WO2020171407A1 - Composition comprising decursinol as active ingredient for prevention or treatment of thrombocytopenia or lymphopenia - Google Patents
Composition comprising decursinol as active ingredient for prevention or treatment of thrombocytopenia or lymphopenia Download PDFInfo
- Publication number
- WO2020171407A1 WO2020171407A1 PCT/KR2020/001376 KR2020001376W WO2020171407A1 WO 2020171407 A1 WO2020171407 A1 WO 2020171407A1 KR 2020001376 W KR2020001376 W KR 2020001376W WO 2020171407 A1 WO2020171407 A1 WO 2020171407A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- thrombocytopenia
- decursinol
- mixture
- polyoxyethylene sorbitan
- pharmaceutical composition
- Prior art date
Links
- 206010043554 thrombocytopenia Diseases 0.000 title claims abstract description 71
- 239000000203 mixture Substances 0.000 title claims abstract description 64
- BGXFQDFSVDZUIW-UHFFFAOYSA-N Decursinol Natural products O1C(=O)C=CC2=C1C=C1OC(C)(C)C(O)CC1=C2 BGXFQDFSVDZUIW-UHFFFAOYSA-N 0.000 title claims abstract description 56
- BGXFQDFSVDZUIW-LBPRGKRZSA-N decursinol Chemical compound O1C(=O)C=CC2=C1C=C1OC(C)(C)[C@@H](O)CC1=C2 BGXFQDFSVDZUIW-LBPRGKRZSA-N 0.000 title claims abstract description 56
- 206010025327 Lymphopenia Diseases 0.000 title abstract description 27
- 231100001023 lymphopenia Toxicity 0.000 title abstract description 26
- 238000011282 treatment Methods 0.000 title abstract description 12
- 239000004480 active ingredient Substances 0.000 title abstract description 6
- 230000002265 prevention Effects 0.000 title abstract description 3
- 238000000034 method Methods 0.000 claims description 20
- 150000005846 sugar alcohols Polymers 0.000 claims description 19
- 239000004094 surface-active agent Substances 0.000 claims description 19
- 230000036541 health Effects 0.000 claims description 18
- 235000013376 functional food Nutrition 0.000 claims description 17
- 150000001413 amino acids Chemical class 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 229940079593 drug Drugs 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 229920001983 poloxamer Polymers 0.000 claims description 12
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 12
- 229920000053 polysorbate 80 Polymers 0.000 claims description 12
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 11
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 11
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 11
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 9
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 8
- 239000004359 castor oil Substances 0.000 claims description 8
- 235000019438 castor oil Nutrition 0.000 claims description 8
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 8
- 230000002163 immunogen Effects 0.000 claims description 8
- 229960000502 poloxamer Drugs 0.000 claims description 8
- 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 claims description 7
- 229930195725 Mannitol Natural products 0.000 claims description 7
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 7
- 239000000594 mannitol Substances 0.000 claims description 7
- 235000010355 mannitol Nutrition 0.000 claims description 7
- -1 nonylphenoxy Chemical group 0.000 claims description 7
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 claims description 7
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 239000008213 purified water Substances 0.000 claims description 7
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 7
- 239000004475 Arginine Substances 0.000 claims description 6
- 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 claims description 6
- 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 claims description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 6
- 239000004472 Lysine Substances 0.000 claims description 6
- 239000013504 Triton X-100 Substances 0.000 claims description 6
- 229920004890 Triton X-100 Polymers 0.000 claims description 6
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 6
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 6
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 6
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 claims description 6
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 claims description 6
- 235000010356 sorbitol Nutrition 0.000 claims description 6
- 239000000600 sorbitol Substances 0.000 claims description 6
- 230000001954 sterilising effect Effects 0.000 claims description 6
- 239000000811 xylitol Substances 0.000 claims description 6
- 235000010447 xylitol Nutrition 0.000 claims description 6
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 6
- 229960002675 xylitol Drugs 0.000 claims description 6
- 239000000832 lactitol Substances 0.000 claims description 5
- 235000010448 lactitol Nutrition 0.000 claims description 5
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol 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-JVCRWLNRSA-N 0.000 claims description 5
- 229960003451 lactitol Drugs 0.000 claims description 5
- 229960002920 sorbitol Drugs 0.000 claims description 5
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 4
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 4
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 4
- 229960001855 mannitol Drugs 0.000 claims description 4
- 239000003921 oil Substances 0.000 claims description 3
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 2
- 210000004698 lymphocyte Anatomy 0.000 abstract description 30
- 210000004369 blood Anatomy 0.000 abstract description 19
- 239000008280 blood Substances 0.000 abstract description 19
- 241000699670 Mus sp. Species 0.000 abstract description 9
- 210000001772 blood platelet Anatomy 0.000 description 42
- 238000004519 manufacturing process Methods 0.000 description 15
- 230000000694 effects Effects 0.000 description 14
- 230000007423 decrease Effects 0.000 description 10
- 230000006378 damage Effects 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- AGABNGOXUSXQDD-XKGFZTIGSA-N [(3s)-2,2-dimethyl-8-oxo-3,4-dihydropyrano[3,2-g]chromen-3-yl] (z)-2-methylbut-2-enoate Chemical compound C1=CC(=O)OC2=C1C=C1C[C@H](OC(=O)C(\C)=C/C)C(C)(C)OC1=C2 AGABNGOXUSXQDD-XKGFZTIGSA-N 0.000 description 6
- 210000000601 blood cell Anatomy 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- AGABNGOXUSXQDD-UHFFFAOYSA-N decursinol angelate Natural products C1=CC(=O)OC2=C1C=C1CC(OC(=O)C(C)=CC)C(C)(C)OC1=C2 AGABNGOXUSXQDD-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- 210000000265 leukocyte Anatomy 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- CUKSFECWKQBVED-INIZCTEOSA-N Decursin Chemical compound C1=CC(=O)OC2=C1C=C1C[C@H](OC(=O)C=C(C)C)C(C)(C)OC1=C2 CUKSFECWKQBVED-INIZCTEOSA-N 0.000 description 5
- CUKSFECWKQBVED-UHFFFAOYSA-N Grandivittin Natural products C1=CC(=O)OC2=C1C=C1CC(OC(=O)C=C(C)C)C(C)(C)OC1=C2 CUKSFECWKQBVED-UHFFFAOYSA-N 0.000 description 5
- 208000032843 Hemorrhage Diseases 0.000 description 5
- 230000000740 bleeding effect Effects 0.000 description 5
- JXZWWIMXTVJNSF-UHFFFAOYSA-N decursin Natural products CC(=CC(=O)OC1Oc2cc3OC(=O)C=Cc3cc2CC1(C)C)C JXZWWIMXTVJNSF-UHFFFAOYSA-N 0.000 description 5
- 210000003743 erythrocyte Anatomy 0.000 description 5
- 208000032467 Aplastic anaemia Diseases 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 208000023275 Autoimmune disease Diseases 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 239000003018 immunosuppressive agent Substances 0.000 description 4
- 210000003593 megakaryocyte Anatomy 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 210000005259 peripheral blood Anatomy 0.000 description 4
- 239000011886 peripheral blood Substances 0.000 description 4
- 208000028529 primary immunodeficiency disease Diseases 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000005063 solubilization Methods 0.000 description 4
- 230000007928 solubilization Effects 0.000 description 4
- 240000001810 Angelica gigas Species 0.000 description 3
- 235000018865 Angelica gigas Nutrition 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 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 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 238000004159 blood analysis Methods 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 150000003722 vitamin derivatives Chemical class 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 208000014311 Cushing syndrome Diseases 0.000 description 2
- 241000991587 Enterovirus C Species 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
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 102000001554 Hemoglobins Human genes 0.000 description 2
- 108010054147 Hemoglobins Proteins 0.000 description 2
- 208000005176 Hepatitis C Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 206010061598 Immunodeficiency Diseases 0.000 description 2
- 208000029462 Immunodeficiency disease Diseases 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 201000005505 Measles Diseases 0.000 description 2
- 241000712079 Measles morbillivirus Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- 208000000474 Poliomyelitis Diseases 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 2
- 102000036693 Thrombopoietin Human genes 0.000 description 2
- 108010041111 Thrombopoietin Proteins 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000000781 anti-lymphocytic effect Effects 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 208000034158 bleeding Diseases 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 2
- 230000035602 clotting Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 208000009190 disseminated intravascular coagulation Diseases 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
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000011134 hematopoietic stem cell transplantation Methods 0.000 description 2
- 230000023597 hemostasis Effects 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000007813 immunodeficiency Effects 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 230000001861 immunosuppressant effect Effects 0.000 description 2
- 208000033065 inborn errors of immunity Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000000845 maltitol Substances 0.000 description 2
- 235000010449 maltitol Nutrition 0.000 description 2
- 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 2
- 229940035436 maltitol Drugs 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 230000002560 nonimmunologic effect Effects 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229920001451 polypropylene glycol Polymers 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229960004063 propylene glycol Drugs 0.000 description 2
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 208000008190 Agammaglobulinemia Diseases 0.000 description 1
- 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 1
- 241000125175 Angelica Species 0.000 description 1
- 206010003594 Ataxia telangiectasia Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000018240 Bone Marrow Failure disease Diseases 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 208000000398 DiGeorge Syndrome Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 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
- 235000001287 Guettarda speciosa Nutrition 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 201000005624 HELLP Syndrome Diseases 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 description 1
- 206010062506 Heparin-induced thrombocytopenia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020983 Hypogammaglobulinaemia Diseases 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
- 208000028622 Immune thrombocytopenia Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- 208000009567 Neonatal Alloimmune Thrombocytopenia Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 206010029379 Neutrophilia Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 208000003286 Protein-Energy Malnutrition Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 206010043561 Thrombocytopenic purpura Diseases 0.000 description 1
- 208000034841 Thrombotic Microangiopathies Diseases 0.000 description 1
- 201000007023 Thrombotic Thrombocytopenic Purpura Diseases 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 208000003441 Transfusion reaction Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 229930003451 Vitamin B1 Natural products 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 229930003471 Vitamin B2 Natural products 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 208000006110 Wiskott-Aldrich syndrome Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 201000004208 acquired thrombocytopenia Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 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
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 229940125691 blood product Drugs 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 208000015322 bone marrow disease Diseases 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 230000001680 brushing effect Effects 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229940037769 calcium carbonate 100 mg Drugs 0.000 description 1
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 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
- 239000000969 carrier Substances 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 1
- 230000037029 cross reaction Effects 0.000 description 1
- ZGFASEKBKWVCGP-UHFFFAOYSA-N cyclocoumarol Chemical class C12=CC=CC=C2OC(=O)C2=C1OC(OC)(C)CC2C1=CC=CC=C1 ZGFASEKBKWVCGP-UHFFFAOYSA-N 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 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
- 238000002474 experimental method Methods 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- FTSSQIKWUOOEGC-RULYVFMPSA-N fructooligosaccharide Chemical compound OC[C@H]1O[C@@](CO)(OC[C@@]2(OC[C@@]3(OC[C@@]4(OC[C@@]5(OC[C@@]6(OC[C@@]7(OC[C@@]8(OC[C@@]9(OC[C@@]%10(OC[C@@]%11(O[C@H]%12O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%12O)O[C@H](CO)[C@@H](O)[C@@H]%11O)O[C@H](CO)[C@@H](O)[C@@H]%10O)O[C@H](CO)[C@@H](O)[C@@H]9O)O[C@H](CO)[C@@H](O)[C@@H]8O)O[C@H](CO)[C@@H](O)[C@@H]7O)O[C@H](CO)[C@@H](O)[C@@H]6O)O[C@H](CO)[C@@H](O)[C@@H]5O)O[C@H](CO)[C@@H](O)[C@@H]4O)O[C@H](CO)[C@@H](O)[C@@H]3O)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@@H](O)[C@@H]1O FTSSQIKWUOOEGC-RULYVFMPSA-N 0.000 description 1
- 229940107187 fructooligosaccharide Drugs 0.000 description 1
- 235000020510 functional beverage Nutrition 0.000 description 1
- FBPFZTCFMRRESA-GUCUJZIJSA-N galactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-GUCUJZIJSA-N 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000002343 gold Chemical class 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000000642 iatrogenic effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 208000007232 portal hypertension Diseases 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 201000011461 pre-eclampsia Diseases 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 201000010434 protein-losing enteropathy Diseases 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960000342 retinol acetate Drugs 0.000 description 1
- 239000011770 retinyl acetate Substances 0.000 description 1
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 1
- 235000019173 retinyl acetate Nutrition 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 208000002491 severe combined immunodeficiency Diseases 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 238000010911 splenectomy Methods 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 1
- 229960000604 valproic acid Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 229940033203 vitamin b6 0.5 mg Drugs 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Images
Classifications
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
- A61K31/37—Coumarins, e.g. psoralen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- 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
-
- 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
- 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
- A23V2250/00—Food ingredients
- A23V2250/30—Other Organic compounds
Definitions
- the present invention relates to a composition for preventing or treating thrombocytopenia or lymphopenia comprising decursinol as an active ingredient, and more specifically, to a composition comprising decursinol solubilized to increase the bioavailability of decursinol. It relates to a composition for preventing or treating thrombocytopenia or lymphopenia.
- Blood moves around the body through blood vessels, supplying oxygen and nutrients, and transporting waste products so that they can be excreted through the kidneys. In addition, it is responsible for the transport of hormones secreted from the endocrine organs, defense against external pathogens, and regulation of body temperature.
- Such blood consists of plasma as a liquid component and blood cells as a cellular component, and blood cells are divided into erythrocytes (red blood cells, RBCs), white blood cells (WBCs), and platelets (thrombocytes).
- Red blood cells carry oxygen molecules through a protein called hemoglobin (Hb, hemoglobin), and white blood cells are divided into granulocytes, monocytes, and lymphocytes, and respond against external invasion. Platelets, along with proteins in plasma, play an important role in blood clotting.
- These blood cells (blood corpuscle) are produced in the bone marrow through the process of hematopoiesis.
- Platelets are fragments of cells that are involved in blood coagulation and inflammatory reactions, produced by megakaryocytes, and are nucleated cells present in mammalian blood. Platelets mediate blood clot formation and hemostasis, play an important role in the repair and regeneration of connective tissue, and release growth factors that promote wound healing. These platelets are derived from pluripotent stem cells of the bone marrow, and humoral factors such as thrombopoietin influence the development of megakaryocytes. In normal blood, there are 150,000 to 400,000 platelets per 1 ⁇ l of blood, and a lower platelet count is called thrombocytopenia.
