CN101199510A - Silybin precursor multiphase lipidosome pharmaceutics and preparing method thereof - Google Patents
Silybin precursor multiphase lipidosome pharmaceutics and preparing method thereof Download PDFInfo
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- CN101199510A CN101199510A CNA2007101914645A CN200710191464A CN101199510A CN 101199510 A CN101199510 A CN 101199510A CN A2007101914645 A CNA2007101914645 A CN A2007101914645A CN 200710191464 A CN200710191464 A CN 200710191464A CN 101199510 A CN101199510 A CN 101199510A
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Abstract
Disclosed is a preparation drug of precursor multiphase liposome of water grind processing thistle bingham, which contains the precursor multiphase liposome of the water grind processing thistle bingham. The preparation drug is mainly composed of the following mass abundance components : 1 portion of water grind processing thistle bingham, 2 to 10 portions of phospholipid, 0.1 to 0.6 portion of cholesterol, 1 to 5 portions of isopropyl myristate, 1 to 5 portions of sodium cholate, and 2 to 10 portions of cane sugar powder. Observed by the sem, the appearance of the prepared precursor multiphase liposome powder of the water grind processing thistle bingham is ball-shaped or similar to the shape of the ball; the surface of the prepared precursor multiphase liposome powder of the water grind processing thistle bingham is smooth; the particle size and the distribution of the prepared precursor multiphase liposome powder of the water grind processing thistle bingham are measured by photon correlation spectroscopy, and the average particle size is 106 nm; the redispersion in the water is good; no burst effect occurs; and the storage stability is good. The total entrapment efficiency of the precursor multiphase liposome of the water grind processing thistle bingham is 96 percent, wherein, 85 percent of the water grind processing thistle bingham is entrapped inside the liposome, and a small part is entrapped inside emulsion and micelle. With high entrapment efficiency, good stability, simple operation and low cost, the precursor multiphase liposome of the water grind processing thistle bingham is easy to be filled , does not need special equipment and is convenient for industrial production. The invention discloses the preparation method of the precursor multiphase liposome of the water grind processing thistle bingham.
Description
Technical field:
The present invention relates to a kind of precursor multiphase lipidosome preparation medicine and preparation method thereof, heterogeneous lipid formulations medicine of particularly a kind of silibinin precursor and preparation method thereof.
Background technology:
Silibinin (Silybin, SLB) be the flavone compound that extraction separation obtains from feverfew Herba Silybi mariani (Silybum marianus) fruit, medicine is repaired in the hepatic injury that belongs to universally acknowledged determined curative effect, various hepatic disease all there is in various degree therapeutical effect, be widely used in the clinical treatment acute, chronic hepatitis at present, hepatopathy such as hepatic fibrosis and early stage liver cirrhosis [referring to: Wu J, Zern MA.Hepatic stellate cells:a target for the treatmentof liver fibrosis.J Gastroenterol, 2000,35 (9): 665; Kvasnicka F., Biba B., Sevcik R., et al.Analysis of the active components of silymarin.JChromatogr, 2003, A990:239; Flora K, Hahn M, Rahn H, et al.Milk thisle (silybummarianum) for the therapy of live disease.Am J Gastroenterol, 1998,93 (13): 139.].Because SLB is insoluble in water, the common oral preparation bioavailability is lower, in the recent period concentrate on the bioavailability that improves its oral formulations about SLB novel form and novel formulation research, as, make the lecithin complex, solid dispersion, cyclodextrin clathrate, lipid nanoparticle, nano-micelle etc. [referring to: GiacomelliS, Gallo D, Apollonio P, et al.Silybin and its bioavailable phospholipid complex (IdBl016) potentiate in vitroand in vivo the activity of cisplatin.Life Sci, 2002,70 (12): 1447; Li Fengqian, Hu Jinhong, Zhu Quangang. the mensuration of total flavones in the silibinin solid dispersion. Chinese herbal medicine, 2002,33 (1): 31; Li Fengqian, Hu Jinhong, Wang Hui waits the .PEG6000 solid dispersion system to the solubilization of insoluble drug silymarin and the relation of lattice variations. Acta Pharmaceutica Sinica, 2002,37 (4): 294; Lirussi F, Beccarello A, ZanetteG, et al.Silybin-beta-cyclodextrin in the treatment of patients with diabetesmellitus and alcoholic liver disease.Efficacy study of a new preparation ofan anti-oxidant agent.Diabets Nutr Metab, 2003,15 (4): 222. Xu Xi are bright, Li Qiang, Zhu Yuan, Deng. research distributes in the preparation of silibinin lipid nanoparticle and the Mus body. CHINA JOURNAL OF CHINESE MATERIA MEDICA, 2005,30 (24): 1912; Xu Ximing, Zhu Yuan, Li Qiang, etc. silybin nanostructured micellar preparation and the research of Mus interior medicine dynamics. Chinese Pharmaceutical Journal, 2005,40 (24): 1874].
