CN1723906A - Cucurbitacine liposome and its prepn. method - Google Patents
Cucurbitacine liposome and its prepn. method Download PDFInfo
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- CN1723906A CN1723906A CN 200410054739 CN200410054739A CN1723906A CN 1723906 A CN1723906 A CN 1723906A CN 200410054739 CN200410054739 CN 200410054739 CN 200410054739 A CN200410054739 A CN 200410054739A CN 1723906 A CN1723906 A CN 1723906A
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- cucurbitacin
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Abstract
A cucurbitacin lipid with high absorptivity, biologic utilization rate and stability for treating tumor and hepatitis and improving immunity is prepared proportionally from vinpocetin, phosphatide, cholesterol and the supporting agent chosen from sorbitol, mannitol, cane sugar, sodium chloride, water-soluble starch, etc.
Description
Technical field
The present invention relates to medical technical field, exactly it is a kind of cucurbitacin liposome (comprising pro-liposome) and preparation method thereof.
Background technology
Cucurbitacin (cucurbitacin) is the composition that extraction separation goes out from the Chinese medicine muskmelon pedicel, has multiple biological activity, and cell toxicant and antitumor are arranged, and protects the liver, and anti-hepatitis improves effects such as immunologic function.Mainly contain Cucurbitacin B, E etc., wherein contain Cucurbitacin B more than 80%, be the active ingredient of treatment hepatitis and hepatocarcinoma.The cucurbitacin sheet is used for the treatment of chronic hepatitis---cucurbitacin sheet pharmacy circular 1986,21 (6): 357), through Shanghai, Beijing, ground such as Chongqing 13 tame hospital clinicals, its effective percentage is 75.2%, obvious effective rate is 44.6% Chinese herbal medicine 1987,18 (10): 1984,3 (2): 21-22, the pharmacology of cucurbitacin and clinical practice Chinese herbal medicine 1992,23 (11), other has literary composition to find Cucurbitacin B, E (II) 20 μ g/ml are 82.6% to the kill rate of cancerous cell, when concentration was increased to 80 μ g/ml, its kill rate reached 94.1%, and the influence of normal person's lymhocyte transformation rate then is respectively 90.6% and 89.5%.Zhejiang College Of Traditional Chinese Medicine journal 1994,18 (4): 18～19, there is document to point out, length can obviously suppress the liver proliferation of fibrous tissue at 6 weeks of the medication course of treatment, prevents fatty degeneration of liver and cirrhotic formation and development; The RP-HPLC method measures 2003 05 phases of content Chinese herbal medicine of Cucurbitacin B in the drop pills of cucurbitacine because the maximum absorption wavelength of Cucurbitacin B is 228nm, and chromatographically pure methanol is about 0.15 at the absorbance of 230nm, background absorbs big, has influence on measurement result to some extent.Having set up acetonitrile 0.1mol/LK2HPO4 is the chromatographic system of mobile phase, makes Cucurbitacin B and other compositions reach good separation.It is targeting and the targeting degree of the Cucurbitacine polylactic acid nano microgranule of 85nm to oral cancer Cervical Lymph Node Metastasis kitchen range that Cucurbitacine polylactic acid nano microgranule is inquired into mean diameter to 2003 06 phases of targeting evaluation West China stomatology magazine of oral cancer Cervical Lymph Node Metastasis kitchen range.Cucurbitacin lipomul mouldability factors influencing Zhang Li, Hou Shixiang, outward appearance, particle diameter, medicament contg and the stability of 2004 02 phases of the Central-South pharmacy of Wang Chang light with the cucurbitacin fat milk is index, investigates respectively that osmotic pressure, high pressure breast is even, factors such as pH, air displacement punishment and sterilization are to the influence of Emulsion mouldability.The research worker of Sichuan University's West China medical college has been studied cucurbitacin polylactic acid nanoparticle lyophilized injection; Bioavailability is low, and cucurbitacin is made liposome and pro-liposome is not seen recommendation.
Summary of the invention
The purpose of this invention is to provide cucurbitacin liposome and pro-liposome and preparation method thereof, be insoluble in water to improve cucurbitacin, oral absorption is poor, and bioavailability is low.As the phospholipid of film material, itself is nontoxic, and can strengthen body immunity, has many health cares simultaneously.
The present invention adds cholesterol by cucurbitacin and phospholipid, also can not add (nanometer) liposome that adjuvants such as cholesterol are prepared from.Preparation method can adopt pro-liposome method, alcohol injection, film dispersion method, reverse phase evaporation, PH gradient method, extrusion molding, Mechanical Method etc. to prepare the whole bag of tricks of liposome and nanometer liposome.Mechanical Method can be the method that various plant equipment such as dispersing emulsification machine, high pressure dispersing emulsification machine, nanometer machine, refiner, high pressure microjet prepare liposome.The phospholipid of preparation liposome, can be soybean lecithin, hydrogenated soya phosphatide, it also can be synthetic phospholipid, prepare the cucurbitacin liposome by alcohol injection, film dispersion method, reverse phase evaporation, extrusion molding, Mechanical Method, its composition comprises: adjuvants such as cucurbitacin phospholipid, cholesterol, VE. wherein the weight ratio of phospholipid and cucurbitacin is 0.1: 1～40: 1, and the weight ratio of C/PL is 0～2: 1.
