CN101095670B - Luteolin phospholipid complexes and method for preparing the same and application thereof - Google Patents
Luteolin phospholipid complexes and method for preparing the same and application thereof Download PDFInfo
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- CN101095670B CN101095670B CN2006100102265A CN200610010226A CN101095670B CN 101095670 B CN101095670 B CN 101095670B CN 2006100102265 A CN2006100102265 A CN 2006100102265A CN 200610010226 A CN200610010226 A CN 200610010226A CN 101095670 B CN101095670 B CN 101095670B
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Abstract
The invention relates to cyanidenon phosphatide compound, the preparation method and its applciaiton. The cyanidenon is gold yellow spicule that is separated from ethanol and contains one crystal water, it is slightly soluble in hot water, insoluble in cold water, and is not stable. So the biological utilization rate is low and medical effect is reduced and the parenteral administration is limited. The key is to increase its solubility, so the cyanidenon phosphatide compound is needed by market. The cyanidenon phosphatide compound comprises cyanidenon and phosphatide, with the weight proportion being 1: 0.2-25. 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 luteolin phospholipid complexes and preparation method thereof.
Background technology
Luteolin (Luteolin) is the effective ingredient of separating from Xinjiang Herba Dracocephali Integrifolii and Anhui Herba Ajugae, belongs to faintly acid kaempferol compounds, can manually synthesize at present.The chemistry of luteolin is called 3 ', 4 ', 5, and 7-kaempferol, chemical formula are C
15H
10O
6, molecular weight is 286.23.Structural formula is as follows:
Summary of the invention
The purpose of this invention is to provide a kind of luteolin phospholipid complexes and preparation method thereof, this luteolin phospholipid complexes is composited by luteolin and phospholipid.
Above-mentioned purpose realizes by following technical scheme:
Luteolin phospholipid complexes, be made up of luteolin, soybean phospholipid and lecithin, the weight ratio of described luteolin and phospholipid is 1: 3, gets luteolin 2g, soybean phospholipid 5g, lecithin 1g adds 40mL acetone and 20mL methanol, and reflux stirs 5h, clarify to solution, reclaim solvent, vacuum drying, complex were pulverized 80 mesh sieves.
The preparation method of described luteolin phospholipid complexes, described luteolin phospholipid complexes is made tablet, capsule, suppository, injection.
The preparation method of described luteolin phospholipid complexes, described luteolin phospholipid complexes is made slow releasing tablet, freeze-dried powder, compound tablet.
Described luteolin phospholipid complexes is as the active component of pharmaceutical preparation.
Described luteolin phospholipid complexes is as active ingredient in pharmaceutical.
This technical scheme has following beneficial effect:
1. the invention has the advantages that, is the luteolin phospholipid complexes that carrier is made with phospholipid, has improved the dissolubility of luteolin greatly, dissolution and stability, thus improved drug effect.
2. luteolin phospholipid complexes of the present invention can be made 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 luteolin crude drug and this product luteolin phospholipid complexes, 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, 150mm * 4.6mm); (1.7mL phosphoric acid adds in the 1000mL water, transfers pH to 4.0 ± 0.1 with triethylamine)-acetonitrile (75: 25) is a mobile phase with 0.3% phosphate buffer; Flow velocity is 1.0mL/min; The detection wavelength is 350nm; Sample size 20 μ L.Number of theoretical plate calculates by the luteolin peak and is not less than 3000, and the separating degree of luteolin peak and adjacent impurity peaks meets the requirements.
The preparation of standard curve
Get the about 10mg of luteolin reference substance, the accurate title, decide, and puts in the 25mL measuring bottle, adds dissolve with methanol and be diluted to scale, shakes up, and gets the stock solution that concentration is about 0.4mg/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 0.5% polyoxyethylene lauryl ether brij35 aqueous solution, shake up, make concentration and be about 2,4,8,16,24, the standard solution of 32 and 40 μ g/mL.By above-mentioned chromatographic condition, sample introduction 20 μ L write down chromatogram respectively, with sample size m (ng) peak area A are carried out linear regression, get linear equation: A=2604.8m-18063, r=0.9994.The result shows that luteolin is in 39.32～786.4ng scope, and sample size and peak area are good linear relationship.Standard curve is seen accompanying drawing 1.
