CN102274274A - Self-microemulsifiable kudzu root flavone oral micro-pill composition and preparation method thereof - Google Patents
Self-microemulsifiable kudzu root flavone oral micro-pill composition and preparation method thereof Download PDFInfo
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- CN102274274A CN102274274A CN 201110223833 CN201110223833A CN102274274A CN 102274274 A CN102274274 A CN 102274274A CN 201110223833 CN201110223833 CN 201110223833 CN 201110223833 A CN201110223833 A CN 201110223833A CN 102274274 A CN102274274 A CN 102274274A
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Abstract
The invention relates to a self-microemulsifiable kudzu root flavone oral micro-pill composition, belonging to the technical field of preparation of medicines. The self-microemulsifiable kudzu root flavone oral micro-pill composition comprises the following components in percentage by mass: 0.1-15% of kudzu root flavone, 5-30% of oil phase, 12.5-75% of emulsifier and 7.5-45% of coemulsifier. The preparation method comprises the following steps: evenly mixing the emulsifier and coemulsifier, adding the oil phase and kudzu root flavone, diluting, and uniformly stirring to obtain the self-microemulsifiable kudzu root flavone oral micro-pill composition. The self-microemulsifiable kudzu root-flavone oral micro-pill composition provided by the invention has the characteristics of the self-microemulsification medicine release system and the slow release micro-pill preparation; and the formed microemulsion is transparent and stable, has uniform particle size (ranging from 30nm to 80nm), and thus, is a novel preparation formulation which is efficient, convenient and easy to operate. The self-microemulsifiable kudzu root flavone oral micro-pill composition can promote the absorption of the medicines in vivo, improve the bioavailability and enhance the compliance and treatment effect of the patient.
Description
Technical field
The present invention relates to oral formulations mixture of a kind of field of medicine preparing technology and preparation method thereof, specifically be a kind of can
Oral pellet composition of Radix Puerariae flavone of self-emulsifying microemulsion and preparation method thereof.
Background technology
The Radix Puerariae flavone Main Ingredients and Appearance includes flavone compounds such as puerarin, hydroxyl puerarin, methoxy puerarin, daidzin, also has triterpenes, Coumarins etc.Radix Puerariae flavone is mainly used in the treatment cardio-cerebralvascular diseases at present, as hypertension, diseases such as hyperlipidemia, migraine, coronary heart disease, myocardial infarction, angina pectoris, retinal artery occlusion, the retinal vein occlusion, sudden deafness substitute the Chinese medicine Radix Puerariae in the Chinese patent medicine.Radix Puerariae flavone can microcirculation improvement, and coronary artery dilator increases brain and coronary artery blood flow, decreased heart rate, reduce the myocardial oxygen consumption index and improve the metabolism of ischemic myocardium, also have the antithrombotic element, improve the effect of high density lipoprotein, vasospasm and reduction platelet aggregation.Puerarin content in Radix Puerariae flavone is bigger, and chemistry is called 4,7-dihydroxy-8 β-D glucone isoflavone.The pharmaceutical research puerarin has the enhancing myocardial contraction, the protecting myocardial cell effect; Blood vessel dilating, bring high blood pressure down, microcirculation improvement; The protection erythrocyte deformability strengthens the hemopoietic system function; Antiplatelet aggregation increases fibrinolytic, reduces blood viscosity; Nephritis, nephropathy renal failure model all there is protective effect; Nonspecific immunity, humoral immunization, cellular immunization there is tangible regulating action.
The Radix Puerariae flavone poorly water-soluble, commercially available Radix Puerariae flavone preparation mainly contains oral formulations at present, as yufeng ningxin tablets, yufeng ningxin pian, Yufengningxin granule, Yufengningxin capsule etc., the problem that exists is that bioavailability is low, daily requirement is repeatedly taken in a large number, compliance is relatively poor, needs a kind of novel Radix Puerariae flavone oral formulations on the market, makes things convenient for the patient to use.
Micropill (pellet) is a kind of dosage decentralized; diameter is generally sphere or the spheric oral formulations of class of 0.5～1.5mm; add controlled slowly releasing adjuncts and can make slow-release micro-pill; wrapping enteric coating is enteric coated micropill; can pack in the capsulae vacuus or be pressed into tablet and use, also can be directly as granule or slow controlled release granule.The advantage of micropill is: 1. take the back extensively, be evenly distributed in gastrointestinal tract, big at gastrointestinal surface distributed area, thus improve bioavailability, reduce or eliminate medicine gastrointestinal is stimulated; 2. pellet is in the influence of the gastrointestinal transhipment unable to take food thing conveying rhythm and pace of moving things, gastric emptying; 3. the release rule of slow controlled release micro pill is than the tablet favorable reproducibility, and indivedual micropills are to the not serious influence of the drug release behavior of whole preparation; 4. the micropill of different rate of releasing drug can be dressed up capsule in proportion, to satisfy different needs; 5. the compound capsule of being made up of different micropills has stability preferably, reduces the interaction between the medicine; 6. micropill is better mobile, helps preparation packing or further molding.