The prescription that is equipped with liposome by the pro-liposome legal system is: cucurbitacin, proppant, phospholipid, cholesterol, VE etc.The weight ratio of phospholipid and cucurbitacin is 0.1: 1～40: 1, and the weight ratio of C/PL is 0～2: 1, and the ratio of proppant and phospholipid is 0.01: 1～400: 1.Proppant can be used medicinal materials or the pharmaceutic adjuvants that can be used for frozen-dried supporting agent such as sorbitol, mannitol, sucrose, sodium chloride, water soluble starch, dextran, glucose, lactose.The method for preparing proliposome can adopt various prilling process and drying and coating methods such as decompression rotating thin film method, spray drying method, fluidized bed process or lyophilization.Adding water or buffer before pro-liposome uses forms liposome, or is prepared into capsule, tablet, granule etc. by jolting, stirring, ultrasonic aquation.In digestive tract, meet the direct spontaneous formation liposome of water.
Can make dosage forms such as tablet, oral liquid, oral breast, capsule, granule, injection, freeze-dried powder, transfusion Emulsion, microemulsion, injectable powder with cucurbitacin liposome (or precursor fat body).
Advantage of the present invention is: it is poor to improve the cucurbitacin oral absorption, and the deficiency that bioavailability is low utilizes phospholipid to make the film material, and cucurbitacin is made liposome, and phospholipid can be worked in coordination with and assosting effect with the cucurbitacin performance, improves the curative effect of cucurbitacin.
The specific embodiment:
Concrete preparation method of the present invention is illustrated by following embodiment, but protection scope of the present invention is not limited to this.
Embodiment 1:
Alcohol injection prepares the cucurbitacin liposome: get soybean phospholipid, cholesterol, VE inject the cucurbitacin aqueous solution after adding anhydrous alcohol solution, the constant temperature high-speed stirred, reduction vaporization is removed ethanol, crosses the microporous filter membrane granulate, promptly get the cucurbitacin liposome, envelop rate can reach 62.8%.
Embodiment 2:
Film dispersion method prepares the cucurbitacin liposome: get soybean phospholipid, cholesterol, VE is dissolved in the 150ml eggplant-shape bottle with the 15ml chloroform, the film forming that reduces pressure on rotary film evaporator also eliminates organic solvent, add 10ml cucurbitacin aqueous solution aquation, cross the microporous filter membrane granulate, get the cucurbitacin liposome, envelop rate can reach 60.1%.
Embodiment 3:
Reverse phase evaporation prepares the cucurbitacin liposome: take by weighing soybean phospholipid, cholesterol, VE adds the 5ml chloroform makes dissolving, add the 10ml ether again, add then in the phosphate buffer of 15ml cucurbitacin, ultrasonic the making of bath formula forms the homogeneous single_phase system, evaporation under reduced pressure removed chloroform ether is to gel formation, continued reduction vaporization 5～10 minutes, it is that liposome forms that vortex vibrates to aqueous suspension.Envelop rate can reach 27.5%.
Embodiment 4:
Decompression rotating thin film legal system is equipped with the cucurbitacin pro-liposome: get sorbitol and cucurbitacin and be placed in the 100ml eggplant-shape bottle with the equivalent method mix homogeneously that progressively increases, in decompression preheating on the Rotary Evaporators of improvement 30 minutes, get soybean phospholipid, cholesterol, VE and be dissolved in ethanol liquid, rotary evaporation in vacuo in right amount.All add the back at ethanol liquid and continued reduction vaporization 30～40 minutes, powder is taken out sieve (40 orders, 450 μ m) after placing exsiccator to spend the night, promptly get the cucurbitacin pro-liposome.Envelop rate can reach 22.8%.
Embodiment 5:
Fluidized bed process prepares the cucurbitacin pro-liposome: sorbitol and cucurbitacin are placed in the fluid bed with the equivalent method mix homogeneously that progressively increases, getting soybean phospholipid, cholesterol, VE is dissolved in the dehydrated alcohol in right amount, by fluid bed boiling one-step palletizing, sieve, promptly get the cucurbitacin pro-liposome.
Embodiment 6:
Fluidized bed process prepares the cucurbitacin pro-liposome: the cucurbitacin adding distil water, and add 0.1N NaOH again and transfer PH to make dissolving, adjust volume (A liquid) with distilled water; Other gets soybean phospholipid, cholesterol, VE and is dissolved in the dehydrated alcohol, by fluid bed boiling one-step palletizing, crosses 20 orders and 60 mesh sieves, promptly gets cucurbitacin pro-liposome granule.
Embodiment 7:
Spray drying method for preparation cucurbitacin pro-liposome: cucurbitacin adds water, and 0.1N NaOH transfers PH to make dissolving, adds lactose and EDTA and makes dissolving (A liquid).Other gets soybean phospholipid, cholesterol, VE and is dissolved in (B liquid) in the 100ml dehydrated alcohol.B liquid is under agitation slowly added in the A liquid, and spray-drying process sieves, and promptly gets the cucurbitacin liposome.
