CN101716135B - Soy isoflavone solid dispersion suppository and preparation method thereof - Google Patents
Soy isoflavone solid dispersion suppository and preparation method thereof Download PDFInfo
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- CN101716135B CN101716135B CN2010100337657A CN201010033765A CN101716135B CN 101716135 B CN101716135 B CN 101716135B CN 2010100337657 A CN2010100337657 A CN 2010100337657A CN 201010033765 A CN201010033765 A CN 201010033765A CN 101716135 B CN101716135 B CN 101716135B
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Abstract
The invention discloses a soy isoflavone vaginal suppository and a preparation method thereof. Raw materials for preparing the suppository comprise soy isoflavone solid dispersion and a water-soluble substrate, wherein the soy isoflavone solid dispersion is prepared from soy isoflavone and a hydrophilic solid dispersion carrier, and the mass ratio of the soy isoflavone and the carrier is 1:1-20. The invention designs and prepares a soy isoflavone solid dispersion suppository for vaginal drug administration on the premise of overcoming the defect of poor absorption effect of the oral administration of the soy isoflavone. The solid dispersion technology improves the dispersity and the hydrophilism of the soy isoflavone and improves the moisture degree on the vagina mucosa, thereby improving the infiltration rate of the prepared suppository by 2-3 times. The suppository greatly improves the curative effect of the soy isoflavone on treating and mitigating a series of diseases of women caused by maladjustment of estrogen level.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of soy isoflavone solid dispersion suppository and preparation method thereof.
Background technology
In recent years, climacteric women so that young woman are improving because of the various diseases that the estrogen level imbalance causes year by year.Soybean isoflavone is claimed " phytoestrogen " again, the intravital estrogen level of people is had dual regulation, and receive women's more than 35 years old favor.At present, the food that occurs numerous soybean isoflavone medicines, functional product on the market and add soybean isoflavone, but because soybean isoflavone oral absorption weak effect (absorbance has only 13～30%), the curative effect of these products allows of no optimist.
Soybean isoflavone (English name: soybean Isoflavone) be yellow or pale yellow powder; Mildly bitter flavor; Constitute by 12 kinds of components; Being divided into 3 types is Semen Glycines glycoside, dyewood glycoside and Glycitein glycoside, exists with free type (aglycon type) and glucosides type (comprising glucoside type, acetyl group glucoside type and malonyl glucoside type) form respectively.Its structural formula is:
The isoflavone genin structural formula
Soybean isoflavone glucoside structural formula
The glucosides type accounts for about 97% of total amount, and non-activity own has only the zymolysis through profitable strain in the intestinal to discharge the aglycon competence exertion effect that has than strong biological activity.Though free type aglycon is a main active, hydrophilic is poor, the difficult absorption in the gastro-intestinal Fluid.
Present stage; The method that improves the soybean isoflavone assimilation effect can be classified as three types: (1) in soybean isoflavone with addition of some nutritional labeling; Like dietary fiber, L-glutaminate, N-acetyl group-D-glucamine etc.; Promote the profitable strain breeding to improve gastrointestinal tract environment, improve the glycocide aglycon and be converted into free type aglycon; (2) preparation high water-soluble soybean isoflavone derivatives; As make soybean isoflavone through inducer, increase its dissolubility, in the environment in vivo in external generation esterification; Soybean isoflavone after the esterification is easy to be hydrolyzed and regenerates soybean isoflavone, brings into play its physiological function; (3) make glycosidic bond hydrolysis under acidity or alkali condition of soybean isoflavone glucoside, the product of aglycon is rich in preparation.The purpose of method (1) and (3) is to make the glycocide aglycon of non-activity change active high desaccharide body aglycon into, but can not solve the difficult problem that absorbs of desaccharide body aglycon; (2) kind method is to improve the water solublity of soybean isoflavone, but can not promote the conversion of glycocide aglycon.Therefore, above-mentioned three kinds of methods all can not fundamentally change the difficult problem that absorbs of free type aglycon, and effect is not fine.