The preparation of sample:
Get luteolin crude drug and this product luteolin phospholipid complexes sample, cross 80 mesh sieves respectively.Fine powder is respectively charged in the capsule, makes luteolin crude drug capsule and luteolin phospholipid complexes capsule.Every capsules contains luteolin 30mg approximately.
Dissolution method
Sample thief, according to dissolution method (two appendix XC second methods of Chinese Pharmacopoeia version in 2005), with 0.5% polyoxyethylene lauryl ether brij35 aqueous solution 900mL is dissolution medium, rotating speed is that per minute 50 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.
Modern pharmacological research proves, luteolin have sterilization, antiinflammatory, spasmolytic, eliminating phlegm and stopping cough, blood pressure lowering, enhancing coronary artery blood flow, anticancer, press down functions such as enzyme, antioxidation, diuresis function of gallbladder promoting.The present invention enlarges the clinical practice and the exploitation luteolin novel form of luteolin, and to making full use of luteolin, the new advantage of developing Chinese medicine in disease treatment is significant.
Luteolin is the isolated golden yellow spicule that contains a water of crystallization from ethanol, is slightly soluble in hot water, is insoluble in cold water, and stable inadequately, and this makes the interior bioavailability of luteolin 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 provided solution preferably.
The stripping curve of luteolin crude drug and phosphatide complexes is seen accompanying drawing 2～4.Dissolution determination is the result show, during 90min, the stripping quantity of luteolin crude drug is 27.8%, and the stripping quantity of luteolin phospholipid complexes is 72.0%, and obviously, the stripping quantity of luteolin phospholipid complexes is significantly improved than the stripping quantity of crude drug.
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 will strengthen pharmaceutically active 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 thinks to combine with hydrogen bond the structure more complicated.
Description of drawings:
Fig. 1 is the standard curve of luteolin;
Fig. 2 is the stripping curve of luteolin crude drug;
Fig. 3 is the stripping curve of luteolin phospholipid complexes;
Fig. 4 is the stripping curve comparison diagram of luteolin crude drug and luteolin phospholipid complexes.
The specific embodiment:
Embodiment 1:
Luteolin phospholipid complexes, its composition comprises: luteolin, soybean phospholipid, the weight ratio of described luteolin and soybean phospholipid is 1:2.5, and its preparation method is: get luteolin 2g, refining soybean phospholipid 5g, add 45mL ethanol, reflux stirs 6h, to the solution clarification, reclaims solvent, vacuum drying promptly gets luteolin phospholipid complexes of the present invention.It is standby that complex was pulverized 80 mesh sieves.
Embodiment 2:
Embodiment 1 described luteolin phospholipid complexes, its composition comprises: the weight ratio of luteolin, lecithin is 1:4, get luteolin 2g, lecithin 8g adds 50mL methanol, and reflux stirs 6h, clarify to solution, reclaim solvent, vacuum drying promptly gets luteolin phospholipid complexes of the present invention.It is standby that complex was pulverized 80 mesh sieves.
Embodiment 3:
Embodiment 1 described luteolin phospholipid complexes, its composition comprises: luteolin, lecithin, the weight ratio of described luteolin and lecithin is 1:2, gets luteolin 2g, lecithin 4g, add the 30mL chloroform, reflux stirs 8h, to the solution clarification, reclaims solvent, vacuum drying promptly gets luteolin phospholipid complexes of the present invention.It is standby that complex was pulverized 80 mesh sieves.
Embodiment 4:
Embodiment 1 described luteolin phospholipid complexes, its composition comprises: luteolin, phospholipid, and the weight ratio of described luteolin and phospholipid is 1:3, gets luteolin 2g, soybean phospholipid 5g, lecithin 1g adds 40mL acetone and 20mL methanol, and reflux stirs 5h, clarify to solution, reclaim solvent, vacuum drying promptly gets luteolin phospholipid complexes of the present invention.It is standby that complex was pulverized 80 mesh sieves.
