CN100594902C - Nano micelle preparation of Catharanthus roseus alkaloids antineoplastic drugs with coating of phospholipid derived from polyethylene glycol - Google Patents
Nano micelle preparation of Catharanthus roseus alkaloids antineoplastic drugs with coating of phospholipid derived from polyethylene glycol Download PDFInfo
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- CN100594902C CN100594902C CN200510098381A CN200510098381A CN100594902C CN 100594902 C CN100594902 C CN 100594902C CN 200510098381 A CN200510098381 A CN 200510098381A CN 200510098381 A CN200510098381 A CN 200510098381A CN 100594902 C CN100594902 C CN 100594902C
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- Prior art keywords
- phospholipid
- catharanthus roseus
- micellar
- polyglycol derivatization
- acid
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- 150000003904 phospholipids Chemical class 0.000 title claims abstract description 73
- 238000002360 preparation method Methods 0.000 title claims abstract description 69
- 239000000693 micelle Substances 0.000 title claims abstract description 55
- 240000001829 Catharanthus roseus Species 0.000 title claims description 60
- 229930013930 alkaloid Natural products 0.000 title claims description 60
- 239000002202 Polyethylene glycol Substances 0.000 title claims description 22
- 229920001223 polyethylene glycol Polymers 0.000 title claims description 22
- 239000002246 antineoplastic agent Substances 0.000 title abstract description 7
- 229940041181 antineoplastic drug Drugs 0.000 title abstract description 7
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- 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
- 230000015572 biosynthetic process Effects 0.000 description 1
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- 210000001124 body fluid Anatomy 0.000 description 1
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- 201000008275 breast carcinoma Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
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- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
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- 208000032839 leukemia Diseases 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
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- 239000011159 matrix material Substances 0.000 description 1
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- 239000002808 molecular sieve Substances 0.000 description 1
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- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 125000001095 phosphatidyl group Chemical group 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
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- 230000003578 releasing effect Effects 0.000 description 1
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
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- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[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 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
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- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- QZZGJDVWLFXDLK-UHFFFAOYSA-M tetracosanoate Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC([O-])=O QZZGJDVWLFXDLK-UHFFFAOYSA-M 0.000 description 1
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- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
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- 229930003799 tocopherol Natural products 0.000 description 1
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- 239000003643 water by type Substances 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
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- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
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- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Medicine | Drug/lipid is than (mol/mol) | Medicine (mg/ml) | Aquation solution |
Vinblastine | 1∶2 | 2 | Citrate buffer solution, pH7.0 |
Vincristine | 1∶2 | 2 | Citrate buffer solution, pH7.0 |
Vindesine | 1∶2 | 2 | Citrate buffer solution, pH7.0 |
Drug/lipid is than (mol/mol) | Medicine (mg/ml) | Aquation solution | Envelop rate (%) |
1∶1 | 2 | Citrate buffer solution, pH7.0 | 91.5 |
1∶2 | 2 | Citrate buffer solution, pH7.0 | 94.5 |
1∶4 | 2 | Citrate buffer solution, pH7.0 | 96 |
1∶6 | 2 | Citrate buffer solution, pH7.0 | 99 |
1∶10 | 2 | Citrate buffer solution, pH7.0 | 99.6 |
Medicine fat than (1: 5, mol/mol), VCR (1mg/ml) | Content (%) | Envelop rate (%) |
0 |
100 | 99.4 |
Envelop rate before the dilution | 99.4 | |
Dilution back envelop rate (100 times) | 98.5 | |
30 days | 98.6 | 99.4 |
Claims (20)
- One kind can intravenous catharanthus roseus alkaloids anti-tumor medicaments nano-micelle preparations, comprise catharanthus roseus alkaloids anti-tumor medicaments, polyglycol derivatization phospholipid, and pharmaceutically acceptable adjuvant, wherein the mol ratio of catharanthus roseus alkaloids anti-tumor medicaments and polyglycol derivatization phospholipid is 1: 0.5 to 1: 10, to be peg molecule by covalent bond combine with nitrogenous base on the phospholipid molecule wherein said polyglycol derivatization phospholipid forms, the fatty acid of phospholipid moiety comprises 10-24 carbon atom in the described polyglycol derivatization phospholipid, fatty acid chain is saturated or fractional saturation, phospholipid in the described polyglycol derivatization phospholipid is PHOSPHATIDYL ETHANOLAMINE, phosphatidylcholine, phosphatidylinositols, Phosphatidylserine, or diphosphatidylglycerol, the molecular weight polyethylene glycol scope in the described polyglycol derivatization phospholipid structure is 200~20000.
