JP2014508189A - 複合生薬抽出物を含有する糖尿病性末梢神経病症の予防又は治療のための組成物 - Google Patents
複合生薬抽出物を含有する糖尿病性末梢神経病症の予防又は治療のための組成物 Download PDFInfo
- Publication number
- JP2014508189A JP2014508189A JP2013558774A JP2013558774A JP2014508189A JP 2014508189 A JP2014508189 A JP 2014508189A JP 2013558774 A JP2013558774 A JP 2013558774A JP 2013558774 A JP2013558774 A JP 2013558774A JP 2014508189 A JP2014508189 A JP 2014508189A
- Authority
- JP
- Japan
- Prior art keywords
- extract
- uchiwadokoro
- peripheral neuropathy
- diabetic peripheral
- mixture
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 92
- 208000032131 Diabetic Neuropathies Diseases 0.000 title claims abstract description 67
- 238000011282 treatment Methods 0.000 title claims abstract description 23
- 230000002265 prevention Effects 0.000 title claims abstract description 17
- 239000000284 extract Substances 0.000 title abstract description 87
- 241000411851 herbal medicine Species 0.000 title description 13
- 239000012676 herbal extract Substances 0.000 claims abstract description 43
- 239000003814 drug Substances 0.000 claims abstract description 32
- 210000002569 neuron Anatomy 0.000 claims abstract description 22
- 230000036541 health Effects 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
- 235000013376 functional food Nutrition 0.000 claims abstract description 14
- 235000004879 dioscorea Nutrition 0.000 claims abstract description 11
- 235000005903 Dioscorea Nutrition 0.000 claims abstract description 9
- 241000908494 Dioscorea nipponica Species 0.000 claims abstract description 9
- 235000017008 Dioscorea nipponica Nutrition 0.000 claims abstract description 9
- 235000000504 Dioscorea villosa Nutrition 0.000 claims abstract description 9
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 5
- 241000234273 Dioscorea Species 0.000 claims abstract 4
- 230000034994 death Effects 0.000 claims abstract 2
- 208000002193 Pain Diseases 0.000 claims description 46
- 230000036407 pain Effects 0.000 claims description 41
- 208000024891 symptom Diseases 0.000 claims description 10
- 239000002775 capsule Substances 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 6
- 239000003826 tablet Substances 0.000 claims description 6
- 235000013361 beverage Nutrition 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000006188 syrup Substances 0.000 claims description 3
- 235000020357 syrup Nutrition 0.000 claims description 3
- 206010040030 Sensory loss Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 206010003694 Atrophy Diseases 0.000 claims 1
- 230000037444 atrophy Effects 0.000 claims 1
- 230000007850 degeneration Effects 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- 108010025020 Nerve Growth Factor Proteins 0.000 abstract description 68
- 102000015336 Nerve Growth Factor Human genes 0.000 abstract description 67
- 229940053128 nerve growth factor Drugs 0.000 abstract description 67
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 34
- 239000006187 pill Substances 0.000 abstract description 30
- 230000000694 effects Effects 0.000 abstract description 23
- 238000001727 in vivo Methods 0.000 abstract description 13
- 210000005036 nerve Anatomy 0.000 abstract description 9
- 230000002195 synergetic effect Effects 0.000 abstract description 7
- 230000001737 promoting effect Effects 0.000 abstract description 5
- 230000008929 regeneration Effects 0.000 abstract description 5
- 238000011069 regeneration method Methods 0.000 abstract description 5
- 230000003449 preventive effect Effects 0.000 abstract description 3
- 230000003247 decreasing effect Effects 0.000 abstract description 2
- 238000000605 extraction Methods 0.000 abstract 1
- 230000010534 mechanism of action Effects 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 59
- 230000001965 increasing effect Effects 0.000 description 26
