases 0.000 abstract description 3
- 206010019708 Hepatic steatosis Diseases 0.000 abstract description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 abstract description 3
- 229910052799 carbon Inorganic materials 0.000 abstract description 3
- 208000010706 fatty liver disease Diseases 0.000 abstract description 3
- 229910001410 inorganic ion Inorganic materials 0.000 abstract description 3
- 208000019423 liver disease Diseases 0.000 abstract description 3
- 230000000813 microbial effect Effects 0.000 abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 3
- 208000017520 skin disease Diseases 0.000 abstract description 3
- 231100000240 steatosis hepatitis Toxicity 0.000 abstract description 3
- 201000004384 Alopecia Diseases 0.000 abstract description 2
- 208000024827 Alzheimer disease Diseases 0.000 abstract description 2
- 206010003210 Arteriosclerosis Diseases 0.000 abstract description 2
- 206010039966 Senile dementia Diseases 0.000 abstract description 2
- 238000007796 conventional method Methods 0.000 abstract description 2
- 238000012258 culturing Methods 0.000 abstract description 2
- 239000001963 growth medium Substances 0.000 abstract description 2
- 238000000034 method Methods 0.000 abstract description 2
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 241000863434 Myxococcales Species 0.000 abstract 3
- 206010048768 Dermatosis Diseases 0.000 abstract 1
- 206010027304 Menopausal symptoms Diseases 0.000 abstract 1
- 201000004681 Psoriasis Diseases 0.000 abstract 1
- 231100000360 alopecia Toxicity 0.000 abstract 1
- 238000005571 anion exchange chromatography Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 230000002028 premature Effects 0.000 abstract 1
- 238000010898 silica gel chromatography Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- 150000004665 fatty acids Chemical group 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- -1 rough 1 dose Chemical compound 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical group NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- YGRUUPPVGMDKDK-UHFFFAOYSA-N O.OC.CC(C)=O.CC(O)=O.ClC(Cl)Cl Chemical compound O.OC.CC(C)=O.CC(O)=O.ClC(Cl)Cl YGRUUPPVGMDKDK-UHFFFAOYSA-N 0.000 description 2
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 2
- 229920002472 Starch Polymers 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
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical group OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 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
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 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
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Chemical group CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 1
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
- 241000693467 Macroporus Species 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000863420 Myxococcus Species 0.000 description 1
- 241000863424 Myxococcus macrosporus Species 0.000 description 1
- 108010009736 Protein Hydrolysates Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Chemical group OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- SIHHLZPXQLFPMC-UHFFFAOYSA-N chloroform;methanol;hydrate Chemical compound O.OC.ClC(Cl)Cl SIHHLZPXQLFPMC-UHFFFAOYSA-N 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical group C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 229910001431 copper ion Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000037336 dry skin Effects 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- 235000019387 fatty acid methyl ester Nutrition 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical group O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229910001437 manganese ion Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000004816 paper chromatography Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Chemical group OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
産粟上互■里立夏
本発明は、種々の薬理作用を有する微生物由来の新規な
リン脂質に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel phospholipids derived from microorganisms having various pharmacological actions.
災米肢術
リン脂質は、動植物界に広く分布し、その細胞膜の構成
成分として、細胞の構造維持に寄与している。また、リ
ン脂質は、大豆、卵黄などより大量に抽出され、天然系
の乳化剤、界面活性剤として、広く一般に利用されてい
る。一方、リン脂質は、それ自体あるいはその代謝産物
が、生体内において種々の薬理作用を示すことが知られ
ており、また医薬品としての有用性も報告されている。Phospholipids are widely distributed in the animal and plant kingdoms, and as constituent components of cell membranes, they contribute to the maintenance of cell structure. Furthermore, phospholipids are extracted in large quantities from soybeans, egg yolks, etc., and are widely used as natural emulsifiers and surfactants. On the other hand, phospholipids themselves or their metabolites are known to exhibit various pharmacological actions in vivo, and their usefulness as pharmaceuticals has also been reported.
例をあげれば、肝臓病（脂肪肝）、動脈硬化症、皮膚病
などである。Examples include liver disease (fatty liver), arteriosclerosis, and skin diseases.
リン脂質の構造は、一般に下式で示されるような構造を
もっている。The structure of phospholipid generally has the structure shown by the following formula.