Liposome (liposome) is a kind of with the superminiature spheroid carrier preparation of drug encapsulation in the lipoids bilayer.
The material that constitutes lipid bilayer mainly contains phospholipid (lecithin, cephalin, fabaceous lecithin) and cholesterol etc.According to the difference of structure, liposome can be divided into single chamber and multilamelar liposome, and the particle diameter of small unilamellar vesicle is at 0.02-0.08 μ m usually, and the particle diameter of large unilamellar vesicle is at 0.1-1 μ m, and the particle diameter of multilamelar liposome is at 1-5 μ m.Liposome has many advantages as pharmaceutical carrier: when liposome forms spherical class Lipid Bilayer Structure, existing hydrophilic group has hydrophobic group again in the molecular structure, thereby, can seal fat-soluble medicine, can seal water soluble drug again, water soluble drug is encapsulated in intermediary hydrophilic group part, and fat-soluble medicine is embedded in the hydrophobic group part; Liposome is a kind of targeted drug carrier, easily by reticuloendothelial system phagocytic, makes medicine be enriched in tissues such as liver, spleen, and control drug release is in diseased region effectively; Liposome can delay drug release, reduces elimination speed in the body, reduces the therapeutic dose of medicine, reduces drug toxicity; Liposome can alleviate allergy and immunoreation, itself is nontoxic, non-immunogenicity, but vivo degradation [referring to: M.Brandl.Liposomesas drug carriers:a technological approach.Biotechnology Annual Review, 2001 (7): 59-85.JinYihua, The developosome ofnovel liposomess.J Pharm Pract, 2003,2l (3): 149].
Because the conventional liposome stability of formulation is not good enough, some novel lipides have appearred in recent years, as: pro-liposome, cationic-liposome, pH sensitive liposome body, immunoliposome etc., wherein pro-liposome is numerous because of advantage, has now received increasing concern.Pro-liposome (proliposome) is weighed again and is built liposome, be that the film material, medicine and the proppant that constitute liposome are made dried forms (being generally the powder with good flow performance) such as graininess, lyophilizing shape with proper method, preserve with solid form, after before adding water hydratable, can disperse or dissolve into liposome.Compare with conventional liposome, pro-liposome does not possess the lipid bilayer structure or has incomplete lipid bilayer structure, can solve conventional liposome because of assembling, sedimentation, drug leakage, the stability problem that exists in stability problem that phospholipid oxidation etc. cause and the storage transportation [referring to: Keon-Hyoung Song, Suk-Jae Chung, Chang-Koo Shim.Preparation and evaluation of proliposomes containing salmon calcitonin.J Journal ofControlled Release, 2002,84 (1-2): 27]; Pro-liposome with dosed administration can increase medicine in the absorption of enteral [referring to Keon-Hyoung Song, Suk-Jae Chung, Chang-Koo Shim.Enhanced intestinalabsorption of salmon calcitonin (sCT) from proliposomes containing bile salts J.Journal ofControlled Release, 2005,106 (3): 298]; In addition, only need dilution or aquation before pro-liposome uses, need not granulate and remove free drug, simple to operate, be beneficial to suitability for industrialized production.
