CN101095684A - Prunol phospholipid complexes and method for preparing the same and the application thereof - Google Patents
Prunol phospholipid complexes and method for preparing the same and the application thereof Download PDFInfo
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- CN101095684A CN101095684A CNA2006100102284A CN200610010228A CN101095684A CN 101095684 A CN101095684 A CN 101095684A CN A2006100102284 A CNA2006100102284 A CN A2006100102284A CN 200610010228 A CN200610010228 A CN 200610010228A CN 101095684 A CN101095684 A CN 101095684A
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- prunol
- phospholipid
- phospholipid complexes
- ursolic acid
- complexes
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Abstract
The invention discloses a prunol phosphatide compound, the preparation method and its application. The prunol is water insoluble and unstable, so the biological utilization rate is very low, the medical effect is reduced, and the parenteral administration is limited. The key is to increase its solubility, so the prunol phosphatide compound is needed by market. The prunol phosphatide compound comprises prunol and phosphatide, with the weight proportion being 1: 0.5-25. The product can be used to prepare various dosage forms and combined with other active components.
Description
Technical field
The present invention relates to medical technical field, be specifically related to prunol phospholipid complexes and preparation method thereof.
Background technology
(Ursolic acid UA) has another name called ursolic acid, maloic acid to ursolic acid, is that (the nonpolar pentacyclic triterpenoid of type of α-amyrin) is an epimer with oleanolic acid on chemical constitution to α-Amyrin, and molecular formula is C
30H
48O
3, molecular weight is 456.68, m.p. is 285～291 ℃.Structural formula is as follows:
Ursolic acid is very wide in distributed in nature, the leaf, the fruit that are present in the ericad Folium Vaccinii vitis-idaeae select the leaf of gloomy ginseng vegetable hair Paulownia, the fruit of Maguireothamnus speciosus Fructus Gardeniae, the leaf of gentianaceae plant humidogene flower bud, oleaceae plant Fructus Ligustri Lucidi, the aerial parts of the plant Westerner of Lagerstroemia indica L. section grass.
Summary of the invention
The purpose of this invention is to provide a kind of prunol phospholipid complexes that is composited by ursolic acid and phospholipid and its production and application.
Above-mentioned purpose realizes by following technical scheme:
A kind of prunol phospholipid complexes, its composition comprises: ursolic acid and phospholipid, the weight ratio of described ursolic acid and phospholipid are 1: 0.1～25.
Above-mentioned prunol phospholipid complexes, described phospholipid are selected from least a in soybean phospholipid, lecithin, phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, the Phosphatidylserine.
The preparation method of above-mentioned prunol phospholipid complexes takes by weighing ursolic acid and phospholipid in proportion, joins in the solvent, and reflux to solution is clarified, and reclaims solvent, and drying is pulverized and promptly got this product.
The preparation method of above-mentioned described prunol phospholipid complexes, described solvent is aprotonic solvents such as aromatic hydrocarbons, halogen derivatives and cyclic ethers, comprises at least a in acetone, ethanol, chloroform, oxolane, ethyl acetate, the methanol.
The preparation method of above-mentioned prunol phospholipid complexes is made tablet or capsule or suppository or granule or injection or lyophilized injectable powder or compound tablet with product of the present invention.
A kind of above-mentioned prunol phospholipid complexes is as the application of the active component of pharmaceutical preparation.
A kind of above-mentioned prunol phospholipid complexes is as the application of active ingredient in pharmaceutical.
This technical scheme has following beneficial effect:
1. the present invention is the prunol phospholipid complexes that carrier is made with phospholipid, has improved the dissolubility of ursolic acid greatly, dissolution and stability, thus improved drug effect.
2. the present invention can make the various preparations on the pharmaceutics, as tablet, capsule, granule, oral liquid, dry suspension, gel, suppository, pill, injection etc., and can form pharmaceutical composition with other active component.
3. following dissolution in vitro The effects the dissolution of ursolic acid crude drug and product prunol phospholipid complexes of the present invention, further specify beneficial effect of the present invention.
HPLC method chromatographic condition and system suitability test
Chromatographic column is the special C of Erie
18Post (5 μ m, 250mm * 4.6mm); With methanol-water-acetic acid (85: 15: 0.2) is mobile phase; Flow velocity is 1.0mL/min; The detection wavelength is 215nm; Sample size 20 μ L.Number of theoretical plate calculates by the ursolic acid peak and is not less than 2000, and the separating degree of ursolic acid peak and adjacent impurity peaks meets the requirements.