を重ねた結果、粘液細菌の菌体内に一般式（Ｉ）式中、
Ｒｔ 、 Ｒ１は炭素数ｌＯ〜２２のアシル基を、Ｘは
コリン、エタノールアミン、セリン、イノシトールなど
を表わす。As a result of overlapping, in the bacterial body of the myxobacterium, in the general formula (I),
Rt and R1 each represent an acyl group having 10 to 22 carbon atoms, and X represents choline, ethanolamine, serine, inositol, or the like.
ここで、Ｒｔ 、 Ｒｍは自然界で知られているものと
しては直鎖のアシル基がほとんどであって、メチル分枝
鎖や水酸基などの官能基をもつものは見出されていない
。Here, most of Rt and Rm known in nature are straight-chain acyl groups, and no one having a functional group such as a methyl branched chain or a hydroxyl group has been found.
Ｂ＜°１ 量
本発明の課題は、新たな薬理作用をもつことが期待され
る、アシル基にメチル分枝構造や水酸基などの官能基を
もつリン脂質を自然界より見出し、これを利用できるよ
うにすることにある。B<°1 Amount The objective of the present invention is to discover phospholipids in nature that have functional groups such as methyl branched structures and hydroxyl groups in their acyl groups, which are expected to have new pharmacological effects, and to find ways to utilize them. It is to make it.
量 ° −の
本発明者は、前記の課題を達成すべく鋭意研究（式中、
Ｒ１、Ｒ１は互に異なっていてもよく、それぞれ
υｉ
で表わされ、ｎは４〜１８の偶数である。）で示される
構造を有する新規なリン脂質を見出し、その抽出、分離
に成功した。これは脂肪酸部（Ｒ１゜ｐりがともに奇数
の炭素数をもち、α位に水酸基を有し、かつイソ型のメ
チル分枝鎖をもつ特異なリン脂質（ホスファチジルエタ
ノールアミン）である。The inventor of the present invention has conducted extensive research (in the formula,
R1 and R1 may be different from each other and are each represented by υi, and n is an even number from 4 to 18. ) We have discovered a new phospholipid with the structure shown in the following figure, and succeeded in extracting and separating it. This is a unique phospholipid (phosphatidylethanolamine) having an odd number of carbon atoms in both the fatty acid moieties (R1゜p), a hydroxyl group at the α-position, and an isotype methyl branched chain.
本発明のリン脂質（Ｉ）を得るには、粘液細菌の菌体か
ら、クロロホルム−メタノール（２：１゜ｖ ／ ｖ
）などの通常の有機溶媒抽出法を用いて粗リン脂質を抽
出し、これを、陰イオン交換クロマトグラフィー、シリ
カゲル薄層クロマトグラフィ、シリカゲルカラムクロマ
トグラフィーなどの通常のリン脂質の精製法を適用すれ
ばよい、粘液細菌の菌体を得るには、炭素源、窒素源、
無機イオン等を含有する通常の培地を用い、常法により
培養すれば良い。炭素源としてはグルコース、フラクト
ース、マルトース、ラフィノース、ラムノース、グリセ
ロース、キシロース、ラフ１ドース、シュークロース、
スターチ等の種類、エタノール、ソルビトール等のアル
コール、酢酸等の有機酸が使用できる。窒素源としては
アンモニウムイオンのほか、アミノ酸、蛋白質、及びこ
れらを含有する酵母エキス、カゼイン加水分解物等が使
用できる。培地には必要によりカリイオン、リン酸イオ
ン、カルシウムイオン、マグネシウムイオン、銅イオン
、亜鉛イオン、マンガンイオン、鉄イオン等の無機イオ
ンを添加する。In order to obtain the phospholipid (I) of the present invention, chloroform-methanol (2:1゜v/v
), crude phospholipids are extracted using a conventional organic solvent extraction method such as To obtain good myxobacterial cells, carbon sources, nitrogen sources,
The culture may be carried out by a conventional method using a conventional medium containing inorganic ions and the like. Carbon sources include glucose, fructose, maltose, raffinose, rhamnose, glycerose, xylose, rough 1 dose, sucrose,
Types such as starch, alcohols such as ethanol and sorbitol, and organic acids such as acetic acid can be used. As the nitrogen source, in addition to ammonium ions, amino acids, proteins, yeast extracts containing these, casein hydrolysates, etc. can be used. Inorganic ions such as potassium ions, phosphate ions, calcium ions, magnesium ions, copper ions, zinc ions, manganese ions, iron ions, etc. are added to the medium as necessary.