Multiphasic liposomes belongs to the carrier of colloidal dispersion, wherein except that the skeletal substance of liposome, also add some non-ionic surface active agents and high-performance solid dispersant, the overwhelming majority is unilamelar liposome and multilamelar liposome in the solution, a small amount of is the solubilising micelle, oil/water or water/oil/water (O/W, W/O/W) type Emulsion isocolloid disperse system.Water solublity, fat-soluble medicine all are encapsulated in the liposome in the multiphasic liposomes prescription, and fat-soluble medicine also can be by solubilising in micelle simultaneously, or be emulsified into O/W, W/O/W type emulsion coexists as in the liposomal systems.All there is physical interface in all these microgranules, and the physics of each several part, chemical property be heterogeneity also, and the existence of heterogeneous system both had been beneficial to the solubilising of medicine, also was beneficial to the absorption of medicine.The free drug that does not wrap into liposome in the multiphasic liposomes suspension can be dispersed into heterogeneous dispersive suspension or Emulsion by non-ionic surface active agent, this system need not to remove free drug by molecular sieving, thereby the system drug loading is big, the envelop rate height, preparation technology is simple.
Because pro-liposome can solve the preparation stability problem, multiphasic liposomes can increase the preparation envelop rate, if SLB is made the silibinin precursor multiphase lipidosome, its remarkable advantage is both can improve stability of formulation, can increase the envelop rate of preparation again, and simple to operate, be beneficial to suitability for industrialized production.
The preparation method of liposome mainly contains: and film dispersion method, injection method, freeze-drying (or rebuilding lyophilization), ultrasonic dispersing method, reverse phase evaporation, gradient active loading method, multi-emulsion method etc. [referring to: Timothy D.HeathMethodology and Experimental Design for the Study of Liposome-Dependent DrugsJ.Methods in Enzymology, 2005,391:186], the preparation method difference, the envelop rate of prepared liposome type, particle diameter and medicine is all different.Usually,, select different preparation methoies for use,, should select reverse phase evaporation, gradient active loading method, multi-emulsion method etc. for use if encapsulated medicine hydrophilic is stronger according to the difference of drug solubility; If encapsulated medicine lipotropy is stronger, should select film dispersion method, injection method etc. for use.The preparation of pro-liposome is to add a certain amount of solid carrier based on the above method, again by certain preparation means, formation has the powder of good fluidity, and with the water hydration, method commonly used has freeze-drying, spray drying method, carrier oven drying method etc. before using.
Summary of the invention:
The present invention has compared outward appearance and the envelop rate of the prepared precursor multiphase lipidosome preparation of film dispersion method, injection method, freeze-drying, carrier oven drying method, propose to adopt thin film dispersion-carrier oven drying method to prepare the precursor multiphase lipidosome preparation medicine, provide that a kind of envelop rate height, cost are low, simple to operate, the preparation method of the new precursor multiphase lipidosome that need not special installation and envelop rate height, particle diameter are little, good stability, silybin precursor multiphase lipidosome pharmaceutics medicine that bioavailability is high.
Technical scheme of the present invention is as follows:
A kind of silybin precursor multiphase lipidosome pharmaceutics medicine, it is the precursor multiphase lipidosome that comprises silibinin, it mainly is made up of following mass component:
1 part of silibinin; Phosphatidase 12-10 part;
Cholesterol 0.1-0.6 part; Isopropyl myristate 1-5 part;
Sodium cholate 1-5 part; Dried cane sugar powder 2-10 part.
Above-mentioned silybin precursor multiphase lipidosome pharmaceutics during its mass component is formed, adds 2-10 part phospholipid, and part is used for forming complex with SLB, and part is as the liposome membrane material; Add 0.1-0.6 part cholesterol as the liposome membrane material; Add 1-5 part sodium cholate as surfactant; Add the oil phase of 1-5 part isopropyl myristate as multiphasic liposomes; Add the carrier of the dried cane sugar powder of 2-10 part as pro-liposome.
