CN101632650B - Self-microemulsifying semisolid skeleton capsule of daidzein and preparation method thereof - Google Patents
Self-microemulsifying semisolid skeleton capsule of daidzein and preparation method thereof Download PDFInfo
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- CN101632650B CN101632650B CN2009100123918A CN200910012391A CN101632650B CN 101632650 B CN101632650 B CN 101632650B CN 2009100123918 A CN2009100123918 A CN 2009100123918A CN 200910012391 A CN200910012391 A CN 200910012391A CN 101632650 B CN101632650 B CN 101632650B
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Abstract
The invention discloses a self-microemulsifying semisolid skeleton capsule of daidzein and a preparation method thereof. The invention is a uniform semisolid skeleton preparation prepared from the following components in percentage by weight: 0.5%-8% of daidzein, 10%-40% of oil phase, 30%-65% of emulsifying agent, 10%-30% of cosurfactant, 0-5% of weak base and the balance of semisolid skeleton carrier. In water bath with the temperature of 60 DEG C, daidzein is firstly dissolved in the cosurfactant, and then, the oil phase, the emulsifying agent, the weak base and the semisolid carrier are added for fusing to be evenly stirred, and the mixture is filled into a hard capsule after cooled slightly. The preparation method of the invention is simple, and the self-microemulsifying semisolid skeleton capsule is easy to be stored. The self-microemulsifying semisolid skeleton capsule of the invention absorbs water in gastrointestinal tracts after being taken orally and automatically is emulsified to form micro emulsion whose grain diameter is between 10-150nm, and the grain diameter thereof is even.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of self-microemulsifying semisolid skeleton capsule of daidzein and preparation method thereof.
Background technology
Daidzein (daidzein), have another name called daidzein, and structural formula is as follows:
Daidzein is the fabaceous effective ingredient such as Chinese medicament kudzu-vine root and Semen Glycines, now can manually synthesize.Through pharmacology and clinical research proof daidzein, have coronary artery dilator, femoral artery, cerebral arteries significantly, increase cerebral blood flow, strengthen the extremity blood circulation, reduce blood viscosity, weaken vascular resistance, reduce myocardial oxygen consumption, improve cardiac function, strengthen microcirculation, increase PBF, hemorheology is changed, blood pressure lowering, improve rhythm of the heart effect.Daidzein has estrogen-like effects, can be used for treatment and the conditioning of climacteric syndrome, can prevent generation and the development of women breast cancer, carcinoma of endometrium simultaneously.Clinical discovery has the aging action that causes of antagonism D-galactose, can strengthen ability of learning and memory, be used to preventing and treating cerebral ischemia, brain injury and cerebral infarction.Therefore, daidzein is that a kind of determined curative effect, clinical practice have the medicine that exploitation is worth extensively, very much.
Have not yet to see abroad about the research of daidzein, domestic commercially available daidzein preparation only limits to oral Tablet and Capsula.It is to use ethanol to be solvent for commercially available daidzein tablet and capsule, makes preparation after the employing solvent method is made into solid dispersion again.This method is due to an organic solvent, and cost is high, and production technology is more complicated.Daidzein belongs to isoflavonoid, whole molecule becomes plane, pile up closely, in addition, it is 7, 4 ' has two phenolic hydroxyl groups, can form intermolecular hydrogen bonding, therefore, arrangement due to lattice, the formation of hydrogen bond etc. makes the intermolecular force of daidzein large, and make its fusing point high, due to these construction featuress of himself, determined that there is a larger shortcoming and defect in daidzein, it is fat-soluble and the equal extreme difference of water solublity, in water, can't dissolve, thereby caused the oral formulations dissolution bad, thereby make bioavailability extremely low, affected the curative effect of existing Tablet and Capsula, limited its extensive use.Therefore be necessary to develop a kind of novel daidzein oral formulations, facilitate the patient.
Summary of the invention
The purpose of this invention is to provide a kind of self-microemulsifying semisolid skeleton capsule of daidzein and preparation method thereof, can overcome the shortcoming of prior art.The present invention adopts self-emulsifying microemulsion technology and semi-solid backbone technology to make the self-microemulsifying semisolid skeleton hard capsule, the spontaneous emulsification under aqueous medium exists of daidzein self-emulsifying microemulsion simmer down to semisolid at room temperature, said preparation forms the microemulsion that particle diameter is less than the oil-in-water type of 150nm.
