CN101632650A - 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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- CN101632650A CN101632650A CN200910012391A CN200910012391A CN101632650A CN 101632650 A CN101632650 A CN 101632650A CN 200910012391 A CN200910012391 A CN 200910012391A CN 200910012391 A CN200910012391 A CN 200910012391A CN 101632650 A CN101632650 A CN 101632650A
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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) has another name called daidzein, and structural formula is as follows:
Daidzein is fabaceous effective ingredient such as Chinese medicine Radix Puerariae and Semen Glycines, now can manually synthesize.Have coronary artery dilator, femoral artery, cerebral arteries significantly through pharmacology and clinical research proof daidzein, the cerebral blood flow increasing amount, strengthen the circulation of extremity blood flow, 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 the treatment and the conditioning of climacteric syndrome, can prevent the 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, is used to prevent and treat 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 capsule.Commercially available daidzein tablet and capsule its to be to use ethanol be solvent, make preparation again after adopting solvent method to be made into solid dispersion.This method is because with an organic solvent, the cost height, and also production technology is 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, because the arrangement of lattice, the formation of hydrogen bond etc. makes the intermolecular force of daidzein big, and make its fusing point height, because these construction featuress of himself have determined daidzein to have a bigger shortcoming and defect, it is fat-soluble and the equal extreme difference of water solublity, in water, can't dissolve, thereby cause the oral formulations dissolution bad, thereby make bioavailability extremely low, influence existing tablet and capsular curative effect, limited its extensive use.Therefore be necessary to develop a kind of novel daidzein oral formulations, make things convenient for 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 microemulsion of daidzein self-emulsifying microemulsion simmer down to semisolid at room temperature, said preparation spontaneous emulsification in the presence of aqueous medium formation particle diameter 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 the 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 the poloxamer 188.
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, the 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, lauric acid polyethyleneglycol glyceride, monostearate polyethyleneglycol glyceride.
The preparation method of self-microemulsifying semisolid skeleton capsule of daidzein of the present invention: in 60 ℃ of water-baths, daidzein is dissolved in co-emulsifier earlier, adds oil phase, emulsifying agent, weak base and semi-solid carrier afterwards, fusion, stir, slightly cooling back 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. are not subjected to the restriction of listed content.
Self-microemulsifying semisolid skeleton capsule of daidzein of the present invention can be used and treat 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 the gastrointestinal tract, spontaneous emulsification forms the microemulsion of particle between 10-150nm.Preparation of the present invention does not need special equipment, and is simple to operate, is easy to preserve, as a kind of novel medicament carrier, the present invention possesses stable in properties, absorbs characteristics such as rapid, and improves the oral absorption of medicine, improve bioavailability of medicament, reduce toxic and side effects, potential applicability in clinical practice is wide.
Description of drawings:
Fig. 1 is oral self-microemulsifying semisolid skeleton capsule of daidzein of Beagle dog and the capsular plasma concentration curve figure of commercially available daidzein
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 is formed and percentage by weight is: daidzein 0.5%, olive oil 17.5%, lecithin 46%, glycerol 15%, poloxamer 22%.
In 60 ℃ of water-baths, daidzein is dissolved in glycerol earlier, add olive oil, lecithin, poloxamer afterwards, fusion stirs, slightly cooling back fill hard capsule.
Prescription is formed 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 is formed 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%, lauric acid polyethyleneglycol glyceride 30%.
Preparation method is with embodiment 1.
Prescription is formed 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 is formed 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 is formed 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 is formed 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 is formed 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 is formed 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 is formed 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 is formed 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.Measure capsular dissolution with reference to two appendix XC of Chinese Pharmacopoeia version in 2005 slurry method.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 table the result as can be seen, the dissolution medium of different pH value is to almost not influence of self-microemulsifying semisolid skeleton capsule of daidzein.
Embodiment 13
Self-microemulsifying semisolid skeleton capsule of daidzein with embodiment 2.Investigate capsular stability with reference to two appendix XIX of Chinese Pharmacopoeia version in 2005 C.Comprise influence factor's test, accelerated test, long term test.
Influence factor's test: hot test perseverance (40 ℃ ± 2 ℃), high wet test (75%), exposure experiments to light (4500Lx ± 500Lx),, the results are shown in following table in the 0th, 5,10 day sampling and measuring.
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.The result shows, self-microemulsifying semisolid skeleton capsule of daidzein under six months accelerated tests condition, the equal no change of character, particle diameter, content and dissolution.
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.The 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 do not have interaction.
Embodiment 14
In order to check the bioavailability of prepared self-microemulsifying semisolid skeleton capsule of daidzein, oral self-microemulsifying semisolid skeleton capsule of daidzein of Beagle dog and the capsular relative bioavailability of commercially available daidzein have been studied.The result shows that the AUC of self-microemulsifying semisolid skeleton capsule of daidzein is 1346.23nghmL
-1, the capsular AUC of commercially available daidzein is 739.22nghmL
-1, relative bioavailability is 182.12%.Resulting drug-time curve is seen 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 (8)
1. self-microemulsifying semisolid skeleton capsule of daidzein, it is the semi-solid preparation of the homogeneous that formed by daidzein, oil phase, emulsifying agent, co-emulsifier, weak base, semi-solid carrier, it is characterized in that component and mass percentage content are:
Daidzein 0.5%-8%
Oil phase 10%-40%
Emulsifying agent 30%-65%
Co-emulsifier 10%-30%
Weak base 0%-5%
Semi-solid backbone carrier surplus.
2. according to the described self-microemulsifying semisolid skeleton capsule of daidzein of claim 1, it is characterized in that: described oil phase is selected from crude vegetal or through after structure of modification or the hydrolysis or a kind of or its mixture in the soybean oil after the improvement, Oleum Arachidis hypogaeae semen, safflower oil, Semen Maydis oil, olive oil; The medium chain fatty glyceride of chain length between C8-C10: 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 the Ethyl linoleate.
3. according to the described self-microemulsifying semisolid skeleton capsule of daidzein of claim 1, it is characterized in that: 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 the poloxamer 188.
4. according to the described self-microemulsifying semisolid skeleton capsule of daidzein of claim 1, it is characterized in that: 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.
5. according to the described self-microemulsifying semisolid skeleton capsule of daidzein of claim 1, it is characterized in that: 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, lauric acid polyethyleneglycol glyceride, monostearate polyethyleneglycol glyceride.
6. according to the described self-microemulsifying semisolid skeleton capsule of daidzein of claim 1, it is characterized in that: described weak base is selected from a kind of or its mixture in ethylenediamine, nicotiamide, acetamide, triethylamine, sodium bicarbonate, the potassium bicarbonate etc.
7. according to any one described self-microemulsifying semisolid skeleton capsule of daidzein of claim 1-7, it is characterized in that: described its particle diameter is even, and under the situation of stirring at room, spontaneous emulsification forms the microemulsion of particle size distribution between 10-150nm.
8. preparation method of self-microemulsifying semisolid skeleton capsule of daidzein according to claim 1, it is characterized in that: in 60 ℃ of water-baths, daidzein is dissolved in co-emulsifier earlier, add oil phase, emulsifying agent, weak base and semi-solid backbone carrier afterwards, fusion, stir, slightly cooling back fill hard capsule.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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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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Patent Citations (5)
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| WO2000069272A1 (en) * | 1999-05-18 | 2000-11-23 | Unilever N.V. | Fat containing products |
| US20070104741A1 (en) * | 2005-11-07 | 2007-05-10 | Murty Pharmaceuticals, Inc. | Delivery of tetrahydrocannabinol |
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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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