A kind of method for preparing above-mentioned silybin precursor multiphase lipidosome pharmaceutics medicine, it is made up of the following step basically:
Step 2. is with the mixture evaporation of step 1 gained, make every gram silibinin consumption be evaporated to the 3-5 milliliter, the cholesterol, isopropyl myristate and the sodium cholate that add formula ratio, add dehydrated alcohol again, the amount that dehydrated alcohol adds is that every gram silibinin consumption adds the 30-80 milliliter, behind the ultrasonic dissolution, rotary evaporation makes every gram silibinin consumption be evaporated to the 10-20 milliliter;
Step 3. adds the sucrose powder of mistake 100 mesh sieves of formula ratio, flings to ethanol fully in 70 ℃ of water-baths, put place 2h in-20 ℃ of refrigerators after, oven dry is pulverized, and promptly gets silibinin precursor multiphase lipidosome powder.
The preparation method of above-mentioned silybin precursor multiphase lipidosome pharmaceutics is filled to the silibinin precursor multiphase lipidosome powder of gained in the capsule, makes silibinin precursor multiphase lipidosome capsule.
Prepared silibinin precursor multiphase lipidosome mean diameter is 106 nanometers, and outward appearance is ball-type or class ball-type, smooth surface; It can the powder type direct packaging, faces and uses preceding hydration; Also can become the powder fill capsule to take.
The schematic flow sheet of preparation process of the present invention is seen Fig. 1.
The invention has the beneficial effects as follows:
1. adopt the silibinin precursor multiphase lipidosome powder of the present invention's preparation, through its form of scanning electron microscopic observation, the results are shown in accompanying drawing 2, as seen, outward appearance is ball-type or class ball-type, smooth surface among the figure, photon correlation spectroscopy is measured its particle diameter and distribution, the results are shown in accompanying drawing 3, as seen, mean diameter is 106nm among the figure; The slight jolting of silibinin precursor multiphase lipidosome powder adding distil water, hydration fully shows that redispersibility is good in the precursor multiphase lipidosome water that the present invention prepares; The outer cumulative release curve of silibinin precursor multiphase lipidosome capsule body meets the zero order kinetics equation; 0.5 the burst size in hour is far below 40%, no burst effect; With silibinin precursor multiphase lipidosome powder-tight, place the stability test case, at RH75%, to place three months under 40 ℃ of conditions of temperature, accelerated tests is investigated its stability, and the result shows: outward appearance does not change; Redispersibility is good in the water; Its form of scanning electron microscopic observation the results are shown in Figure 4, and as seen, precursor multiphase lipidosome is still spherical in shape or class is spherical behind the stability test among the figure, and smooth surface and does not have significantly difference before the stability test; Laser particle size analyzer is measured particle diameter and distribution, the results are shown in Figure 5, and as seen, mean diameter is 173nm, is normal distribution among the figure, and compares before the stability test, and particle diameter has slightly and becomes greatly; Liposome encapsulation does not change substantially before and after the stability test.Percolation ratio and accelerated tests prove: silibinin precursor multiphase lipidosome percolation ratio in acid-base medium is less, and bin stability is good.
2. the present invention makes multiphasic liposomes with silibinin, and one of its remarkable advantage is the envelop rate that has obviously improved liposome.The conventional liposome suspension generally need obtain the pastille liposome of an entrapped drug by molecular sieve or the centrifugal free drug of removing; Compare with the conventional liposome suspension, the multiphasic liposomes of the present invention's development belongs to colloidal dispersion system, it forms the overwhelming majority is single chamber or multilamelar liposome, a small amount of is solubilising micelle and O/W or W/O/W type Emulsion, in the prescription except that the skeletal substance (phospholipid and cholesterol) of medicine and liposome, also add moderate oil phase of proportioning and surfactant, the most of medicine of liposome turbid liquor of preparation is wrapped in the liposome, the small-amount free medicine is dispensed in micelle or the Emulsion, need not molecular sieving, selected for use isopropyl myristate and sodium cholate to make oil phase and surfactant, the multiphasic liposomes of preparation has not only solved fat-soluble or the insufficient problem of insoluble drug retention volume, and saved this loaded down with trivial details step of removal free drug, preparation is simple.The silibinin precursor multiphase lipidosome that the present invention obtains, adopting the membrane filtration method to record total envelop rate is 96%, and wherein, about 85% silibinin is encapsulated in the liposome, and small part is encapsulated in Emulsion and the micelle.