この他、グルタミン酸醗酵等の醗酵菌体を唯一の栄養源
として用いることができる。In addition, fermentation microbial cells such as glutamic acid fermentation can be used as the sole nutrient source.
培養は好気的条件下で行うのが良＜ｐＨ４から９の範囲
の適当なｐＨに調節しつつ培養すればより好ましい結果
が得られる。培養温度は２５°Ｃから３８°Ｃの範囲が
好ましい。Cultivation is preferably carried out under aerobic conditions; more favorable results can be obtained by culturing while adjusting the pH to an appropriate pH within the range of 4 to 9. The culture temperature is preferably in the range of 25°C to 38°C.
かくして得られたリン脂質（Ｉ）は、展開溶媒としてク
ロロホルム−アセトン−メタノール−酢酸−水（Ｉ０：
４：２：２：１．ｖ／ｖ）を用いたシリカゲル薄層クロ
マトグラフィー（Ｍｅｒｃｋ１３７９４ ”）を行うと
、Ｒｆ値０．３５に単一スポットを与える。The thus obtained phospholipid (I) was prepared using chloroform-acetone-methanol-acetic acid-water (I0:
4:2:2:1. Silica gel thin-layer chromatography (Merck 13794'') with v/v) gives a single spot at an Rf value of 0.35.
また、このリン脂質を弱アルカリ処理して（Ｒ。In addition, this phospholipid was treated with a weak alkali (R.
Ｍ、ＣＤａｗｓｏｎ、 Ｂｉｏｃｈｅｓ、 Ｊ、、 ７
５．４５（Ｉ９６１））、脱アシル化したものは、ペー
パークロマトグラフィー上で、標品のホスファチジルエ
タノールアミンの脱アシル化物と全く同一のＲｆ値を示
した。M., C. Dawson, Bioches, J., 7
5.45 (I961)), and the deacylated product showed exactly the same Rf value as the standard deacylated product of phosphatidylethanolamine on paper chromatography.
このリン脂質の一般的な性質は次のとおりである。The general properties of this phospholipid are as follows.
（Ｉ）形状：無色、半固体状。(I) Shape: Colorless, semi-solid.
（２）分子量；脂肪酸部のＲ１、Ｒ１はメチルエステル
として、１６０．１８８，２１６゜
２４４．２７２，３００，３２８゜
３５６のいずれか。(2) Molecular weight: R1 and R1 of the fatty acid moiety are either 160.188, 216°244.272, 300, or 328°356 as methyl ester.
（−例としてＧＣ−ＭＳのスペクトルを第１図に示す、
）
（３） ’ Ｈ−ＮＭＲ、メチル分枝構造を有する（第
２図に示す。）。(-As an example, the GC-MS spectrum is shown in Figure 1,
) (3) 'H-NMR, has a methyl branched structure (shown in Figure 2).
（４）溶解性；メタノール、エタノール、クロロホルム
に易溶。(4) Solubility: Easily soluble in methanol, ethanol, and chloroform.
アセトン、ヘキサンに難溶。Slightly soluble in acetone and hexane.
（５）呈色性：ディットマ−（Ｄｉｔｔｍｅｒ）試薬（
リン酸基）、ニンヒドリン（Ｎｉｎｈｙｄｒｉｎ）試薬
（アミノ基）ともに陽性。(5) Color development: Dittmer reagent (
Both phosphate group) and ninhydrin reagent (amino group) were positive.
作−■
本発明のリン脂質（Ｉ）は、水酸基を２個有するために
親水性が高くなり、それ自身の水溶解性が向上する他に
、薬剤や酵素を封じ込めた担体あるいはマイクロカプセ
ル（リポソーム）としても、その内抱水量が増加し、リ
ポソームの安定性も改良される。また脂肪酸部が、通常
のものと、全く異なっているため、新たなあるいは改善
された薬理作用が発現される。効果のある病気としては
、肝臓病（脂肪肝）、動脈硬化、高コレステロール血症
、乾層などの皮膚病、更年期症、老人性痴呆症、若年性
ハゲなどである。Since the phospholipid (I) of the present invention has two hydroxyl groups, it has high hydrophilicity and improves its own water solubility. ), the amount of water retained within the liposome increases and the stability of the liposome is also improved. Furthermore, since the fatty acid moiety is completely different from normal fatty acids, new or improved pharmacological effects are expressed. Diseases for which it is effective include liver disease (fatty liver), arteriosclerosis, hypercholesterolemia, skin diseases such as dry skin, menopause, senile dementia, and early baldness.