- 2. according to the micellar preparation of claim 1, wherein the mol ratio of catharanthus roseus alkaloids anti-tumor medicaments and polyglycol derivatization phospholipid is 1: 1 to 1: 6.
- 3. according to the micellar preparation of claim 1, wherein said catharanthus roseus alkaloids anti-tumor medicaments is selected from down the medicine of group for one or more: vinblastine, vincristine and vindesine.
- 4. micellar preparation according to claim 1, the fatty acid of phospholipid moiety is lauric acid, myristic acid, Palmic acid, stearic acid or oleic acid or linoleic acid, twenty acid or mountain Yu's acid in the wherein said polyglycol derivatization phospholipid.
- 5. micellar preparation according to claim 1, the phospholipid in the wherein said polyglycol derivatization phospholipid are DSPE, two palmityl PHOSPHATIDYL ETHANOLAMINE, DOPE.
- 6. micellar preparation according to claim 5, the molecular weight polyethylene glycol scope in the wherein said polyglycol derivatization phospholipid structure is 500~10000.
- 7. micellar preparation according to claim 6, the molecular weight polyethylene glycol scope in the wherein said polyglycol derivatization phospholipid structure is 1000~10000.
- 8. micellar preparation according to claim 7, the molecular weight polyethylene glycol in the wherein said polyglycol derivatization phospholipid structure is 2000.
- 9. micellar preparation according to claim 1, wherein said polyglycol derivatization phospholipid are the Macrogol 2000 DSPE.
- 10. micellar preparation according to claim 1, wherein said micellar preparation are solution form or lyophilized form.
- 11. micellar preparation according to claim 1, wherein said pharmaceutically acceptable adjuvant are pharmaceutically acceptable antioxidant, osmotic pressure regulator, pH value regulator.
- 12. micellar preparation according to claim 11, wherein said pH value regulator are citric acid-sodium citrate, acetic acid-sodium acetate or phosphate or its combination.
- 13. one kind prepare according to claim 1 can intravenous catharanthus roseus alkaloids anti-tumor medicaments the method for nano-micelle preparations, comprise catharanthus roseus alkaloids anti-tumor medicaments is wrapped in the nano-micelle that polyglycol derivatization phospholipid forms, but make the nano-micelle preparations of the catharanthus roseus alkaloids anti-tumor medicaments of injection for intravenous.
- 14. the method according to claim 13 may further comprise the steps:(1) catharanthus roseus alkaloids anti-tumor medicaments and polyglycol derivatization phospholipid are dissolved in the organic solvent;(2) remove organic solvent, make the polymer adipose membrane of catharanthus roseus alkaloids anti-tumor medicaments;(3) in the polymer adipose membrane that above-mentioned (2) obtain, add entry or buffer solution, 25 ℃~60 ℃ following aquations;(4) vortex jolting or ultrasonic obtains wrapping the polyglycol derivatization phospholipid nano-micelle that carries catharanthus roseus alkaloids anti-tumor medicaments.
- 15. according to the method for claim 13 or 14, wherein the envelop rate of catharanthus roseus alkaloids anti-tumor medicaments in described micelle is at least 90%.
- 16. according to the method for claim 14, wherein this method comprises one of following feature in addition:Described organic solvent in step (1) is methanol, ethanol, chloroform or their mixture;In step (2), remove organic solvent and/or under vacuum condition, remove organic solvent by decompression;Buffer solution in step (3) is citric acid or phosphate buffer;In step (3) in 25 ℃-60 ℃ water-bath aquation 1~2 hour; WithStep (4) mesoscale eddies jolting or ultrasonic 1-5 minute.
- 17. according to the method for claim 16, wherein said step (3) aquation 1~2 hour in 35 ℃-45 ℃ water-bath.
- 18., further comprise with the pH regulator agent pH value of the micellar solution that obtains is adjusted to 3.0-8.0 according to the method for claim 14.