3. the present invention forms complex with silibinin and phospholipid earlier, utilizes the complex solubilising, increases the dissolubility of silibinin, prepares precursor multiphase lipidosome with the gained complex again, and one of its remarkable advantage is the bioavailability that has obviously improved silibinin.Silibinin precursor multiphase lipidosome and commercial preparation water woods that the present invention obtains is good oral to dog respectively, in measuring the dog body, different time points dissociates in the blood plasma and total silibinin concentration after the administration, the results are shown in Figure 6 and Fig. 7, among the figure as seen: compare with commercially available control formulation, the silybin precursor multiphase lipidosome pharmaceutics of oral the present invention's preparation, the relative bioavailability of free and total blood drug level is respectively 110.9% and 120.1% in the blood plasma, and the silybin precursor multiphase lipidosome pharmaceutics bioavailability is higher than reference preparation; The inside and outside correlation research shows: it is good to absorb dependency in the release in vitro of silibinin precursor multiphase lipidosome and the body, can reflect absorbing state in the body of precursor multiphase lipidosome with the extracorporeal releasing experiment result.
4. the present invention has compared the effect that thin film dispersion-carrier oven drying method, thin film dispersion-freeze-drying, injection-freeze-drying prepare precursor multiphase lipidosome, and the result shows: injection-freeze-drying envelop rate is lower; Thin film dispersion-freeze-drying and thin film dispersion-carrier oven drying method envelop rate do not have significant difference, but thin film dispersion-freeze-drying gained liposome powder viscosity is bigger, unsuitable fill; Adopt the precursor multiphase lipidosome of thin film dispersion-carrier oven drying method preparation, its remarkable advantage is the envelop rate height, and good stability is convenient to fill, and is simple to operate, need not special installation, and cost is lower, is convenient to suitability for industrialized production.
Description of drawings
Fig. 1 is the schematic flow sheet of preparation process of the present invention.
Fig. 2 is a silibinin precursor multiphase lipidosome sem photograph of the present invention.
Fig. 3 is the particle size distribution figure of silibinin precursor multiphase lipidosome of the present invention.
Fig. 4 is a sem photograph behind the silibinin precursor multiphase lipidosome stability test of the present invention.
Fig. 5 is the particle size distribution figure behind the silibinin precursor multiphase lipidosome stability test of the present invention.
Fig. 6 is a silibinin precursor multiphase lipidosome dog oral free plasma concentration curve of the present invention
Fig. 7 is the oral total plasma concentration curve of silibinin precursor multiphase lipidosome dog of the present invention
The specific embodiment
Following examples material therefor and instrument and equipment are:
Experiment material: soybean phospholipid (Shanghai Taiwei Pharmaceutical Co., Ltd.); cholesterol (Shanghai chemical reagents corporation); sodium cholate (Chemical Reagent Co., Ltd., Sinopharm Group); isopropyl myristate (IPM) (Chemical Reagent Co., Ltd., Sinopharm Group); sucrose (Shanghai reagent two factories); acetone (Chemical Reagent Co., Ltd., Sinopharm Group), dehydrated alcohol (Shanghai development chemical industry one factory).
Experimental apparatus: Alpha2-4 type freezer dryer (German CHRIST), Rotary Evaporators (German Heidolph company), 85-2 temperature control magnetic stirring apparatus (Jintan Medical Instruments factory), vacuum drying oven (on whenever make a leapleap forward medical apparatus and instruments factory).