１隻貫 以下、実施例により本発明を具体的に説明する。1 piece Hereinafter, the present invention will be specifically explained with reference to Examples.
なお、本発明は以下の実施例により限定されるものでは
ない。Note that the present invention is not limited to the following examples.
実施例１（リン脂質の製造）
第１表に示した培地１０００ｊ１１！を容量５０００ｍ
の肩付フラスコに入れ殺菌した。ミキソコッカス・マク
ロスポラス（ＡＴＣＣ２９６１９）を１白金耳接種し、
３０°Ｃで５日間培養した。得られた培養液を遠心分離
して４．５ｇの湿菌体を得た。Example 1 (Production of phospholipids) Culture medium 1000j11 shown in Table 1! The capacity is 5000m
The mixture was placed in a shoulder flask and sterilized. One platinum loop of Myxococcus macrosporus (ATCC29619) was inoculated,
Cultured at 30°C for 5 days. The obtained culture solution was centrifuged to obtain 4.5 g of wet bacterial cells.
得られた湿菌体４ｇに対しメタノール、クロロホルム、
水を順次５０ｒＩ１１．５０Ｉｎ１．２〇−加えてよ（
攪拌しく１０分間）、脂質を抽出した。遠心分離後、ク
ロロホルム層（下層）を分取し、減圧乾固して、粗リン
脂質を得た。これを、ＤＥＡＦ！−）ヨパールカラム（
酢酸型）にかけ、クロロホルム−メタノール（Ｉ： ４
）で溶出させた。得られた活性画分を減圧濃縮後、シリ
カゲル薄層クロマトグラフィー（メルクＮ１１１３７９
４）に線状にスポットし、クロロホルム−アセトン−メ
タノール−酢酸−水（Ｉ０：４：２：２：１．ｖ／ｖ）
の溶媒系（Ｉ）で展開した。ディットマー、ニンヒドリ
ン両試薬に陽性でＲｆ値が０．３８付近のバンドをかき
とり、クロロホルム−メタノール（Ｉ１）、メタノール
各３０ｄで順次溶出した。溶出液を合わせて減圧濃縮し
、再びシリカゲル薄層クロマトグラフィー（同上）にス
ポットし、クロロホルム−メタノール−水（０，５：
２５ ： ４． ｖ／ｖ）の溶媒系（ＩＩ）で展開し
、ディットマー、ニンヒトリン試薬陽性バンドを同様に
かきとり後抽出した。この方法で、約０．８ｍｇのリン
脂質が得られた。このリン脂質を５％ＨＣｆｆｉ−メタ
ノール中で１００°Ｃ，３ｈｒメタツリシスを行ったの
ち、生じた脂肪酸メチルエステルをヘキサン抽出後、ガ
スクロマトグラフィー、ガスクロマトグラフィー−マス
フラグメントグラフィーにかけて分析したところ、その
脂肪酸組成は２−ヒドロキシ−イソミリスチン酸（７，
２％）、２−ヒドロキシ−イソパルミチン酸（９２，８
％）のみより構成されていた。Methanol, chloroform,
Add 50rI11.50In1.20- of water one by one (
The mixture was stirred vigorously for 10 minutes) to extract the lipids. After centrifugation, the chloroform layer (lower layer) was separated and dried under reduced pressure to obtain crude phospholipids. This is DEAF! −) Yopal column (
acetic acid form) and chloroform-methanol (I: 4
) was eluted. The obtained active fraction was concentrated under reduced pressure and then subjected to silica gel thin layer chromatography (Merck N111379).