- Thrombocytopenia is a phenomenon in which the number of platelets responsible for clotting and hemostasis of blood decreases, and the platelet count is defined as 150,000/ ⁇ l or less (Kim Hwang-min, 2004). In general, mild thrombocytopenia does not cause any special symptoms. However, as the platelet decrease becomes more severe, the tendency to bleed increases, which can lead to bleeding gums or bruising the skin during brushing. If the number of platelets is reduced to 20,000/ ⁇ l or less, bleeding can occur in major organs without trauma, so stability and treatment are required.
- the main mechanism of platelet count reduction is decreased platelet production and increased destruction.
- Typical examples of decreased production are bone marrow failure diseases such as aplastic anemia, myelodysplastic syndrome, and thrombocytopenia due to anticancer drugs, and increased destruction is such as disseminated intravascular coagulation (DIC) and thrombotic microangiopathy.
- DIC disseminated intravascular coagulation
- platelet sequestration and blood dilution can be a mechanism for platelet reduction. Platelet isolation is characterized by the relocation of platelets from peripheral blood to the spleen in congestive splenic enlargements caused by portal hypertension. Blood dilution is a case of receiving blood products with low colloids, crystalloids, and platelets due to massive bleeding (Ahn Jeong-yeol, et al., 2014).
- thrombocytopenia is treated differently depending on the underlying disease or the degree of reduction. In the case of thrombocytopenia caused by an infection or drug, it can be improved after stopping the treatment of the infection and taking the drug being taken. However, in the case of thrombocytopenia, which is caused by an abnormal immune system, an immunosuppressant such as steroids is preferentially used, and if the effect of the immunosuppressant is not good, a drug such as immunoglobulin may be used or splenectomy may be considered as a surgical method.
- an immunosuppressant such as steroids is preferentially used, and if the effect of the immunosuppressant is not good, a drug such as immunoglobulin may be used or splenectomy may be considered as a surgical method.
- bone marrow diseases such as acute leukemia or aplastic anemia
- anticancer treatment or immunosuppression treatment suitable for the cause disease is required, and in some cases, hematopoietic stem cell transplantation (bone marrow transplantation) may be required for cure.
- Platelet transfusion or bone marrow transplant is the only currently approved treatment for many patients with regard to thrombocytopenia.
- repeated platelet transfusion may lose the therapeutic effect due to the development of alloantibodies, and in the case of transfusion, side effects such as infection, hypersensitivity and hemolytic reaction may occur.
- Platelet production promoting factor plays a role in promoting platelet production from megakaryocytes. Recombinant platelet production promoting factor induces antibody production and cross-reaction with endogenous platelet production promoting factor, causing secondary thrombocytopenia and bleeding.
- Cytokines interleukin and GM-CSF granulocyte-macrophage colony-stimulating factor
- GM-CSF granulocyte-macrophage colony-stimulating factor
- Lymphocytes are divided into T lymphocytes and B lymphocytes. It is difficult to evaluate the process of lymphocyte generation and differentiation, because these processes occur in various organs, such as the bone marrow, lymph nodes, spleen, and thymus, and circulate through the peripheral blood and re-enter some organs. Despite the many variables affecting lymphocytes, the number of lymphocytes in the peripheral blood remains constant (normal range 2-4 ⁇ 10 3 / ⁇ l).
- Lymphopenia is a case in which the number of lymphocytes decreases to less than 1.5 ⁇ 10 3 / ⁇ l, and in severe cases, the number of lymphocytes decreases to less than 0.7 ⁇ 10 3 / ⁇ l. Lymphopenia is caused by a variety of causes. The most common case of lymphocytic abnormality is proteincalorie malnutrition. In a nutrient-deficient state, immunity decreases, increasing the risk of infection. Radiation therapy and immunosuppressive agents such as antithyme-globulins and alkylating agents cause lymphopenia by inhibiting proliferation of hematopoietic progenitor cells and blocking differentiation into lymphocytes. Some viruses infect the cells of the lymphatic system and cause cell destruction, reducing the number of lymphocytes.
- lymphopenia of this type is a temporary phenomenon that returns to normal within 24 to 48 hours, and does not functionally cause immune decline. It is a common iatrogenic cause because steroids administered for therapeutic purposes have the same effect. In autoimmune diseases including rheumatic diseases, lymphopenia may also occur in cases of anti-lymphocyte antibody, protein-losing enteropathy, and severe heart failure (Park, SK, 2010).
- lymphopenia occurs as a secondary symptom of the underlying disease, so it is important to find and treat the underlying disease.
- Intravenous immunoglobulin administration may help reduce infectious complications in patients with lymphopenia with hypomaglobulinemia.
- hematopoietic stem cell transplantation or cytokine treatment may be considered, but additional studies are needed on clinical effects.
- decursinol is a physiologically active component of Angelicae and has analgesic effects, protection against neurotoxicity, prevention of dementia, treatment of sepsis, and antioxidants.
- Decursinol can be isolated from Angelica gigas , but its content is very small, and it is present less than other physiologically active ingredients of Angelica gigas , decursin and decursinol angelate. Therefore, a large amount of decursinol can be obtained by hydrolysis through a base from decursin and decursinol angelate.
- decursinol and decursinol angelate when administered orally, decursinol has low bioavailability due to low absorption in the intestine, and when its purity is low, serious problems that cause high blood pressure may occur.
- the inventors of the present invention have registered a patent in relation to a method for producing high-purity decursinol in the process of continuing research on the extract of Korean Angelica Angelica (Korean Patent No. 1600961), and poorly soluble such as decursin and decursinol angelate.
- a patent has been registered for the solubilization technology of a substance (Korean Patent No. 1717672).
- the present inventors can complete the present invention by confirming that decursinol is solubilized while performing an experiment using decursinol to increase bioavailability, and that the solubilized decursinol increases the number of platelets or lymphocytes in the blood. there was.
- Korean Patent Nos. 0697212 and 1153436 describe the effect of treating thrombocytopenia of a composition comprising an Angelicae extract, but the effect of increasing the number of platelets or lymphocytes of decercinol of the present invention is not described.
- the present invention relates to a pharmaceutical composition for preventing or treating thrombocytopenia or lymphopenia comprising decursinol, a surfactant, a basic amino acid and a polyhydric alcohol.
- the present invention relates to a health functional food for improving thrombocytopenia or lymphopenia, including dekercinol, surfactant, basic amino acid and polyhydric alcohol.
- the pharmaceutical composition or health functional food is a first step of preparing a first mixture by mixing a surfactant with decercinol; A second step of preparing a second mixture by adding ethanol to the first mixture, adding a basic amino acid and purified water to dissolve it, adding polyhydric alcohol, adjusting the pH to 7.0 to 8.6; And a third step of sterilizing the secondary mixture. It may be manufactured through a process consisting of.
- the surfactant is sodium dodecyl sulfate (sodium dodecyl sulfate), polyoxyethylene sorbitan monooleate (polyoxyethylene sorbitan monooleate, Tween-80), polyoxyethylene sorbitan monostearate (polyoxyethylene sorbitan monostearate, Tween- 60), polyoxyethylene sorbitan monopalmitate (Tween-40), polyoxyethylene sorbitan monolaurate (Tween-20), triton X-100 (triton X-100), It may be one or more selected from the group consisting of nonyl phenoxypolyethoxylethanol (NP-40), caster oil, and poloxamer.
- NP-40 nonyl phenoxypolyethoxylethanol
- caster oil and poloxamer.
- the basic amino acid may be arginine, lysine, histidine, or a mixture thereof.
- the polyhydric alcohol may be at least one selected from the group consisting of mannitol, sorbitol, xylitol, and lactitol.
- the decursinol may be administered at 0.5-10 mg/kg.
- the thrombocytopenia may be non-immunologic causes of thrombocytopenia, immunologic causes of thrombocytopenia, or drug-induced thrombocytopenia.
- Lymphopenia is immunodeficiency, cancer, viral infection, autoimmune disease, lymphocyte destruction by treatment, lymphocyte loss, lymphoma, Cushing's syndrome, stress, neutrophilia, immunogenic thrombocytopenia, hepatitis C-related thrombocytopenia,
- the number of lymphocytes in the blood may be reduced to less than 1,500/ ⁇ l due to aplastic anemia or a mixture thereof.
- the present invention relates to a composition for preventing or treating thrombocytopenia or lymphopenia comprising decursinol, a surfactant, a basic amino acid and a polyhydric alcohol.
- the decursinol is a physiologically active component of Angelicae and is a derivative of pyranocoumarin.
- the decursinol can be isolated from the Angelicae extract.
- the decursinol can be obtained by hydrolyzing through a base from decursin and decursinol angelate.
- Decursinol isolated from the Angelicae extract can increase blood pressure when administered as the purification rate of decursinol is lower. Therefore, the decursinol of the present invention may have a purification rate of 50% or more. It is preferably 70% or more, and more preferably 90% or more. Most preferably, it is 99% or more.
- the Angelica Angelica may be a Angelica Angelica, but is not limited thereto.
- the decursinol of the present invention may be prepared according to a conventional method in the art, and may be prepared as a pharmaceutically acceptable salt.
- the composition comprises a first step of preparing a first mixture by mixing a surfactant with decercinol; A second step of preparing a second mixture by adding ethanol to the first mixture, adding a basic amino acid and purified water to dissolve it, adding polyhydric alcohol, adjusting the pH to 7.0 to 8.6; And a third step of sterilizing the secondary mixture. It may be decursinol solubilized through.
- the solubilization refers to a phenomenon in which the solubility of a substance that is not well soluble in water increases, and the solubilization method may be used to increase the bioavailability by increasing the solubility of the decursinol of the present invention, which is a poorly soluble substance.
- the surfactants are sodium dodecyl sulfate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monolaurate, triton X-100, It may be one or more selected from the group consisting of nonylphenoxypolyethoxylethanol, castor oil, and poloxamer.
- castor oil is a fatty oil extracted from castor seeds, has a unique adhesiveness, and is used as a suspending agent for a poorly soluble substance insoluble in water as a nonionic surfactant.
- the castor oil of the present invention is to solubilize decursinol, and to prevent decursinol from being aggregated and precipitated together with the dispersion of decursinol.
- the castor oil may be polyoxyl 35 castor oil.
- the polyoxyl 35 castor oil is a product commercialized under the trade name of Kolliphor EL or Cremophor EL, which is a combination of 35 moles of ethylene oxide and one molecule of castor oil. However, it is not limited thereto.
- polystyrene resin is also called pluronics, and as a hydrophilic polymer, it has polyoxypropylene in the center and polyoxyethylene in both sides, and polyoxypropylene Various types such as P123 and P407 exist depending on the molecular weight of and the composition ratio of polyoxyethylene.
- the poloxamer of the present invention is Pluronic P407, the molecular weight of polypropylene is 4000 g/mol, and the composition ratio of polyethylene is 70%, and Pluronic P407 is the most preferred surfactant, and the solubility of poorly soluble substances. It can be used to increase or to promote micelles.
- the surfactants are i) sodium dodecyl sulfate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monolaurate, triton X- 100, and at least one selected from the group consisting of nonylphenoxypolyethoxylethanol; ii) castor oil; And iii) poloxamer; Can be used by mixing.
- Mixtures thereof include i) sodium dodecyl sulfate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monolaurate, and Triton X- 100, and at least one selected from the group consisting of nonylphenoxypolyethoxylethanol; ii) pizza horse oil; And iii) poloxamer; May be mixed in a weight ratio of 1:0.1 to 1:1. If the weight ratio is out of the above, non-specific itching caused by castor oil may appear, which is not preferable.
- the surfactant may be added in an amount of 0.01% by weight or more based on the total weight of the composition. It is preferably 0.01 to 1% by weight. If the surfactant is less than 0.01% by weight of the total weight of the composition, it is difficult to solubilize dekercinol, and if it exceeds 1% by weight, it may cause vomiting, etc. due to excessive use of the surfactant, and may cause cell lysis. It is not desirable.
- the basic amino acid is used as a dissolution aid, and may be arginine, lysine, histidine, or a mixture thereof, preferably arginine, lysine, or a mixture thereof.
- the basic amino acid may contain 0.1 to 4% [w/v] based on the composition. If the content of basic amino acids is less than 0.1%[w/v], it is difficult to assist solubility and no practical effect appears. If it exceeds 4%[w/v], gelation may occur due to excessive viscosity. It is also not desirable.
- polyhydric alcohol is a type of sugar containing two or more hydroxyl groups, and the polyhydric alcohol of the present invention has a property of intercalating between poorly soluble substances, preventing poorly soluble substances from being aggregated together, and Even in the case, it is possible to prevent unit molecules from clumping together.
- the polyhydric alcohol may be one or more selected from mannitol, maltitol, galactitol, erythritol, sorbitol, xylitol, lactitol, propylene glycol, glycerol, butylene glycol, and the like. Preferably, it is at least one selected from mannitol, sorbitol, xylitol and lactitol.
- the polyhydric alcohol may be added in an amount of 100% by weight or more compared to decercinol.
- the polyhydric alcohol is less than 100% by weight, precipitates are generated in the composition, resulting in poor stability of the composition, and it is difficult to maintain uniformity.
- the polyhydric alcohol cannot exceed a maximum of 2% by weight based on the total weight of the composition.
- the polyhydric alcohol exceeds 2% by weight based on the total weight of the composition, it is not preferable to cause pain.
- the composition may increase the number of platelets or lymphocytes as well as increase the number of white blood cells.
- composition provides a pharmaceutical composition for preventing or treating thrombocytopenia or lymphopenia comprising the solubilized decursinol and a pharmaceutically acceptable excipient.
- the solubilized decercinol may be added in an amount of preferably 0.001 to 50% by weight, more preferably 0.001 to 40% by weight, and most preferably 0.001 to 30% by weight based on the total weight of the pharmaceutical composition.
- compositions may be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, solutions, aerosols, etc., external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods. have.
- Carriers, excipients and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose , Methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oils.
- Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations are at least one excipient, such as starch, calcium carbonate, and water in the solubilized decurcinol of the present invention. It is prepared by mixing cross or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.
- Liquid preparations for oral use include suspensions, liquid solutions, emulsions, syrups, etc.
- various excipients such as wetting agents, sweetening agents, fragrances, preservatives, acidulants, etc.
- Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories.
- non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used.
- As a base for suppositories witepsol, macrogol, tween-61, cacao butter, laurin paper, glycerogelatin, and the like may be used.
- the dosage of the pharmaceutical composition of the present invention will vary depending on the age, sex, and weight of the subject to be treated, the specific disease or pathology to be treated, the severity of the disease or pathology, the route of administration, and the judgment of the prescriber. Dosage determination based on these factors is within the level of one of skill in the art, and dosages generally range from 0.01 mg/kg/day to approximately 500 mg/kg/day. A preferred dosage is from 0.1 mg/kg/day to 200 mg/kg/day, and a more preferred dosage is from 1 mg/kg/day to 200 mg/kg/day. Administration may be administered once a day, or may be divided several times. The above dosage does not in any way limit the scope of the present invention.