In the pharmaceutics, poorly water soluble drugs being processed suppository, through cavity/canal drug administration, is a kind of means that overcome its oral absorption weak effect.With intimate estradiol of soybean isoflavone and metabolite estriol vaginal suppository thereof, research is arranged both at home and abroad more.They for postmenopausal women after, vaginal atrophy, the drying that occurs because of estrogen deficiency, symptom such as tickle have sure curative effect.
Summary of the invention
The purpose of this invention is to provide a kind of soy isoflavone vaginal suppository and preparation method thereof.This vaginal suppository can effectively increase the dissolution and the infiltration rate of soybean isoflavone, improves stability of drug and can promote drug absorption.
Soy isoflavone vaginal suppository provided by the present invention; The raw material of processing it comprises soy isoflavone solid dispersion and water-soluble base; Wherein, Said soy isoflavone solid dispersion is processed by soybean isoflavone and solid hydrophilic dispersion carrier, and the mass ratio of said soybean isoflavone and carrier is 1: 1-20.
Above-mentioned soy isoflavone vaginal suppository also can only be processed by soy isoflavone solid dispersion and water-soluble base, and wherein, the mass ratio of soy isoflavone solid dispersion and water-soluble base can be 1: 2-20.
During preparation, also can add following additives as required: sclerosing agent, thickening agent, absorption enhancer, antioxidant, antiseptic etc.
Soy isoflavone solid dispersion described in the present invention can adopt following any one method to prepare: solvent method, freeze-drying, fusion method and polishing.
The concrete method for preparing of soy isoflavone solid dispersion is following:
(1) solvent method (or claiming coprecipitation)
Get carrier material and soybean isoflavone by 1: after the mixed of 1-20, use organic solvent dissolution, boil off solvent after, vacuum drying, pulverizing, cross 80 mesh sieves, promptly get soy isoflavone solid dispersion of the present invention.
Above-mentioned carrier material can be Polyethylene Glycol (molecular weight is 4000,6000), polyvidone k30, poloxamer, the hard ester acid of polyoxyethylene lipid, and the organic solvent in this method can be selected ethanol, dichloromethane, acetone, chloroform etc.Said solvent boils off with Rotary Evaporators, and its bath temperature is 20-65 ℃.Vacuum drying temperature is that be 10-48 hour drying time between room temperature to 60 ℃.
(2) fusion method
Carrier material is heated in 50-200 ℃ water-bath or oil bath, make its fusion.(mass ratio of carrier and soybean isoflavone can select 1: 1-20) under stirring condition, to add soybean isoflavone with organic solvent dissolution; After continuing to stir 30-150min it is poured on the stainless sheet steel; Make straticulation, place-20 ℃ refrigerator then, cool off rapidly and solidify.Be placed on drying in vacuum drying oven or the exsiccator after the curing, dry thing promptly gets soy isoflavone solid dispersion of the present invention after pulverizing, crossing 80 mesh sieves.
Above-mentioned carrier material can be selected Polyethylene Glycol, carbamide, citric acid, succinic acid; Organic solvent can be selected 95% ethanol, ethanol, acetone, chloroform etc.Be 2-10h hardening time, and the vacuum drying temperature is between room temperature to 65 ℃, and be 12-48 hour drying time, or placed exsiccator 2-5 days.
(3) freeze-drying
Carrier and soybean isoflavone are dissolved in the solvent according to mass ratio 1: 1-20 altogether, and behind the stirring and evenly mixing, lyophilization is to eliminate solvent.Grind, cross 80 mesh sieves, promptly get soy isoflavone solid dispersion of the present invention.
Carrier material can be selected polyvidone k30, cyclodextrin, mannitol, lactose, gelatin hydrolysate; Solvent can be selected ethanol, 95% ethanol, and it is suitable that quantity of solvent selects that carrier and soybean isoflavone at room temperature can just all be dissolved as.
(4) polishing
With soybean isoflavone and carrier material mix homogeneously, put altogether in the mortar, grind, milling time 10-50min crosses 200 mesh sieves, gets the soy isoflavone solid dispersion powder.
Said carrier material can be selected Macrogol 4000, polyethylene glycol 6000, microcrystalline Cellulose PH102, microcrystalline Cellulose PH301, microcrystalline Cellulose PH302, microcrystalline Cellulose PH M06, microcrystalline Cellulose PH M15, microcrystalline Cellulose PH M25, microcrystalline Cellulose PH KG801, microcrystalline Cellulose and sodium carboxymethyl cellulose RCA591NF, cyclodextrin, 30 POVIDONE K 30 BP/USP 30 or lactose.
Above-mentioned soy isoflavone solid dispersion vaginal suppository can prepare according to following method:
Get soy isoflavone solid dispersion and water-soluble base with 1: the mass ratio of 2-20 mixes; Heating makes the said mixture fusion, injects the bolt mould that has coated lubricant then, cools off under the room temperature; The demoulding promptly gets soy isoflavone solid dispersion suppository of the present invention.
Said water-soluble base can be selected glycerol gelatin matrix, Polyethylene Glycol (PEG), polyoxyethylene monostearate (like S-40) or poloxamer (like poloxamer-188), is preferably glycerol gelatin matrix.
Said glycerol gelatin matrix is to be made up of water, gelatin, glycerol.Get gelatin and place evaporating dish, adding distil water is an amount of, soaks 30 minutes, makes its expansion deliquescing, and drop goes redundant moisture.Add glycerol, heating makes the gelatin dissolving in water-bath, continues heating content weight is reached till the required weight, and process glycerol: gelatin: the quality ratio is 7: 2: 1 a glycerol gelatin matrix.
Optional PEG1000 (fusing point 38-40 ℃), PEG1540 (fusing point 42-46 ℃), PEG4000 (fusing point 53-56 ℃), the PEG6000 (fusing point 55-63 ℃) of selecting of said Polyethylene Glycol substrate.If the PEG with different molecular weight merges with the certain proportion heating, can be made into the suppository base of suitable hardness.
Said Myrj 45 (polyoxyl 40stearate) is the monostearate of Polyethylene Glycol and the mixture of distearate, and contains free glycols.Commercial disignation is " S-40 ".
Said poloxamer (Poloxamer) is the block polymer of polyoxyethylene, polyoxypropylene, and these article model has multiple, increases with the degree of polymerization, and states of matter can be used as suppository base from liquid, semi-solid to waxy solid, soluble in water.Model commonly used is 188 types; Be poloxamer-188, fusing point is 52 ℃.Can promote the absorption of medicine and play slow release and the prolongation of effect effect.
When preparation soy isoflavone vaginal suppository of the present invention, can add following additives as required: sclerosing agent, thickening agent, absorption enhancer, antioxidant, antiseptic etc.
The present invention is directed to the shortcoming of soybean isoflavone oral absorption weak effect, designing and preparing a kind of soy isoflavone solid dispersion suppository that supplies vagina administration.Adopt solid dispersion technology to improve the dispersion and the hydrophilic of soybean isoflavone, improved wetness degree, thereby make the infiltration rate of the suppository of processing improve 2-3 doubly vaginal mucosa.This suppository has improved soybean isoflavone in treatment with alleviate the curative effect of a series of diseases that the women caused because of the estrogen level imbalance.
Description of drawings
Fig. 1 is the external stripping curve of 2: 1 solid dispersion suppository, physical mixture suppository and crude drug suppository for the PEG4000 and soybean isoflavone (ISO) mass ratio of embodiment 1 preparation.
Fig. 2 is the PEG6000 of embodiment 2 preparations and the stripping curve of solid dispersion suppository, physical mixture suppository and crude drug suppository that the ISO mass ratio is 5: 1.
Fig. 3 is the PEG6000 of embodiment 3 preparations and the stripping curve of solid dispersion suppository, physical mixture suppository and crude drug suppository that the ISO mass ratio is 2: 1.
Fig. 4 is the PEG6000 of embodiment 4 preparations and the stripping curve of solid dispersion suppository, physical mixture suppository and crude drug suppository that the ISO mass ratio is 5: 1.
Fig. 5 is the PVP of embodiment 5 preparations and the stripping curve of solid dispersion suppository, physical mixture suppository and crude drug suppository that the ISO mass ratio is 2: 1.
Fig. 6 is the PVP of embodiment 6 preparations and the stripping curve of solid dispersion suppository, physical mixture suppository and crude drug suppository that the ISO mass ratio is 5: 1.
The specific embodiment
The present invention will be described through specific embodiment below, but the present invention is not limited thereto.
Experimental technique described in the following embodiment like no specified otherwise, is conventional method; Said reagent and material like no specified otherwise, all can obtain from commercial sources.
The preparation of embodiment 1, soy isoflavone vaginal suppository
1) fusion method prepares soy isoflavone solid dispersion
Take by weighing soybean isoflavone and 10.0g PEG4000 congruent melting that 5.0g crosses 80 mesh sieves in 80 ℃ of water-baths; Stir 1h, be positioned over rapidly in-20 ℃ of refrigerator-freezers and cool off 4h, take out and place balance 48h in the exsiccator; Pulverized 80 mesh sieves, soybean isoflavone and PEG4000 mass ratio are 1: 2 solid dispersion.
2) preparation suppository
Adopt the classical matrix gelatin of suppository: glycerol: water=7: 2: 1 substrate as soy isoflavone solid dispersion suppository.Get the evaporating dish that gelatin 2.0g places known weight, adding distil water is an amount of, soaks 30 minutes, makes the expansion deliquescing, and drop goes redundant moisture.Adding glycerol 7.0g heats in water-bath makes the gelatin dissolving, continues heating content weight is reached till the required weight, processes glycerol gelatin matrix (glycerol: gelatin: 10.0g water=7: 2: 1).
The soy isoflavone solid dispersion of step 1) preparation is mixed with mass ratio with glycerol gelatin matrix at 1: 10; Stir, heating makes the said mixture fusion, injects the bolt mould that has coated lubricant while hot; Cool off under the room temperature; The demoulding is inhaled the water that goes to the suppository surface with absorbent paper, promptly gets soy isoflavone solid dispersion suppository.
The preparation of embodiment 2, soy isoflavone vaginal suppository
1) fusion method prepares soy isoflavone solid dispersion
Take by weighing 5.0g soybean isoflavone powder and 25.0g PEG6000 mix homogeneously, cross 80 mesh sieves, place evaporating dish; Heating in water bath makes it to melt vigorous stirring to about 80 ℃; Put cooling rapidly in the cryosel bath, freezing 3h makes it abundant curing; Put in the exsiccator of 40～50 ℃ of constant temperature and grind behind the 72h, cross 200 mesh sieves, soybean isoflavone and PEG6000 mass ratio are 1: 5 solid dispersion.
2) preparation suppository
Soy isoflavone solid dispersion and embodiment 1 step 2 with step 1) preparation) glycerol gelatin matrix for preparing mixes with mass ratio at 1: 10; Stir, heating makes the said mixture fusion, injects the bolt mould that has coated lubricant while hot; Cool off under the room temperature; The demoulding is inhaled the water that goes to the suppository surface with absorbent paper, promptly gets soy isoflavone solid dispersion suppository.
The preparation of embodiment 3, soy isoflavone vaginal suppository
1) fusion method prepares soy isoflavone solid dispersion
Take by weighing soybean isoflavone and 10.0g PEG6000 congruent melting that 5.0g crosses 80 mesh sieves in 80 ℃ of water-baths; Stir 1h, be positioned over rapidly in-20 ℃ of refrigerator-freezers and cool off 4h, take out and place balance 48h in the exsiccator; Pulverized 80 mesh sieves, soybean isoflavone and PEG6000 mass ratio are 1: 2 solid dispersion.
2) preparation suppository
Soy isoflavone solid dispersion and embodiment 1 step 2 with step 1) preparation) glycerol gelatin matrix for preparing mixes with mass ratio at 1: 10; Stir, heating makes the said mixture fusion, injects the bolt mould that has coated lubricant while hot; Cool off under the room temperature; The demoulding is inhaled the water that goes to the suppository surface with absorbent paper, promptly gets soy isoflavone solid dispersion suppository.
The preparation of embodiment 4, soy isoflavone vaginal suppository
1) fusion method prepares soy isoflavone solid dispersion
Take by weighing 5.0g soybean isoflavone powder and 25.0g PEG6000 mix homogeneously, cross 80 mesh sieves, place evaporating dish; Heating in water bath makes it fusing, vigorous stirring to about 80 ℃; Put cooling rapidly in the cryosel bath, freezing 3h makes it abundant curing; Put in the exsiccator of 40～50 ℃ of constant temperature and grind behind the 72h, cross 200 mesh sieves, soybean isoflavone and PEG6000 mass ratio are 1: 5 solid dispersion.
2) preparation suppository
Soy isoflavone solid dispersion and embodiment 1 step 2 with step 1) preparation) glycerol gelatin matrix for preparing mixes with mass ratio at 1: 10; Stir, heating makes the said mixture fusion, injects the bolt mould that has coated lubricant while hot; Cool off under the room temperature; The demoulding is inhaled the water that goes to the suppository surface with absorbent paper, promptly gets soy isoflavone solid dispersion suppository.
The preparation of embodiment 5, soy isoflavone vaginal suppository
1) solvent method prepares soy isoflavone solid dispersion
Take by weighing 5.0g soybean isoflavone powder (80 order), be dissolved in (heated and stirred) in the 500mL ethanol, take by weighing the PVP-K30 powder that 10.0g crosses 80 mesh sieves again, add in the above-mentioned ethanol liquid, stir and make it dissolving.With this ethanol liquid place rotate on the Rotary Evaporators dried (60 ℃ of water temperatures, P＜0.1pa) take out, and put balance 48h in the exsiccator, pulverize 80 mesh sieves, soybean isoflavone and PVP mass ratio are 1: 2 solid dispersion, place exsiccator subsequent use.
2) preparation suppository
Soy isoflavone solid dispersion and embodiment 1 step 2 with step 1) preparation) glycerol gelatin matrix for preparing mixes with mass ratio at 1: 10; Stir, heating makes the said mixture fusion, injects the bolt mould that has coated lubricant while hot; Cool off under the room temperature; The demoulding is inhaled the water that goes to the suppository surface with absorbent paper, promptly gets soy isoflavone solid dispersion suppository.
The preparation of embodiment 6, soy isoflavone vaginal suppository
1) freeze-drying prepares soy isoflavone solid dispersion
Take by weighing 5.0g soybean isoflavone powder (80 order) and 25.0g PVP-K30 powder and be dissolved in (ethanol that is added can just dissolve ISO and PVP is advisable) in the adequate amount of ethanol solvent altogether, lyophilization eliminates ethanol.Grind, cross 80 mesh sieves, soybean isoflavone and PVP mass ratio are 1: 5 solid dispersion.
2) preparation suppository
Soy isoflavone solid dispersion and embodiment 1 step 2 with step 1) preparation) glycerol gelatin matrix for preparing mixes with mass ratio at 1: 10; Stir, heating makes the said mixture fusion, injects the bolt mould that has coated lubricant while hot; Cool off under the room temperature; The demoulding is inhaled the water that goes to the suppository surface with absorbent paper, promptly gets soy isoflavone solid dispersion suppository.
The preparation of embodiment 7, soy isoflavone vaginal suppository
1) polishing prepares soy isoflavone solid dispersion
Take by weighing 5.0g soybean isoflavone powder and 100g PEG6000 mix homogeneously, put altogether in the mortar, grind 30min, cross 200 mesh sieves, soybean isoflavone and PEG6000 mass ratio are 1: 20 solid dispersion.
2) preparation suppository
Soy isoflavone solid dispersion and embodiment 1 step 2 with step 1) preparation) glycerol gelatin matrix for preparing mixes with mass ratio at 1: 10; Stir, heating makes the said mixture fusion, injects the bolt mould that has coated lubricant while hot; Cool off under the room temperature; The demoulding is inhaled the water that goes to the suppository surface with absorbent paper, promptly gets soy isoflavone solid dispersion suppository.
The preparation of embodiment 8, soy isoflavone vaginal suppository
1) polishing prepares soy isoflavone solid dispersion
Take by weighing 5.0g soybean isoflavone powder and 5g PEG6000 mix homogeneously, put altogether in the mortar, grind 30min, cross 200 mesh sieves, soybean isoflavone and PEG6000 mass ratio are 1: 1 solid dispersion.
2) preparation suppository
Soy isoflavone solid dispersion and embodiment 1 step 2 with step 1) preparation) glycerol gelatin matrix for preparing mixes with mass ratio at 1: 2; Stir, heating makes the said mixture fusion, injects the bolt mould that has coated lubricant while hot; Cool off under the room temperature; The demoulding is inhaled the water that goes to the suppository surface with absorbent paper, promptly gets soy isoflavone solid dispersion suppository.
The preparation of embodiment 9, soy isoflavone vaginal suppository
1) polishing prepares soy isoflavone solid dispersion
Take by weighing 5.0g soybean isoflavone powder and 5g PEG6000 mix homogeneously, put altogether in the mortar, grind 30min, cross 200 mesh sieves, soybean isoflavone and PEG6000 mass ratio are 1: 1 solid dispersion.
2) preparation suppository
Soy isoflavone solid dispersion and embodiment 1 step 2 with step 1) preparation) glycerol gelatin matrix for preparing mixes with mass ratio at 1: 20; Stir, heating makes the said mixture fusion, injects the bolt mould that has coated lubricant while hot; Cool off under the room temperature; The demoulding is inhaled the water that goes to the suppository surface with absorbent paper, promptly gets soy isoflavone solid dispersion suppository.
The dissolution test of embodiment 10, soy isoflavone vaginal suppository and transdermal test
Adopt the dissolution of external stripping measuring soybean isoflavone suppository.The medicament disperser is measured its infiltration rate.
1, dissolution test
The suppository that adopts commentaries on classics basket method (2005 editions two appendix XC first methods of the Pharmacopoeia of the People's Republic of China) that embodiment 1-6 is prepared carries out the dissolution test, and rotating speed is 100rpmmin
-1, temperature is (37 ± 1) ℃, dissolution medium is that the pH of 0.2mol/L is 4.5 sodium dihydrogen phosphate buffers.
The stripping curve figure of embodiment 1-6 suppository sees Fig. 1-6 successively.
Fig. 1 result shows that the accumulative total dissolution of the soy isoflavone solid dispersion suppository 1h of embodiment 1 preparation is 79.98%, is 1.94 times of physical mixture suppository, is 2.98 times of crude drug suppository.
Fig. 2 result shows that the accumulative total dissolution of the soy isoflavone solid dispersion suppository 1h of embodiment 2 preparation is 80.69%, is 1.85 times of physical mixture suppository, 3.00 times of crude drug suppository.
Fig. 3 result shows that the accumulative total dissolution of the soy isoflavone solid dispersion suppository 1h of embodiment 3 preparation is 88.82%, is 1.87 times of physical mixture suppository, 3.31 times of crude drug suppository.
Fig. 4 result shows that the accumulative total dissolution of the soy isoflavone solid dispersion suppository of embodiment 4 preparation is 82.08%, is 1.94 times of physical mixture suppository, 3.06 times of crude drug suppository.
Fig. 5 result shows that the accumulative total dissolution of the soy isoflavone solid dispersion suppository 1h of embodiment 5 preparation is 79.98%, is 1.80 times of physical mixture suppository, 2.63 times of crude drug suppository.
Fig. 6 result shows that the accumulative total dissolution of the soy isoflavone solid dispersion suppository 1h of embodiment 6 preparation is 65.52%, is 1.52 times of physical mixture suppository, 2.43 times of crude drug suppository.
