CN102319438A - The preparation and preparation method thereof and the purposes that comprise the genistein clathrate - Google Patents
The preparation and preparation method thereof and the purposes that comprise the genistein clathrate Download PDFInfo
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- CN102319438A CN102319438A CN 201110235014 CN201110235014A CN102319438A CN 102319438 A CN102319438 A CN 102319438A CN 201110235014 CN201110235014 CN 201110235014 CN 201110235014 A CN201110235014 A CN 201110235014A CN 102319438 A CN102319438 A CN 102319438A
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Abstract
The invention discloses a kind of genistein clathrate, comprise preparation of genistein clathrate and preparation method thereof.Inclusion agents preferred cyclodextrin of the present invention or cyclodextrin derivative.The genistein clathrate is counted with weight portion: genistein 1-100 part, cyclodextrin or cyclodextrin derivative 5-800 part.The present invention is through cyclodextrin or the cyclodextrin derivative clathration to genistein; Improved the water solublity of genistein; The various dosage forms that this clathrate can further prepare clinically to be suitable for, and improved the bioavailability of genistein greatly.Genistein clathrate provided by the invention and preparation thereof have good preventing and therapeutic effect for osteoporosis, climacteric syndrome, tumor and cardio-cerebrovascular diseases.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation thereof, specifically, the present invention relates to a kind of genistein clathrate, comprise the preparation of genistein clathrate, belong to field of medicaments.
Background technology
Genistein is dissolved in DMSO and ethanol, and water-soluble hardly, structure is following:
Genistein is the isoflavonoid that derives from bean and dentation plant, and chemistry is called 4 ', 5, the 7-trihydroxy-isoflavone.Be the main active ingredient of soybean isoflavone, have estrogen-like effects in the metabolism in vivo, be called as plant estrogen class medicine.Genistein has multiple pharmacological effect and biological activitys such as the early atherosclerosis of preventing and chronic angiopathy, antitumor, climacteric syndrome.Genistein is the inhibitor of powerful LCK and topoisomerase, through the regulation and control to oncogene, thereby realizes that multipath suppresses growth of tumor and transfer.Its anticancer mechanism is unique, through growth, diffusion, the transfer of the direct anticancer of regulation and control oncogene; Genistein antitumor action mechanism comprises seven approach: CKIs tryrosinase phosphorylation; Suppress the topoisomerase enzymatic activity; Suppress cell cycle; The inducing cell differentiation; Cell death inducing; Suppress cell blood vessel hyperplasia and antioxidation.In the body, experiment in vitro and epidemiology shows that all genistein all has inhibitory action to kinds of tumors, like breast carcinoma, carcinoma of prostate, renal carcinoma, gastric cancer, colorectal cancer, bladder cancer, pulmonary carcinoma, uterus carcinoma, skin carcinoma, leukemia, lymphoma, neuroblastoma and head and neck cancer etc.Genistein not only has prevention and inhibitory action also with many antitumor drug (like tamoxifen, cisplatin, bcnu, daunorubicin, tiazofurine) the synergistic antitumor effect to be arranged to kinds of tumors separately.
Genistein is water-soluble hardly; The water solublity that it is relatively poor through the preparation that traditional formulation method is prepared from, is difficult to after oral, reach the bioavailability that the treatment disease requires; Simultaneously also big limitations process the kind of preparation, like dosage forms such as soluble powder or intravenous administration formulations.In addition; The content of genistein in preparation is lower, and in order to reach medicine concentration, can only improve curative effect through the using dosage that increases preparation; But strengthened again so to a certain extent the risk of untoward reaction taking place, but also can increase drug cost.
Summary of the invention
The present invention provides a kind of genistein clathrate, has comprised preparation of genistein clathrate and preparation method thereof for solving the problem that exists in the above-mentioned prior art.Clathrate provided by the invention can be prepared into various stable dosage forms, and has improved the bioavailability of genistein greatly.Genistein clathrate provided by the invention and preparation thereof have good preventing and therapeutic effect for osteoporosis, climacteric syndrome, tumor and cardio-cerebrovascular diseases.