The preparation of standard curve
Get the about 22mg of ursolic acid reference substance, the accurate title, decide, and puts in the 10mL measuring bottle, adds dissolve with methanol and be diluted to scale, shakes up, and gets the stock solution that concentration is about 2mg/mL.Precision is measured stock solution 0.05,0.1,0.2,0.4,0.6,0.8 and 1.0mL, put respectively in the 10mL measuring bottle, be diluted to scale with 0.3% polyoxyethylene lauryl ether brij35 aqueous solution, shake up, make concentration and be about 0.01,0.02,0.04,0.08,0.12,0.16 and the standard solution of 0.2mg/mL.By above-mentioned chromatographic condition, sample introduction 20 μ L write down chromatogram respectively, with sample size m (μ g) peak area A are carried out linear regression, get linear equation: A=2.28976 * 10
5M-298.06, r=0.9999.The result shows that ursolic acid is in 0.211～4.22 μ g scope, and sample size and peak area are good linear relationship.Standard curve is seen accompanying drawing 1.
The preparation of sample
Get ursolic acid crude drug and product prunol phospholipid complexes sample of the present invention, cross 80 mesh sieves respectively.Fine powder is respectively charged in the capsule, makes ursolic acid crude drug capsule and prunol phospholipid complexes capsule.Every capsules contains ursolic acid 20mg approximately.
Dissolution method
Sample thief, according to dissolution method (two appendix XC of Chinese Pharmacopoeia version in 2005 three therapeutic methods of traditional Chinese medicine), with 0.3% polyoxyethylene lauryl ether brij35 aqueous solution 100mL is dissolution medium, rotating speed is that per minute 100 changes, and temperature is 37 ± 1 ℃, in accordance with the law operation, respectively 15,30,45,60,75 and get solution 5mL (adding the equal-volume dissolution medium simultaneously) during 90min, 0.45 μ m filtering with microporous membrane, precision are measured subsequent filtrate 20 μ L, inject chromatograph of liquid, measure by above-mentioned chromatographic condition, the record chromatogram, the substitution standard curve calculates the stripping quantity of every capsules.
The stripping curve of ursolic acid crude drug and phosphatide complexes is seen accompanying drawing 2～4.Dissolution determination is the result show, during 90min, the stripping quantity of ursolic acid crude drug is 33.4%, and the stripping quantity of prunol phospholipid complexes is 77.7%, and obviously, the stripping quantity of prunol phospholipid complexes is significantly improved than the stripping quantity of crude drug.
Ursolic acid has biological effect widely, and it has significantly stable and cooling effect to the central nervous system; External to G
+And G
-Bacterium and yeast all have antibacterial activity; The effect of anti-diabetic, antiulcer and blood fat reducing is arranged; Multiple carcinogenic, short cancer thing there is resistant function; Multiple malignant cell there is the growth of inhibition effect; Ursolic acid and derivant thereof have the activity of inhibition to virus; In addition, can induce the F9 teratocarcinoma cell to become the endoderm cell, and have blood vessel formation against function, very likely become low toxicity new type anticancer medicine efficiently.Therefore, ursolic acid widely pharmacologically active more and more cause relevant expert's concern.
Ursolic acid is water insoluble, and stable inadequately, and this makes the interior bioavailability of ursolic acid body very low, thereby reduces its drug effect, and has limited the parenterai administration approach.Improving such compound dissolution degree is the key that solves its bioavailability and parenterai administration.The present invention has effectively solved this problem.
Advantages such as phospholipid is biomembranous basis, extensively is present in the natural animal and plant seed, has the source extensively, and is nontoxic.Phospholipid molecule has a hydrophilic head and two hydrophobic long-chains, have emulsifying owing to it is amphipathic, disperse, help ooze, characteristic such as moistening, and stronger affinity is arranged with cell surface, in pharmaceutical preparation, be used as dispersant, surfactant, stabilizing agent, pharmaceutical carrier etc., the present invention strengthens pharmaceutically active with it as excipient substance, reduce drug toxicity, improve medicine stability, make drug targeting be discharged into focal zone, prolong drug effect, be beneficial to drug absorption, improve the effect of bioavailability.
Phosphatide complexes is to be a kind of drug delivery system of carrier with phospholipid, and from the solid preparation angle, phosphatide complexes is a kind of comparatively special solid dispersion.Many discovering has special affinity between the active skull cap components of a lot of types and the phospholipid, mainly is to combine with hydrogen bond among the present invention, the structure more complicated.
Description of drawings:
Accompanying drawing 1 is the standard curve of ursolic acid;
Accompanying drawing 2 is the stripping curve of ursolic acid crude drug;
Accompanying drawing 3 is the stripping curve of prunol phospholipid complexes;
Accompanying drawing 4 is the stripping curve comparison diagram of ursolic acid crude drug and prunol phospholipid complexes.