4) in a linear manner, chloroform-acetone-methanol-acetic acid-water (I0:4:2:2:1.v/v)
Developed with solvent system (I). A band positive to both Dittmar and ninhydrin reagents and having an Rf value of around 0.38 was scraped off and sequentially eluted with chloroform-methanol (I1) and methanol for 30 d each. The eluates were combined and concentrated under reduced pressure, spotted again on silica gel thin layer chromatography (same as above), and chloroform-methanol-water (0,5:
25: 4. v/v) and the Dittmer and Ninchtrin reagent positive bands were similarly scraped off and extracted. Approximately 0.8 mg of phospholipid was obtained in this way. This phospholipid was subjected to metalysis in 5% HCffi-methanol at 100°C for 3 hours, and the resulting fatty acid methyl ester was extracted with hexane and analyzed by gas chromatography and gas chromatography-mass fragmentography. The composition is 2-hydroxy-isomyristic acid (7,
2%), 2-hydroxy-isopalmitic acid (92,8
%).
第 １ 表
培地
０．１％
０．１％
０．１％
０．１％
ラフィノース
シュークロス
ガラクトース
可溶性澱粉
０．１％ 酵母エキス
０．０５％ Ｍｇ５Ｏ，・７Ｈ２０
０，０２５％ Ｋ！）ｌＰＯ４
ｐＨ７，４
以上説明したように、
本発明によれば、
アシル
基にメチル分枝構造や水酸基などの官能基をもち、水溶
解性などの物性や薬理作用の改善されたリン脂質を提供
することができる。Table 1 Medium 0.1% 0.1% 0.1% 0.1% Raffinose Sucrose Galactose Soluble Starch 0.1% Yeast Extract 0.05% Mg5O,・7H20 0,025% K! )lPO4 pH 7.4 As explained above, according to the present invention, a phospholipid having a functional group such as a methyl branched structure or a hydroxyl group in the acyl group and improved physical properties such as water solubility and pharmacological action is provided. can do.
第１図は本発明の一実施例を示し、ミキソコッカス・マ
クロポラスを接種培養した湿菌体から抽出分離したリン
脂質の構成脂肪酸である２−ヒドロキシ−イソパルミチ
ン酸のメチルエステルのマススペクトルを示すグラフ、
第２図は２−ヒドロキシ−イソパルミチン酸のメチルエ
ステルの’）ｌ−ＮＭＲスペクトル（ＣＤＣＩｌｓ）を
示すグラフである。FIG. 1 shows an embodiment of the present invention, and is a graph showing the mass spectrum of methyl ester of 2-hydroxy-isopalmitic acid, which is a constituent fatty acid of phospholipids extracted and separated from wet bacterial cells inoculated and cultured with Myxococcus macroporus. , FIG. 2 is a graph showing the ')l-NMR spectrum (CDCIls) of methyl ester of 2-hydroxy-isopalmitic acid.
Claims (1)
れぞれ ▲数式、化学式、表等があります▼ で表わされ、ｎは４〜１８の偶数である。）で示される
ホスファチジルエタノールアミン型リン脂質。[Claims] General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R^1 and R^2 may be different from each other, and each ▲mathematical formula, chemical formula, A phosphatidylethanolamine type phospholipid represented by ▼, where n is an even number from 4 to 18.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21535089A JPH02250890A (en) | 1988-10-20 | 1989-08-22 | New phospholipid |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26446688 | 1988-10-20 | ||
| JP63-264466 | 1988-10-20 | ||
| JP63-291643 | 1988-11-17 | ||
| JP21535089A JPH02250890A (en) | 1988-10-20 | 1989-08-22 | New phospholipid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02250890A true JPH02250890A (en) | 1990-10-08 |
Family
ID=26520829
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP21535089A Pending JPH02250890A (en) | 1988-10-20 | 1989-08-22 | New phospholipid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02250890A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005112731A (en) * | 2003-10-03 | 2005-04-28 | Fancl Corp | Hepatic function ameliorating agent |
| EP2845596A3 (en) * | 2000-01-10 | 2015-07-15 | Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. | Use of lipid conjugates in the treatment of disease |
| CN109730028A (en) * | 2019-01-31 | 2019-05-10 | 青岛市市立医院 | A method of Models of Nonalcoholic Fatty Liver Disease is established using mouse |
-
1989
- 1989-08-22 JP JP21535089A patent/JPH02250890A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2845596A3 (en) * | 2000-01-10 | 2015-07-15 | Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. | Use of lipid conjugates in the treatment of disease |
| JP2005112731A (en) * | 2003-10-03 | 2005-04-28 | Fancl Corp | Hepatic function ameliorating agent |
| CN109730028A (en) * | 2019-01-31 | 2019-05-10 | 青岛市市立医院 | A method of Models of Nonalcoholic Fatty Liver Disease is established using mouse |
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