The present invention is achieved through the following technical solutions:
The component of self-microemulsifying semisolid skeleton capsule of daidzein of the present invention and mass percentage content are:
Daidzein 0.5%-8%
Emulsifying agent 30%-65%
Co-emulsifier 10%-30%
Weak base 0%-5%
Semi-solid backbone carrier surplus
Described oil phase is selected from soybean oil, Oleum Arachidis hypogaeae semen, safflower oil, Semen Maydis oil, olive oil, medium chain triglyceride, the oleic acid polyethyleneglycol glyceride, oleic acid sorbic alcohol ester, olein: propylene glycol (90: 10), Oleum Cocois C8/C10 monoglyceride/dibasic acid esters, Oleum Cocois C8/C10 propylene glycol dibasic acid esters, Oleum Cocois C8/C10 triglyceride, olein, glyceryl linoleate, Polyethylene Glycol lauryl alcohol glyceride, the acetylizad monoglyceride of purification, purification Helianthi monoglyceride, ethyl oleate, a kind of or mixture in Ethyl linoleate.
Described emulsifying agent is selected from lecithin, polyoxyethylene sorbitan monolaurate, the polyethenoxy sorbitan monopalmitate, the polyethenoxy sorbitan monostearate, polyoxyethylene sorbitan monooleate dehydration, the polyethenoxy sorbitan trioleate, polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini, the C8/C10 polyethyleneglycol glyceride, polyoxyethylene (25) triolein, the polyethylene glycol glycerol monoesters, the polyethylene glycol glycerol dibasic acid esters, polyethylene glycol glycerol three esters, the medium chain monoglyceride, medium chain glycerol dibasic acid esters, a kind of or its mixture in PLURONICS F87.
Described co-emulsifier is selected from ethanol, 1,2-propylene glycol, molecular weight a kind of or its mixture in the Polyethylene Glycol of 200-600, ethylene glycol monomethyl ether, dimethyl Soquad, glycerol, n-butyl alcohol, n-octyl alcohol, n-heptanol.
Described weak base is selected from a kind of or its mixture in ethylenediamine, nicotiamide, acetamide, triethylamine, sodium bicarbonate, potassium bicarbonate etc.
Described semi-solid backbone carrier is selected from poloxamer, molecular weight a kind of or its mixture in the Polyethylene Glycol of 4000-6000, Myrj 52, polyoxyethylene sorbitan monostearate, C12-C18 fatty glyceride, Gelucire 44/14, monostearate polyethyleneglycol glyceride.
The preparation method of self-microemulsifying semisolid skeleton capsule of daidzein of the present invention: in 60 ℃ of water-baths, daidzein first is dissolved in to co-emulsifier, adds afterwards oil phase, emulsifying agent, weak base and semi-solid carrier, melting, stir, slightly cooling rear fill hard capsule.Preparation method of the present invention is simple, is easy to preserve.
Preparation of the present invention can add additives as required, as thickening agent, and antioxidant, antiseptic etc., be not subjected to the restriction of listed content.
Self-microemulsifying semisolid skeleton capsule of daidzein of the present invention can be applied and be treated in the aspect medicines such as hypertension, angina pectoris, myocardial infarction, cerebral thrombosis, sudden deafness, climacteric syndrome.
Compared with prior art, self-microemulsifying semisolid skeleton capsule of daidzein of the present invention, oral after, absorb moisture in gastrointestinal tract, spontaneous emulsification forms the microemulsion of particle between 10-150nm.Preparation of the present invention does not need special equipment, simple to operate, is easy to preserve, as a kind of novel pharmaceutical carrier, the present invention possesses stable in properties, absorbs the characteristics such as rapid, and improves the oral absorption of medicine, improve the bioavailability of medicine, reduce toxic and side effects, potential applicability in clinical practice is wide.
The accompanying drawing explanation:
Fig. 1 is the plasma concentration curve figure of the oral self-microemulsifying semisolid skeleton capsule of daidzein of Beagle dog and commercially available daidzein capsules
The specific embodiment
The following examples will be made a more detailed description to the present invention.But, should be understood that, protection scope of the present invention is not limited to following embodiment.
Embodiment 1
Prescription forms and percentage by weight is: daidzein 0.5%, olive oil 17.5%, lecithin 46%, glycerol 15%, poloxamer 22%.
In 60 ℃ of water-baths, daidzein first is dissolved in to glycerol, add afterwards olive oil, lecithin, poloxamer, melting, stir, slightly cooling rear fill hard capsule.