- 210000003497 sciatic nerve Anatomy 0.000 description 23
- 241000700159 Rattus Species 0.000 description 20
- 229940079593 drug Drugs 0.000 description 19
- 210000003079 salivary gland Anatomy 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 13
- 230000028327 secretion Effects 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 10
- 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 9
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 9
- 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 9
- 229960001031 glucose Drugs 0.000 description 9
- 240000001439 Opuntia Species 0.000 description 8
- 235000013389 Opuntia humifusa var. humifusa Nutrition 0.000 description 8
- 239000008103 glucose Substances 0.000 description 8
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 210000003007 myelin sheath Anatomy 0.000 description 8
- 230000004770 neurodegeneration Effects 0.000 description 8
- 230000000638 stimulation Effects 0.000 description 8
- 244000281702 Dioscorea villosa Species 0.000 description 7
- 230000000773 effect on pain Effects 0.000 description 7
- 239000000796 flavoring agent Substances 0.000 description 7
- 235000013305 food Nutrition 0.000 description 7
- 235000019136 lipoic acid Nutrition 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 210000000056 organ Anatomy 0.000 description 7
- 208000033808 peripheral neuropathy Diseases 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 229960002663 thioctic acid Drugs 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 6
- 239000000287 crude extract Substances 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 230000014511 neuron projection development Effects 0.000 description 6
- 239000013641 positive control Substances 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 230000035807 sensation Effects 0.000 description 6
- 235000019615 sensations Nutrition 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 102000007339 Nerve Growth Factor Receptors Human genes 0.000 description 5
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 5
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 210000002241 neurite Anatomy 0.000 description 5
- 230000026731 phosphorylation Effects 0.000 description 5
- 238000006366 phosphorylation reaction Methods 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 5
- 229960001052 streptozocin Drugs 0.000 description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
- 235000002722 Dioscorea batatas Nutrition 0.000 description 4
- 240000001811 Dioscorea oppositifolia Species 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 4
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 229940015508 gabapentin 100 mg Drugs 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 235000002639 sodium chloride Nutrition 0.000 description 4
- 235000000891 standard diet Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 4
- 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 3
- 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 3
- 235000006536 Dioscorea esculenta Nutrition 0.000 description 3
- 235000003416 Dioscorea oppositifolia Nutrition 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 208000032612 Glial tumor Diseases 0.000 description 3
- 206010018338 Glioma Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 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 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- -1 dioscin Chemical class 0.000 description 3
- 230000005750 disease progression Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 3
- 230000014537 nerve growth factor production Effects 0.000 description 3
- 201000001119 neuropathy Diseases 0.000 description 3
- 230000007823 neuropathy Effects 0.000 description 3
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 3