Take by weighing 1 gram silibinin, 10 gram phospholipid are dissolved in 50 milliliters of acetone, in the reaction of 40 ℃ of stirred in water bath after 3 hours, boil off most of acetone to 5 milliliter, add 0.6 gram cholesterol, 5 gram isopropyl myristates, 5 gram sodium cholate, 80 milliliters of dehydrated alcohol, ultrasonic dissolution, rotary evaporation to 20 milliliter adds the 10 sucrose powder that restrained 100 mesh sieves, in 70 ℃ of water-baths, fling to ethanol fully, put in-20 ℃ of refrigerators place 2h after, oven dry, pulverize, promptly get silibinin precursor multiphase lipidosome powder.
Embodiment 2.
Take by weighing 1 gram silibinin, 2 gram phospholipid are dissolved in 20 milliliters of acetone, in the reaction of 40 ℃ of stirred in water bath after 3 hours, boil off most of acetone to 3 milliliter, add 0.1 gram cholesterol, 1 gram isopropyl myristate, 1 gram sodium cholate, 30 milliliters of dehydrated alcohol, ultrasonic dissolution, rotary evaporation to 10 milliliter adds the 2 sucrose powder that restrained 100 mesh sieves, in 70 ℃ of water-baths, fling to ethanol fully, put in-20 ℃ of refrigerators place 2h after, oven dry, pulverize, promptly get silibinin precursor multiphase lipidosome powder.
Embodiment 3.
Take by weighing 1 gram silibinin, 6 gram phospholipid are dissolved in 35 milliliters of acetone, in the reaction of 40 ℃ of stirred in water bath after 3 hours, boil off most of acetone to 4 milliliter, add 0.35 gram cholesterol, 3 gram isopropyl myristates, 3 gram sodium cholate, 55 milliliters of dehydrated alcohol, ultrasonic dissolution, rotary evaporation to 15 milliliter adds the 6 sucrose powder that restrained 100 mesh sieves, in 70 ℃ of water-baths, fling to ethanol fully, put in-20 ℃ of refrigerators place 2h after, oven dry, pulverize, promptly get silibinin precursor multiphase lipidosome powder.
Embodiment 4.
Take by weighing 1 gram silibinin, 6 gram phospholipid are dissolved in 35 milliliters of acetone, in the reaction of 40 ℃ of stirred in water bath after 3 hours, boil off most of acetone to 4 milliliter, add 0.35 gram cholesterol, 3 gram isopropyl myristates, 3 gram sodium cholate, 55 milliliters of dehydrated alcohol, ultrasonic dissolution, rotary evaporation to 15 milliliter adds the 6 sucrose powder that restrained 100 mesh sieves, in 70 ℃ of water-baths, fling to ethanol fully, put in-20 ℃ of refrigerators place 2h after, oven dry, pulverize, promptly get silibinin precursor multiphase lipidosome powder.Silibinin precursor multiphase lipidosome powder is filled in the capsule, makes silibinin precursor multiphase lipidosome capsule, for oral.
Take by weighing 1 gram silibinin, 10 gram phospholipid are dissolved in 20 milliliters of acetone, in the reaction of 40 ℃ of stirred in water bath after 3 hours, boil off most of acetone to 3 milliliter, add 0.1 gram cholesterol, 1 gram isopropyl myristate, 1 gram sodium cholate, 30 milliliters of dehydrated alcohol, ultrasonic dissolution, rotary evaporation to 10 milliliter adds the 2 sucrose powder that restrained 100 mesh sieves, in 70 ℃ of water-baths, fling to ethanol fully, put in-20 ℃ of refrigerators place 2h after, oven dry, pulverize, promptly get silibinin precursor multiphase lipidosome powder.
Embodiment 6.
Take by weighing 1 gram silibinin, 2 gram phospholipid are dissolved in 50 milliliters of acetone, in the reaction of 40 ℃ of stirred in water bath after 3 hours, boil off most of acetone to 5 milliliter, add 0.6 gram cholesterol, 5 gram isopropyl myristates, 5 gram sodium cholate, 80 milliliters of dehydrated alcohol, ultrasonic dissolution, rotary evaporation to 20 milliliter adds the 10 sucrose powder that restrained 100 mesh sieves, in 70 ℃ of water-baths, fling to ethanol fully, put in-20 ℃ of refrigerators place 2h after, oven dry, pulverize, promptly get silibinin precursor multiphase lipidosome powder; Silibinin precursor multiphase lipidosome powder is filled in the capsule, makes silibinin precursor multiphase lipidosome capsule, for oral.
