TWI597071B - 包含雷公藤內酯醇衍生物之組合物及其用途 - Google Patents
包含雷公藤內酯醇衍生物之組合物及其用途 Download PDFInfo
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- TWI597071B TWI597071B TW103109891A TW103109891A TWI597071B TW I597071 B TWI597071 B TW I597071B TW 103109891 A TW103109891 A TW 103109891A TW 103109891 A TW103109891 A TW 103109891A TW I597071 B TWI597071 B TW I597071B
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- Prior art keywords
- triptolide
- composition
- oil
- group
- sodium
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- DFBIRQPKNDILPW-CIVMWXNOSA-N Triptolide Chemical class O=C1OCC([C@@H]2C3)=C1CC[C@]2(C)[C@]12O[C@H]1[C@@H]1O[C@]1(C(C)C)[C@@H](O)[C@]21[C@H]3O1 DFBIRQPKNDILPW-CIVMWXNOSA-N 0.000 title claims description 155
- 239000000203 mixture Substances 0.000 title claims description 136
- YKUJZZHGTWVWHA-UHFFFAOYSA-N triptolide Natural products COC12CC3OC3(C(C)C)C(O)C14OC4CC5C6=C(CCC25C)C(=O)OC6 YKUJZZHGTWVWHA-UHFFFAOYSA-N 0.000 claims description 119
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 73
- 150000001875 compounds Chemical class 0.000 claims description 72
- 238000009472 formulation Methods 0.000 claims description 65
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- 239000003814 drug Substances 0.000 claims description 29
- 150000003904 phospholipids Chemical class 0.000 claims description 28
- 235000011187 glycerol Nutrition 0.000 claims description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 23
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 claims description 22
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 18
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- 229940093609 tricaprylin Drugs 0.000 claims description 9
- VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 claims description 9
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- WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 claims description 7
- 229960001231 choline Drugs 0.000 claims description 7
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 6
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- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
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- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical class CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
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- 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 3
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- DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 claims description 2
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- AAYACJGHNRIFCT-YRJJIGPTSA-M sodium glycochenodeoxycholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC([O-])=O)C)[C@@]2(C)CC1 AAYACJGHNRIFCT-YRJJIGPTSA-M 0.000 claims description 2
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- IYPNVUSIMGAJFC-HLEJRKHJSA-M sodium;2-[[(4r)-4-[(3r,5s,7r,8r,9s,10s,13r,14s,17r)-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)CC1 IYPNVUSIMGAJFC-HLEJRKHJSA-M 0.000 claims description 2
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- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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- 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
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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| US201361794926P | 2013-03-15 | 2013-03-15 | |
| PCT/US2014/030041 WO2014145303A1 (en) | 2013-03-15 | 2014-03-15 | Intravenous emulsions of triptolide as immunomodulators and anticancer agents i |
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| TW201440812A TW201440812A (zh) | 2014-11-01 |
| TWI597071B true TWI597071B (zh) | 2017-09-01 |
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| ES2881878T3 (es) * | 2015-09-11 | 2021-11-30 | Ys Ac Co Ltd | Composición para el tratamiento del cáncer que combina el anticuerpo anti-CD26 y otro antineoplásico |
| US10342797B2 (en) | 2016-03-13 | 2019-07-09 | LivePet, LLC | Solubility of therapeutic agents |
| CN107663225A (zh) * | 2016-07-29 | 2018-02-06 | 欣凯医药化工中间体(上海)有限公司 | 一种氟代雷公藤内酯醇内酯环衍生物 |
| CN108530511B (zh) * | 2017-03-02 | 2021-06-22 | 欣凯医药化工中间体(上海)有限公司 | 一种c19-酰基化雷公藤甲素衍生物 |
| CN106946975B (zh) * | 2017-03-16 | 2020-08-14 | 上海天氏利医药科技有限公司 | 一种雷公藤甲素衍生物及其制备方法与制剂 |
| CN106994129A (zh) * | 2017-05-15 | 2017-08-01 | 王晓辉 | 雷公藤甲素及其衍生物在制备治疗和/或预防肺损伤疾病的药物中的应用 |
| WO2018222351A1 (en) * | 2017-05-27 | 2018-12-06 | Pharmagenesis, Inc. | Triptolide lactone derivatives as immunomodulators and anticancer agents |
| WO2019173526A1 (en) * | 2018-03-07 | 2019-09-12 | Andrew Xian Chen | Aqueous formulations for insoluble drugs |
| CN109771430A (zh) * | 2019-03-15 | 2019-05-21 | 大连大学 | 甘氨胆酸在制备抗肿瘤药物中的应用 |
| CN111494319A (zh) * | 2020-06-15 | 2020-08-07 | 沈阳药科大学 | 雷公藤甲素复方组合物及其制备方法与应用 |
| CN115466269A (zh) * | 2021-06-11 | 2022-12-13 | 复旦大学 | 一种胆碱碳酸酯类前药及其制备方法和应用 |
| CN114569554A (zh) * | 2022-03-01 | 2022-06-03 | 福建省医学科学研究院 | 一种肿瘤靶向性雷公藤内酯醇乳液及其制备方法 |
| CN114831962A (zh) * | 2022-04-29 | 2022-08-02 | 福建省医学科学研究院 | 一种雷公藤内酯醇固体脂质纳米粒及其滴丸的制备方法 |
| CN117088935A (zh) * | 2022-05-20 | 2023-11-21 | 上海维洱生物医药科技有限公司 | 一种雷公藤甲素木蜡酸酯及其脂质体与制备方法 |
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| JP2006513209A (ja) * | 2002-12-17 | 2006-04-20 | ファーマジェネシス, インコーポレイテッド | 免疫調節因子および抗癌剤としてのトリプトライド誘導体 |
| US7863464B2 (en) * | 2004-03-02 | 2011-01-04 | Pharmagenesis, Inc. | Triptolide lactone ring derivatives as immunomodulators and anticancer agents |
| AP2626A (en) * | 2005-08-29 | 2013-03-26 | Sepsicure Llc | Method for treatment or prevention of conditions caused by gram-positive bacteria |
| CN101485629B (zh) * | 2008-01-16 | 2013-01-23 | 沈阳药科大学 | 一种给药系统及其制备方法 |
| TW201138782A (en) * | 2010-04-26 | 2011-11-16 | Besins Healthcare Lu Sarl | Low-oil pharmaceutical emulsion compositions comprising progestogen |
| CN102793674B (zh) * | 2011-05-26 | 2014-11-26 | 澳门科技大学 | 一种雷公藤甲素固体脂质纳米颗粒及其制备方法和应用 |
| CN102552137B (zh) * | 2012-02-22 | 2013-04-10 | 福建医科大学 | 雷公藤内酯醇脂肪乳注射剂及其制备方法 |
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| HK1219228A1 (zh) | 2017-03-31 |
| US20160038454A1 (en) | 2016-02-11 |
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| EP2968140A4 (en) | 2016-11-16 |
| TW201440812A (zh) | 2014-11-01 |
| JP2016515530A (ja) | 2016-05-30 |
| EP2968140A1 (en) | 2016-01-20 |
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