- 238000011552 rat model Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 229960002920 sorbitol Drugs 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000002636 symptomatic treatment Methods 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 235000002723 Dioscorea alata Nutrition 0.000 description 2
- 235000007056 Dioscorea composita Nutrition 0.000 description 2
- 235000009723 Dioscorea convolvulacea Nutrition 0.000 description 2
- 235000005362 Dioscorea floribunda Nutrition 0.000 description 2
- 240000008955 Dioscorea japonica Species 0.000 description 2
- 235000005251 Dioscorea japonica Nutrition 0.000 description 2
- 235000004868 Dioscorea macrostachya Nutrition 0.000 description 2
- 235000005361 Dioscorea nummularia Nutrition 0.000 description 2
- 235000005360 Dioscorea spiculiflora Nutrition 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 208000004454 Hyperalgesia Diseases 0.000 description 2
- 208000035154 Hyperesthesia Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 101150111783 NTRK1 gene Proteins 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 239000003288 aldose reductase inhibitor Substances 0.000 description 2
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 229940125681 anticonvulsant agent Drugs 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 235000017663 capsaicin Nutrition 0.000 description 2
- 229960002504 capsaicin Drugs 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- CJNUQCDDINHHHD-APRUHSSNSA-N dioscin Natural products C[C@@H]1CC[C@@]2(OC1)O[C@H]3C[C@H]4[C@@H]5CC=C6C[C@H](CC[C@@H]6[C@H]5CC[C@]4(C)[C@H]3[C@@H]2C)O[C@@H]7O[C@H](CO)[C@@H](O[C@@H]8O[C@@H](C)[C@H](O)[C@@H](O)[C@H]8O)[C@H](O)[C@H]7O[C@@H]9O[C@@H](C)[C@H](O)[C@@H](O)[C@H]9O CJNUQCDDINHHHD-APRUHSSNSA-N 0.000 description 2
- 238000000635 electron micrograph Methods 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 229960002870 gabapentin Drugs 0.000 description 2
- VZCCETWTMQHEPK-UHFFFAOYSA-N gamma-Linolensaeure Natural products CCCCCC=CCC=CCC=CCCCCC(O)=O VZCCETWTMQHEPK-UHFFFAOYSA-N 0.000 description 2
- VZCCETWTMQHEPK-QNEBEIHSSA-N gamma-linolenic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/CCCCC(O)=O VZCCETWTMQHEPK-QNEBEIHSSA-N 0.000 description 2
- 235000020664 gamma-linolenic acid Nutrition 0.000 description 2
- 229960002733 gamolenic acid Drugs 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 235000013402 health food Nutrition 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 238000013220 male mouse model Methods 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 230000009103 reabsorption Effects 0.000 description 2
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 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
- HDXIQHTUNGFJIC-UHFFFAOYSA-N (25R)-spirost-5-en-3beta-ol 3-O-<O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside> Natural products O1C2(OCC(C)CC2)C(C)C(C2(CCC3C4(C)CC5)C)C1CC2C3CC=C4CC5OC1OC(CO)C(O)C(O)C1OC1OC(C)C(O)C(O)C1O HDXIQHTUNGFJIC-UHFFFAOYSA-N 0.000 description 1
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-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
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 241000208140 Acer Species 0.000 description 1
- 108010087765 Antipain Proteins 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 101100222854 Bacillus subtilis (strain 168) czcO gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- VNONINPVFQTJOC-RXEYMUOJSA-N Collettiside III Natural products O([C@@H]1[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@H](O)[C@@H](O)[C@H](C)O2)[C@H](CO)O[C@@H]1O[C@@H]1CC=2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]5[C@H](C)[C@@]6(O[C@H]5C4)OC[C@H](C)CC6)CC3)CC=2)CC1)[C@H]1[C@H](O)[C@H](O)[C@@H](O)[C@H](C)O1 VNONINPVFQTJOC-RXEYMUOJSA-N 0.000 description 1