- 19., further comprise with the pH regulator agent pH value of the micellar solution that obtains is adjusted to 6.0-7.4 according to the method for claim 14.
- 20. according to the method for claim 13 or 14, further comprise the micellar solution lyophilization that to obtain, make the preparation of lyophilized form.
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200510098381A CN100594902C (en) | 2005-09-09 | 2005-09-09 | Nano micelle preparation of Catharanthus roseus alkaloids antineoplastic drugs with coating of phospholipid derived from polyethylene glycol |
US12/066,066 US8765181B2 (en) | 2005-09-09 | 2006-09-08 | Nano anticancer micelles of vinca alkaloids entrapped in polyethylene glycolylated phospholipids |
JP2008529454A JP2009507049A (en) | 2005-09-09 | 2006-09-08 | Nanomicelle formulation of vinca alkaloid anticancer drug encapsulated in polyethylene glycol derivative of phospholipid |
PCT/CN2006/002327 WO2007028341A1 (en) | 2005-09-09 | 2006-09-08 | Nano anticancer micelles of vinca alkaloids entrapped in polyethylene glycolylated phospholipids |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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CN200510098381A CN100594902C (en) | 2005-09-09 | 2005-09-09 | Nano micelle preparation of Catharanthus roseus alkaloids antineoplastic drugs with coating of phospholipid derived from polyethylene glycol |
Publications (2)
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CN1927203A CN1927203A (en) | 2007-03-14 |
CN100594902C true CN100594902C (en) | 2010-03-24 |
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CN102133172B (en) * | 2011-01-24 | 2012-11-14 | 北京大学 | Paclitaxel nano micelle and application thereof |
CN102198086B (en) * | 2011-05-27 | 2012-12-26 | 上海交通大学医学院 | Solid-phase nano micelle and preparation method thereof |
CN102327208B (en) * | 2011-10-10 | 2012-10-03 | 广东药学院 | Vinpocetine polymer micelle preparation and preparation method thereof |
CN103462891B (en) * | 2013-09-13 | 2016-01-13 | 上海海虹实业(集团)巢湖今辰药业有限公司 | A kind of Allyl isothiocyanate micelle preparation |
CN105343006B (en) * | 2015-12-02 | 2019-05-14 | 北京大学 | A kind of nanometer shell system and its preparation method and application carrying insoluble drug |
CN107987825A (en) * | 2017-12-19 | 2018-05-04 | 国家纳米科学中心 | A kind of preparation for cell imaging and its preparation method and application |
US11752165B2 (en) * | 2020-04-13 | 2023-09-12 | US Nano Food & Drug, Inc | Basic chemotherapeutic intratumour injection formulation |
CN111744011B (en) * | 2020-06-15 | 2022-06-14 | 天津力博生物科技有限公司 | Application of micelle formed by polyethylene glycol derivative in photodynamic therapy medicine |
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Non-Patent Citations (6)
Title |
---|
Micelles from lipid derivatives of water-soluble polymers asdelivery systems for poorly soluble drugs. Anatoly N.Lukyanov,et.al.ADVANCED DRUG DELIVERY REVIEWS,Vol.56 . 2004 |
Micelles from lipid derivatives of water-soluble polymers asdelivery systems for poorly soluble drugs. Anatoly N.Lukyanov,et.al.ADVANCED DRUG DELIVERY REVIEWS,Vol.56. 2004 * |
Micelles frompolyethylene glycol/phosphatidylethanolamine conjugates fortumor drug delivery. Anatoly N.Lukyanov,et.al.JOURNAL OF CONTROLLED RELEASE,Vol.91 . 2003 |
Micelles frompolyethylene glycol/phosphatidylethanolamine conjugates fortumor drug delivery. Anatoly N.Lukyanov,et.al.JOURNAL OF CONTROLLED RELEASE,Vol.91. 2003 * |
Structure and design of polymeric surfactant-baseddrugdelivery systems. Vladimir P. Torchilin.JOURNAL OF CONTROLLED RELEASE,Vol.73 . 2001 |
Structure and design of polymeric surfactant-baseddrugdelivery systems. Vladimir P. Torchilin.JOURNAL OF CONTROLLED RELEASE,Vol.73. 2001 * |
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