Embodiment 7.
With the silibinin precursor multiphase lipidosome and the good dog single oral dose of giving respectively of commercial preparation water woods of the embodiment of the invention 6 preparations, after the administration, free and total silibinin concentration in the blood plasma in different time points is measured the dog body.Mensuration process: adopt cross matching mode at random, tried dog with four and be divided into two groups, fasting 12h before the administration, silibinin precursor multiphase lipidosome capsule that deturs talis dosis respectively and the good capsule of water woods, after the administration in 0.25,0.5,1,2,4,6,8,10,12h forelimb vein is got blood 4ml, at interval after the week, intersection is taken medicine, with time point blood sampling, blood sample anticoagulant heparin, centrifuging and taking blood plasma measures that free water flies Ji guest concentration and total concentration in the blood plasma, the results are shown in Figure 6 and Fig. 7.Measurement result shows: compare with commercially available control formulation, the single oral dose silybin precursor multiphase lipidosome pharmaceutics, the relative bioavailability of free and total blood drug level is respectively 110.9% and 120.1% in the blood plasma, and the silybin precursor multiphase lipidosome pharmaceutics bioavailability is higher than reference preparation.
Claims (3)
1. silybin precursor multiphase lipidosome pharmaceutics medicine, it is the precursor multiphase lipidosome that comprises silibinin, it is characterized in that it mainly is made up of following mass component:
1 part of silibinin; Phosphatidase 12-10 part;
Cholesterol 0.1-0.6 part; Isopropyl myristate 1-5 part;
Sodium cholate 1-5 part; Dried cane sugar powder 2-10 part.
2. method for preparing the described silybin precursor multiphase lipidosome pharmaceutics medicine of claim 1, it is characterized in that: it is made up of the following step basically:
Step 1. was dissolved in the acetone by silibinin and phospholipid that prescription takes by weighing, and the consumption of acetone is that every gram silibinin adds acetone 20-50 milliliter, 40 ℃ of stirred in water bath reactions 3 hours;
Step 2. is with the mixture evaporation of step 1 gained, make every gram silibinin consumption be evaporated to the 3-5 milliliter, the cholesterol, isopropyl myristate and the sodium cholate that add formula ratio, add dehydrated alcohol again, the amount that dehydrated alcohol adds is that every gram silibinin consumption adds the 30-80 milliliter, behind the ultrasonic dissolution, rotary evaporation makes every gram silibinin consumption be evaporated to the 10-20 milliliter;
Step 3. adds the sucrose powder of mistake 100 mesh sieves of formula ratio, flings to ethanol fully in 70 ℃ of water-baths, put place 2h in-20 ℃ of refrigerators after, oven dry is pulverized, and promptly gets silibinin precursor multiphase lipidosome powder.
3. the preparation method of silybin precursor multiphase lipidosome pharmaceutics according to claim 2 is characterized in that:
The silibinin precursor multiphase lipidosome powder of gained is filled in the capsule, makes silibinin precursor multiphase lipidosome capsule.
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| CN104367546A (en) * | 2014-11-13 | 2015-02-25 | 中国人民解放军第四军医大学 | Preparation method of targeted temperature-controlled water-loading silibinin temperature-sensitive lipidosome-microbubble complex drug delivery system |
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| CN1264509C (en) * | 2004-03-24 | 2006-07-19 | 中国药科大学 | Precursor liposome preparation containing silybum marianum extract and its preparing process |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104367546A (en) * | 2014-11-13 | 2015-02-25 | 中国人民解放军第四军医大学 | Preparation method of targeted temperature-controlled water-loading silibinin temperature-sensitive lipidosome-microbubble complex drug delivery system |
| CN104367546B (en) * | 2014-11-13 | 2017-03-15 | 中国人民解放军第四军医大学 | A kind of preparation method of the load silibinin thermal sensitive liposome microvesicle complex delivery system of targeting temperature control |
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