The specific embodiment:
Embodiment 1:
A kind of prunol phospholipid complexes, its composition comprises: ursolic acid and phospholipid, the weight ratio of described ursolic acid and phospholipid is 1: 5, and its preparation technology is: get ursolic acid 2g, refining soybean phospholipid 10g, add 100mL ethanol, reflux stirs 6h, to the solution clarification, reclaims solvent, vacuum drying promptly gets prunol phospholipid complexes of the present invention.It is standby that complex was pulverized 80 mesh sieves.
Embodiment 2:
A kind of prunol phospholipid complexes, its composition comprises: ursolic acid and phospholipid, the weight ratio of described ursolic acid and phospholipid is 1: 4, and its preparation technology is: get ursolic acid 2g, lecithin 8g, add 75mL methanol, reflux stirs 6h, to the solution clarification, reclaims solvent, vacuum drying promptly gets prunol phospholipid complexes of the present invention.It is standby that complex was pulverized 80 mesh sieves.
Embodiment 3:
Get ursolic acid 2g, refining soybean phospholipid 5g, lecithin 7g adds 50mL chloroform and 70mL acetone, and reflux stirs 8h, to the solution clarification, reclaims solvent, and vacuum drying promptly gets prunol phospholipid complexes of the present invention.It is standby that complex was pulverized 80 mesh sieves.
Embodiment 4:
Get ursolic acid 2g, soybean phospholipid 15g, lecithin 5g adds 100mL acetone and 50mL oxolane, and reflux stirs 10h, to the solution clarification, reclaims solvent, and vacuum drying promptly gets prunol phospholipid complexes of the present invention.It is standby that complex was pulverized 80 mesh sieves.
Embodiment 5:
Embodiment 6:
Embodiment 7:
The preparation of prunol phospholipid complexes tablet
Get the prunol phospholipid complexes that embodiment 1 makes, add lactose, microcrystalline Cellulose and make filler in right amount, add low-substituted hydroxypropyl cellulose and make disintegrating agent in right amount, behind the mix homogeneously, make binding agent in right amount with 3% polyvidone alcoholic solution, the system soft material is crossed 18 mesh sieves and is granulated, dry, granulate adds 1% magnesium stearate and makes lubricant, behind the mix homogeneously, tabletting promptly gets tablet of the present invention.
Embodiment 8:
The preparation of prunol phospholipid complexes slow releasing tablet
Get the prunol phospholipid complexes that embodiment 2 makes, add hydroxypropyl emthylcellulose, sodium alginate and make blocker in right amount, add microcrystalline Cellulose and make filler in right amount, behind the mix homogeneously, make binding agent in right amount with 1% polyvidone alcoholic solution, the system soft material is crossed 18 mesh sieves and is granulated, dry, granulate adds 1% magnesium stearate and makes lubricant, behind the mix homogeneously, tabletting promptly gets slow releasing tablet of the present invention.
Embodiment 9:
The preparation of prunol phospholipid complexes capsule
Get the prunol phospholipid complexes that embodiment 3 makes, add starch, microcrystalline Cellulose is made filler in right amount, add polyvinylpolypyrrolidone and make disintegrating agent in right amount, behind the mix homogeneously, make binding agent in right amount with 3% polyvidone alcoholic solution, the system soft material, cross 24 mesh sieves and granulate drying, granulate, add 1% micropowder silica gel and make lubricant, behind the mix homogeneously, in common gelatine capsule, get capsule of the present invention with particles filled; In enteric coated capsule, get enteric coated capsule of the present invention with particles filled.
Embodiment 10:
The preparation of prunol phospholipid complexes slow releasing capsule
Getting the prunol phospholipid complexes that embodiment 4 makes, is binding agent with the polyvidone alcoholic solution, and the polyvidone alcoholic solution that will contain prunol phospholipid complexes loads on the sucrose blank pill in the heart by fluidization, makes the pastille microgranule; With the ethyl cellulose is coating material, and triethyl citrate is a plasticizer, and Polyethylene Glycol-400 is a porogen, and ethanol is the coating solvent, makes coating solution, with pastille microgranule coating solution coating, makes sustained-release microparticle; Sustained-release microparticle is filled in the suitable hungry area softgel shell, makes slow releasing capsule.
Embodiment 11:
The preparation of prunol phospholipid complexes suppository
Get the prunol phospholipid complexes that embodiment 4 makes, it is an amount of to add cocoa butter, behind the heating and melting, in the impouring suppository mold, pours out after the cooling, promptly gets suppository of the present invention.