- 241000270722 Crocodylidae Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 241000234272 Dioscoreaceae Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102000009025 Endorphins Human genes 0.000 description 1
- 108010049140 Endorphins Proteins 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000001512 FEMA 4601 Substances 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
- 208000003098 Ganglion Cysts Diseases 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 102100035108 High affinity nerve growth factor receptor Human genes 0.000 description 1
- 101710091869 High affinity nerve growth factor receptor Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 235000006350 Ipomoea batatas var. batatas Nutrition 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
- 229930195725 Mannitol Natural products 0.000 description 1
- 101100537961 Methanosarcina mazei (strain ATCC BAA-159 / DSM 3647 / Goe1 / Go1 / JCM 11833 / OCM 88) trkA2 gene Proteins 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 206010056677 Nerve degeneration Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 206010029333 Neurosis Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000000114 Pain Threshold Diseases 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102100024304 Protachykinin-1 Human genes 0.000 description 1
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 101800003906 Substance P Proteins 0.000 description 1
- 208000005400 Synovial Cyst Diseases 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 230000035581 baroreflex Effects 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-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
- 239000011230 binding agent Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- LNNWVNGFPYWNQE-GMIGKAJZSA-N desomorphine Chemical compound C1C2=CC=C(O)C3=C2[C@]24CCN(C)[C@H]1[C@@H]2CCC[C@@H]4O3 LNNWVNGFPYWNQE-GMIGKAJZSA-N 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- VNONINPVFQTJOC-ZGXDEBHDSA-N dioscin Chemical compound O([C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O[C@H]1[C@@H]([C@H](O)[C@@H](O)[C@H](C)O1)O)O[C@@H]1CC2=CC[C@H]3[C@@H]4C[C@H]5[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@@H]([C@]1(OC[C@H](C)CC1)O5)C)[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O VNONINPVFQTJOC-ZGXDEBHDSA-N 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000011363 dried mixture Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
- CHNUOJQWGUIOLD-NFZZJPOKSA-N epalrestat Chemical compound C=1C=CC=CC=1\C=C(/C)\C=C1/SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-NFZZJPOKSA-N 0.000 description 1
- 229950010170 epalrestat Drugs 0.000 description 1
- CHNUOJQWGUIOLD-UHFFFAOYSA-N epalrestate Natural products C=1C=CC=CC=1C=C(C)C=C1SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 235000019860 lauric fat Nutrition 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000007514 neuronal growth Effects 0.000 description 1
- 230000009689 neuronal regeneration Effects 0.000 description 1
- 208000015238 neurotic disease Diseases 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 230000003040 nociceptive effect Effects 0.000 description 1
- 229960002748 norepinephrine Drugs 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
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000037040 pain threshold Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 229940116257 pepper extract Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- VNONINPVFQTJOC-UHFFFAOYSA-N polyphyllin III Natural products O1C2(OCC(C)CC2)C(C)C(C2(CCC3C4(C)CC5)C)C1CC2C3CC=C4CC5OC(C(C1O)OC2C(C(O)C(O)C(C)O2)O)OC(CO)C1OC1OC(C)C(O)C(O)C1O VNONINPVFQTJOC-UHFFFAOYSA-N 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 230000007441 retrograde transport Effects 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 235000017709 saponins Nutrition 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 235000021055 solid food Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 101150025395 trkA gene Proteins 0.000 description 1