Embodiment 8:
The liposome of alcohol injection, film dispersion method preparation, spray drying promptly gets the cucurbitacin pro-liposome.
Embodiment 9:
Prepare the cucurbitacin liposome by pro-liposome.Get the pro-liposome 2g that embodiment 7 makes,, add water 10ml jolting 10 minutes and aquation, promptly get the cucurbitacin liposome, microscope amplifies 1000 times of observations can see liposome.
Embodiment 10:
Freeze-drying prepares the cucurbitacin pro-liposome: soybean phospholipid, cholesterol, an amount of VE slowly inject the cucurbitacin aqueous solution in high-speed stirred after adding anhydrous alcohol solution, and reduction vaporization is removed ethanol.Lyophilization 24 hours gets the cucurbitacin pro-liposome.
Embodiment 11:
The cucurbitacin liposome is crossed the sterilization of 0.22 μ m microporous filter membrane, inflated with nitrogen, embedding gets the cucurbitacin lipidosome injection.
Embodiment 12:
The cucurbitacin liposome is added 10% sucrose, cross the sterilization of 0.22 μ m microporous filter membrane, packing, lyophilization gets injectable powder.
Embodiment 13:
The cucurbitacin pro-liposome is sieved, and packing gets the agent of cucurbitacin liposome particles.
Embodiment 14:
The cucurbitacin pro-liposome is sieved, encapsulated, get the cucurbitacin lipidosome capsule.
Embodiment 15:
The cucurbitacin pro-liposome is sieved, and tabletting gets the cucurbitacin liposome tablet.
The invention is not restricted to above-described embodiment.
Claims (8)
1, cucurbitacin liposome and preparation method thereof is characterized in that: the liposome or the pro-liposome that are prepared from by adjuvants such as cucurbitacin and phospholipid.
2, cucurbitacin liposome according to claim 1 is characterized in that: wherein can add cholesterol and proppant.
3, cucurbitacin liposome according to claim 1 or pro-liposome is characterized in that: film material phospholipid can adopt natural phospholipid, also can be to adopt hydrogenated soya phosphatide and synthetic phospholipid etc.
4, cucurbitacin liposome according to claim 1 or pro-liposome is characterized in that: the weight ratio of phospholipid and medicine is 0.1: 1～40: 1.
5, cucurbitacin liposome or the pro-liposome of stating according to claim 2, it is characterized in that: proppant can sorbitol, mannitol, sucrose, sodium chloride, water soluble starch, dextran, stevioside, glucose, lactose etc., and wherein the ratio of proppant and phospholipid is: 0.01: 1～400: 1.
6, cucurbitacin liposome according to claim 1 or pro-liposome is characterized in that: can make dosage forms such as capsule, tablet, granule, injection, oral liquid, freeze-dried powder, transfusion with this liposome or pro-liposome.
7, a kind of preparation method of cucurbitacin liposome as claimed in claim 1 is characterized in that: preparation method can adopt pro-liposome method, alcohol injection, film dispersion method, reverse phase evaporation, extrude instrument, Mechanical Method, PH gradient method etc.; Mechanical Method comprises that various plant equipment such as using homogenizer, dispersing emulsification machine, extruder, nanometer machine, refiner, high pressure microjet prepare the method for liposome.
8, a kind of preparation method of cucurbitacin pro-liposome as claimed in claim 7, it is characterized in that: adopt the pro-liposome legal system to be equipped with the cucurbitacin liposome, prepare pro-liposome earlier, pro-liposome by preparation forms liposome before use, or pro-liposome is prepared into capsule, tablet, granule etc., the direct spontaneous formation liposome of chance water in digestive tract.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410054739 CN1723906A (en) | 2004-07-19 | 2004-07-19 | Cucurbitacine liposome and its prepn. method |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200410054739 CN1723906A (en) | 2004-07-19 | 2004-07-19 | Cucurbitacine liposome and its prepn. method |
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| CN1723906A true CN1723906A (en) | 2006-01-25 |
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| CN 200410054739 Pending CN1723906A (en) | 2004-07-19 | 2004-07-19 | Cucurbitacine liposome and its prepn. method |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101062041B (en) * | 2007-05-31 | 2011-11-16 | 沈阳药科大学 | Novel medical function of cucurbitacin |
| CN106137966A (en) * | 2015-03-26 | 2016-11-23 | 天津药物研究院有限公司 | Cucurbitacin B nanometer liposome and preparation thereof |
-
2004
- 2004-07-19 CN CN 200410054739 patent/CN1723906A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101062041B (en) * | 2007-05-31 | 2011-11-16 | 沈阳药科大学 | Novel medical function of cucurbitacin |
| CN106137966A (en) * | 2015-03-26 | 2016-11-23 | 天津药物研究院有限公司 | Cucurbitacin B nanometer liposome and preparation thereof |
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