Embodiment 12:
The preparation of prunol phospholipid complexes injection
Get the prunol phospholipid complexes that embodiment 1 makes, add pool Luo Samu and do solubilizing agent in right amount, add NaCl and regulate in right amount to wait and ooze, add the injection water and dissolve in right amount, fill is sterilized, and promptly gets injection of the present invention.
Embodiment 13:
The preparation of ursolic acid glycosides phosphatide complexes freeze-dried powder
Get the prunol phospholipid complexes that embodiment 2 makes, add pool Luo Samu and do solubilizing agent in right amount, make excipient in right amount, add the injection water and dissolve in right amount with mannitol, lactose, fill, lyophilizing, sterilization promptly gets freeze-dried powder of the present invention.
Embodiment 14:
The preparation of prunol phospholipid complexes compound tablet
Get the prunol phospholipid complexes that embodiment 3 makes, add oleanolic acid or oleanolic acid phospholipid compound and form the compound recipe composition in right amount, add starch, lactose, dextrin are made filler in right amount, add carboxymethyl starch sodium and make disintegrating agent in right amount, behind the mix homogeneously, make binding agent in right amount, the system soft material with 5% starch slurry, cross 18 mesh sieves and granulate drying, granulate, add 1% magnesium stearate and make lubricant, behind the mix homogeneously, tabletting promptly gets compound tablet of the present invention.
Embodiment 15:
A kind of embodiment 1 described prunol phospholipid complexes is as the application of the active component of pharmaceutical preparation.
Embodiment 14:
A kind of embodiment 1 described prunol phospholipid complexes is as the application of active ingredient in pharmaceutical.
Claims (7)
1. prunol phospholipid complexes, its composition comprises: ursolic acid and phospholipid is characterized in that: the weight ratio of described ursolic acid and phospholipid is 1: 0.1～25.
2. prunol phospholipid complexes according to claim 1 is characterized in that: described phospholipid is selected from least a in soybean phospholipid, lecithin, phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, the Phosphatidylserine.
3. the preparation method of claim 1 or 2 described prunol phospholipid complexes, it is characterized in that: take by weighing ursolic acid and phospholipid in proportion, join in the solvent, reflux to solution is clarified, and reclaims solvent, and drying is pulverized and is promptly got this product.
4. the preparation method of described prunol phospholipid complexes according to claim 3, it is characterized in that: described solvent is aprotonic solvents such as aromatic hydrocarbons, halogen derivatives and cyclic ethers, comprises at least a in acetone, ethanol, chloroform, oxolane, ethyl acetate, the methanol.
5. the preparation method of described prunol phospholipid complexes according to claim 3 is characterized in that: product of the present invention is made tablet or capsule or suppository or granule or injection or lyophilized injectable powder or compound tablet.
6. the described prunol phospholipid complexes of claim 1 is as the application of the active component of pharmaceutical preparation.
7. the described prunol phospholipid complexes of claim 1 is as the application of active ingredient in pharmaceutical.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100102284A CN101095684A (en) | 2006-06-28 | 2006-06-28 | Prunol phospholipid complexes and method for preparing the same and the application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100102284A CN101095684A (en) | 2006-06-28 | 2006-06-28 | Prunol phospholipid complexes and method for preparing the same and the application thereof |
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|---|---|
| CN101095684A true CN101095684A (en) | 2008-01-02 |
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ID=39009905
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| CNA2006100102284A Pending CN101095684A (en) | 2006-06-28 | 2006-06-28 | Prunol phospholipid complexes and method for preparing the same and the application thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104906044A (en) * | 2015-05-22 | 2015-09-16 | 广州中科蓝华生物科技有限公司 | Decoquinate nanometer preparation and preparing method and application thereof |
| IT201900020492A1 (en) * | 2019-11-06 | 2021-05-06 | Indena Spa | SOLID DISPERSIONS OF URSOLIC ACID SALTS |
-
2006
- 2006-06-28 CN CNA2006100102284A patent/CN101095684A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104906044A (en) * | 2015-05-22 | 2015-09-16 | 广州中科蓝华生物科技有限公司 | Decoquinate nanometer preparation and preparing method and application thereof |
| IT201900020492A1 (en) * | 2019-11-06 | 2021-05-06 | Indena Spa | SOLID DISPERSIONS OF URSOLIC ACID SALTS |
| WO2021089433A1 (en) | 2019-11-06 | 2021-05-14 | Indena S.P.A. | Solid dispersions of ursolic acid potassium salt |
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Open date: 20080102 |