- 101150113435 trkA1 gene Proteins 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/894—Dioscoreaceae (Yam family)
- A61K36/8945—Dioscorea, e.g. yam, Chinese yam or water yam
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K9/08—Solutions
-
- 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
- A61K9/20—Pills, tablets, discs, rods
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/15—Preparation or pretreatment of starting material involving mechanical treatment, e.g. chopping up, cutting or grinding
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Mycology (AREA)
- Botany (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Diabetes (AREA)
- Dermatology (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
【解決手段】本発明による山薬(Dioscorea Rhizoma)とウチワドコロ(Dioscorea nipponica)の山薬:ウチワドコロ=3.5:1(w/w)の混合物の生薬抽出物は、山薬またはウチワドコロの単独抽出物、山薬とウチワドコロの他の重量比の生薬混合物の抽出物に比べて、糖尿病の発病により減少している生体内神経成長因子の含量を増加させる作用機序を通じて神経細胞の死滅を防止し、神経の再生を促進させる効果において相乗的な上昇効果を示すことができる。従って、糖尿病性末梢神経病症の予防及び治療用薬学組成物及び健康機能食品で使用され得る。
【選択図】図1
Description
本研究は、大韓民国知識経済省戦略的R&D企画局(OSP)のGlobal Leading Technology Programに支援された(No.10039303)。
本発明の他の目的は、前記生薬組成物を有効成分とする糖尿病性末梢神経病症の予防及び治療に有用な医薬組成物及び健康機能食品を提供することにある。
本発明による山薬とウチワドコロ混合生薬抽出物の製造
韓国京東市場の漢方薬材商で乾燥された山薬(Dioscorea Rhizoma)とウチワドコロ(Dioscorea nipponica)を購入した。不純物を除去してカッターで粉砕し、山薬:ウチワドコロ=3.5:1の重量比で混合した。2kgの混合物に10Lの50%エタノール水溶液を添加して、室温で48時間撹拌しながらインキュベートした。濾過により生薬混合物を除去し、濾液は減圧濃縮した後、凍結乾燥して混合生薬抽出物(粗抽出物)を得て、実施例1を製造した(表1参照)。
山薬抽出物の製造
2kgの混合物の代りに山薬2kgを使用したこと以外は、実施例1と同一な方法で製造して、山薬抽出物(粗抽出物)を製造した(表2参照)。
<比較例2>
ウチワドコロ抽出物の製造
2kgの混合物の代りにウチワドコロ2kgを使用したこと以外は、実施例1と同じ方法で山薬抽出物(粗抽出物)を製造した(表2参照)。
山薬及びウチワドコロの混合生薬粗抽出物の製造
前記実施例1で使われた山薬及びウチワドコロと同一の生薬を実験に使用した。カッターで粉砕した状態の山薬とウチワドコロを各々表3に記載したように混合した。各混合物2kgに10Lの50%エタノール水溶液を添加して、室温で48時間撹拌しながらインキュベートした。生薬混合物は濾過により除去し、濾液は減圧濃縮した後、凍結乾燥して混合生薬抽出物(粗抽出物)を得た。
生体内神経成長因子の含量評価のための正常ラットモデル実験
実施例1の50%エタノール粗抽出物を使用して、生体内神経成長因子の分泌を誘導するかを評価した(O.Arrieta and J.Sotelo et al., Retinoic acid increases tissue and plasma contents of nerve growth factor and prevents neuropathy in diabetic mice. European Journal of Clinical Investigation(2005) 35)。
採取した血液は、10,000rpmで10分間遠心分離して血漿を得た後、ELISA法により血漿内神経成長因子の含量を測定した(ABS 450nm)。坐骨神経及び唾液腺は、重量を測定した後、100mM Tris−HCl、1M NaCl、2% BSA、4mM EDTA、2.0% Trtion X−100、0.02% sodium azide、0.1mg/mL pepstatin A、5mg/mL aprotonin、0.5mg/mL antipain、167mg/mL benzamidine、5.2mg/mL PMSFを含む溶液を重量に応じて加えた後、ホモジナイズした。その後、1N HClを 1μL/50μLで入れた後、酸化のために15分間放置し、1N NaOHを1μL/50μLで入れて中和させた。10,000rpmで10分間遠心分離した後、上清液を採取した。その後、血漿と同様にELISA法により坐骨神経及び唾液腺内に存在する神経成長因子の含量を測定した。
実験データは、血漿神経成長因子の含量については下記表4に示し、坐骨神経内の神経成長因子の含量については表5に示し、唾液腺内の神経成長因子の含量については下記表6に示した。
血漿は神経成長因子が分泌されてから目標臓器に移動する経路であるので、血漿内神経成長因子含量の増加は、神経成長因子の分泌が促進されたことを意味する。従って、本発明の山薬:ウチワドコロ=3.5:1(w/w)の混合物の抽出物は、山薬またはウチワドコロの単独抽出物、山薬とウチワドコロの他の重量比の混合物の抽出物に比べて、神経成長因子の分泌を促進し、生体内の神経成長因子(NGF:Nerve Growth Factor)量を有意に増加させることができる。
従って、本発明の山薬:ウチワドコロ=3.5:1の混合物の抽出物は、血液内へのNGFの分泌を誘導することができるので、目標臓器である坐骨神経内の神経成長因子(NGF:Nerve Growth Factor)量を有意に増加させることができる。
また、生体内の神経成長因子量の有意な上昇能により、本発明の山薬:ウチワドコロ=3.5:1(w/w)の混合物の生薬抽出物は、糖尿病性末梢神経病症の治療及び予防のための医薬組成物及び健康機能食品に使用されることができる。
ストレプトゾトシンで1型糖尿病が誘発されたSD雄性ラット(SD male rat)を利用した痛み、神経成長因子分泌及び神経変性に対する効果評価実験
実施例1の山薬:ウチワドコロ=3.5:1の混合物の抽出物、及び比較例1〜比較例10の抽出物を使用して、1型糖尿病SD雄性ラットモデルにおける痛み、生体内の神経成長因子含量及び神経変性程度に対する効果を評価した。
従って、本発明の山薬:ウチワドコロ=3.5:1の混合物の生薬抽出物は、1型糖尿病動物でも生体内の目標臓器(坐骨神経、唾液腺)において、神経成長因子含量の有意な増加を誘導することが立証された。
機械的刺激に対する閾値の増加は痛みに対する閾値の増加を意味し、テールフリックテスト(tail flick test)における痛み反応までの潜伏時間の増加も、熱刺激に対する閾値の増加に相当するから、痛みに対する緩和効果を示す。
従って、本発明の山薬とウチワドコロの山薬:ウチワドコロ=3.5:1の重量比で混合された生薬抽出物は、1型糖尿病による末梢神経病症の症状である痛みの相乗的な緩和効果を示した。