Concrete, the present invention has improved the water solublity of genistein through cyclodextrin or the cyclodextrin derivative clathration to genistein, the various dosage forms that this clathrate can further prepare clinically to be suitable for.
Genistein clathrate provided by the invention is made up of genistein and inclusion agents, and the consumption of preparation used genistein of genistein clathrate and inclusion agents is counted with weight portion:
Genistein 1-100
Inclusion agents 5-800
The consumption of used genistein and inclusion agents is preferably in weight portion:
Genistein 10-100
Inclusion agents 50-600.
The consumption of used genistein and inclusion agents is preferably in weight portion again:
Genistein 10-30
Inclusion agents 200-500
The consumption of used genistein and inclusion agents is in weight portion more preferably:
Genistein 10-20
Inclusion agents 400-500
The consumption of used genistein and inclusion agents most preferably is in weight portion:
Genistein 10
Inclusion agents 300
The source of genistein can be through extracted form natural plant or chemosynthesis and gets among the present invention.
Inclusion agents according to the invention is preferably cyclodextrin or cyclodextrin derivative, can be selected from one or more the combination in alpha-cyclodextrin, gamma-cyclodextrin, hydroxyethyl-, HP-, dihydroxypropyl beta-schardinger dextrin-, methyl-beta-schardinger dextrin-, glucose ring dextrin, maltose cyclodextrin, maltotriose cyclodextrin, carboxymethyl cyclodextrin, the sulfoalkyl cyclodextrin.Inclusion agents more preferably HP-, dihydroxypropyl beta-schardinger dextrin-or HP-and glucose ring dextrin by weight 1: 2 combination.
The method for preparing of genistein clathrate can adopt any in the methods such as solvent method, polishing, ultrasonic method, freeze-drying, spray drying method among the present invention.
The method for preparing of genistein cyclodextrin or cyclodextrin derivant clathrate among the present invention can be that cyclodextrin or cyclodextrin derivative and genistein are placed colloid mill or mortar, adds suitable solvent and stirs; Make into pastel; Ground 1～5 hour, and got the viscous pastes of homogeneous, filter; 40 ℃～80 ℃ dryings promptly get solid genistein cyclodextrin or cyclodextrin derivant clathrate.
The method for preparing of genistein cyclodextrin or cyclodextrin derivant clathrate among the present invention; Can also be genistein to be joined among the NaOH of an amount of 0.01mol/L dissolve; According to the weight part ratio of genistein and cyclodextrin or cyclodextrin derivative, cyclodextrin or cyclodextrin derivative are added wherein, stir to clarify clear solution; Regulate pH value to neutral with the dilute hydrochloric acid of 1.0mol/L then, promptly get liquid genistein cyclodextrin or cyclodextrin derivant clathrate.
The method for preparing of genistein cyclodextrin or cyclodextrin derivant clathrate among the present invention; Can be that liquid genistein cyclodextrin or cyclodextrin derivant clathrate are concentrated into cyclodextrin or the cyclodextrin derivative concentration range solution at 10～15% (W/V); Cold preservation 12 hours makes it separate out white precipitate, filters; In 40 ℃～80 ℃ dryings, promptly get solid genistein cyclodextrin or cyclodextrin derivant clathrate.
The preferred for preparation method of genistein clathrate provided by the invention comprises the steps:
(a) genistein is joined in the suitable solvent after the dissolving, add inclusion agents;
(b) heating, stir, to clear solution, promptly get liquid genistein clathrate.
Step (b) preferably under temperature 25-80 ℃, magnetic agitation 0.5-2 hour.More preferably temperature is that 40 ℃ of lower magnetic forces stirred 0.5 hour.
The preferred for preparation method of genistein clathrate provided by the invention comprises the steps: that also (c) is dry with liquid genistein prime ring clathrate, promptly gets solid genistein clathrate.Step (c) is preferable under 40 ℃～80 ℃ the temperature dry.Most preferably 60 ℃
The said drying means of step (c) can use drying meanss such as convection drying, spray drying, lyophilization.