Prescription forms and percentage by weight is: daidzein 1%, ethyl oleate 20%, polyoxyethylene sorbitan monooleate dehydration 45%, ethanol 14%, poloxamer 20%.
Preparation method is with embodiment 1.
Embodiment 3
Prescription forms and percentage by weight is: daidzein 1.5%, Oleum Cocois C8/C10 monoglyceride/dibasic acid esters 10%, polyoxyethylene hydrogenated Oleum Ricini 40%, ethylene glycol monomethyl ether 18%, nicotiamide 0.5%, Gelucire 44/14 30%.
Preparation method is with embodiment 1.
Prescription forms and percentage by weight is: daidzein 2%, glyceryl linoleate 40%, polyoxyethylene hydrogenated Oleum Ricini 30%, 1,2-propylene glycol 10%, Myrj 52 18%.Preparation method is with embodiment 1.
Embodiment 5
Prescription forms and percentage by weight is: daidzein 2.5%, soybean oil 21%, polyethenoxy sorbitan trioleate 30%, n-heptanol 14%, ethylenediamine 2.5%, polyethylene glycol 6000 18%, Macrogol 4000 12%.
Preparation method is with embodiment 1.
Prescription forms and percentage by weight is: daidzein 3%, purification Helianthi monoglyceride 13%, polyethylene glycol glycerol monoesters 31%, polyethylene glycol glycerol dibasic acid esters 34%, n-butyl alcohol 10%, Macrogol 4000 9%.
Preparation method is with embodiment 1.
Embodiment 7
Prescription forms and percentage by weight is: daidzein 3%, Semen Maydis oil 12%, polyoxyethylene castor oil 20%, polyethenoxy sorbitan monostearate 25%, ethylene glycol monomethyl ether 30%, polyoxyethylene sorbitan monostearate 10%.
Preparation method is with embodiment 1.
Prescription forms and percentage by weight is: daidzein 4%, medium chain triglyceride 18%, polyoxyethylene castor oil 43%, ethanol 10%, acetamide 5%, poloxamer 10%, Myrj 52 10%.
Preparation method is with embodiment 1.
Embodiment 9
Prescription forms and percentage by weight is: daidzein 5%, Ethyl linoleate 17%, C8/C10 polyethyleneglycol glyceride 40%, 1,2-propylene glycol 18%, triethylamine 2%, Myrj 52 20%.
Preparation method is with embodiment 1.
Prescription forms and percentage by weight is: daidzein 6%, soybean oil 12%, glyceryl linoleate 18%, polyoxyethylene hydrogenated Oleum Ricini 34%, PEG400 12%, potassium bicarbonate 3%, Myrj 52 10%, Macrogol 4000 5%.
Embodiment 11
Prescription forms and percentage by weight is: daidzein 8%, oleic acid sorbic alcohol ester 15%, polyoxyethylene hydrogenated Oleum Ricini 25%, C8/C10 polyethyleneglycol glyceride 15%, 1,2-propylene glycol 10%, sodium bicarbonate 5%, Myrj 52 22%.
Preparation method is with embodiment 1.
Self-microemulsifying semisolid skeleton capsule of daidzein with embodiment 1.With reference to two appendix XC slurry methods of Chinese Pharmacopoeia version in 2005, measure the dissolution of capsule.Respectively with distilled water, 0.1molL
-1Hydrochloric acid, pH 6.8 phosphate buffer 500ml are solvent, and rotating speed is 100 ± 1rmin
-1, operation in accordance with the law, sampling in the time of 5,10,15,30,45,60 minutes respectively, ultraviolet spectrophotometer is measured daidzein concentration.
The release kilsyth basalt of self-microemulsifying semisolid skeleton capsule of daidzein of the present invention in different medium sees the following form.From result table, can find out, the dissolution medium of different pH value is on almost not impact of self-microemulsifying semisolid skeleton capsule of daidzein.
Embodiment 13
Self-microemulsifying semisolid skeleton capsule of daidzein with embodiment 2.With reference to two appendix XIX C of Chinese Pharmacopoeia version in 2005, investigate the stability of capsule.Comprise influence factor's test, accelerated test, long term test.
Influence factor's test: hot test permanent (40 ℃ ± 2 ℃), high wet test (75%), exposure experiments to light (4500Lx ± 500Lx), in the 0th, 5,10 days sampling and measuring, the results are shown in following table.
Hot test
High wet test
Exposure experiments to light
Accelerated test: sample thief is put in the temperature and humidity regulator of 40 ± 2 ℃ of temperature, humidity RH65% ± 5%, and in 0,1,2,3,6 the end of month sampling and measuring, the results are shown in following table.Result shows, self-microemulsifying semisolid skeleton capsule of daidzein is under the acceleration experiment condition of six months, and character, particle diameter, content and dissolution are all unchanged.
Long term test: sample thief is put at ambient temperature and is placed, and in 0,3, sampling and measuring in the time of 6,9 months, the results are shown in following table.Result shows, the essentially no variation of the every investigation index of self-microemulsifying semisolid skeleton capsule of daidzein illustrates that said preparation is stable, and content and capsule shells are without interaction.
Embodiment 14
In order to check the bioavailability of prepared self-microemulsifying semisolid skeleton capsule of daidzein, studied the relative bioavailability of the oral self-microemulsifying semisolid skeleton capsule of daidzein of Beagle dog and commercially available daidzein capsules.Result shows that the AUC of self-microemulsifying semisolid skeleton capsule of daidzein is 1346.23nghmL
-1, the AUC of commercially available daidzein capsules is 739.22nghmL
-1, relative bioavailability is 182.12%.Resulting drug-time curve as shown in Figure 1.This self-microemulsifying semisolid skeleton capsule is compared with commercially available capsule as seen from Figure 1, and the Cmax of self-microemulsifying semisolid skeleton capsule is higher, and it is close with peak time that medicine is eliminated time MRT.
Claims (2)
1. a self-microemulsifying semisolid skeleton capsule of daidzein, is characterized in that, component and mass percentage content are:
Daidzein 0.5%, olive oil 17.5%, lecithin 46%, glycerol 15%, poloxamer 22%;
And preparation as follows: in 60 ℃ of water-baths, daidzein first is dissolved in to glycerol, adds afterwards olive oil, lecithin, poloxamer, melting, stir, slightly cooling rear fill hard capsule.
2. a self-microemulsifying semisolid skeleton capsule of daidzein, is characterized in that, component and mass percentage content are:
Daidzein 1%, ethyl oleate 20%, polyoxyethylene sorbitan monooleate dehydration 45%, ethanol 14%, poloxamer 20%;
And preparation as follows: in 60 ℃ of water-baths, daidzein first is dissolved in to ethanol, adds afterwards ethyl oleate, polyoxyethylene sorbitan monooleate dehydration, poloxamer, melting, stir, slightly cooling rear fill hard capsule.
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| CN102114012B (en) * | 2009-12-31 | 2013-10-16 | 四川科伦药物研究有限公司 | Medicinal composition for treating heart cerebrovascular diseases as well as preparation method and application thereof |
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| WO2000069272A1 (en) * | 1999-05-18 | 2000-11-23 | Unilever N.V. | Fat containing products |
| CN100998864A (en) * | 2006-12-26 | 2007-07-18 | 沈阳药科大学 | Cyclosporin A semisolid skeleton capsule and its preparation method |
| CN101045045A (en) * | 2006-03-30 | 2007-10-03 | 中国科学院上海药物研究所 | Medicine composition containing soya bean aglycone and its preparing method |
| CN101204392A (en) * | 2007-12-13 | 2008-06-25 | 上海交通大学 | Self-emulsifying microemulsion daidzein oral liquid preparation composite and preparation method thereof |
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| JP2009514890A (en) * | 2005-11-07 | 2009-04-09 | マーティ・ファーマシューティカルズ・インク | Improved delivery of tetrahydrocannabinol |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000069272A1 (en) * | 1999-05-18 | 2000-11-23 | Unilever N.V. | Fat containing products |
| CN101045045A (en) * | 2006-03-30 | 2007-10-03 | 中国科学院上海药物研究所 | Medicine composition containing soya bean aglycone and its preparing method |
| CN100998864A (en) * | 2006-12-26 | 2007-07-18 | 沈阳药科大学 | Cyclosporin A semisolid skeleton capsule and its preparation method |
| CN101204392A (en) * | 2007-12-13 | 2008-06-25 | 上海交通大学 | Self-emulsifying microemulsion daidzein oral liquid preparation composite and preparation method thereof |
Non-Patent Citations (1)
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| 王丽君，等.环孢菌素A自乳化半固体骨架胶囊的制备.《沈阳药科大学学报》.2007,第24卷(第8期),第470-473、478页. * |
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