- the pharmaceutical composition of the present invention can be administered to mammals such as mice, livestock, and humans by various routes. All modes of administration can be expected and can be administered, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injection and skin application. Deckercinol of the present invention has almost no toxicity and side effects, so it is a drug that can be safely used even when taken for a long time for prophylactic purposes.
- composition provides a health functional food for improving thrombocytopenia or lymphopenia, comprising the solubilized decursinol and a food pharmaceutically acceptable food additive.
- the health functional food may be added with the solubilized dekersinol preferably 0.001 to 50% by weight, more preferably 0.001 to 30% by weight, and most preferably 0.001 to 10% by weight based on the total weight of the health functional food. have.
- the health functional food includes the form of tablets, capsules, pills, liquids, etc.
- foods to which the solubilized decursinol of the present invention can be added include, for example, various foods, beverages, gum, tea, There are vitamin complexes and health functional foods.
- thrombocytopenia refers to a phenomenon in which the number of platelets decreases, and when the number of platelets in humans is based, the platelet count is 150,000/ ⁇ l or less.
- the thrombocytopenia may be non-immunologic causes of thrombocytopenia, immunologic causes of thrombocytopenia, or drug-induced thrombocytopenia.
- the non-immunogenic thrombocytopenia is disseminated intravascular coagulation, thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome, pregnancy addiction, and preeclampsia. pre-eclampisa), HELLP syndrome, thrombocytopenia caused by massive blood transfusion, thrombocytopenia caused by massive blood transfusion, thrombocytopenia caused by liver disease, thrombocytopenia due to infection, or thrombocytopenia due to hematopoietic deficiency. hematinic deficiencies).
- the immunogenic thrombocytopenia may be alloantibody-mediated thrombocytopenia or autoantibody-mediated thrombocytopenia.
- the alloantibody-mediated thrombocytopenia may be neonatal alloimmune thrombocytopenia or post-transfusion purpura.
- the autoantibody-mediated thrombocytopenia may be idiopathic thrombocytopenic purpura (immune throbocytopenic purpura), chronic immune thrombocytopenic purpura, or secondary immune thrombotopenia. .
- the drug-induced thrombocytopenia may be heparin-induced thrombocytopenia or other drugs causing immune-mediated platelet destruction.
- anticancer drugs quinidine, quinine, gold salts, valproic acid, rapamycine, and sulfa antibiotics. Etc. However, it is not limited thereto.
- lymphopenia is a condition in which the number of lymphocytes in peripheral blood is absolutely decreased, and the number of lymphocytes decreases to less than 1500 cells/ ⁇ l, and in severe cases, it decreases to less than 700 cells/ ⁇ l.
- the lymphopenia may be caused by immunodeficiency, cancer, viral infection, autoimmune disease, destruction by treatment, loss of lymphocytes, lymphoma, Cushing syndrome, stress, and an increase in neutrophils.
- the lymphopenia may be caused by immunogenic thrombocytopenia, hepatitis C-related thrombocytopenia, aplastic anemia, or the like.
- the immunodeficiency syndrome may be congenital immunodeficiency syndrome or acquired immunodeficiency syndrome (AIDS).
- AIDS acquired immunodeficiency syndrome
- the congenital immunodeficiency syndrome includes Di George's syndrome, Wiskott-Aldrich syndrome, ataxia telangiectasia, agammaglobulinemia, and severe complex immunodeficiency syndrome. severe combined immunodeficiency, SCID).
- an immunosuppressive substance produced by tumor cells causes lymphocyte reduction.
- Lymphopenia caused by viral infection is the destruction of lymphocytes by infected measles, polio, and human immunodeficiency virus (HIV).
- HIV human immunodeficiency virus
- Lymphopenia caused by the autoimmune disease is systemic lupus erythematosus, in which lymphocytes are destroyed by anti-lymphocyte autoantibodies.
- Lymphocytopenia caused by the above treatment destroys lymphocytes by administration of anticancer agents, irradiation, or steroids.
- the loss of lymphocytes may be protein loss gastrointestinal disease or thoracic lymphatic drainage.
- the present invention relates to a composition for preventing or treating thrombocytopenia or lymphopenia comprising decursinol as an active ingredient, and as a result of administration of solubilized decursinol to mice to increase the bioavailability of decursinol, It was confirmed that the number of platelets or lymphocytes in the blood of rats was increased.
- composition capable of preventing or treating thrombocytopenia or lymphopenia using the solubilized decursinol of the present invention can be developed.
- Decercinol is a poorly soluble substance and has low bioavailability.
- solubilized decercinol was prepared by referring to the method described in Korean Patent No. 1917672 of the present inventor.
- decursinol was mass-produced and used with decursinol having a purification rate of 99% or more, referring to the method for producing decursinol in Korean Patent No. 1600961 of the present inventor.
- mice 23-week-old SD (Sprague Dawley) mice were purchased and adapted in an animal room for 1 week, and then randomly divided into the experimental groups shown in Table 1 below.
- 1 ml of physiological saline was administered orally once a day for 3 weeks, and the composition corresponding to the following Table 1 was administered intraperitoneally to the remaining experimental groups once a day, 1 ml each for 3 weeks.
- mice were fasted to collect blood, and after administration of the composition for 3 weeks, the mice were anesthetized and blood was collected to conduct blood analysis, and the results are shown in Table 2 and FIG. 1 below. Blood analysis was performed using an automatic blood analyzer of the Anti-aging Industry Promotion Center of Pusan National University.
- decursinol increases the absorption of decursinol in vivo, thereby increasing the pharmacological activity of decursinol, and that decursinol increases the number of platelets, lymphocytes and white blood cells in the blood. I could see that.
- solubilized decursinol of the present invention was mixed with 175.9 g of lactose, 180 g of potato starch and 32 g of colloidal silicic acid. After adding a 10% gelatin solution to this mixture, it was pulverized and passed through a 14 mesh sieve. This was dried, and 160 g of potato starch, 50 g of active and 5 g of magnesium stearate were added thereto, and the resulting mixture was made into tablets.
- solubilized decercinol of the present invention 100 mg was solubilized decercinol of the present invention, 0.6 g of sodium chloride, and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. This solution was put in a bottle and sterilized by heating at 20° C. for 30 minutes.
- solubilized decursinol of the present invention appropriate amount of vitamin mixture, vitamin A acetate 70 ⁇ g, vitamin E 1.0 mg, vitamin B1 0.13 mg, vitamin B2 0.15 mg, vitamin B6 0.5 mg, vitamin B12 0.2 ⁇ g, vitamin C 10 mg, Biotin 10 ⁇ g, nicotinic acid amide 1.7mg, folic acid 50 ⁇ g, calcium pantothenate 0.5mg, an appropriate amount of inorganic mixture, ferrous sulfate 1.75mg, zinc oxide 0.82mg, magnesium carbonate 25.3mg, potassium monophosphate 15mg, dicalcium phosphate 55 mg, potassium citrate 90 mg, calcium carbonate 100 mg, and magnesium chloride 24.8 mg were mixed to form granules, but can be prepared by modifying various formulations according to the use.
- the composition ratio of the vitamin and mineral mixture may be arbitrarily modified, and may be prepared by mixing the above ingredients according to a conventional health functional food manufacturing method.
- a beverage was prepared by mixing 1 g of solubilized decercinol of the present invention, 0.1 g of citric acid, 100 g of fructooligosaccharide, and 900 g of purified water, followed by stirring, heating, filtration, sterilization, and refrigeration according to a conventional beverage preparation method.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dermatology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Molecular Biology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a composition comprising decursinol as an active ingredient for prevention or treatment of thrombocytopenia. As a result of administering decursinol solubilized for the increase in bioavailability thereof to mice, the platelet and lymphocyte counts in the blood of the mice were verified to increase, so that the use of the solubilized decursinol of the present invention is expected to develop a composition capable of preventing or treating thrombocytopenia or lymphopenia.
Description
본 발명은 데커시놀(decursinol)을 유효성분으로 포함하는 혈소판 감소증 또는 림프구 감소증 예방 또는 치료용 조성물에 관한 것으로, 보다 구체적으로는 데커시놀의 생체이용률 증가를 위해 가용화시킨 데커시놀을 포함하는 혈소판 감소증 또는 림프구 감소증 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating thrombocytopenia or lymphopenia comprising decursinol as an active ingredient, and more specifically, to a composition comprising decursinol solubilized to increase the bioavailability of decursinol. It relates to a composition for preventing or treating thrombocytopenia or lymphopenia.
혈액은 혈관을 통해 온몸을 돌면서 산소와 영양소 등을 공급해주고 노폐물을 운반하여 신장을 통해 배설될 수 있도록 한다. 또한, 내분비기관에서 분비되는 호르몬의 운반, 외부 병원체에 대한 방어 및 체온 조절을 담당한다. 이러한 혈액은 액체 성분인 혈장과 세포 성분인 혈구로 이루어져 있으며, 혈구는 적혈구(erythrocyte, red blood cell, RBC), 백혈구(white blood cell, WBC) 및 혈소판(platelet, thrombocyte)으로 구분된다. 적혈구는 헤모글로빈(hemoglobin, Hb, 혈색소)이라는 단백질을 통해 산소 분자를 운반하고, 백혈구는 과립구(granulocyte), 단핵구(monocyte), 림프구(lymphocyte)로 나뉘며, 외부의 침입에 대항하여 반응한다. 혈소판은 혈장 내의 단백질과 함께 혈액 응고에 중요한 역할을 한다. 이러한 혈구(blood corpuscle)는 골수에서 조혈(hematopoiesis) 과정을 통해 생성된다. Blood moves around the body through blood vessels, supplying oxygen and nutrients, and transporting waste products so that they can be excreted through the kidneys. In addition, it is responsible for the transport of hormones secreted from the endocrine organs, defense against external pathogens, and regulation of body temperature. Such blood consists of plasma as a liquid component and blood cells as a cellular component, and blood cells are divided into erythrocytes (red blood cells, RBCs), white blood cells (WBCs), and platelets (thrombocytes). Red blood cells carry oxygen molecules through a protein called hemoglobin (Hb, hemoglobin), and white blood cells are divided into granulocytes, monocytes, and lymphocytes, and respond against external invasion. Platelets, along with proteins in plasma, play an important role in blood clotting. These blood cells (blood corpuscle) are produced in the bone marrow through the process of hematopoiesis.
혈소판은 거핵세포(megakaryocyte)에서 생성되는, 혈액 응고와 염증 반응에 관여하는 세포의 단편으로 포유동물 혈액에 존재하는 무핵 세포이다. 혈소판은 혈전(blood clot) 형성과 지혈을 매개하고 결합 조직의 회복 및 재생에 중요한 역할을 하며, 상처 치유를 촉진하는 성장인자들을 방출한다. 이러한 혈소판은 골수의 만능 줄기세포로부터 유래되며 혈소판생성촉진인자(thrombopoietin)와 같은 체액 인자는 거핵세포 발달에 영향을 미친다. 정상적인 혈액 내에는 혈액 1㎕당 150,000~400,000개의 혈소판이 존재하며, 이보다 혈소판 수치가 감소한 경우를 혈소판 감소증(thrombocytopenia)이라 한다. Platelets are fragments of cells that are involved in blood coagulation and inflammatory reactions, produced by megakaryocytes, and are nucleated cells present in mammalian blood. Platelets mediate blood clot formation and hemostasis, play an important role in the repair and regeneration of connective tissue, and release growth factors that promote wound healing. These platelets are derived from pluripotent stem cells of the bone marrow, and humoral factors such as thrombopoietin influence the development of megakaryocytes. In normal blood, there are 150,000 to 400,000 platelets per 1 µl of blood, and a lower platelet count is called thrombocytopenia.
혈소판 감소증은 혈액의 응고와 지혈을 담당하는 혈소판의 수가 감소하는 현상으로, 혈소판 수치가 150,000/㎕ 이하로 정의된다(김황민, 2004). 일반적으로 경도의 혈소판 감소증이 있는 경우에는 특별한 증상이 생기지 않는다. 그러나 혈소판 감소가 심해질수록 출혈 경향이 증가하여 양치시 잇몸 출혈이 발생하거나 피부에 멍이 잘 들 수 있다. 혈소판 수가 20,000/㎕ 이하로 감소하면 외상이 없이도 주요 장기에 출혈이 발생할 수 있기 때문에 안정 및 치료가 필요하다. Thrombocytopenia is a phenomenon in which the number of platelets responsible for clotting and hemostasis of blood decreases, and the platelet count is defined as 150,000/µl or less (Kim Hwang-min, 2004). In general, mild thrombocytopenia does not cause any special symptoms. However, as the platelet decrease becomes more severe, the tendency to bleed increases, which can lead to bleeding gums or bruising the skin during brushing. If the number of platelets is reduced to 20,000/µl or less, bleeding can occur in major organs without trauma, so stability and treatment are required.
혈소판 수치 감소의 주된 기전은 혈소판의 생산 감소와 파괴 증가이다. 생산 감소의 전형적인 예는 재생불량빈혈, 골수형성이상증후군, 항암제에 의한 혈소판 감소증 등과 같은 골수부전 질환이며, 파괴 증가는 파종혈관내응고(disseminated intravascular coagulation, DIC)와 혈전성 미세혈관병증과 같은 상황에서 보인다. 이외에도 혈소판 격리(sequestration)와 혈액 희석이 혈소판 수치 감소의 기전이 될 수 있다. 혈소판 격리는 문맥 고혈압에 의한 울혈성 비장종대에서 혈소판이 말초혈액에서 비장으로 재배치되는 것이 특징이다. 혈액 희석은 대량출혈로 인한 콜로이드, 크리스탈로이드, 혈소판이 적은 혈액제제를 투여 받은 경우이다(안정열, et al., 2014). The main mechanism of platelet count reduction is decreased platelet production and increased destruction. Typical examples of decreased production are bone marrow failure diseases such as aplastic anemia, myelodysplastic syndrome, and thrombocytopenia due to anticancer drugs, and increased destruction is such as disseminated intravascular coagulation (DIC) and thrombotic microangiopathy. Looks at. In addition, platelet sequestration and blood dilution can be a mechanism for platelet reduction. Platelet isolation is characterized by the relocation of platelets from peripheral blood to the spleen in congestive splenic enlargements caused by portal hypertension. Blood dilution is a case of receiving blood products with low colloids, crystalloids, and platelets due to massive bleeding (Ahn Jeong-yeol, et al., 2014).