それゆえ、本発明の抽出物は、目標臓器において、組織学的な側面でも神経再生を上昇させ、神経変性を緩和することができる。
本発明の抽出物は、1型糖尿病でも、糖尿病性末梢神経病症の治療及び予防効果において有意な相乗効果を示すことができるので、医薬組成物に使用され得る。
ストレプトゾトシンで1型糖尿が誘発されたICR雄性マウス(ICR male mouse)を用いた痛み、神経成長因子の分泌及び神経変性に対する効果評価実験
実施例1で調製された山薬:ウチワドコロ=3.5:1の混合物の生薬抽出物を使用して、1型糖尿病ICR雄性マウスモデルにおける痛み、生体内の神経成長因子の含量変化及び神経変性程度に対する効果を評価した。
その後、マウスを屠殺して坐骨神経及び唾液腺を採取した。坐骨神経及び唾液腺は、実験例1と同様に処理した後、ELISA法により神経成長因子の含量を測定した。その結果を表11に示した。
従って、本発明の山薬:ウチワドコロ=3.5:1の混合物の生薬抽出物は、1型糖尿病SDラット(SD rat)モデルだけではなく、1型糖尿病ICRマウス(ICR mouse)においても、生体内の目標臓器(坐骨神経、唾液腺)で神経成長因子の有意な増加を誘導することが立証された。
本発明の抽出物は、1型糖尿病SDラット(SD rat)モデルだけではなく、1型糖尿病ICRマウス(ICR mouse)でも、神経の変性を改善することができ、組織学的側面においても、目標臓器で神経再生を増加させることができる。
従って、本発明の生薬抽出物は、1型糖尿病から誘発される糖尿病性末梢神経病症の治療及び予防において相乗的効果を示すことができるので、医薬組成物に使用され得る。
遺伝的に2型糖尿病が誘発される遺伝子変形雄性マウス(db/db male mouse)を使用した痛み、神経成長因子の含量変化に対する効果評価実験
実施例1で調製された山薬:ウチワドコロ=3.5:1の混合物の生薬抽出物を使用して、2型糖尿病db/db雄性マウスモデルにおける痛み及び生体内の神経成長因子含量に対する効果を評価した。
その後、マウスを屠殺して坐骨神経を採取した。坐骨神経は、実験例1と同様に処理した後、ELISA法により神経成長因子の含量を測定した。その結果を表14に示した。
本発明の山薬:ウチワドコロ=3.5:1の混合物の生薬抽出物は、2型糖尿病でも生体内目標臓器において、神経成長因子の含量増加を有意に誘導することが立証された。
従って、本発明の生薬抽出物は、生体内神経成長因子の含量を有意に増加させることで、1型または2型糖尿病により誘発される糖尿病性末梢神経病症の治療及び予防のための医薬組成物及び健康機能食品で使用され得る。
C6ラットグリオーマ(C6 Rat Glioma)細胞とPC12神経細胞を用いた神経成長因子の生成及び神経細胞の増殖誘導活性試験
実施例1で調製した山薬:ウチワドコロ=3.5:1(w/w)の混合物の生薬抽出物を使用して、ラットグリオーマ(rat glioma)細胞であるC6細胞における神経成長因子の生成、ラット神経細胞であるPC12細胞の増殖誘導能を評価した。
従って、山薬:ウチワドコロ=3.5:1の混合物の生薬抽出物は、神経成長因子の生成促進を最大限に誘導することが立証された。
従って、本発明の山薬:ウチワドコロ=3.5:1の混合物の生薬抽出物は、神経細胞の増殖に有意な効果を有することが立証された。
PC12神経細胞における神経成長因子受容体のリン酸化実験
実施例1で調製された山薬:ウチワドコロ=3.5:1の混合物の生薬抽出物を使用して、PC12ラット神経細胞における神経成長因子NGF受容体のリン酸化促進能を評価した。
ラット由来DRG神経細胞における神経突起形成促進活性の評価実験
実施例1で調製した山薬:ウチワドコロ=3.5:1の混合物の生薬抽出物を使用して、ラットの胎児から得たDRG(Dorsal root ganglion)神経細胞の神経突起形成促進活性を評価した。
実施例1の抽出物.............................. ..100mg
メタ重亜硫酸ナトリウム.......................... .3.0mg
メチルパラベン............................... ....0.8mg
プロピルパラベン............................... ..0.1mg
注射用滅菌蒸溜水................................. 適量
前記成分を混合し、通常の方法で2mLにした後、2mL容量のアンプルに充填して滅菌し、注射剤を製造する。
実施例1の抽出物.................................200mg
乳糖.............................................100mg
澱粉.............................................100mg
ステアリン酸マグネシウム..........................適量
前記成分を混合し、通常の錠剤の製造方法により打錠して、錠剤を製造する。
実施例1の抽出物.............................. ..100mg
乳糖.............................................50mg
澱粉.............................................50mg
タルク......................................... ...2mg
ステアリン酸マグネシウム..........................適量
前記成分を混合し、通常のカプセル剤の製造方法によってゼラチンカプセルに充填して、カプセル剤を製造する。
実施例1のエタノール抽出物.......................1000mg
砂糖.............................................20g
異性化糖... ....................................20g
レモン香料.......................................適量
精製水を加えて全容量.............................100mL
前記成分を通常の液剤の製造方法によって混合して100mLの茶色ボトルに充填し、滅菌して液剤を製造する。
Claims (5)
- 山薬(Dioscorea Rhizoma)とウチワドコロ(Dioscorea nipponica)の山薬:ウチワドコロ=3.5:1(w/w)の混合物の生薬抽出物を有効成分とし、薬学的に許容可能な担体を含むことを特徴とする、糖尿病性末梢神経病症の予防または治療用医薬組成物。
- 糖尿病性末梢神経病症は、神経細胞の萎縮、変性及び死滅を含む群から選択された少なくとも一つの原因による疾患であることを特徴とする、請求項1に記載の糖尿病性末梢神経病症の予防または治療用医薬組成物。
- 糖尿病性末梢神経病症は、焼きつくような痛み、刺すような痛み、疼痛、締め付けられるような痛み、触覚、振動覚または温度覚の感覚喪失、及びこれらの組合せを含む群から選択された症状を示すことを特徴とする、請求項1に記載の糖尿病性末梢神経病症の予防または治療用医薬組成物。
- 山薬(Dioscorea Rhizoma)とウチワドコロ(Dioscorea nipponica)の山薬:ウチワドコロ=3.5:1(w/w)の混合物の生薬抽出物を含有することを特徴とする、糖尿病性末梢神経病症の予防または改善用健康機能食品。
- 前記生薬抽出物は、粉末、顆粒、錠剤、カプセル、シロップ剤及び飲料を含む群から選択される剤形で製造されることを特徴とする、請求項4に記載の糖尿病性末梢神経病症の予防または改善用健康機能食品。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2011-0023564 | 2011-03-16 | ||
KR1020110023564A KR101341692B1 (ko) | 2011-03-16 | 2011-03-16 | 복합생약추출물을 함유하는 당뇨병성 말초 신경병증의 치료 및 예방을 위한 조성물 |
PCT/KR2011/010294 WO2012124888A2 (en) | 2011-03-16 | 2011-12-29 | Composition comprising the extract of herbal combination for preventing or treating diabetic peripheral neuropathy |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2014508189A true JP2014508189A (ja) | 2014-04-03 |