Self-emulsifying drug delivery system (self-emulsifying drug delivery systems, SEDDS) form by oil phase, surfactant and cosurfactant, take the back under physiology body temperature, gastrointestinal motility effect, meet water or gastro-intestinal Fluid and be dispersed into the microemulsion of particle diameter below 500nm, for some good water solubility and the relatively poor medicine of mucosa permeability is made and can be improved mucosa behind the w/o microemulsion and see through ability, improve the intestinal absorption of medicine.Compare with common Emulsion or microemulsion, the SEDDS physical property is more reordered, and is easy to preparation.Oral back forms good microemulsion, so its precursor that is otherwise known as concentrates breast.SEDDS compares with capsule with traditional tablet, and gastric emptying speed is fast, but the medicine fast Absorption.For good self-emulsifying drug delivery systems, can form the emulsion droplet that includes dissolved substance when contacting with gastro-intestinal Fluid.Therefore, the medicine in the microemulsion emulsion droplet has bigger surface area and medicine can maintain dissolved state in intestinal, thereby can disperse permeate through cell membranes better.
Summary of the invention
The present invention is directed to the deficiency that prior art exists, a kind of oral pellet composition of Radix Puerariae flavone of self-microemulsion is provided
And preparation method thereof, preparation manipulation is simple, and the compositions particle size distribution that obtains is evenly and be easy to preserve.
The present invention is achieved by the following technical solutions,
First aspect the present invention relates to a kind of oral pellet preparations compositions of Radix Puerariae flavone of self-microemulsion, comprises each component of following quality percentage composition:
Radix Puerariae flavone 0.1～15%
Oil phase 5～30%
Emulsifying agent 12.5～75%
Co-emulsifier 7.5～45%.
Preferably, described compositions also comprises acceptable accessories.
Preferably, described acceptable accessories is for being that 6:1 mixes the mixture that obtains with hypromellose and microcrystalline Cellulose by mass ratio.
Preferably, described oil phase is an Oleum Ricini, soybean oil, the mixture of one or more in isopropyl myristate and the oleic acid polyethyleneglycol glyceride.
Preferably, described emulsifying agent is a Tween 80, the mixture of one or more in polyoxyethylene castor oil and the sorbester p17.
Preferably, described co-emulsifier is 1,2-propylene glycol, ethanol, the mixture of one or more in PEG400 and the glycerol.
Preferably, the microemulsion particle diameter of the oral pellet preparations compositions of the Radix Puerariae flavone of described self-microemulsion is 30～80nm.
Second aspect the invention still further relates to a kind of oral pellet preparations method for compositions of Radix Puerariae flavone for preparing aforementioned self-microemulsion, comprises the steps: emulsifying agent and co-emulsifier mix homogeneously, add oil phase and Radix Puerariae flavone afterwards again, dilution stirs, promptly.
Preferably, described preparation method comprises the steps: emulsifying agent and co-emulsifier mix homogeneously are added oil phase and Radix Puerariae flavone again, add afterwards adhesive stir solution, acceptable accessories is added in the solution, and utilization is extruded spheronizator and is extruded, and gets pellet composition.
Further preferably, described adhesive is that volume fraction is 75% alcoholic solution.
The present invention has following beneficial effect: self-emulsifying microemulsion pueraria flavone micro pill compositions of the present invention is taken into account the characteristics of self-micro-emulsification medicine-releasing system and sustained-release pellet preparation, formed microemulsion transparent and stable, particle diameter is even, be distributed in 30～80nm, it is a kind of novel dosage form that efficiently makes things convenient for easy operating, can promote the medicine absorption in vivo, improve bioavailability, also improve patient's compliance and therapeutic effect.
Description of drawings
Fig. 1 is a Radix Puerariae flavone self-microemulsion oral micropill particle size distribution;
Fig. 2 is a Radix Puerariae flavone self-microemulsion oral micropill sem photograph;
Fig. 3 is a Radix Puerariae flavone self-microemulsion oral micropill release in vitro curve;
Fig. 4 is that Radix Puerariae flavone self-microemulsion oral micropill Beagle dog body giving drugs into nose is for kinetics blood drug level-time graph.
The specific embodiment
The present invention is described in detail below in conjunction with specific embodiment.Following examples will help those skilled in the art further to understand the present invention, but not limit the present invention in any form.Should be pointed out that to those skilled in the art, without departing from the inventive concept of the premise, can also make some distortion and improvement.These all belong to protection scope of the present invention.
Embodiment 1～4
The component of embodiment 1～4 compositions sees Table 1.Following examples preparation of compositions method is: measure emulsifying agent and co-emulsifier, mix homogeneously adds oil phase and Radix Puerariae flavone again, and mix homogeneously adds 1000 times of distilled water dilutings, 100rpm magnetic agitation under 25 ℃ of conditions, promptly.Fig. 1 is a Radix Puerariae flavone self-microemulsion oral micropill particle size distribution; Fig. 2 is a Radix Puerariae flavone self-microemulsion oral micropill sem photograph; The compositions mean diameter of embodiment preparation is at 30～80nm, and centralized particle diameter meets in the pharmaceutics requirement to microemulsion formulation; Smaller particle size makes the medicine degree of scatter higher, has improved bioavailability.
Table 1
Embodiment 5～7
The component of embodiment 5～7 compositionss sees Table 2.Following examples preparation of compositions method is: measure emulsifying agent and co-emulsifier, mix homogeneously adds oil phase and Radix Puerariae flavone again, and mix homogeneously adds 1000 times of distilled water dilutings, 100rpm magnetic agitation under 25 ℃ of conditions, promptly.The compositions mean diameter of embodiment preparation is at 30～80nm, and wherein, the mean diameter of embodiment 5 is 40.1 nm, and the mean diameter of embodiment 6 and 7 compositionss is 30.6 nm.Centralized particle diameter meets in the pharmaceutics requirement to microemulsion formulation; Smaller particle size makes the medicine degree of scatter higher, has improved bioavailability.
Table 2
The component of present embodiment compound sees Table 3, present embodiment preparation of compositions method is: with polyoxyethylene castor oil and 1, the 2-mixed with propylene glycol is even, add Oleum Ricini and Radix Puerariae flavone again, add volume fraction afterwards and be 75% alcoholic acid aqueous solution, stir solution, be that 6:1 mixes and adds in the solution with hypromellose and microcrystalline Cellulose by mass ratio, utilization is extruded spheronizator and is extruded, and gets pellet composition.The compositions mean diameter of present embodiment preparation is at 30～80nm, and centralized particle diameter meets in the pharmaceutics requirement to microemulsion formulation; Smaller particle size makes the medicine degree of scatter higher, has improved bioavailability.
Table 3
The extracorporeal releasing experiment of embodiment 9, the oral micropill of self-microemulsion Radix Puerariae flavone
Get Radix Puerariae flavone self-microemulsion oral micropill, adopt the basket method (50rpm) of changeing, with pH6.8 phosphate is solvent, 37 ± 0.5 ℃ of temperature, carry out the release test, cumulative release percentage rate and time are carried out curve fitting, and release profiles is seen Fig. 3, and this prescription satisfies 1,4,8, the release of 10h should be respectively 20～40%, 40～60%, 60～80%, the designing requirement more than 90%.With the Higuchi equation Radix Puerariae flavone slow-release micro-pill release profiles is carried out match, the result is Q=35.916T1/2-11.705, r=0.991.From the release in vitro curve, to compare with the street drug yufeng ningxin tablets, yufeng ningxin pian, the oral micropill of self-emulsifying microemulsion Radix Puerariae flavone discharges slowly, and is stable.
Embodiment 10, the oral micropill Beagle of self-emulsifying microemulsion Radix Puerariae flavone dog body giving drugs into nose are for dynamic experiment
Get 6 of Beagle dogs, fasting is 12 hours before the experiment, is divided into three groups at random.Oral administration group dosage is 40mg/ only (SMEDDS) and 40mg/ (yufeng ningxin tablets, yufeng ningxin pian), after administration 10,20,30,45,60,90,120,150,180,240,300,360,420,480,540min gets blood 1mL, put into centrifuge tube, 10000rpm is centrifugal, and 10min gets supernatant, handles the content that the back high performance liquid chromatogram detects Radix Puerariae flavone in the blood plasma.Calculate the Radix Puerariae flavone plasma drug level, draw blood drug level-time graph (Fig. 4).Pharmacokinetic parameters sees Table 4.As seen, the oral micropill of self emulsifying Radix Puerariae flavone is compared with ordinary tablet among the present invention, and peak time and mean residence time be significant prolongation all, and AUC obviously increases, and slow releasing function is obvious.Relative bioavailability is 259.70%, and the bioavailability of Radix Puerariae flavone self-microemulsion slow-release micro-pill is 2.5 times of conventional tablet.
The pharmacokinetic parameters of table 4 Beagle dog intravenous injection and oral administration
In sum, self-emulsifying microemulsion pueraria flavone micro pill compositions of the present invention is taken into account the characteristics of self-micro-emulsification medicine-releasing system and sustained-release pellet preparation, formed microemulsion transparent and stable, particle diameter is even, being distributed in 30～80nm, is a kind of novel dosage form that efficiently makes things convenient for easy operating, can promote the medicine absorption in vivo, improve bioavailability, also improve patient's compliance and therapeutic effect.
Claims (10)
1. the oral pellet preparations compositions of the Radix Puerariae flavone of a self-microemulsion is characterised in that, comprises each component of following quality percentage composition:
Radix Puerariae flavone 0.1～15%
Oil phase 5～30%
Emulsifying agent 12.5～75%
Co-emulsifier 7.5～45%.
2. the oral pellet preparations compositions of the Radix Puerariae flavone of self-microemulsion according to claim 1 is characterized in that described compositions also comprises acceptable accessories.
3. preparation method as claimed in claim 2 is characterized in that, described acceptable accessories is for being that 6:1 mixes the mixture that obtains with hypromellose and microcrystalline Cellulose by mass ratio.
4. the oral pellet preparations compositions of the Radix Puerariae flavone of self-microemulsion according to claim 1 is characterized in that,
Described oil phase is an Oleum Ricini, soybean oil, the mixture of one or more in isopropyl myristate and the oleic acid polyethyleneglycol glyceride.
5. the oral pellet preparations compositions of the Radix Puerariae flavone of self-microemulsion according to claim 1 is characterized in that, described emulsifying agent is a Tween 80, the mixture of one or more in polyoxyethylene castor oil and the sorbester p17.
6. the oral pellet preparations compositions of the Radix Puerariae flavone of self-microemulsion according to claim 1 is characterized in that, described co-emulsifier is 1,2-propylene glycol, ethanol, the mixture of one or more in PEG400 and the glycerol.
7. the oral pellet preparations compositions of the Radix Puerariae flavone of self-microemulsion according to claim 1 is characterized in that, the microemulsion particle diameter of the oral pellet preparations compositions of the Radix Puerariae flavone of described self-microemulsion is 30～80nm.
8. the oral pellet preparations method for compositions of Radix Puerariae flavone for preparing each described self-microemulsion of claim 1-7 is characterized in that, comprises the steps: emulsifying agent and co-emulsifier mix homogeneously, add oil phase and Radix Puerariae flavone afterwards again, dilution stirs, promptly.
9. preparation method according to claim 8, it is characterized in that, comprise the steps: emulsifying agent and co-emulsifier mix homogeneously, add oil phase and Radix Puerariae flavone again, add afterwards adhesive stir solution, acceptable accessories is added in the solution, and utilization is extruded spheronizator and is extruded, and gets pellet composition.
10. preparation method according to claim 9 is characterized in that, described adhesive is that volume fraction is 75% alcoholic solution.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102552491A (en) * | 2012-01-11 | 2012-07-11 | 福建中医药大学 | Dai-dai fruit total flavonoid self-microemulsion micro pill and preparation method thereof |
| CN115624526A (en) * | 2022-10-19 | 2023-01-20 | 江苏集萃新型药物制剂技术研究所有限公司 | Lipid-lowering liver-protecting biphasic composition |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1457795A (en) * | 2003-06-02 | 2003-11-26 | 沈阳药科大学 | Pueraria root flavone self-microemulsified soft capsule and its preparing method |
| CN101978977A (en) * | 2010-11-07 | 2011-02-23 | 上海交通大学 | Self-emulsifying brucea javanica oil oral preparation composition and preparation method thereof |
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- 2011-08-05 CN CN2011102238330A patent/CN102274274B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1457795A (en) * | 2003-06-02 | 2003-11-26 | 沈阳药科大学 | Pueraria root flavone self-microemulsified soft capsule and its preparing method |
| CN101978977A (en) * | 2010-11-07 | 2011-02-23 | 上海交通大学 | Self-emulsifying brucea javanica oil oral preparation composition and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102552491A (en) * | 2012-01-11 | 2012-07-11 | 福建中医药大学 | Dai-dai fruit total flavonoid self-microemulsion micro pill and preparation method thereof |
| CN102552491B (en) * | 2012-01-11 | 2013-12-18 | 福建中医药大学 | Dai-dai fruit total flavonoid self-microemulsion micro pill and preparation method thereof |
| CN115624526A (en) * | 2022-10-19 | 2023-01-20 | 江苏集萃新型药物制剂技术研究所有限公司 | Lipid-lowering liver-protecting biphasic composition |
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Granted publication date: 20131120 Termination date: 20170805 |