혈소판 감소증은 원인 질환이나 감소증의 정도에 따라 치료 방법이 달라진다. 감염이나 약물에 의한 혈소판 감소증의 경우에는 감염 치료 및 복용중인 약물의 복용을 중단한 뒤 호전될 수 있다. 그러나 면역계 이상으로 나타나는 혈소판 감소증의 경우에는 스테로이드 등의 면역 억제제를 우선적으로 사용하며, 면역 억제제의 효과가 좋지 않을 경우에는 면역글로불린 같은 약제를 사용하거나 수술적 방법으로 비장절제술을 고려해 볼 수 있다. 급성백혈병이나 재생불량성빈혈 등 골수의 질병에 의한 경우에는 원인 질환에 맞는 항암제 치료나 면역 억제 치료가 필요하며, 경우에 따라 완치를 위해 조혈모세포 이식(골수 이식)이 필요할 수도 있다. Thrombocytopenia is treated differently depending on the underlying disease or the degree of reduction. In the case of thrombocytopenia caused by an infection or drug, it can be improved after stopping the treatment of the infection and taking the drug being taken. However, in the case of thrombocytopenia, which is caused by an abnormal immune system, an immunosuppressant such as steroids is preferentially used, and if the effect of the immunosuppressant is not good, a drug such as immunoglobulin may be used or splenectomy may be considered as a surgical method. In the case of bone marrow diseases such as acute leukemia or aplastic anemia, anticancer treatment or immunosuppression treatment suitable for the cause disease is required, and in some cases, hematopoietic stem cell transplantation (bone marrow transplantation) may be required for cure.
혈소판 감소증과 관련하여 현재 많은 환자에 대해 유일하게 승인된 치료 방식은 혈소판 수혈이나 골수이식이다. 그러나 반복적인 혈소판 수혈은 동종항체의 발달로 치료 효과를 잃어버릴 수 있으며, 수혈의 경우에는 감염, 과민증 및 용혈 반응과 같은 부작용이 나타날 수 있다. Platelet transfusion or bone marrow transplant is the only currently approved treatment for many patients with regard to thrombocytopenia. However, repeated platelet transfusion may lose the therapeutic effect due to the development of alloantibodies, and in the case of transfusion, side effects such as infection, hypersensitivity and hemolytic reaction may occur.
혈소판생성촉진인자(thrombopoietin)는 거핵세포로부터 혈소판 생성을 촉진시키는 역할을 하는데, 재조합 혈소판생성촉진인자는 항체 생성을 유도하고 내인성 혈소판생성촉진인자와의 교차반응을 나타내어 이차 혈소판 감소증 및 출혈을 야기하여 사용이 중단되었다(Li, J., et al., 2001). 사이토카인(cytokine)인 인터루킨(interleukin)과 GM-CSF(granulocyte-macrophage colony-stimulating factor)은 동물에서 거핵세포들의 생성에 관여하는 것으로 알려져있고(Ciurea, S.O., et al., 2007), 임상 연구에서 혈소판 신생 활성이 있음을 확인하였다. 그러나 이들 각각이 심각한 독성과 같은 부작용이 있는 것으로 나타나 혈소판 감소증 치료에 있어 제한적이다. 따라서, 혈소판 감소증 예방 또는 치료 효과가 우수한 약물의 개발이 시급한 실정이다. Platelet production promoting factor (thrombopoietin) plays a role in promoting platelet production from megakaryocytes. Recombinant platelet production promoting factor induces antibody production and cross-reaction with endogenous platelet production promoting factor, causing secondary thrombocytopenia and bleeding. Was discontinued (Li, J., et al., 2001). Cytokines interleukin and GM-CSF (granulocyte-macrophage colony-stimulating factor) are known to be involved in the production of megakaryocytes in animals (Ciurea, SO, et al., 2007), and clinical studies. It was confirmed that there is platelet angiogenesis activity. However, each of these has been shown to have side effects such as severe toxicity, which is limited in the treatment of thrombocytopenia. Therefore, there is an urgent need to develop a drug having an excellent effect of preventing or treating thrombocytopenia.
림프구(lymphocyte)는 T 림프구와 B 림프구로 나뉜다. 림프구의 생성과 분화 과정을 평가하는 것은 어려운데, 이는 이들 과정이 골수를 비롯하여 림프절, 비장, 흉선 등과 같은 여러 장기에서 이루어지며 말초혈액을 통하여 순환되었다가 일부의 장기로 재진입하기 때문이다. 림프구에 영향을 주는 많은 변수에도 불구하고 말초 혈액 내의 림프구 수는 일정하게 유지된다(정상범위 2~4×103/㎕). Lymphocytes are divided into T lymphocytes and B lymphocytes. It is difficult to evaluate the process of lymphocyte generation and differentiation, because these processes occur in various organs, such as the bone marrow, lymph nodes, spleen, and thymus, and circulate through the peripheral blood and re-enter some organs. Despite the many variables affecting lymphocytes, the number of lymphocytes in the peripheral blood remains constant (normal range 2-4×10 3 /µl).
림프구 감소증(lymphopenia)은 림프구가 1.5×103/㎕ 미만으로 감소한 경우이며, 중증의 경우는 림프구 수가 0.7×103/㎕ 미만으로 감소한다. 림프구 감소증은 다양한 원인에 의해 발생한다. 림프구 생성 이상으로 가장 흔한 경우가 단백열량영양실조(proteincalorie malnutrition)이다. 영양 결핍 상태에서는 면역 저하를 초래하여 감염 위험성이 높아진다. 방사선 치료와 항흉선-글로불린, 알킬화제와 같은 면역 억제제는 조혈전구세포 증식을 억제하고 림프구로의 분화를 차단함으로써 림프구 감소증을 초래한다. 일부 바이러스는 림프계 세포에 감염 된 후 세포 파괴를 일으켜 림프구 수를 감소시킨다. 홍역, 폴리오, HIV 등이 이에 해당한다. 세균성 감염, 수술, 외상, 출혈 등과 같이 신체적으로 심한 스트레스를 주는 경우에는 내인성 글루코코르티코이드(glucocorticoid)가 많이 분비됨으로써 순환 중인 B 림프구와 T 림프구가 급격하게 감소하게 된다. 이런 종류의 림프구 감소증은 일시적인 현상으로 24~48시간 내에 정상으로 회복되며, 기능적으로 면역 저하를 초래하지 않는다. 치료 목적으로 투여된 스테로이드도 동일한 효과를 보이기 때문에 흔한 의원성(iatrogenic) 원인이다. 류마티스 질환을 포함한 자가면역질환에서 항림프구 항체가 있는 경우와 단백소실창자병증(protein-losing enteropathy), 중증 심부전 등에 의해서도 림프구 감소증이 나타날 수 있다(Park, S.K., 2010). Lymphopenia is a case in which the number of lymphocytes decreases to less than 1.5×10 3 /µl, and in severe cases, the number of lymphocytes decreases to less than 0.7×10 3 /µl. Lymphopenia is caused by a variety of causes. The most common case of lymphocytic abnormality is proteincalorie malnutrition. In a nutrient-deficient state, immunity decreases, increasing the risk of infection. Radiation therapy and immunosuppressive agents such as antithyme-globulins and alkylating agents cause lymphopenia by inhibiting proliferation of hematopoietic progenitor cells and blocking differentiation into lymphocytes. Some viruses infect the cells of the lymphatic system and cause cell destruction, reducing the number of lymphocytes. These include measles, polio, and HIV. In the case of severe physical stress such as bacterial infection, surgery, trauma, bleeding, etc., endogenous glucocorticoids are secreted, resulting in a rapid decrease in circulating B lymphocytes and T lymphocytes. Lymphopenia of this type is a temporary phenomenon that returns to normal within 24 to 48 hours, and does not functionally cause immune decline. It is a common iatrogenic cause because steroids administered for therapeutic purposes have the same effect. In autoimmune diseases including rheumatic diseases, lymphopenia may also occur in cases of anti-lymphocyte antibody, protein-losing enteropathy, and severe heart failure (Park, SK, 2010).
많은 경우에서 림프구 감소증이 기저질환에 의한 이차적인 증상으로 발생하기 때문에 기저질환을 찾아 치료하는 것이 중요하다. 저감마글로불린혈증을 동반한 림프구 감소증 환자에서 정맥주사용 면역글로불린의 투여는 감염성 합병증 을 줄이는 데 도움이 될 수 있다. 중증의 경우 조혈모세포이식이나 사이토카인 치료를 고려할 수 있으나 임상적 효과에 대해서 추가적인 연구가 필요한 상태이다.In many cases, lymphopenia occurs as a secondary symptom of the underlying disease, so it is important to find and treat the underlying disease. Intravenous immunoglobulin administration may help reduce infectious complications in patients with lymphopenia with hypomaglobulinemia. In severe cases, hematopoietic stem cell transplantation or cytokine treatment may be considered, but additional studies are needed on clinical effects.
데커시놀(decursinol)은 당귀의 생리활성 성분으로 진통 효과, 신경독성에 대한 보호, 치매 예방, 패혈증 치료, 항산화 등과 같은 효능이 있음이 보고되었다. 데커시놀은 참당귀(Angelica
gigas)로부터 분리할 수 있으나, 그 함량이 극히 미량으로 당귀의 또 다른 생리활성 성분인 데커신(decursin)과 데커시놀 안젤레이트(decursinol angelate)보다 적게 존재한다. 따라서 대량의 데커시놀은 데커신과 데커시놀 안젤레이트로부터 염기를 통해 가수분해하여 얻을 수 있다. It has been reported that decursinol is a physiologically active component of Angelicae and has analgesic effects, protection against neurotoxicity, prevention of dementia, treatment of sepsis, and antioxidants. Decursinol can be isolated from Angelica gigas , but its content is very small, and it is present less than other physiologically active ingredients of Angelica gigas , decursin and decursinol angelate. Therefore, a large amount of decursinol can be obtained by hydrolysis through a base from decursin and decursinol angelate.
그러나 데커시놀은 데커신과 데커시놀 안젤레이트에 비해 경구로 투여 시 장내에서의 흡수도가 낮아 생체이용률이 낮으며, 순도가 낮을 경우에는 고혈압을 유발하는 심각한 문제가 발생할 수 있어, 데커시놀의 유익한 생리학적 효능을 위해서는 순도가 높은 데커시놀을 이용하여 생체이용률을 증가시키는 방안을 마련하는 것이 필요하다. However, compared to decursinol and decursinol angelate, when administered orally, decursinol has low bioavailability due to low absorption in the intestine, and when its purity is low, serious problems that cause high blood pressure may occur. For the beneficial physiological efficacy of the drug, it is necessary to prepare a plan to increase the bioavailability using high-purity decercinol.
본 발명자들은 참당귀 추출물을 지속적으로 연구하는 과정에서 순도가 높은 데커시놀을 제조하는 방법과 관련하여 특허 등록하였고(한국등록특허 제1600961호), 데커신 및 데커시놀 안젤레이트와 같은 난용성 물질의 가용화 기술에 대한 특허를 등록한 바 있다(한국등록특허 제1717672호). The inventors of the present invention have registered a patent in relation to a method for producing high-purity decursinol in the process of continuing research on the extract of Korean Angelica Angelica (Korean Patent No. 1600961), and poorly soluble such as decursin and decursinol angelate. A patent has been registered for the solubilization technology of a substance (Korean Patent No. 1717672).
이에 본 발명자들은, 데커시놀을 이용해 실험을 수행하던 중에 데커시놀을 가용화시켜 생체이용률을 높이고, 이러한 가용화된 데커시놀이 혈액 내 혈소판 또는 림프구의 수를 증가시킨다는 확인함으로써 본 발명을 완성할 수 있었다. Accordingly, the present inventors can complete the present invention by confirming that decursinol is solubilized while performing an experiment using decursinol to increase bioavailability, and that the solubilized decursinol increases the number of platelets or lymphocytes in the blood. there was.
종래선행기술인 한국등록특허 제0697212호 및 제1153436호에는 당귀 추출물을 포함하는 조성물의 혈소판 감소증 치료 효과가 기재되어 있으나, 본 발명의 데커시놀의 혈소판 또는 림프구 수의 증가 효과는 기재되어 있지 않다. Prior art, Korean Patent Nos. 0697212 and 1153436 describe the effect of treating thrombocytopenia of a composition comprising an Angelicae extract, but the effect of increasing the number of platelets or lymphocytes of decercinol of the present invention is not described.
또한, 비특허선행문헌인 Lee, Y.Y., et al.(2003)에는 당귀 뿌리로부터 분리한 데커신 및 데커시놀 안젤레이트를 포함하는 코우마린계 화합물의 혈소판 응집 억제 효과가 기재되어 있으나, 본 발명의 데커시놀의 혈소판 또는 림프구 수 증가 효과는 기재되어 있지 않다.In addition, the non-patent precedent literature Lee, YY, et al. (2003) describes the effect of inhibiting platelet aggregation of coumarine-based compounds including decursin and decursinol angelate isolated from Angelica roots, but the present invention The effect of increasing the number of platelets or lymphocytes of decursinol is not described.
본 발명의 목적은 데커시놀을 유효성분으로 포함하는 혈소판 감소증 또는 림프구 감소증 예방 또는 치료용 조성물을 제공하는 데 있다.It is an object of the present invention to provide a composition for preventing or treating thrombocytopenia or lymphopenia comprising dekercinol as an active ingredient.
본 발명은 데커시놀(decursinol), 계면활성제, 염기성 아미노산 및 다가알코올을 포함하는 혈소판 감소증 또는 림프구 감소증 예방 또는 치료용 약학 조성물에 관한 것이다. The present invention relates to a pharmaceutical composition for preventing or treating thrombocytopenia or lymphopenia comprising decursinol, a surfactant, a basic amino acid and a polyhydric alcohol.
또한, 본 발명은 데커시놀, 계면활성제, 염기성 아미노산 및 다가알코올을 포함하는 혈소판 감소증 또는 림프구 감소증 개선용 건강기능식품에 관한 것이다. In addition, the present invention relates to a health functional food for improving thrombocytopenia or lymphopenia, including dekercinol, surfactant, basic amino acid and polyhydric alcohol.
상기 약학 조성물 또는 건강기능식품은 데커시놀에 계면활성제를 혼합하여 1차 혼합물을 제조하는 제1단계; 상기 1차 혼합물에 에탄올을 넣은 후, 염기성 아미노산 및 정제수를 첨가하여 녹이고 다가알코올 첨가 후, pH를 7.0~8.6이 되도록 맞추어 2차 혼합물을 제조하는 제2단계; 및, 상기 2차 혼합물을 멸균 처리하는 제3단계; 로 이루어진 과정을 통해 제조된 것일 수 있다.The pharmaceutical composition or health functional food is a first step of preparing a first mixture by mixing a surfactant with decercinol; A second step of preparing a second mixture by adding ethanol to the first mixture, adding a basic amino acid and purified water to dissolve it, adding polyhydric alcohol, adjusting the pH to 7.0 to 8.6; And a third step of sterilizing the secondary mixture. It may be manufactured through a process consisting of.
상기 계면활성제(detergent)는 소듐 도데실 설페이트(sodium dodecyl sulfate), 폴리옥시에틸렌 소르비탄 모노올레이트(polyoxyethylene sorbitan monooleate, Tween-80), 폴리옥시에틸렌 소르비탄 모노스테아레이트(polyoxyethylene sorbitan monostearate, Tween-60), 폴리옥시에틸렌 소르비탄 모노팔미테이트(polyoxyethylene sorbitan monopalmitate, Tween-40), 폴리옥시에틸렌 소르비탄 모노라우레이트(polyoxyethylene sorbitan monolaurate, Tween-20), 트리톤 X-100(triton X-100), 노닐페녹시폴리에톡실에탄올(nonyl phenoxypolyethoxylethanol, NP-40), 피마자 오일(caster oil) 및 폴록사머(poloxamer)로 이루어진 군에서 선택되는 1종 이상일 수 있다.The surfactant (detergent) is sodium dodecyl sulfate (sodium dodecyl sulfate), polyoxyethylene sorbitan monooleate (polyoxyethylene sorbitan monooleate, Tween-80), polyoxyethylene sorbitan monostearate (polyoxyethylene sorbitan monostearate, Tween- 60), polyoxyethylene sorbitan monopalmitate (Tween-40), polyoxyethylene sorbitan monolaurate (Tween-20), triton X-100 (triton X-100), It may be one or more selected from the group consisting of nonyl phenoxypolyethoxylethanol (NP-40), caster oil, and poloxamer.
상기 염기성 아미노산은 아르기닌, 라이신, 히스티딘 또는 이들의 혼합물일 수 있다. The basic amino acid may be arginine, lysine, histidine, or a mixture thereof.
상기 다가알코올은 만니톨(mannitol), 소르비톨(sorbitol), 자일리톨(xylitol) 및 락티톨(lactitol)로 이루어진 군에서 선택되는 1종 이상일 수 있다. The polyhydric alcohol may be at least one selected from the group consisting of mannitol, sorbitol, xylitol, and lactitol.
상기 데커시놀은 0.5~10㎎/㎏로 투여할 수 있다. The decursinol may be administered at 0.5-10 mg/kg.
상기 혈소판 감소증(thrombocytopenia)은 비면역원성 혈소판 감소증(non-immunologic causes of thrombocytopenia), 면역원성 혈소판 감소증(immunologic causes of thrombocytopenia) 또는 약물-유도 혈소판 감소증(drug-induced thrombocytopenia)일 수 있다.The thrombocytopenia may be non-immunologic causes of thrombocytopenia, immunologic causes of thrombocytopenia, or drug-induced thrombocytopenia.
상기 림프구 감소증(lymphopenia)은 면역결핍증, 암, 바이러스 감염, 자가면역질환, 치료에 의한 림프구 파괴, 림프구 상실, 림프종, 쿠싱 증후군, 스트레스, 호중구 증가, 면역원성 혈소판 감소증, C형 간염 관련 혈소판 감소증, 재생불량성빈혈 또는 이들의 혼합에 의해 혈액 내 림프구 수가 1,500개/㎕ 미만으로 감소한 것일 수 있다. Lymphopenia is immunodeficiency, cancer, viral infection, autoimmune disease, lymphocyte destruction by treatment, lymphocyte loss, lymphoma, Cushing's syndrome, stress, neutrophilia, immunogenic thrombocytopenia, hepatitis C-related thrombocytopenia, The number of lymphocytes in the blood may be reduced to less than 1,500/µl due to aplastic anemia or a mixture thereof.
이하 본 발명을 상세하게 설명한다. Hereinafter, the present invention will be described in detail.
본 발명은 데커시놀, 계면활성제, 염기성 아미노산 및 다가알코올을 포함하는 혈소판 감소증 또는 림프구 감소증 예방 또는 치료용 조성물에 관한 것이다. The present invention relates to a composition for preventing or treating thrombocytopenia or lymphopenia comprising decursinol, a surfactant, a basic amino acid and a polyhydric alcohol.
상기 데커시놀은 당귀의 생리활성 성분으로 피라노코우마린(pyranocoumarin) 유도체이다. The decursinol is a physiologically active component of Angelicae and is a derivative of pyranocoumarin.
상기 데커시놀은 당귀 추출물로부터 분리할 수 있다. 또한 상기 데커시놀은 데커신(decursin)과 데커시놀 안젤레이트(decursinol angelate)로부터 염기를 통해 가수분해하여 얻을 수 있다. The decursinol can be isolated from the Angelicae extract. In addition, the decursinol can be obtained by hydrolyzing through a base from decursin and decursinol angelate.
상기 당귀 추출물로부터 분리된 데커시놀은, 데커시놀의 정제율이 낮을수록 투여 시 혈압을 높일 수 있다. 따라서, 본 발명의 데커시놀은 정제율이 50% 이상일 수 있다. 바람직하게는 70% 이상이고, 더 바람직하게는 90% 이상이다. 가장 바람직하게는 99% 이상이다. Decursinol isolated from the Angelicae extract can increase blood pressure when administered as the purification rate of decursinol is lower. Therefore, the decursinol of the present invention may have a purification rate of 50% or more. It is preferably 70% or more, and more preferably 90% or more. Most preferably, it is 99% or more.
상기 당귀는 참당귀일 수 있으나, 이에 한정되는 것은 아니다. The Angelica Angelica may be a Angelica Angelica, but is not limited thereto.
한편, 본 발명의 데커시놀은 당해 기술 분야에서 통상적인 방법에 따라 제조될 수 있으며, 약학적으로 허용 가능한 염으로 제조될 수도 있다. Meanwhile, the decursinol of the present invention may be prepared according to a conventional method in the art, and may be prepared as a pharmaceutically acceptable salt.
상기 조성물은 데커시놀에 계면활성제를 혼합하여 1차 혼합물을 제조하는 제1단계; 상기 1차 혼합물에 에탄올을 넣은 후, 염기성 아미노산 및 정제수를 첨가하여 녹이고 다가알코올 첨가 후, pH를 7.0~8.6이 되도록 맞추어 2차 혼합물을 제조하는 제2단계; 및, 상기 2차 혼합물을 멸균 처리하는 제3단계; 를 통해 가용화시킨 데커시놀일 수 있다. The composition comprises a first step of preparing a first mixture by mixing a surfactant with decercinol; A second step of preparing a second mixture by adding ethanol to the first mixture, adding a basic amino acid and purified water to dissolve it, adding polyhydric alcohol, adjusting the pH to 7.0 to 8.6; And a third step of sterilizing the secondary mixture. It may be decursinol solubilized through.
상기 가용화(solubilization)는 물에 잘 녹지 않은 물질의 용해도가 증가하는 현상을 말하는 것으로, 난용성 물질인 본 발명의 데커시놀의 용해도를 높여 생체이용율을 높이기 위해 상기 가용화 방법을 이용할 수 있다. The solubilization refers to a phenomenon in which the solubility of a substance that is not well soluble in water increases, and the solubilization method may be used to increase the bioavailability by increasing the solubility of the decursinol of the present invention, which is a poorly soluble substance.
상기 계면활성제는 소듐 도데실 설페이트, 폴리옥시에틸렌 소르비탄 모노올레이트, 폴리옥시에틸렌 소르비탄 모노스테아레이트, 폴리옥시에틸렌 소르비탄 모노팔미테이트, 폴리옥시에틸렌 소르비탄 모노라우레이트, 트리톤 X-100, 노닐페녹시폴리에톡실에탄올, 피마자유 및 폴록사머로 이루어진 군에서 선택되는 1종 이상 일 수 있다. The surfactants are sodium dodecyl sulfate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monolaurate, triton X-100, It may be one or more selected from the group consisting of nonylphenoxypolyethoxylethanol, castor oil, and poloxamer.
본 발명에 있어서, "피마자유(castor oil)"는 피마자 씨에서 추출한 지방유로 독특한 점착성을 가지고 있으며, 비이온성 계면활성제로서 물에 녹지 않는 난용성 물질의 현탁화제의 목적으로 이용된다. In the present invention, "castor oil" is a fatty oil extracted from castor seeds, has a unique adhesiveness, and is used as a suspending agent for a poorly soluble substance insoluble in water as a nonionic surfactant.
본 발명의 피마자유는 데커시놀을 가용화하기 위한 것으로, 데커시놀의 분산과 함께 데커시놀이 서로 뭉쳐서 침전되는 것을 방지하기 위한 것이다. The castor oil of the present invention is to solubilize decursinol, and to prevent decursinol from being aggregated and precipitated together with the dispersion of decursinol.
상기 피마자유는 폴리옥실 35 피마자유(polyoxyl 35 castor oil)일 수 있다. 상기 폴리옥실 35 피마자유는 Kolliphor EL 또는 Cremophor EL의 상품명으로 상용화된 제품으로, 35몰(mole)의 에틸렌 옥사이드(ethylene oxide)와 1분자의 피마자유(castor oil)가 결합된 것이다. 그러나 이에 한정되는 것은 아니다.The castor oil may be polyoxyl 35 castor oil. The polyoxyl 35 castor oil is a product commercialized under the trade name of Kolliphor EL or Cremophor EL, which is a combination of 35 moles of ethylene oxide and one molecule of castor oil. However, it is not limited thereto.
본 발명에 있어서, "폴록사머(poloxamer)"는 플루로닉(pluronics)이라고도 불리며, 친수성 고분자로써 중심에는 폴리옥시프로필렌(polyoxypropylene)을, 양쪽에는 폴리옥시에틸렌(plyoxyethylene)을 가지고 있으며, 폴리옥시프로필렌의 분자량과 폴리옥시에틸렌의 구성 비율에 따라서 P123, P407 등 다양한 종류가 존재한다. In the present invention, "poloxamer" is also called pluronics, and as a hydrophilic polymer, it has polyoxypropylene in the center and polyoxyethylene in both sides, and polyoxypropylene Various types such as P123 and P407 exist depending on the molecular weight of and the composition ratio of polyoxyethylene.
본 발명의 폴록사머는 플루로닉 P407로, 폴리프로필렌의 분자량이 4000g/mol, 폴리에틸렌의 구성비율이 70%인 폴록사머이며, 플루로닉 P407은 가장 선호되는 계면활성제로서 난용성 물질의 가용성을 높이기 위하여 사용하거나 미셀(micelle)화를 증진시킬 목적으로도 사용할 수 있다.
The poloxamer of the present invention is Pluronic P407, the molecular weight of polypropylene is 4000 g/mol, and the composition ratio of polyethylene is 70%, and Pluronic P407 is the most preferred surfactant, and the solubility of poorly soluble substances. It can be used to increase or to promote micelles.
상기 계면활성제는 i) 소듐 도데실 설페이트, 폴리옥시에틸렌 소르비탄 모노올레이트, 폴리옥시에틸렌 소르비탄 모노스테아레이트, 폴리옥시에틸렌 소르비탄 모노팔미테이트, 폴리옥시에틸렌 소르비탄 모노라우레이트, 트리톤 X-100, 및 노닐페녹시폴리에톡실에탄올로 이루어진 군에서 선택되는 1종 이상; ii) 피마자유; 및 iii) 폴록사머; 를 혼합하여 사용할 수 있다. 이들의 혼합은 i) 소듐 도데실 설페이트, 폴리옥시에틸렌 소르비탄 모노올레이트, 폴리옥시에틸렌 소르비탄 모노스테아레이트, 폴리옥시에틸렌 소르비탄 모노팔미테이트, 폴리옥시에틸렌 소르비탄 모노라우레이트, 트리톤 X-100, 및 노닐페녹시폴리에톡실에탄올로 이루어진 군에서 선택되는 1종 이상; ii) 피자마유; 및 iii) 폴록사머; 가 1:0.1~1:1 중량비율로 혼합된 것일 수 있다. 상기 중량비율을 벗어나면 피마자유에 의한 비특이적 가려움증이 나타날 수 있어 바람직하지 못하다. The surfactants are i) sodium dodecyl sulfate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monolaurate, triton X- 100, and at least one selected from the group consisting of nonylphenoxypolyethoxylethanol; ii) castor oil; And iii) poloxamer; Can be used by mixing. Mixtures thereof include i) sodium dodecyl sulfate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monolaurate, and Triton X- 100, and at least one selected from the group consisting of nonylphenoxypolyethoxylethanol; ii) pizza horse oil; And iii) poloxamer; May be mixed in a weight ratio of 1:0.1 to 1:1. If the weight ratio is out of the above, non-specific itching caused by castor oil may appear, which is not preferable.
상기 계면활성제는 조성물 총 중량 대비 0.01중량% 이상으로 첨가될 수 있다. 바람직하게는 0.01~1중량%이다. 상기 계면활성제가 조성물 총 중량 대비 0.01중량% 미만일 경우에는 데커시놀을 가용화시키기 어려우며, 1중량%를 초과할 경우에는 계면활성제의 과도한 사용으로 인해 구토 등을 유발할 수 있고, 세포 용해를 유발할 수 있어 바람직하지 못하다.The surfactant may be added in an amount of 0.01% by weight or more based on the total weight of the composition. It is preferably 0.01 to 1% by weight. If the surfactant is less than 0.01% by weight of the total weight of the composition, it is difficult to solubilize dekercinol, and if it exceeds 1% by weight, it may cause vomiting, etc. due to excessive use of the surfactant, and may cause cell lysis. It is not desirable.
상기 염기성 아미노산은 용해 보조제로 활용하는 것으로, 아르기닌, 라이신, 히스티딘 또는 이들의 혼합물일 수 있으며, 바람직하게는 아르기닌, 라이신 또는 이들의 혼합물이다. The basic amino acid is used as a dissolution aid, and may be arginine, lysine, histidine, or a mixture thereof, preferably arginine, lysine, or a mixture thereof.
상기 염기성 아미노산은 조성물을 기준으로 0.1~4%[w/v]가 포함될 수 있다. 염기성 아미노산의 함량이 0.1%[w/v] 미만일 경우에는 용해성을 보조하기가 어렵고 실질적인 효과가 나타나지 않으며, 4%[w/v]를 초과할 경우에는 과도한 점성으로 인해 겔화가 될 수 있으며, 경제적으로도 바람직하지 못하다.The basic amino acid may contain 0.1 to 4% [w/v] based on the composition. If the content of basic amino acids is less than 0.1%[w/v], it is difficult to assist solubility and no practical effect appears. If it exceeds 4%[w/v], gelation may occur due to excessive viscosity. It is also not desirable.
본 발명에 있어서, "다가알코올"은 하이드록실기가 2개 이상 포함된 당 종류로서, 본 발명의 다가알코올은 난용성 물질 사이로 끼어들어가는 성질이 있어 난용성 물질들이 서로 뭉치는 것을 방지하며 고분자의 경우에도 단위 분자들이 서로 뭉치는 것을 방지할 수 있다. In the present invention, "polyhydric alcohol" is a type of sugar containing two or more hydroxyl groups, and the polyhydric alcohol of the present invention has a property of intercalating between poorly soluble substances, preventing poorly soluble substances from being aggregated together, and Even in the case, it is possible to prevent unit molecules from clumping together.
상기 다가알코올은 만니톨, 말티톨, 갈락티톨, 에리스리톨, 소르비톨, 자일리톨, 락티톨, 프로필렌글리콜, 글리세롤, 부틸렌글리콜 등에서 선택되는 1종 이상일 수 있다. 바람직하게는 만니톨, 소르비톨, 자일리톨 및 락티톨에서 선택되는 1종 이상이다. The polyhydric alcohol may be one or more selected from mannitol, maltitol, galactitol, erythritol, sorbitol, xylitol, lactitol, propylene glycol, glycerol, butylene glycol, and the like. Preferably, it is at least one selected from mannitol, sorbitol, xylitol and lactitol.
상기 다가알코올은 데커시놀 대비 100중량% 이상으로 첨가될 수 있다. 다가알코올이 100중량% 미만일 경우에는 조성물 내 침전물이 생성되어 조성물의 안정성이 떨어지며 균일성을 유지하기가 어렵다. The polyhydric alcohol may be added in an amount of 100% by weight or more compared to decercinol. When the polyhydric alcohol is less than 100% by weight, precipitates are generated in the composition, resulting in poor stability of the composition, and it is difficult to maintain uniformity.
또한, 상기 다가알코올은 조성물 총 중량 대비 최대 2중량%를 넘을 수 없다. 상기 다가알코올이 조성물 총 중량 대비 2중량%를 초과할 경우에는 통증을 유발하여 바람직하지 못하다. In addition, the polyhydric alcohol cannot exceed a maximum of 2% by weight based on the total weight of the composition. When the polyhydric alcohol exceeds 2% by weight based on the total weight of the composition, it is not preferable to cause pain.
상기 조성물은 혈소판 또는 림프구 수를 증가시킬 뿐만 아니라 백혈구의 수를 증가시킬 수 있다. The composition may increase the number of platelets or lymphocytes as well as increase the number of white blood cells.
상기 조성물은 상기 가용화된 데커시놀 및 약학적으로 허용 가능한 부형제를 포함하는 혈소판 감소증 또는 림프구 감소증 예방 또는 치료용 약학 조성물을 제공한다.The composition provides a pharmaceutical composition for preventing or treating thrombocytopenia or lymphopenia comprising the solubilized decursinol and a pharmaceutically acceptable excipient.
상기 가용화된 데커시놀은 약학 조성물 총 중량에 대하여 바람직하게는 0.001~50중량%, 더 바람직하게는 0.001~40중량%, 가장 바람직하게는 0.001~30중량%로 하여 첨가될 수 있다. The solubilized decercinol may be added in an amount of preferably 0.001 to 50% by weight, more preferably 0.001 to 40% by weight, and most preferably 0.001 to 30% by weight based on the total weight of the pharmaceutical composition.
상기 약학 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 액제, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균주사용액의 형태로 제형화하여 사용될 수 있다. 상기 약학 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제, 감미제, 산미제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 본 발명의 가용화된 데커시놀에 적어도 하나 이상의 부형제, 예를 들면, 전분, 탄산칼슘, 수크로스 또는 락토즈, 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 스테아린산 마그네슘, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제, 산미제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween)-61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. The pharmaceutical compositions may be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, solutions, aerosols, etc., external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods. have. Carriers, excipients and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose , Methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oils. In the case of formulation, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, sweeteners, and acidulants that are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations are at least one excipient, such as starch, calcium carbonate, and water in the solubilized decurcinol of the present invention. It is prepared by mixing cross or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, liquid solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, fragrances, preservatives, acidulants, etc. Can be included. Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween-61, cacao butter, laurin paper, glycerogelatin, and the like may be used.
본 발명의 약학 조성물의 투여량은 치료받을 대상의 연령, 성별, 체중과, 치료할 특정 질환 또는 병리 상태, 질환 또는 병리 상태의 심각도, 투여 경로 및 처방자의 판단에 따라 달라질 것이다. 이러한 인자에 기초한 투여량 결정은 당업자의 수준 내에 있으며, 일반적으로 투여량은 0.01㎎/㎏/일 내지 대략 500㎎/㎏/일의 범위이다. 바람직한 투여량은 0.1㎎/㎏/일 내지 200㎎/㎏/일이며, 더 바람직한 투여량은 1㎎/㎏/일 내지 200㎎/㎏/일이다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. The dosage of the pharmaceutical composition of the present invention will vary depending on the age, sex, and weight of the subject to be treated, the specific disease or pathology to be treated, the severity of the disease or pathology, the route of administration, and the judgment of the prescriber. Dosage determination based on these factors is within the level of one of skill in the art, and dosages generally range from 0.01 mg/kg/day to approximately 500 mg/kg/day. A preferred dosage is from 0.1 mg/kg/day to 200 mg/kg/day, and a more preferred dosage is from 1 mg/kg/day to 200 mg/kg/day. Administration may be administered once a day, or may be divided several times. The above dosage does not in any way limit the scope of the present invention.
본 발명의 약학 조성물은 쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관 내 주사 및 피부 도포에 의해 투여될 수 있다. 본 발명의 데커시놀은 독성 및 부작용이 거의 없으므로 예방 목적으로 장기간 복용시에도 안심하고 사용할 수 있는 약제이다. The pharmaceutical composition of the present invention can be administered to mammals such as mice, livestock, and humans by various routes. All modes of administration can be expected and can be administered, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injection and skin application. Deckercinol of the present invention has almost no toxicity and side effects, so it is a drug that can be safely used even when taken for a long time for prophylactic purposes.
상기 조성물은 상기 가용화된 데커시놀 및 식품학적으로 허용 가능한 식품 보조 첨가제를 포함하는 혈소판 감소증 또는 림프구 감소증 개선용 건강기능식품을 제공한다. The composition provides a health functional food for improving thrombocytopenia or lymphopenia, comprising the solubilized decursinol and a food pharmaceutically acceptable food additive.
상기 건강기능식품은 가용화된 데커시놀이 건강기능식품 총 중량에 대하여 바람직하게는 0.001~50중량%, 더 바람직하게는 0.001~30중량%, 가장 바람직하게는 0.001~10중량%로 하여 첨가될 수 있다. The health functional food may be added with the solubilized dekersinol preferably 0.001 to 50% by weight, more preferably 0.001 to 30% by weight, and most preferably 0.001 to 10% by weight based on the total weight of the health functional food. have.
상기 건강기능식품은 정제, 캡슐제, 환제 또는 액제 등의 형태를 포함하며, 본 발명의 가용화된 데커시놀을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강기능성식품류 등이 있다. The health functional food includes the form of tablets, capsules, pills, liquids, etc., and foods to which the solubilized decursinol of the present invention can be added include, for example, various foods, beverages, gum, tea, There are vitamin complexes and health functional foods.
본 발명에 있어서, "혈소판 감소증"은 혈소판의 수가 감소하는 현상으로 인간의 혈소판 수를 기준으로 하는 경우, 혈소판 수치가 150,000/㎕ 이하인 상태를 의미한다. In the present invention, "thrombocytopenia" refers to a phenomenon in which the number of platelets decreases, and when the number of platelets in humans is based, the platelet count is 150,000/µl or less.
상기 혈소판 감소증은 비면역원성 혈소판 감소증(non-immunologic causes of thrombocytopenia), 면역원성 혈소판 감소증(immunologic causes of thrombocytopenia) 또는 약물-유도 혈소판 감소증(drug-induced thrombocytopenia)일 수 있다. The thrombocytopenia may be non-immunologic causes of thrombocytopenia, immunologic causes of thrombocytopenia, or drug-induced thrombocytopenia.
상기 비면역원성 혈소판 감소증은 파종혈관내응고(disseminated intravascular coagulation), 혈전성 혈소판 감소성 자반증(thrombotic thrombocytopenic purpura, TTP), 용혈성 요독성 증후군(hemolytic uremic syndrome), 임신중독증(pregnancy addiction), 자간전증(pre-eclampisa), 헬프증후군(HELLP syndrome), 대량 수혈로 인한 혈소판 감소증(thrombocytopenia caused by massive blood transfusion), 간 질환에 의한 혈소판 감소증, 감염에 의한 혈소판 감소증 또는 조혈제 결핍에 의한 혈소판 감소증(thrombocytopenia due to hematinic deficiencies)일 수 있다. The non-immunogenic thrombocytopenia is disseminated intravascular coagulation, thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome, pregnancy addiction, and preeclampsia. pre-eclampisa), HELLP syndrome, thrombocytopenia caused by massive blood transfusion, thrombocytopenia caused by massive blood transfusion, thrombocytopenia caused by liver disease, thrombocytopenia due to infection, or thrombocytopenia due to hematopoietic deficiency. hematinic deficiencies).
상기 면역원성 혈소판 감소증은 동종항체-매개성 혈소판 감소증(alloantibody-mediated thrombocytopenia) 또는 자가항체-매개성 혈소판 감소증(autoantibody-mediated thrombocytopenia)일 수 있다.The immunogenic thrombocytopenia may be alloantibody-mediated thrombocytopenia or autoantibody-mediated thrombocytopenia.
상기 동종항체-매개성 혈소판 감소증은 신생아 동종면역 혈소판 감소증(neonatal alloimmune thrombocytopenia) 또는 수혈 후 자색반(post-transfusion purpura)일 수 있다. The alloantibody-mediated thrombocytopenia may be neonatal alloimmune thrombocytopenia or post-transfusion purpura.
상기 자가항체-매개성 혈소판 감소증은 특발성 혈소판 감소성 자반증(idiopathic thrombocytopenic purpura, immune throbocytopenic purpura), 만성 면역성 혈소판 감소성 자반증(chronic immune thrombocytopenic purpura) 또는 2차 면역성 혈소판 감소증(secondary immune thrombocytopenia)일 수 있다. The autoantibody-mediated thrombocytopenia may be idiopathic thrombocytopenic purpura (immune throbocytopenic purpura), chronic immune thrombocytopenic purpura, or secondary immune thrombotopenia. .
상기 약물-유도 혈소판 감소증은 헤파린 기인성 혈소판 감소증(heparin-induced thrombocytopenia) 또는 면역 매개 혈소판 파괴를 일으키는 다른 약물에 의한 혈소판 감소증(other drugs causing immune-mediated platelet destruction)일 수 있다. The drug-induced thrombocytopenia may be heparin-induced thrombocytopenia or other drugs causing immune-mediated platelet destruction.
상기 면역 매개 혈소판 파괴를 일으키는 다른 약물은 항암제, 퀴니딘(quinidine), 퀴닌(quinine), 금염(gold salts), 발프로산(valproic acid), 라파마이신(rapamycine), 술파(sulfa)계의 항생제 등 일 수 있다. 그러나 이에 한정되지 않는다. Other drugs that cause the immune-mediated platelet destruction are anticancer drugs, quinidine, quinine, gold salts, valproic acid, rapamycine, and sulfa antibiotics. Etc. However, it is not limited thereto.
본 발명에 있어서, "림프구 감소증(lymphopenia)"은 말초 혈액 중의 림프구 수가 절대적으로 감소한 상태로, 림프구 수가 1500개/㎕ 미만으로 감소한 경우이며, 중증의 경우에는 700개/㎕ 미만으로 감소한다. In the present invention, "lymphopenia" is a condition in which the number of lymphocytes in peripheral blood is absolutely decreased, and the number of lymphocytes decreases to less than 1500 cells/µl, and in severe cases, it decreases to less than 700 cells/µl.
상기 림프구 감소증은 면역결핍증, 암, 바이러스 감염, 자가면역질환, 치료에 의한 파괴, 림프구 상실, 림프종, 쿠싱 증후군(Cushing syndrome), 스트레스, 호중구 증가 등이 원인이 되어 나타날 수 있다. The lymphopenia may be caused by immunodeficiency, cancer, viral infection, autoimmune disease, destruction by treatment, loss of lymphocytes, lymphoma, Cushing syndrome, stress, and an increase in neutrophils.
또한, 상기 림프구 감소증은 면역원성 혈소판 감소증, C형 간염 관련 혈소판 감소증, 재생불량성 빈혈 등에 의해 나타날 수 있다. In addition, the lymphopenia may be caused by immunogenic thrombocytopenia, hepatitis C-related thrombocytopenia, aplastic anemia, or the like.
상기 면역결핍증은 선천성 면역결핍증 또는 후천성 면역결핍증후군(acquired immunodeficiency syndrome, AIDS)일 수 있다. 상기 선천성 면역결핍증은 디죠지 증후군(Di George's syndrome), 위스코트-알드리치 증후군(Wiskott-Aldrich syndrome), 모세혈관확장성 운동실조증(ataxia telangiectasia), 무감마글로불린혈증(agammaglobulinemia) 및 중증 복합면역결핍증(severe combined immunodeficiency, SCID)에서 선택될 수 있다. The immunodeficiency syndrome may be congenital immunodeficiency syndrome or acquired immunodeficiency syndrome (AIDS). The congenital immunodeficiency syndrome includes Di George's syndrome, Wiskott-Aldrich syndrome, ataxia telangiectasia, agammaglobulinemia, and severe complex immunodeficiency syndrome. severe combined immunodeficiency, SCID).
상기 암에 의한 림프구 감소증은 종양세포가 생산하는 면역 억제물질이 림프구 감소를 유발한다. In the case of cancer-induced lymphopenia, an immunosuppressive substance produced by tumor cells causes lymphocyte reduction.
상기 바이러스 감염에 의한 림프구 감소증은 감염된 홍역, 폴리오, 인간 면역결핍바이러스(human immunodeficiency virus, HIV)에 의해 림프구가 파괴되는 것이다. Lymphopenia caused by viral infection is the destruction of lymphocytes by infected measles, polio, and human immunodeficiency virus (HIV).
상기 자가면역질환에 의한 림프구 감소증은 전신홍반루푸스로 항림프구 자가항체에 의해 림프구가 파괴된다. Lymphopenia caused by the autoimmune disease is systemic lupus erythematosus, in which lymphocytes are destroyed by anti-lymphocyte autoantibodies.
상기 치료에 의한 림프구 감소증은 항암제, 방사선 조사, 스테로이드제 등의 투여에 의해 림프구가 파괴된다. Lymphocytopenia caused by the above treatment destroys lymphocytes by administration of anticancer agents, irradiation, or steroids.
상기 림프구 상실은 단백상실성위장증 또는 가슴림프관 배액술(drainage)일 수 있다.The loss of lymphocytes may be protein loss gastrointestinal disease or thoracic lymphatic drainage.
본 발명은 데커시놀(decursinol)을 유효성분으로 포함하는 혈소판 감소증 또는 림프구 감소증 예방 또는 치료용 조성물에 관한 것으로, 데커시놀의 생체이용률 증가를 위해 가용화시킨 데커시놀을 쥐에 투여한 결과, 쥐의 혈액 내 혈소판 또는 림프구 수가 증가하는 것을 확인하였다. The present invention relates to a composition for preventing or treating thrombocytopenia or lymphopenia comprising decursinol as an active ingredient, and as a result of administration of solubilized decursinol to mice to increase the bioavailability of decursinol, It was confirmed that the number of platelets or lymphocytes in the blood of rats was increased.
이를 통해, 본 발명의 가용화된 데커시놀을 이용하여 혈소판 감소증 또는 림프구 감소증을 예방 또는 치료할 수 있는 조성물을 개발할 수 있을 것으로 기대된다.Through this, it is expected that a composition capable of preventing or treating thrombocytopenia or lymphopenia using the solubilized decursinol of the present invention can be developed.
도 1은 본 발명의 가용화된 데커시놀의 투여에 의한 쥐의 혈액 내 혈소판 수(A) 및 림프구 수(B) 증가를 확인한 결과를 보여주고 있다. 1 shows the results of confirming the increase in the number of platelets (A) and the number of lymphocytes (B) in the blood of mice by administration of the solubilized decursinol of the present invention.
이하 본 발명의 바람직한 실시예를 상세히 설명하기로 한다. 그러나 본 발명은 여기서 설명되는 실시예에 한정되지 않고 다른 형태로 구체화될 수도 있다. 오히려, 여기서 소개되는 내용이 철저하고 완전해지고, 당업자에게 본 발명의 사상을 충분히 전달하기 위해 제공하는 것이다. Hereinafter, a preferred embodiment of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, the content introduced herein becomes thorough and complete, and is provided to sufficiently convey the spirit of the present invention to those skilled in the art.
<<
실시예Example
1. One.
가용화된Solubilized
데커시놀Deckercinol
제조> Manufacturing>
데커시놀은 난용성 물질로서 생체이용률이 낮다. 이에, 데커시놀의 생체이용률을 높이기 위해 본 발명자의 한국등록특허 제1717672호에 기재된 방법을 참고하여 가용화된 데커시놀을 제조하였다. 이때, 데커시놀은 본 발명자의 한국등록특허 제1600961호의 데커시놀 제조 방법을 참고하여, 99% 이상의 정제율을 가진 데커시놀을 대량 생산하여 이용하였다. Decercinol is a poorly soluble substance and has low bioavailability. Thus, in order to increase the bioavailability of decercinol, solubilized decercinol was prepared by referring to the method described in Korean Patent No. 1917672 of the present inventor. At this time, decursinol was mass-produced and used with decursinol having a purification rate of 99% or more, referring to the method for producing decursinol in Korean Patent No. 1600961 of the present inventor.
데커시놀 0.1g에 폴리옥시에틸렌 소르비탄 모노올레이트 0.8g, 폴리옥시에틸렌 소르비탄 모노라우레이트 0.2g을 넣고 균일하게 혼합한 후, 95%[v/v] 에탄올 1㎖을 넣고 섞어주었다. 여기에 염기성 아미노산인 라이신 또는 아르기닌 1.5g과 정제수 약 90㎖을 첨가하여 혼합한 후, 만니톨 0.4g을 첨가하고 6M HCl 또는 6M NaOH를 이용하여 pH가 8.6이 되도록 맞추었다. 이후에 정제수를 총 부피가 100㎖이 되도록 넣어주고, 이 용액을 고온증기멸균 처리하여 가용화된 데커시놀을 제조하였다.0.8 g of polyoxyethylene sorbitan monooleate and 0.2 g of polyoxyethylene sorbitan monolaurate were added to 0.1 g of decercinol, and after uniformly mixing, 1 ml of 95% [v/v] ethanol was added and mixed. 1.5 g of basic amino acids such as lysine or arginine and about 90 ml of purified water were added and mixed, and then 0.4 g of mannitol was added and the pH was adjusted to 8.6 using 6M HCl or 6M NaOH. Thereafter, purified water was added to a total volume of 100 ml, and this solution was subjected to hot steam sterilization to prepare solubilized decercinol.
상기 폴리옥시에틸렌 소르비탄 모노올레이트 및 폴리옥시에틸렌 소르비탄 모노라우레이트 대신에 폴리옥시에틸렌 소르비탄 모노올레이트 또는 폴리옥시에틸렌 소르비탄 모노라우레이트를 각각 단독으로 이용한 경우에도 데커시놀이 가용화되는 것은 확인하였다. Even when polyoxyethylene sorbitan monooleate or polyoxyethylene sorbitan monolaurate is used alone instead of polyoxyethylene sorbitan monooleate and polyoxyethylene sorbitan monolaurate, decercinol is solubilized Confirmed.
<<
실시예Example
2. 2.
가용화된Solubilized
데커시놀의Dekercinol
혈구 세포에의 영향 확인> Checking the effect on blood cells>
본 발명의 가용화된 데커시놀의 혈소판, 림프구 등과 같은 혈구 세포에의 영향을 확인하기 위해 쥐에 투여 후 혈액 분석을 수행하였다. In order to confirm the effect of the solubilized decursinol of the present invention on blood cells such as platelets and lymphocytes, blood analysis was performed after administration to mice.
23주령의 SD(Sprague Dawley) 쥐를 구입하여 동물실에서 1주일간 적응시킨 후, 하기 표 1의 실험군으로 무작위적으로 나누었다. 대조군의 경우에는 생리식염수 1㎖을 1일 1회, 3주 동안 경구투여 하였고, 나머지 실험군에는 하기 표 1에 해당되는 조성물을 1일 1회, 1㎖씩 3주 동안 복강투여 하였다. 조성물을 투여하기 하루 전에 쥐를 절식하여 채혈을 하였고, 조성물을 3주간 투여 후에 쥐를 마취하고 혈액을 채취하여 혈액 분석을 진행하였고, 그 결과를 하기 표 2 및 도 1에 나타내었다. 혈액 분석은 부산대학교 항노화산업육성센터의 혈액자동분석기를 이용하였다. 23-week-old SD (Sprague Dawley) mice were purchased and adapted in an animal room for 1 week, and then randomly divided into the experimental groups shown in Table 1 below. In the case of the control group, 1 ml of physiological saline was administered orally once a day for 3 weeks, and the composition corresponding to the following Table 1 was administered intraperitoneally to the remaining experimental groups once a day, 1 ml each for 3 weeks. One day before administration of the composition, mice were fasted to collect blood, and after administration of the composition for 3 weeks, the mice were anesthetized and blood was collected to conduct blood analysis, and the results are shown in Table 2 and FIG. 1 below. Blood analysis was performed using an automatic blood analyzer of the Anti-aging Industry Promotion Center of Pusan National University.
하기 표 1의 데커신은 중국의 Core Science 사에서 구입하였고, 당귀 추출물은 본 발명자가 건조된 참당귀를 이용하여 직접 추출하였다. 또한, 가용화된 당귀 추출물 및 데커신은 상기 실시예 1의 데커시놀의 가용화 방법과 동일한 방법을 이용하여 가용화시킨 것을 이용하였다. Deckercin in Table 1 was purchased from Core Science of China, and the Angelicae extract was directly extracted using the Angelicae dried by the present inventor. In addition, the solubilized Angelicae extract and decursine were solubilized using the same method as the method of solubilizing decursinol of Example 1.
도 1 및 상기 표 2에서 보듯이, 대조군과 비교하여 상기 실시예 1의 가용화된 데커시놀을 투여한 실험군 6의 경우에 혈소판의 수가 증가하는 것을 확인하였고, 가용화되지 않은 데커시놀을 투여한 실험군 3의 경우에는 혈소판의 수가 대조군과 유사한 것을 확인하였다. 또한, 상기 실시예 1의 가용화된 데커시놀을 투여한 실험군 6이 대조군과 비교하여 혈소판뿐만 아니라 백혈구 및 림프구 수를 증가시키는 반면에 적혈구 및 단핵구에는 영향을 주지 않는다는 것을 확인하였다.As shown in Figure 1 and Table 2, it was confirmed that the number of platelets increased in the case of Experimental Group 6 to which the solubilized decursinol of Example 1 was administered compared to the control group, and the non-solubilized decursinol was administered. In the case of experimental group 3, it was confirmed that the number of platelets was similar to that of the control group. In addition, it was confirmed that the experimental group 6 to which the solubilized decursinol of Example 1 was administered increased the number of white blood cells and lymphocytes as well as platelets compared to the control group, but did not affect red blood cells and monocytes.
이를 통해, 데커시놀의 가용화에 의해 데커시놀의 생체 내 흡수가 증가하여 데커시놀의 약리학적 활성이 증가된다는 것을 예측할 수 있었으며, 데커시놀이 혈액 내 혈소판, 림프구 및 백혈구의 수를 증가시킨다는 것을 알 수 있었다. Through this, it could be predicted that the solubilization of decursinol increases the absorption of decursinol in vivo, thereby increasing the pharmacological activity of decursinol, and that decursinol increases the number of platelets, lymphocytes and white blood cells in the blood. I could see that.
<<
제제예Formulation example
1. 약학적 제제> 1. Pharmaceutical preparations>
제제예Formulation example
1-1. 정제의 제조 1-1. Manufacture of tablets
본 발명의 가용화된 데커시놀 200㎎을 락토즈 175.9g, 감자전분 180g 및 콜로이드성 규산 32g과 혼합하였다. 이 혼합물에 10% 젤라틴 용액을 첨가시킨 후, 분쇄하여 14 메쉬체를 통과시켰다. 이것을 건조시키고 여기에 감자전분 160g, 활성 50g 및 스테아린산 마그네슘 5g을 첨가해서 얻은 혼합물을 정제로 만들었다. 200 mg of solubilized decursinol of the present invention was mixed with 175.9 g of lactose, 180 g of potato starch and 32 g of colloidal silicic acid. After adding a 10% gelatin solution to this mixture, it was pulverized and passed through a 14 mesh sieve. This was dried, and 160 g of potato starch, 50 g of active and 5 g of magnesium stearate were added thereto, and the resulting mixture was made into tablets.
제제예Formulation example
1-2. 주사액제의 제조 1-2. Preparation of injection solution
본 발명의 가용화된 데커시놀 100㎎, 염화나트륨 0.6g 및 아스코르브산 0.1g을 증류수에 용해시켜서 100㎖를 만들었다. 이 용액을 병에 넣고 20℃에서 30분간 가열하여 멸균시켰다. 100 mg of solubilized decercinol of the present invention, 0.6 g of sodium chloride, and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. This solution was put in a bottle and sterilized by heating at 20° C. for 30 minutes.
<<
제제예Formulation example
2. 건강기능식품의 제조> 2. Manufacture of health functional food>
제제예Formulation example
2-1. 건강기능식품의 제조 2-1. Manufacturing of health functional food
본 발명의 가용화된 데커시놀 2g, 비타민 혼합물 적량, 비타민 A 아세테이트 70㎍, 비타민 E 1.0㎎, 비타민 B1 0.13㎎, 비타민 B2 0.15㎎, 비타민 B6 0.5㎎, 비타민 B12 0.2㎍, 비타민 C 10㎎, 비오틴 10㎍, 니코틴산아미드 1.7㎎, 엽산 50㎍, 판토텐산 칼슘 0.5㎎, 무기질 혼합물 적량, 황산제1철 1.75㎎, 산화아연 0.82㎎, 탄산 마그네슘 25.3㎎, 제1인산칼륨 15㎎, 제2인산칼슘 55㎎, 구연산칼륨 90㎎, 탄산칼슘 100㎎, 염화마그네슘 24.8㎎을 섞어 과립으로 제조하였으나, 용도에 따라 다양한 제형으로 변형시켜 제조할 수 있다. 또한, 상기의 비타민 및 미네랄 혼합물의 조성비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능식품 제조방법에 따라 상기의 성분을 혼합하여 제조할 수 있다.2g of solubilized decursinol of the present invention, appropriate amount of vitamin mixture, vitamin A acetate 70 ㎍, vitamin E 1.0 mg, vitamin B1 0.13 mg, vitamin B2 0.15 mg, vitamin B6 0.5 mg, vitamin B12 0.2 μg, vitamin C 10 mg, Biotin 10㎍, nicotinic acid amide 1.7mg, folic acid 50㎍, calcium pantothenate 0.5mg, an appropriate amount of inorganic mixture, ferrous sulfate 1.75mg, zinc oxide 0.82mg, magnesium carbonate 25.3mg, potassium monophosphate 15mg, dicalcium phosphate 55 mg, potassium citrate 90 mg, calcium carbonate 100 mg, and magnesium chloride 24.8 mg were mixed to form granules, but can be prepared by modifying various formulations according to the use. In addition, the composition ratio of the vitamin and mineral mixture may be arbitrarily modified, and may be prepared by mixing the above ingredients according to a conventional health functional food manufacturing method.
제제예Formulation example
2-2. 건강기능성 음료의 제조 2-2. Manufacturing of health functional beverages
본 발명의 가용화된 데커시놀 1g, 구연산 0.1g, 프락토올리고당 100g, 정제수 900g을 섞어 통상의 음료 제조방법에 따라 교반, 가열, 여과, 살균, 냉장하여 음료를 제조하였다.A beverage was prepared by mixing 1 g of solubilized decercinol of the present invention, 0.1 g of citric acid, 100 g of fructooligosaccharide, and 900 g of purified water, followed by stirring, heating, filtration, sterilization, and refrigeration according to a conventional beverage preparation method.
Claims (11)
- 데커시놀(decursinol), 계면활성제, 염기성 아미노산 및 다가알코올을 포함하는 것을 특징으로 하는 혈소판 감소증 예방 또는 치료용 약학 조성물에 있어서, 상기 혈소판 감소증은 비면역원성 혈소판 감소증, 면역원성 혈소판 감소증 또는 약물-유도 혈소판 감소증인 것을 특징으로 하는 혈소판 감소증 예방 또는 치료용 약학 조성물.In a pharmaceutical composition for preventing or treating thrombocytopenia comprising decursinol, a surfactant, a basic amino acid and a polyhydric alcohol, the thrombocytopenia is non-immunogenic thrombocytopenia, immunogenic thrombocytopenia or drug- A pharmaceutical composition for preventing or treating thrombocytopenia, characterized in that it is induced thrombocytopenia.