JP5763224B2 JP5763224B2 (ja) | 2015-08-12 |
Family
ID=46831143
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013558774A Active JP5763224B2 (ja) | 2011-03-16 | 2011-12-29 | 複合生薬抽出物を含有する糖尿病性末梢神経病症の予防又は治療のための組成物 |
Country Status (11)
Country | Link |
---|---|
US (4) | US20140017345A1 (ja) |
EP (1) | EP2685997B1 (ja) |
JP (1) | JP5763224B2 (ja) |
KR (1) | KR101341692B1 (ja) |
CN (1) | CN103619346B (ja) |
ES (1) | ES2583641T3 (ja) |
HU (1) | HUE029291T2 (ja) |
PL (1) | PL2685997T3 (ja) |
PT (1) | PT2685997T (ja) |
RU (1) | RU2566721C2 (ja) |
WO (1) | WO2012124888A2 (ja) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101180174B1 (ko) | 2010-04-23 | 2012-09-05 | 동아제약주식회사 | 신규한 벤즈아미드 유도체 |
KR101341692B1 (ko) | 2011-03-16 | 2013-12-20 | 동아에스티 주식회사 | 복합생약추출물을 함유하는 당뇨병성 말초 신경병증의 치료 및 예방을 위한 조성물 |
KR101341693B1 (ko) | 2011-03-16 | 2013-12-16 | 동아에스티 주식회사 | 생약추출물을 함유하는 퇴행성 신경질환의 치료 및 예방을 위한 조성물 |
KR101457789B1 (ko) | 2013-02-13 | 2014-11-03 | 동아제약 주식회사 | 상처 치료용 필름형성 약제학적 조성물 및 그의 제조방법 |
KR101538846B1 (ko) | 2013-07-30 | 2015-07-22 | 동아에스티 주식회사 | 신규한 바이페닐 유도체 및 그의 제조방법 |
US9898642B2 (en) * | 2013-09-09 | 2018-02-20 | Apple Inc. | Device, method, and graphical user interface for manipulating user interfaces based on fingerprint sensor inputs |
CN103677526B (zh) * | 2013-12-17 | 2019-06-28 | 北京猎豹移动科技有限公司 | 一种交互方法、客户端装置、移动终端及服务器 |
TWI774746B (zh) * | 2017-03-31 | 2022-08-21 | 日商東麗股份有限公司 | 環狀胺衍生物或其藥理學上可容許的鹽之用途 |
KR102323577B1 (ko) * | 2019-06-17 | 2021-11-09 | 한국한의학연구원 | 부채마와 백년초의 혼합추출물을 포함하는 우울증 예방 또는 치료용 조성물 |
CN112220905B (zh) * | 2020-11-13 | 2021-12-28 | 广东省中医院(广州中医药大学第二附属医院、广州中医药大学第二临床医学院、广东省中医药科学院) | 一种用于治疗糖尿病痛性神经病变的中药制剂 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009513626A (ja) * | 2005-10-28 | 2009-04-02 | キム・スンヨウ | ヤマノイモ科植物の抽出物、及びこれを含む末梢神経障害の予防用または治療用の組成物 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2161039C1 (ru) * | 2000-06-01 | 2000-12-27 | Научно-исследовательский центр традиционной фитотерапии | Способ лечения инсулинзависимого сахарного диабета и лекарственный сбор для лечения инсулинзависимого сахарного диабета |
KR20070018570A (ko) | 2005-08-10 | 2007-02-14 | 대구한의대학교산학협력단 | 육미지황탕을 포함하는 치매 예방 및 치료용 조성물 |
KR100811683B1 (ko) | 2006-11-21 | 2008-03-11 | 영남대학교 산학협력단 | 마 추출물을 유효성분으로 포함하는 장 기능 개선용 조성물및 이를 함유하는 기능성 건강식품 |
KR20100002668A (ko) * | 2008-06-30 | 2010-01-07 | 강원대학교산학협력단 | 항당뇨 조성물 |
KR20100084926A (ko) * | 2009-01-19 | 2010-07-28 | 주식회사 유니베라 | 염증, 알러지 질환 또는 성인병의 예방 또는 치료용 산약 추출물 |
RU2012145116A (ru) | 2010-03-24 | 2014-04-27 | Донг-А Фарм. Ко., Лтд. | Фармацевтическая композиция для предупреждения или лечения неалкогольного жирового гепатоза и способ предупреждения или лечения неалкогольного жирового гепатоза с ее использованием |
KR101180174B1 (ko) | 2010-04-23 | 2012-09-05 | 동아제약주식회사 | 신규한 벤즈아미드 유도체 |
SG190914A1 (en) | 2010-11-24 | 2013-07-31 | Dong A St Co Ltd | Quinoline derivative compound, method for preparing same, and pharmaceutical composition containing same |
WO2012070700A1 (ko) | 2010-11-24 | 2012-05-31 | 동아제약주식회사 | 퀴놀린 유도체 화합물, 이의 제조방법 및 이를 포함하는 약학 조성물 |
SI2675907T1 (en) | 2011-02-14 | 2018-04-30 | Xyleco, Inc. | Processing of paper raw materials |
KR101341692B1 (ko) | 2011-03-16 | 2013-12-20 | 동아에스티 주식회사 | 복합생약추출물을 함유하는 당뇨병성 말초 신경병증의 치료 및 예방을 위한 조성물 |
KR101341693B1 (ko) | 2011-03-16 | 2013-12-16 | 동아에스티 주식회사 | 생약추출물을 함유하는 퇴행성 신경질환의 치료 및 예방을 위한 조성물 |
-
2011
- 2011-03-16 KR KR1020110023564A patent/KR101341692B1/ko active IP Right Grant
- 2011-12-29 ES ES11860864.5T patent/ES2583641T3/es active Active
- 2011-12-29 EP EP11860864.5A patent/EP2685997B1/en active Active
- 2011-12-29 US US14/003,087 patent/US20140017345A1/en not_active Abandoned
- 2011-12-29 JP JP2013558774A patent/JP5763224B2/ja active Active