In the method for preparing of genistein clathrate provided by the invention; Said solvent is selected from a kind of or any two kinds and the above mixed solvent in water, ethanol, methanol, propanol, isopropyl alcohol, ethylene glycol, propylene glycol, glycerin, the acetone, wherein most preferably is ethanol.The above drying means can use drying meanss such as convection drying, spray drying, lyophilization.
Genistein clathrate provided by the invention and pharmaceutic adjuvant can be prepared into various dosage forms, like tablet, capsule, suspensoid, solution, Emulsion, injection, ointment, gel or membrane etc.Wherein injection comprises liquid drugs injection injection, freeze-dried powder or transfusion.
Genistein essence injecta of the present invention comprises solution type injection agent and freeze-dried powder; Solution type injection agent comprises aqueous injection and the transfusion of medicine carrying type.
With this area method commonly used, can genistein clathrate of the present invention be prepared into various preparations.
The aqueous solution of genistein clathrate of the present invention can be prepared into aqueous injection through sterilization;
Genistein clathrate aqueous solution of the present invention adds an amount of osmotic pressure regulator and can be made into the transfusion of medicine carrying type through pressure sterilizing, comprises sodium chloride injection and glucose injection.
The aqueous solution of genistein clathrate of the present invention adds an amount of excipient and can be made into freeze-dried powder through lyophilization.In the method for preparing of preferred genistein clathrate freeze-dried powder provided by the invention, the weight portion of genistein clathrate and excipient is respectively:
Genistein clathrate 15～30
Excipient 5～60
The weight portion of genistein clathrate and excipient is preferably:
Genistein clathrate 20～30
Excipient 15～50
The weight part ratio of genistein clathrate and excipient most preferably is:
Genistein clathrate 20～25
Excipient 40～50
Excipient in the above-mentioned freeze-dried powder can adopt various pharmaceutical excipients commonly used, is preferably in mannitol, glucose, sorbitol, sodium chloride, dextran, sucrose, lactose, gelatin hydrolysate and the Polyethylene Glycol one or more; Further be preferably in mannitol, sorbitol, dextran, lactose, gelatin hydrolysate and the Polyethylene Glycol one or more.
The invention provides a kind of injection that comprises above-mentioned genistein clathrate and preparation method thereof, it comprises the steps:
A, take by weighing the genistein clathrate, and get pH value regulator, medical active carbon and water for injection ready by recipe quantity;
B, add proper amount of water for injection in the container in preparation; Getting load weighted genistein clathrate adds in the preparation container; Stirring makes it to dissolve fully; After-teeming is penetrated water to full dose; Regulate pH and add medical active carbon stirring and adsorbing
minute, filtration that the weight of used medicinal charcoal is
to
..Fill promptly got after filtrating added adjuvant according to the requirement of above-mentioned different dosage form.
The above-mentioned regulator that is used to regulate pH value can be used hydrochloric acid, acetic acid, citric acid, tartaric acid, acidic amino acid, sodium bicarbonate, sodium acetate, ethylenediamine, basic amino acid etc., and in preferably citric acid, tartaric acid, sodium bicarbonate or the sodium acetate one or more.
That injection provided by the invention has is easy to use, curative effect is rapid, characteristics such as safe and reliable; Be used for muscle and intravenous administration; Be applicable to clinical treatment, particularly can not eat because of various reasons or gastrointestinal function obstacle and patient that can not oral administration can intravenously administrables some; Its preparation technology is easy, economical, be easy to suitability for industrialized production, and economic and social benefits are high.
The present invention also provides a kind of dry suspension that comprises above-mentioned genistein clathrate and preparation method thereof.
Above-mentioned dry suspension, it comprises genistein and pharmaceutic adjuvant, the weight portion of said genistein and pharmaceutic adjuvant is:
Said filler is selected from one or more the combination in sorbitol, sucrose, mannitol, the lactose;
Said disintegrating agent is selected from carboxymethylstach sodium, microcrystalline Cellulose, low one or more the combination that replaces light propyl cellulose, polyvinylpolypyrrolidone, crosslinked carboxymethylstach sodium, hydroxypropyl starch;
Said suspending agent is selected from one or more the combination in arabic gum, tragakanta, sodium alginate, polyvidone, hydroxypropyl cellulose, xanthan gum, the Resina persicae;
Said binding agent is selected from alcoholic solution or polyvinylpyrrolidone alcoholic solution.
The weight portion of a kind of dry suspension that comprises above-mentioned genistein clathrate provided by the invention is more preferably:
But said inclusion agents is preferably HP-HP-and glucose ring dextrin by weight 1: 2 combination.
The weight ratio that said filler is preferably compositions, mannitol and the lactose of mannitol and lactose is preferably 1: 3.
Said disintegrating agent is preferably crosslinked carboxymethyl fecula sodium, and suspending agent is preferably xanthan gum, and binding agent is preferably 80% alcoholic solution.
The dry suspension that comprises the genistein clathrate provided by the invention, said pharmaceutic adjuvant also comprises the correctives of 3-5 weight portion, said correctives is flavorant or edible glucin.
The invention provides the above-mentioned method for preparing that comprises the dry suspension of genistein clathrate, it comprises the steps:
A, preparation clathrate: genistein joins in the alcoholic solution and dissolves in will writing out a prescription, and adds the inclusion agents magnetic agitation again, and is concentrated, dry then, crosses 120 mesh sieves;
B, will write out a prescription in filler, disintegrating agent, suspending agent cross the 80-100 mesh sieve respectively, clathrate, filler, disintegrating agent, the suspending agent of preparation press recipe quantity mix, mixture;
In c, the mixture, make soft material with binding agent stirring adding above-mentioned steps b gained;
D, granulation, packing: soft material is crossed 20 mesh sieves and is granulated, 55-80 ℃ of oven dry down, 18 mesh sieve granulate, dress compound membrane bag or bottle.
The invention has the beneficial effects as follows through cyclodextrin or cyclodextrin derivative genistein is carried out enclose; Genistein is embedded in the tubular structure of cyclodextrin or cyclodextrin derivative molecule; Become the clathrate of genistein cyclodextrin or cyclodextrin derivative; Thereby improve the water solublity of genistein; Make this active component of genistein directly apply to solid, liquid dosage form, solved the shortcoming that the genistein water solublity is low, can not directly be used for injection type with the form of clathrate.
Cyclodextrin or cyclodextrin derivative be a kind of toxicity less the water solublity pharmaceutic adjuvant, the genistein cyclodextrin or the cyclodextrin derivant clathrate of the present invention preparation are suitable for processing various liquid preparation and solid preparation.Genistein cyclodextrin or cyclodextrin derivant clathrate have good water solubility, characteristics that blood vessel irritation is little, have the advantages that with the solid preparation of its preparation disintegrate is fast, stripping good, bioavailability is high, are more conducive to clinical practice.Preparation of the present invention has better prevention and therapeutic effect for osteoporosis, climacteric syndrome, tumor and cardio-cerebrovascular diseases.
Blood vessel irritation with the genistein hydroxypropyl-beta-cyclodextrin inclusion carries out is tested as follows:
Get 8 of rabbit and be divided into two groups, i.e. test group and matched group, test group is by rabbit ear edge vein this clathrate that slowly instils, and once a day, dosage 1.62g/kg adds 5% glucose injection 40ml, drips successive administration 3 days fast 1.5ml/ minute; Matched group gives 10% glacial acetic acid; In the negative contrast of 5% glucose injection of instiling of the offside rabbit ear; Successive administration 3 days, the result shows: test group successive administration 3 days, local no abnormality seen; With the same, and inject visible contrafluxion, thickening behind 10% glacial acetic acid, ooze out side injection 5% glucose injection.
The preparation stability that comprises genistein clathrate of the present invention is investigated test as follows:
One, genistein essence injecta study on the stability test
1, influence factor's test
High temperature, exposure experiments to light
Get each 2 parts of genistein freezing-dried powder and genistein injection, carry out high temperature and exposure experiments to light respectively:
1). hot test: sample is put in the sealing clean container, 60 ℃ of condition held 5 days, sampling check and analysis, result and sample comparison in 0 day.
2). exposure experiments to light: sample places the transparent sealing container, is placed in the lighting box that daylight lamp is housed, and in the condition held of 4500 ± 500LX illuminance 5 days, the analysis of taking a sample to check, result and 0 day sample are relatively.
The sample size of 5 days accelerated tests of table 1 is measured the result
Conclusion: under the accelerated test condition, genistein essence injecta appearance color does not have change, and content reduces seldom, the basic no change of impurity, and the result shows that genistein chemical property behind enclose is stable.
2, long-time stability are investigated test
Get genistein freezing-dried powder and injection,, investigate 0,3,6,9 intending under the listing packing GMP storage condition, relevant indexs such as the character of sample, acidity, clarity of solution and color, related substance, changes of contents in the time of 12,24 months, result of the test is following:
Table 2 genistein freezing-dried powder long-time stability are investigated test
Table 3 genistein injection experimental result
Result of the test, genistein freezing-dried powder and injection are good at 24 months internal stabilities.
Two, genistein dry suspension study on the stability test
Influence factor's test: genistein dry suspension of the present invention is placed illumination (4500LX), high temperature (60 ℃), high humidity (humidity 75%; 92.5%) after 5 day, 10 days; Measure its genistein cellulose content respectively, the volume sedimentation is its related substances when, and the result sees table one and table two.
Table one genistein dry suspension influence factor result of the test (5 days)
| Condition | Time (my god) | Content (%) | Volume settling ratio (30min) |
| Illumination (4500LX) | 5 | 99.57 | Qualified |
| 60℃ | 5 | 99.74 | Qualified |
| Humidity 75% | 5 | 99.34 | Qualified |
| Humidity 92.5% | 5 | 99.52 | Qualified |
Table two genistein dry suspension influence factor result of the test (10 days)
| Condition | Time (my god) | Content (%) | Volume settling ratio (30min) |
| Illumination (4500LX) | 10 | 99.35 | Qualified |
| 60℃ | 10 | 99.54 | Qualified |
| Humidity 75% | 10 | 99.37 | Qualified |
| Humidity 92.5% | 10 | 99.27 | Qualified |
According to the formulation characteristic of dry suspension, the selection of suspending agent is most important, if select improperly, in passes during brewing, can produce lamination, so we screens to suspending agent.
According to the Chinese Pharmacopoeia relevant requirements, than for main detection index, (get test sample 50ml with the plug graduated cylinder according to the detection method that NF provides with settling volume; Firmly jolting is 1 minute; Write down the beginning height H 0 of suspended matter, left standstill 3 hours, write down the final height H of suspended matter; By formula " settling volume ratio=H/H0 " calculates) suspending agent is screened, the result is following:
The specific embodiment
Further specify the present invention below in conjunction with the specific embodiment, but the scope that the present invention requires to protect is not limited to following embodiment.
Embodiment 1: the preparation of genistein freezing-dried powder
Take by weighing genistein 2.0g, 60.0 gram HP-s, mannitol 124g respectively, earlier genistein is dissolved in the 130ml ethanol, add HP-after the stirring and dissolving, magnetic agitation 2 hours; 50 ℃ of temperature, behind the enclose, ethanol is removed in decompression, adds mannitol and water for injection 1000ml stirring and makes it dissolving; After-teeming is penetrated water to the 2000ml full dose, with citron acid for adjusting pH to 3.3, adds medical active carbon stirring and adsorbing 15 minutes; The amount of used medicinal charcoal is 0.03%, filters, and filtrating is sub-packed in the cillin bottle; Lyophilization is taken out behind the vacuum gland, and jewelling lid labeling promptly gets the lyophilizing finished product.
Embodiment 2: the preparation of genistein sodium chloride injection
Take by weighing 40.0g HP-, genistein 1.0g and 9.0g sodium chloride for injection respectively; Genistein is joined in the 60ml ethanol; Add HP-and sodium chloride for injection after the stirring and dissolving; Magnetic agitation 1 hour (speed controlling does not outwards produce at liquid and splashes), 60 ℃ of temperature are observed the genistein hydroxypropyl-beta-cyclodextrin inclusion solution that obtains clear.Ethanol is removed in decompression, adds water for injection and stirs to 600ml, and back after-teeming is penetrated water to the 1000ml full dose; With winestone acid for adjusting pH to 3.8; Added medical active carbon stirring and adsorbing 20 minutes, the amount of used medicinal charcoal is 0.03%, filters; Be sub-packed in the infusion bottle by predetermined close, 115 ℃ of pressure sterilizings promptly got in 30 minutes.
Embodiment 3: the preparation of genistein glucose injection
Take by weighing 50.0g HP-, genistein 2.0g, glucose for injection 50g respectively; Genistein is joined in the 150ml ethanol; Add HP-after the stirring and dissolving; Magnetic agitation 1 hour (speed controlling does not outwards produce at liquid and splashes), 55 ℃ of temperature are observed the genistein hydroxypropyl-beta-cyclodextrin inclusion solution that obtains clear.Ethanol is removed in decompression.After glucose for injection added injection water 100ml stirring and dissolving, Glucose Liquid is poured in the clathrate, moisturizing is to 800ml; With winestone acid for adjusting pH to 3.8; Added medical active carbon stirring and adsorbing 20 minutes, the amount of used medicinal charcoal is 0.03%, filters; Be sub-packed in the infusion bottle by predetermined close, 115 ℃ of pressure sterilizings promptly got in 30 minutes.
Embodiment 4: preparation genistein aseptic powder injection
Indoor in the sterile working; Take by weighing 30.0g HP-and genistein 1.0g; Add 80ml ethanol stirring and dissolving, add HP-after the stirring and dissolving, magnetic agitation 1.5 hours (speed controlling does not outwards produce at liquid and splashes); 70 ℃ of temperature are observed the genistein hydroxypropyl-beta-cyclodextrin inclusion solution that obtains clear.Moisturizing with winestone acid for adjusting pH to 3.5, added medical active carbon stirring and adsorbing 20 minutes to 1000ml after the inclusion complex in solution drying under reduced pressure that obtains removed ethanol, and the amount of used medicinal charcoal is 0.03%, filter, and lyophilization, packing promptly gets.
Embodiment 5: the preparation of genistein injection
Take by weighing genistein 2.0g, 70.0 gram HP-s respectively, earlier genistein is dissolved in the 140ml ethanol, add HP-after the stirring and dissolving, magnetic agitation 2 hours; 80 ℃ of temperature, behind the enclose, ethanol is removed in decompression, adds water for injection 800ml stirring and makes it dissolving; After-teeming is penetrated water to the 1000ml full dose, with citron acid for adjusting pH to 3.3, adds medical active carbon stirring and adsorbing 15 minutes; The amount of used medicinal charcoal is 0.03%, filters, and packing promptly gets.
Embodiment 6: the preparation of genistein freezing-dried powder
Take by weighing genistein 3.0g, 100.0 gram HP-s, mannitol 258g respectively, earlier genistein is dissolved in the 200ml ethanol, add HP-after the stirring and dissolving, magnetic agitation 1.5 hours; 55 ℃ of temperature, behind the enclose, ethanol is removed in decompression, adds mannitol and water for injection 2000ml stirring and makes it dissolving; After-teeming is penetrated water to the 3000ml full dose, with winestone acid for adjusting pH to 3.7, adds medical active carbon stirring and adsorbing 20 minutes; The amount of used medicinal charcoal is 0.03%, filters, and filtrating is sub-packed in the cillin bottle; Lyophilization is taken out behind the vacuum gland, and jewelling lid labeling promptly gets the lyophilizing finished product.
Embodiment 7: the preparation of genistein dry suspension
Genistein is joined in the 600ml ethanol, stirring and dissolving, the back adds beta-schardinger dextrin-and magnetic agitation, and is concentrated, dry then, pulverizes, and crosses 120 mesh sieves; Filler, disintegrating agent, suspending agent are crossed 100 mesh sieves respectively, and be subsequent use.By recipe quantity take by weighing genistein clathrate, lactose and mannitol, carboxymethylstach sodium, xanthan gum mixes, and stirs more than 30 minutes mix homogeneously.Saccharin sodium, the flavoring pineapple essence of recipe quantity put in 60% ethanol dissolve, be binding agent, the system soft material.20 mesh sieves are granulated, 55-60 ℃ of oven dry; 18 mesh sieve granulate.Dress compound membrane bag or bottle.
Embodiment 8: the preparation of genistein dry suspension
Genistein is joined in the 720ml ethanol, stirring and dissolving, the back adds HP-and magnetic agitation, and is concentrated, dry then, pulverizes, and crosses 120 mesh sieves; Filler, disintegrating agent, suspending agent are crossed 100 mesh sieves respectively, and be subsequent use.By recipe quantity take by weighing genistein clathrate, sucrose and mannitol, hydroxypropyl starch, xanthan gum mixes, and stirs more than 30 minutes mix homogeneously.10% polyvinylpyrrolidone alcoholic solution is stirred in the above-mentioned main ingredient that mixes of adding the system soft material.20 mesh sieves are granulated, 55-60 ℃ of oven dry; 18 mesh sieve granulate.Dress compound membrane bag or bottle.
Embodiment 9: the preparation of genistein dry suspension
Genistein is joined in the 750ml ethanol, stirring and dissolving, the back adds dihydroxypropyl beta-schardinger dextrin-and magnetic agitation, and is concentrated, dry then, pulverizes, and crosses 120 mesh sieves; Filler, disintegrating agent, suspending agent are crossed 100 mesh sieves respectively, and be subsequent use.By recipe quantity take by weighing genistein clathrate, lactose and mannitol, carboxymethylstach sodium, tragacanth mixes, and stirs more than 30 minutes mix homogeneously.Saccharin sodium, the flavoring pineapple essence of recipe quantity put in 60% ethanol dissolve, be binding agent, the system soft material.20 mesh sieves are granulated, 55-60 ℃ of oven dry;
18 mesh sieve granulate.Dress compound membrane bag or bottle.
Embodiment 10: the preparation of genistein dry suspension
Genistein is joined in the 1000ml ethanol, stirring and dissolving, the back adds glucose ring dextrin and magnetic agitation, and is concentrated, dry then, pulverizes, and crosses 120 mesh sieves; Filler, disintegrating agent, suspending agent are crossed 100 mesh sieves respectively, and be subsequent use.By the taking by weighing genistein clathrate, lactose, lowly replace light propyl cellulose of recipe quantity, xanthan gum mixes, and stirs more than 30 minutes mix homogeneously.Saccharin sodium, the flavoring pineapple essence of recipe quantity put in 60% ethanol dissolve, be binding agent, the system soft material.20 mesh sieves are granulated, 55-60 ℃ of oven dry; 18 mesh sieve granulate.Dress compound membrane bag or bottle.
Obviously, the above embodiment of the present invention only be for clearly the present invention is described and is done for example, and be not to be qualification to embodiment of the present invention.For the those of ordinary skill in affiliated field, on the basis of above-mentioned explanation, can also make other multi-form variation or change.Here need not also can't give exhaustive to all embodiments.And these belong to conspicuous variation or the change that spirit of the present invention extended out and still are among protection scope of the present invention.
Claims (17)
1. genistein clathrate is characterized in that genistein and inclusion agents count with weight portion:
Genistein 1-100
Inclusion agents 5-800
2. a kind of genistein clathrate according to claim 1 is characterized in that genistein and inclusion agents count with weight portion:
Genistein 10-100
Inclusion agents 50-600.
3. a kind of genistein clathrate according to claim 2 is characterized in that genistein and inclusion agents count with weight portion:
Genistein 10-30
Inclusion agents 200-500
4. a kind of genistein clathrate according to claim 3 is characterized in that genistein and inclusion agents count with weight portion:
Genistein 10-20
Inclusion agents 400-500
5. a kind of genistein clathrate according to claim 4 is characterized in that genistein and inclusion agents count with weight portion:
Genistein 10
Inclusion agents 300
6. according to the described a kind of genistein clathrate of arbitrary claim among the claim 1-5, the source that it is characterized in that genistein is for getting through extracted form natural plant or chemosynthesis.
7. according to the described a kind of genistein clathrate of arbitrary claim among the claim 1-5, it is characterized in that said inclusion agents is selected from and be cyclodextrin or cyclodextrin derivative.
8. a kind of genistein clathrate according to claim 7 is characterized in that said inclusion agents is selected from one or more the combination in alpha-cyclodextrin, gamma-cyclodextrin, hydroxyethyl-, HP-, dihydroxypropyl beta-schardinger dextrin-, methyl-beta-schardinger dextrin-, glucose ring dextrin, maltose cyclodextrin, maltotriose cyclodextrin, carboxymethyl cyclodextrin, the sulfoalkyl cyclodextrin.
9. a kind of genistein clathrate according to claim 8 is characterized in that said inclusion agents is selected from HP-and dihydroxypropyl beta-schardinger dextrin-.
10. a kind of genistein clathrate according to claim 8 is characterized in that said inclusion agents is HP-and glucose ring dextrin by weight 1: 2 combination.
11. a pharmaceutical composition that comprises the described genistein clathrate of arbitrary claim among the claim 1-10 is characterized in that it being the medically acceptable any dosage form that is prepared from genistein clathrate and pharmaceutic adjuvant.
12. a kind of pharmaceutical composition that comprises the described genistein clathrate of arbitrary claim among the claim 1-11 according to claim 11 is characterized in that described dosage form comprises tablet, capsule, suspensoid, solution, Emulsion, injection, ointment, gel or membrane.
13. a kind of pharmaceutical composition that comprises the described genistein clathrate of arbitrary claim among the claim 1-11 according to claim 12 is characterized in that described injection comprises liquid drugs injection injection, freeze-dried powder and transfusion.
14. the method for preparing of a genistein clathrate is characterized in that comprising the steps:
(a) genistein is joined in the suitable solvent after the dissolving, add inclusion agents;
(b) under temperature 25-80 ℃, magnetic agitation 0.5-2 hour,, promptly get liquid genistein clathrate to clear solution.
15. the method for preparing of a kind of genistein clathrate according to claim 14 is characterized in that also comprising the steps: that (c) is dry under 40 ℃～80 ℃ temperature with liquid genistein clathrate.
16., it is characterized in that solvent described in the step (a) is selected from a kind of or any two kinds and the above mixed solvent in water, ethanol, methanol, propanol, isopropyl alcohol, ethylene glycol, propylene glycol, glycerin, the acetone according to the method for preparing of claim 14 or 15 described a kind of genistein clathrates.
17. the method for preparing of a kind of genistein clathrate according to claim 17 is characterized in that solvent is an ethanol described in the step (a); Step (b) is to stir 0.5 hour at 40 ℃ of lower magnetic forces; Step (c) is 60 ℃ of dryings down.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110235014 CN102319438A (en) | 2011-08-16 | 2011-08-16 | The preparation and preparation method thereof and the purposes that comprise the genistein clathrate |
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| CN102579400A (en) * | 2012-03-26 | 2012-07-18 | 扬州大学 | Method for preparing microcapsules capable of controlling to release magnetic medicines in timing mode |
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| 《中国药学杂志》 20041130 雷英杰等 染料木素-beta-环糊精包合物的制备和鉴定 第39卷, 第11期 * |
| 《化工新型材料》 20040630 严春美等 beta-环糊精球的制备及其药物控释行为研究 第32卷, 第06期 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102579400A (en) * | 2012-03-26 | 2012-07-18 | 扬州大学 | Method for preparing microcapsules capable of controlling to release magnetic medicines in timing mode |
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