- 제1항에 있어서, The method of claim 1,상기 약학 조성물은,The pharmaceutical composition,데커시놀에 계면활성제를 혼합하여 1차 혼합물을 제조하는 제1단계; A first step of preparing a first mixture by mixing a surfactant with decercinol;상기 1차 혼합물에 에탄올을 넣은 후, 염기성 아미노산 및 정제수를 첨가하여 녹이고, 다가알코올 첨가 후, pH를 7.0~8.6이 되도록 맞추어 2차 혼합물을 제조하는 제2단계; 및, A second step of preparing a second mixture by adding ethanol to the first mixture, dissolving by adding basic amino acids and purified water, and adjusting the pH to 7.0 to 8.6 after addition of polyhydric alcohol; And,상기 2차 혼합물을 멸균 처리하는 제3단계;로 이루어진 과정을 통해 제조되는 것을 특징으로 하는 혈소판 감소증 예방 또는 치료용 약학 조성물.A pharmaceutical composition for preventing or treating thrombocytopenia, characterized in that produced through a process consisting of; a third step of sterilizing the secondary mixture.
- 제1항 또는 제2항에 있어서, The method according to claim 1 or 2,상기 계면활성제는 소듐 도데실 설페이트(sodium dodecyl sulfate), 폴리옥시에틸렌 소르비탄 모노올레이트(polyoxyethylene sorbitan monooleate, Tween-80), 폴리옥시에틸렌 소르비탄 모노스테아레이트(polyoxythylene sorbitan monostearate, Tween-60), 폴리옥시에틸렌 소르비탄 모노팔미테이트(polyoxyethylene sorbitan monopalmitate, Tween-40), 폴리옥시에틸렌 소르비탄 모노라우레이트(polyoxyethylene sorbitan monolaurate, Tween-20), 트리톤 X-100(triton X-100), 노닐페녹시폴리에톡실에탄올(nonylphenoxypolyethoxylethanol, NP-40), 피마자 오일(caster oil), 및 폴록사머(poloxamer)로 이루어진 군에서 선택되는 1종 이상인 것을 특징으로 하는 혈소판 감소증 예방 또는 치료용 약학 조성물.The surfactant is sodium dodecyl sulfate, polyoxyethylene sorbitan monooleate (Tween-80), polyoxyethylene sorbitan monostearate (Tween-60), Polyoxyethylene sorbitan monopalmitate (Tween-40), polyoxyethylene sorbitan monolaurate (Tween-20), triton X-100 (triton X-100), nonylphenoxy A pharmaceutical composition for preventing or treating thrombocytopenia, characterized in that it is at least one selected from the group consisting of polyethoxylethanol (nonylphenoxypolyethoxylethanol, NP-40), caster oil, and poloxamer.
- 제1항 또는 제2항에 있어서, The method according to claim 1 or 2,상기 염기성 아미노산은 아르기닌, 라이신, 히스티딘 또는 이들의 혼합물인 것을 특징으로 하는 혈소판 감소증 예방 또는 치료용 약학 조성물.The basic amino acid is arginine, lysine, histidine, or a pharmaceutical composition for preventing or treating thrombocytopenia, characterized in that a mixture thereof.
- 제1항 또는 제2항에 있어서, The method according to claim 1 or 2,상기 다가알코올은 만니톨(mannitol), 소르비톨(sorbitol), 자일리톨(xylitol) 및 락티톨(lactitol)로 이루어진 군에서 선택되는 1종 이상인 것을 특징으로 하는 혈소판 감소증 예방 또는 치료용 약학 조성물.The polyhydric alcohol is at least one selected from the group consisting of mannitol, sorbitol, xylitol, and lactitol. A pharmaceutical composition for preventing or treating thrombocytopenia.
- 제1항 또는 제2항에 있어서, The method according to claim 1 or 2,상기 데커시놀은 0.5~10㎎/㎏로 투여하는 것을 특징으로 하는 혈소판 감소증 예방 또는 치료용 약학 조성물.The decursinol is a pharmaceutical composition for preventing or treating thrombocytopenia, characterized in that administered at 0.5-10 mg/kg.
- 데커시놀, 계면활성제, 염기성 아미노산 및 다가알코올을 포함하는 것을 특징으로 하는 혈소판 감소증 개선용 건강기능식품에 있어서, 상기 혈소판 감소증은 비면역원성 혈소판 감소증, 면역원성 혈소판 감소증 또는 약물-유도 혈소판 감소증인 것을 특징으로 하는 혈소판 감소증 개선용 건강기능식품.In the health functional food for improving thrombocytopenia comprising dekercinol, a surfactant, a basic amino acid, and a polyhydric alcohol, the thrombocytopenia is non-immunogenic thrombocytopenia, immunogenic thrombocytopenia or drug-induced thrombocytopenia. Health functional food for improving thrombocytopenia, characterized in that.
- 제7항에서 있어서, In claim 7,상기 건강기능식품은, The health functional food,데커시놀에 계면활성제를 혼합하여 1차 혼합물을 제조하는 제1단계;A first step of preparing a first mixture by mixing a surfactant with decercinol;상기 1차 혼합물에 에탄올을 넣은 후, 염기성 아미노산 및 정제수를 첨가하여 녹이고, 다가알코올 첨가 후, pH를 7.0~8.6이 되도록 맞추어 2차 혼합물을 제조하는 제2단계; 및, A second step of preparing a second mixture by adding ethanol to the first mixture, dissolving by adding basic amino acids and purified water, and adjusting the pH to 7.0 to 8.6 after addition of polyhydric alcohol; And,상기 2차 혼합물을 멸균 처리하는 제3단계;로 이루어진 과정을 통해 제조되는 것을 특징으로 하는 혈소판 감소증 개선용 건강기능식품.A third step of sterilizing the secondary mixture; health functional food for improving thrombocytopenia, characterized in that produced through a process consisting of.
- 제7항 또는 제8항에 있어서, The method according to claim 7 or 8,상기 계면활성제는 소듐 도데실 설페이트, 폴리옥시에틸렌 소르비탄 모노올레이트, 폴리옥시에틸렌 소르비탄 모노스테아레이트, 폴리옥시에틸렌 소르비탄 모노팔미테이트, 폴리옥시에틸렌 소르비탄 모노라우레이트, 트리톤 X-100, 노닐페녹시폴리에톡실에탄올, 피마자 오일, 및 폴록사머로 이루어진 군에서 선택되는 1종 이상인 것을 특징으로 하는 혈소판 감소증 개선용 건강기능식품.The surfactants are sodium dodecyl sulfate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monolaurate, triton X-100, Nonylphenoxypolyethoxylethanol, castor oil, and health functional food for improving thrombocytopenia, characterized in that at least one selected from the group consisting of poloxamer.
- 제7항 또는 제8항에 있어서, The method according to claim 7 or 8,상기 염기성 아미노산은 아르기닌, 라이신, 히스티딘 또는 이들의 혼합물인 것을 특징으로 하는 혈소판 감소증 개선용 건강기능식품.The basic amino acid is a health functional food for improving thrombocytopenia, characterized in that arginine, lysine, histidine, or a mixture thereof.
- 제7항 또는 제8항에 있어서, The method according to claim 7 or 8,상기 다가알코올은 만니톨, 소르비톨, 자일리톨 및 락티톨로 이루어진 군에서 선택되는 1종 이상인 것을 특징으로 하는 혈소판 감소증 개선용 건강기능식품.The polyhydric alcohol is a health functional food for improving thrombocytopenia, characterized in that at least one selected from the group consisting of mannitol, sorbitol, xylitol and lactitol.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2019-0020875 | 2019-02-22 | ||
KR1020190020875A KR102035106B1 (en) | 2019-02-22 | 2019-02-22 | Composition for preventing or treating of thrombocytopenia or lymphopenia comprising decursinol |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2020171407A1 true WO2020171407A1 (en) | 2020-08-27 |
Family
ID=68460709
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2020/001376 WO2020171407A1 (en) | 2019-02-22 | 2020-01-29 | Composition comprising decursinol as active ingredient for prevention or treatment of thrombocytopenia or lymphopenia |
Country Status (2)
Country | Link |
---|---|
KR (1) | KR102035106B1 (en) |
WO (1) | WO2020171407A1 (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102035106B1 (en) * | 2019-02-22 | 2019-10-23 | 심마니산삼영농조합법인 | Composition for preventing or treating of thrombocytopenia or lymphopenia comprising decursinol |
KR102557210B1 (en) | 2022-06-23 | 2023-07-20 | 주식회사 피에프네이처 | Composition for Anti-glycation Property Comprising Decurcinol as Active Ingredient |
KR102526200B1 (en) | 2022-08-12 | 2023-04-26 | 양지혜 | Composition for Skin Moisturizing and Whitening Comprising Decurcinol as Active Ingredient |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101153436B1 (en) * | 2010-03-24 | 2012-06-05 | 경희대학교 산학협력단 | Composition of herb medicine containing kmkkt extract for preventing or treating cytopenia |
KR20150040198A (en) * | 2013-10-04 | 2015-04-14 | 경성대학교 산학협력단 | Pharmaceutical Composition Using extract of Angelica gigas, nakai for prevention of leukopenia decrease and leukopenia recovery |
KR101600961B1 (en) * | 2015-06-19 | 2016-03-08 | 경성대학교 산학협력단 | Injectable suspension formulations manufacture method containing as an active pharmaceutical ingredient Decursin |
KR101717672B1 (en) * | 2015-12-03 | 2017-03-17 | 경성대학교 산학협력단 | Injections or eye drops, and its preparation method for producing a homogeneous solution was formed by solubilizing poorly soluble active pharmaceutical ingredient |
KR101927404B1 (en) * | 2017-10-11 | 2018-12-10 | 경성대학교 산학협력단 | Liquid composition comprising compound K at high concentration and producing method thereof |
KR102035106B1 (en) * | 2019-02-22 | 2019-10-23 | 심마니산삼영농조합법인 | Composition for preventing or treating of thrombocytopenia or lymphopenia comprising decursinol |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100697212B1 (en) | 2005-01-29 | 2007-03-22 | 서울향료(주) | Hematopoietic enhancer comprising herbal mixture extract of Astragali Radix and Angelicae Gigantis Radix for treating side-effect caused by administrating anticancer agent |
-
2019
- 2019-02-22 KR KR1020190020875A patent/KR102035106B1/en active IP Right Grant
-
2020
- 2020-01-29 WO PCT/KR2020/001376 patent/WO2020171407A1/en active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101153436B1 (en) * | 2010-03-24 | 2012-06-05 | 경희대학교 산학협력단 | Composition of herb medicine containing kmkkt extract for preventing or treating cytopenia |
KR20150040198A (en) * | 2013-10-04 | 2015-04-14 | 경성대학교 산학협력단 | Pharmaceutical Composition Using extract of Angelica gigas, nakai for prevention of leukopenia decrease and leukopenia recovery |
KR101600961B1 (en) * | 2015-06-19 | 2016-03-08 | 경성대학교 산학협력단 | Injectable suspension formulations manufacture method containing as an active pharmaceutical ingredient Decursin |
KR101717672B1 (en) * | 2015-12-03 | 2017-03-17 | 경성대학교 산학협력단 | Injections or eye drops, and its preparation method for producing a homogeneous solution was formed by solubilizing poorly soluble active pharmaceutical ingredient |
KR101927404B1 (en) * | 2017-10-11 | 2018-12-10 | 경성대학교 산학협력단 | Liquid composition comprising compound K at high concentration and producing method thereof |
KR102035106B1 (en) * | 2019-02-22 | 2019-10-23 | 심마니산삼영농조합법인 | Composition for preventing or treating of thrombocytopenia or lymphopenia comprising decursinol |
Also Published As
Publication number | Publication date |
---|---|
KR102035106B1 (en) | 2019-10-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2020171407A1 (en) | Composition comprising decursinol as active ingredient for prevention or treatment of thrombocytopenia or lymphopenia | |
WO2020027466A1 (en) | Method for lyophilizing exosome | |
US10555962B2 (en) | Use of icaritin in preparing medicament for preventing or treating hematocytopenia | |
WO2014189328A1 (en) | Anti-obesity composition containing lycium chinense miller leaf extract powder and betaine as active ingredients | |
EP1951233B1 (en) | Pirfenidone/toll-like receptor (tlr) agonist compositions and methods for using them to stimulate production of granulocyte colonizing stimulating factor (g-csf) | |
WO2018131779A1 (en) | Composition for treating neonatal hie | |
WO2021118324A1 (en) | Pharmaceutical composition for preventing or treating cancer | |
WO2017014502A1 (en) | Pharmaceutical composition for preventing or treating il-6-mediated diseases comprising rosa rugosa flower extract as active ingredient | |
WO2017086608A1 (en) | Composition for preventing or treating bone diseases and joint diseases, containing, as active ingredients, water-soluble ionized calcium and fructooligosaccharide complex | |
WO2016010346A1 (en) | Composition containing neuropeptide y for inhibiting side effects of anticancer agents | |
AU677786B2 (en) | Lysozyme dimer and compositions containing the same | |
WO2020116862A1 (en) | Lonicera japonica flower water extract-containing pharmaceutical composition for preventing or treating helicobacter pylori infection | |
WO2023085741A1 (en) | Composition for preventing or treating multiple organ failure caused by infection, comprising 3'-sialyllactose, 6'-sialyllactose, or salt thereof as active ingredient | |
CN1207004C (en) | Freeze-dried plasma without blood group and its preparation method | |
WO2014042426A1 (en) | Composition comprising saikosaponin a, berberine, and licoisoflavone b for preventing or treating gastric diseases | |
WO2012112007A2 (en) | Composition containing inducer of sirt1 expression for preventing or treating sepsis or septic shock | |
WO2019083201A2 (en) | Use of composition comprising adipose stem cell-derived exosome as effective ingredient in improving renal function | |
CA3079031C (en) | Formulation containing a-decarbonized-5-alpha androstane compound for increasing white blood cell and use thereof | |
KR20090130349A (en) | Therapeutic agent for ulcerative colitis comprising mizoribine | |
CN112409439B (en) | Glycyrrhizic acid derivative, preparation method and application | |
CN108670951A (en) | A kind of compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals and preparation method thereof | |
CN105310985B (en) | A kind of pharmaceutical composition and its preparation method and application | |
KR101996880B1 (en) | Composition comprising compound K for preventing or treating of thrombocytopenia | |
WO2017222305A1 (en) | Method for producing allergenic component-free purified bee venom using yolk, and allergenic component-free purified bee venom produced thereby | |
WO2018012901A1 (en) | Composition for cell protection containing cyclo histidine-proline as active ingredient |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 20758596 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 20758596 Country of ref document: EP Kind code of ref document: A1 |