- 2011-12-29 HU HUE11860864A patent/HUE029291T2/en unknown
- 2011-12-29 PT PT118608645T patent/PT2685997T/pt unknown
- 2011-12-29 CN CN201180070202.8A patent/CN103619346B/zh active Active
- 2011-12-29 WO PCT/KR2011/010294 patent/WO2012124888A2/en active Application Filing
- 2011-12-29 RU RU2013146102/15A patent/RU2566721C2/ru active
- 2011-12-29 PL PL11860864.5T patent/PL2685997T3/pl unknown
-
2017
- 2017-04-10 US US15/484,067 patent/US10813973B2/en active Active
-
2018
- 2018-07-12 US US16/034,288 patent/US10398747B2/en active Active
-
2020
- 2020-09-30 US US17/039,120 patent/US20210113648A1/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009513626A (ja) * | 2005-10-28 | 2009-04-02 | キム・スンヨウ | ヤマノイモ科植物の抽出物、及びこれを含む末梢神経障害の予防用または治療用の組成物 |
Also Published As
Publication number | Publication date |
---|---|
US20140017345A1 (en) | 2014-01-16 |
ES2583641T3 (es) | 2016-09-21 |
PL2685997T3 (pl) | 2016-11-30 |
RU2013146102A (ru) | 2015-04-27 |
EP2685997B1 (en) | 2016-04-20 |
JP5763224B2 (ja) | 2015-08-12 |
KR20120106914A (ko) | 2012-09-27 |
WO2012124888A2 (en) | 2012-09-20 |
CN103619346A (zh) | 2014-03-05 |
US10813973B2 (en) | 2020-10-27 |
EP2685997A2 (en) | 2014-01-22 |
KR101341692B1 (ko) | 2013-12-20 |
RU2566721C2 (ru) | 2015-10-27 |
WO2012124888A3 (en) | 2012-11-08 |
US20180318377A1 (en) | 2018-11-08 |
PT2685997T (pt) | 2016-07-27 |
US20170209515A1 (en) | 2017-07-27 |
CN103619346B (zh) | 2016-01-06 |
US10398747B2 (en) | 2019-09-03 |
US20210113648A1 (en) | 2021-04-22 |
HUE029291T2 (en) | 2017-02-28 |
EP2685997A4 (en) | 2014-08-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5763224B2 (ja) | 複合生薬抽出物を含有する糖尿病性末梢神経病症の予防又は治療のための組成物 | |
JP5718468B2 (ja) | ハリグワ及びヨクイニンを含む肥満抑制又は血糖降下用組成物、並びにその用途 | |
KR101898688B1 (ko) | 복합 추출물을 포함하는 근위축의 예방, 치료 또는 개선용 조성물 | |
KR101189108B1 (ko) | 황칠나무 추출물을 포함하는 남성 성기능 개선용 조성물 | |
KR100798639B1 (ko) | 복분자, 석곡 또는 고련피의 생약 추출물을 포함하는스트레스성 질환의 치료 및 예방용 조성물 | |
KR20150015305A (ko) | 주박 추출물을 유효성분으로 함유하는 비만의 예방 또는 치료용 약학적 조성물 및 건강 기능 식품 | |
KR20080008929A (ko) | 오록실린 a를 함유하는 인지 기능 장애 관련 질환의 예방및 개선용 건강기능식품 | |
KR101248378B1 (ko) | 관절염 치료 및 예방용 약학조성물 | |
KR20130082249A (ko) | 담쟁이 덩쿨 추출물을 함유하는 대사성 질환 예방 또는 개선용 조성물 | |
JP2014155489A (ja) | サルトリイバラ葉抽出物を含有する糖尿予防及び治療用の組成物 | |
KR102588131B1 (ko) | 쑥 및 삼백초 혼합 추출물을 포함하는 미세먼지로 인한 뇌질환 예방 또는 치료용 조성물 | |
KR102545762B1 (ko) | 세모가사리 추출물을 유효성분으로 포함하는 골관절염의 예방 또는 치료용 조성물 | |
KR101348471B1 (ko) | 라리아 큐네폴리아 추출물을 유효성분으로 하는 폐경기 증후군의 예방 및 치료용 조성물 | |
KR102158852B1 (ko) | 베타인 함량이 증대된 구기자 추출물을 유효성분으로 함유하는 고혈압의 예방 또는 치료용 약학적 조성물 및 건강 기능 식품 | |
KR102216211B1 (ko) | 풋사과 추출물을 유효성분으로 함유하는 당뇨병의 예방 또는 치료용 약학적 조성물 및 건강 기능 식품 | |
KR101166698B1 (ko) | 알파-글루코시데이즈 억제 활성을 갖는 팥 근연종 추출물 | |
KR20070087951A (ko) | Acp 혼합생약 추출물을 포함하는 관절염의 예방 및 치료용 조성물 | |
KR20240006283A (ko) | 비파나무 열매 추출물을 유효성분으로 함유하는 우울증의 개선, 예방 또는 치료용 조성물 | |
KR20240006282A (ko) | 모과 추출물을 유효성분으로 함유하는 우울증의 개선, 예방 또는 치료용 조성물 | |
KR20230174777A (ko) | 육군자탕을 유효성분으로 포함하는 기억력 증진 및 인지기능 장애의 예방, 개선 또는 치료용 조성물 | |
KR20160073566A (ko) | 복합추출물을 유효성분으로 포함하는 비만, 고지혈증, 및 지방간의 예방 또는 치료용 약학적 조성물 | |
KR100846522B1 (ko) | 대황 추출물로부터 분리된 피시온 화합물을 유효성분으로함유하는 인지 기능 장애의 예방 및 치료용 조성물 | |
KR20240006284A (ko) | 비파나무 열매 추출물을 유효성분으로 함유하는 인지기능 개선, 예방 또는 치료용 조성물 | |
KR20100128668A (ko) | 붉나무 추출물을 포함하는 당뇨병 치료 또는 예방용 조성물 | |
KR20200003772A (ko) | 토사자 추출물을 유효성분으로 포함하는 허혈성 질환의 예방 또는 치료용 조성물 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130918 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A132 Effective date: 20140916 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141211 |
|
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: 20150526 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150610 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5763224 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 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |