CN102274274B - 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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- CN102274274B CN102274274B CN2011102238330A CN201110223833A CN102274274B CN 102274274 B CN102274274 B CN 102274274B CN 2011102238330 A CN2011102238330 A CN 2011102238330A CN 201110223833 A CN201110223833 A CN 201110223833A CN 102274274 B CN102274274 B CN 102274274B
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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 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 the flavone compounds such as puerarin, hydroxyl puerarin, methoxy puerarin, daidzin, also has triterpenes, Coumarins etc.Radix Puerariae flavone is mainly used in treating cardio-cerebralvascular diseases at present, as hypertension, the diseases such as hyperlipidemia, migraine, coronary heart disease, myocardial infarction, angina pectoris, retinal artery occlusion, the retinal vein occlusion, sudden deafness, substitute the Chinese medicament kudzu-vine root in Chinese patent medicine.Radix Puerariae flavone can improve microcirculation, 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 antithromboxin, improve the effect of high density lipoprotein, vasospasm and reduction platelet aggregation.Puerarin content in Radix Puerariae flavone is larger, chemistry 4,7-dihydroxy by name-8 β-D glucone isoflavone.The pharmaceutical research puerarin has the enhancing myocardial contraction, the protecting myocardial cell effect; Blood vessel dilating, reduce blood pressure, improve microcirculation; The protection erythrocyte deformability, strengthen the hemopoietic system function; Antiplatelet aggregation, increase fibrinolytic, reduces blood viscosity; Nephritis, nephropathy renal failure model all there is protective effect; Nonspecific immunity, humoral immunization, cellular immunization there is obvious 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, Yufeng Ningxin Capsules etc., the problem that exists is that bioavailability is low, daily requirement is repeatedly taken in a large number, compliance is poor, needs a kind of novel Radix Puerariae flavone oral formulations on market, facilitates the patient to use.
Micropill (pellet) is a kind of dosage decentralized; diameter is generally the spherical of 0.5～1.5mm or oral formulations that class is spherical; add controlled slowly releasing adjuncts and can make slow-release micro-pill; wrapping enteric coating is enteric coated micropill; can pack in 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 rear extensively, be evenly distributed in gastrointestinal tract, large at gastrointestinal surface distributed area, thus improve bioavailability, reduce or eliminate medicine gastrointestinal is stimulated; 2. pellet is in the impact 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 on the not serious impact 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 meet different needs; 5. the compound capsule that is comprised of different micropills, have stability preferably, reduces the interaction between medicine; 6. the micropill mobility is better, is conducive to preparation packing or further molding.
Self-emulsifying drug delivery system (self-emulsifying drug delivery systems, SEDDS) formed by oil phase, surfactant and cosurfactant, take rear 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 poor medicine of mucosa permeability is made after the w/o microemulsion and can be improved mucosa and see through ability, improve the intestinal absorption of medicine.With emulsion or microemulsion phase ratio, the SEDDS physical property is more reordered, and is easy to preparation.The good microemulsion of oral rear formation, so its concentrated breast of precursor that is otherwise known as.SEDDS compares with capsule with traditional tablet, and gastric emptying speed is fast, and medicine can absorb fast., for good self-emulsifying drug delivery systems, can form the emulsion droplet that includes dissolved substance while with gastro-intestinal Fluid, contacting.Therefore, the medicine in the microemulsion emulsion droplet has larger surface area and medicine can maintain dissolved state in intestinal, thereby can disperse better permeate through cell membranes.
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 pharmaceutically acceptable adjuvant.
Preferably, described pharmaceutically acceptable adjuvant for hypromellose and microcrystalline Cellulose in mass ratio example mix the mixture that obtains for 6:1.
Preferably, described oil phase is Oleum Ricini, soybean oil, the mixture of one or more in isopropyl myristate and oleic acid polyethyleneglycol glyceride.
Preferably, described emulsifying agent is Tween 80, the mixture of one or more in polyoxyethylene castor oil and sorbester p17.
Preferably, described co-emulsifier is 1,2-PD, ethanol, the mixture of one or more in PEG400 and 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 method for preparing the oral pellet preparations compositions of Radix Puerariae flavone of aforementioned self-microemulsion, comprises the steps: emulsifying agent and co-emulsifier mix homogeneously, add again afterwards oil phase and Radix Puerariae flavone, dilution, stir, and obtains.
Preferably, described preparation method comprises the steps: emulsifying agent and co-emulsifier mix homogeneously, then adds oil phase and Radix Puerariae flavone, add afterwards the adhesive solution that stirs to obtain, pharmaceutically acceptable adjuvant is added in solution, and utilization is extruded spheronizator and is extruded, and obtains 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 facilitates easy operating, can promote medicine absorption in vivo, improve bioavailability, also improve patient's compliance and therapeutic effect.
Description of drawings
Fig. 1 is Radix Puerariae flavone self-microemulsion oral micropill particle size distribution;
Fig. 2 is Radix Puerariae flavone self-microemulsion oral micropill scanning electron microscope (SEM) photograph;
Fig. 3 is 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 in any form the present invention.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 is in Table 1.The preparation method of following examples compositions is: measure emulsifying agent and co-emulsifier, and mix homogeneously, then add oil phase and Radix Puerariae flavone, and mix homogeneously, add 1000 times of distilled water dilutings, and 100rpm magnetic agitation under 25 ℃ of conditions, obtain.Fig. 1 is Radix Puerariae flavone self-microemulsion oral micropill particle size distribution; Fig. 2 is Radix Puerariae flavone self-microemulsion oral micropill scanning electron microscope (SEM) photograph; The compositions mean diameter of embodiment preparation is at 30～80nm, and centralized particle diameter meets in pharmaceutics the requirement to microemulsion formulation; Less particle diameter makes the medicine degree of scatter higher, has improved bioavailability.
Table 1
Embodiment 5～7
The component of embodiment 5～7 compositionss is in Table 2.The preparation method of following examples compositions is: measure emulsifying agent and co-emulsifier, and mix homogeneously, then add oil phase and Radix Puerariae flavone, and mix homogeneously, add 1000 times of distilled water dilutings, and 100rpm magnetic agitation under 25 ℃ of conditions, obtain.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, meet in pharmaceutics the requirement to microemulsion formulation; Less particle diameter makes the medicine degree of scatter higher, has improved bioavailability.
Table 2
Embodiment 8
The component of the present embodiment compound is in Table 3, the preparation method of the present embodiment compositions is: with polyoxyethylene castor oil and 1, the 2-mixed with propylene glycol is even, add again Oleum Ricini and Radix Puerariae flavone, adding afterwards volume fraction is the aqueous solution of 75% ethanol, and the solution that stirs to obtain, add hypromellose in solution for 6:1 mixes in mass ratio with microcrystalline Cellulose, utilization is extruded spheronizator and is extruded, and obtains pellet composition.The compositions mean diameter of the present embodiment preparation is at 30～80nm, and centralized particle diameter meets in pharmaceutics the requirement to microemulsion formulation; Less particle diameter 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, employing turns basket method (50rpm), take pH6.8 phosphate as solvent, 37 ± 0.5 ℃ of temperature, carry out dissolution test, cumulative release percentage rate and time are carried out curve fitting, and release profiles is seen Fig. 3, and this prescription meets 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, 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, before experiment, fasting is 12 hours, is divided at random three groups.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, and after processing, high performance liquid chromatogram detects the content of Radix Puerariae flavone in blood plasma.Calculate the Radix Puerariae flavone plasma drug level, draw blood drug level-time graph (Fig. 4).Pharmacokinetic parameters is in Table 4.As seen, in the present invention, the oral micropill of self emulsifying Radix Puerariae flavone is compared with ordinary tablet, 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 facilitates easy operating, can promote medicine absorption in vivo, improve bioavailability, also improve patient's compliance and therapeutic effect.
Claims (1)
1. the oral pellet preparations compositions of the Radix Puerariae flavone of a self-microemulsion, be characterised in that, comprises each component of following quality percentage composition:
Surplus is adjuvant, described adjuvant be hypromellose and microcrystalline Cellulose in mass ratio example mix for 6:1;
The preparation method of described compositions comprises the steps: polyoxyethylene castor oil and 1, the 2-mixed with propylene glycol is even, add again Oleum Ricini and Radix Puerariae flavone, adding afterwards volume fraction is the aqueous solution of 75% ethanol, solution stirs to obtain, hypromellose is added in solution for 6:1 mixes in mass ratio with microcrystalline Cellulose, and utilization is extruded spheronizator and is extruded, and obtains pellet composition; The microemulsion particle diameter of the oral pellet preparations compositions of the Radix Puerariae flavone of described self-microemulsion is 30～80nm.
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| 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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| 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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