Embodiment 5:
At least a in soybean phospholipid, lecithin, phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, Phosphatidylserine of embodiment 1～4 described luteolin phospholipid complexes, described phospholipid.
Embodiment 6:
The preparation method of embodiment 1～4 described luteolin 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.
Embodiment 7:
The preparation of luteolin phospholipid complexes tablet
Get the luteolin 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 luteolin phospholipid complexes slow releasing tablet
Get the luteolin 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 luteolin phospholipid complexes capsule
Get the luteolin 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 luteolin phospholipid complexes suppository
Get the luteolin 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 11:
The preparation of luteolin phospholipid complexes injection
Get the luteolin phospholipid complexes that embodiment 1 makes, add pool Luo Samu and do solubilizing agent in right amount, add NaCI 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 12:
The preparation of luteolin glycosides phosphatide complexes freeze-dried powder
Get the luteolin 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 13:
The preparation of luteolin phospholipid complexes compound tablet
Get the luteolin phospholipid complexes that embodiment 3 makes, add apigenin, hesperetin 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 14:
A kind of embodiment 1 described luteolin phospholipid complexes is as the application of the active component of pharmaceutical preparation.
Embodiment 15:
A kind of embodiment 1 or 2 described luteolin phospholipid complexes are as the application of active ingredient in pharmaceutical.
Claims (5)
1. luteolin phospholipid complexes, be made up of luteolin, soybean phospholipid and lecithin, it is characterized in that: the weight ratio of described luteolin and phospholipid is 1: 3, gets luteolin 2g, soybean phospholipid 5g, lecithin 1g adds 40mL acetone and 20mL methanol, and reflux stirs 5h, clarify to solution, reclaim solvent, vacuum drying, complex were pulverized 80 mesh sieves.
2. the preparation method of luteolin phospholipid complexes according to claim 1, it is characterized in that: described luteolin phospholipid complexes is made tablet, capsule, suppository, injection.
3. the preparation method of luteolin phospholipid complexes according to claim 1, it is characterized in that: described luteolin phospholipid complexes is made slow releasing tablet, freeze-dried powder, compound tablet.
4. the described luteolin phospholipid complexes of claim 1 is as the active component of pharmaceutical preparation.
5. the described luteolin phospholipid complexes of claim 1 is as active ingredient in pharmaceutical.
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| CN103211830B (en) * | 2012-01-18 | 2016-05-04 | 浙江中医药大学 | A kind of drug matching component that is used for the treatment of high blood pressure |
| WO2017061627A1 (en) * | 2015-10-09 | 2017-04-13 | 三栄源エフ・エフ・アイ株式会社 | Polyphenol-containing solid composition |
| CN106692979A (en) * | 2016-12-29 | 2017-05-24 | 广东药科大学 | Atorvastatin calcium and phospholipid compound and preparation method thereof |
| CN106581699B (en) * | 2016-12-30 | 2018-04-17 | 江西宜信堂医疗科技有限公司 | A kind of antibacterial type sterile solid medical supersonic coupled patch and preparation method thereof |
| CN108969483A (en) * | 2018-08-31 | 2018-12-11 | 西南交通大学 | A kind of luteolin nano-micelle and the preparation method and application thereof |
| CN113244176A (en) * | 2021-05-31 | 2021-08-13 | 桂林医学院 | Luteolin-arginine co-amorphous solid dispersion and preparation method thereof |
| CN113350515B (en) * | 2021-05-31 | 2023-03-17 | 浙江中医药大学 | Fisetin phospholipid complex and preparation method and application thereof |
| CN113663083A (en) * | 2021-08-16 | 2021-11-19 | 重庆第二师范学院 | Fisetin phospholipid complex, weight-losing medicine/health food and application thereof |
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