2, transdermal experiment
Get suitable area through the good dialyzer of pre-treatment (molecular cut off 12000～14000), be fixed in that (diffusion area is 2.54cm between the Supply House and receiving chamber of transdermal disperser
2), suppository is cut into small pieces, take by weighing 2.0g and be placed on the dialyzer; In receiving chamber, inject reception liquid (phosphate buffer of pH=4.5), dialyzer is fully contacted with acceptable solution, whole device is in (37 ± 1) ℃ water-bath; Open magnetic stirring apparatus, rotating speed is 300r/min.Respectively at 1,2,4,6,8,10, the 24h sampling is got at every turn and is received liquid 2mL, all adds the fresh acceptable solution of equal volume after the sampling rapidly and removes the bubble in the receiving chamber.Sample is got 20 μ l sample introductions behind filtering with microporous membrane, with high-performance liquid chromatogram determination soybean isoflavone concentration, and press following formula calculating cumulative transit dose Q:
c
nBe n sample point concentration, c
iBe i sample point concentration, A is the diffusion cell area, and 6.5 for accepting pool volume (mL).With Q time t is made linear regression, the collinear slope of gained is steady-state permeation speed constant J
sThe result is as shown in table 1:
The transdermal experiment result (n=3) of table 1 solid dispersion suppository and physical mixture suppository
It is thus clear that the solid dispersion suppository of different carriers material and different proportion all is higher than physical mixture through the infiltration rate of dialyzer, its steady-state permeation speed is 2～3 times of physical mixture.
The pharmacodynamics test of embodiment 11, soy isoflavone vaginal suppository
PEG6000 with embodiment 3 preparations: ISO is that 2: 1 suppository is that example is carried out pharmacodynamic experiment.
Female Wistar rats is carried out bilateral oophorectomy.About postoperative 10 days, carry out vaginal smear and observed 4 days, show that like vaginal smear the sexual cycle disorder is the modeling success.
Per 10 one group of 60 rat of modeling success are divided into solid dispersion suppository group, physical mixture suppository group, crude drug suppository group, solid dispersion oral administration mixed suspension group, physical mixture oral administration mixed suspension group and crude drug oral administration mixed suspension group according to randomly assigne.The dosage administration once a day of press 0.1mg/100g in postoperative 15 days blood sampling back, respectively at one week of administration, two weeks, all around, six week the back take a blood sample, separation of serum carries out the mensuration of estradiol content with magnetic affinity immunoassay.The result is as shown in table 2.
Table 2 different tests group estradiol content is measured result (unit: pg/ml)
Table 2 is the result show: solid dispersion technology can significantly improve the regulating action of soybean isoflavone to the rat estrogen level; Postoperative rat estradiol level is all below determination limit, and the drug effect of solid dispersion suppository group and oral group all is superior to physical mixture group and crude drug group under the same terms after the medication.The drug effect of solid dispersion suppository group and oral group does not have notable difference, and the intravital estradiol content of rat reaches level before the art basically after the medication.Through vagina administration, help medicine to directly act on ovary, to treatment with alleviate the women causes because of estrogen deficiency before and after climacteric vaginal atrophy, drying, tickle and other symptom is expected to be superior to oral formulations.
Claims (7)
1. soy isoflavone vaginal suppository, the raw material of processing it comprises soy isoflavone solid dispersion and water-soluble base; Wherein, said soy isoflavone solid dispersion is processed by soybean isoflavone and solid hydrophilic dispersion carrier, and the mass ratio of said soybean isoflavone and solid hydrophilic dispersion carrier is 1: (1-20);
Said solid hydrophilic dispersion carrier adopts following 1)-4) in any one method prepare:
1) said soy isoflavone solid dispersion adopts solvent method to prepare, and said solid hydrophilic dispersion carrier is the hard ester acid of Polyethylene Glycol, polyvidone, a poloxamer or polyoxyethylene fat;
2) said soy isoflavone solid dispersion adopts fusion method to prepare, and said solid hydrophilic dispersion carrier is Polyethylene Glycol, carbamide, citric acid or succinic acid;
3) said soy isoflavone solid dispersion adopts freeze-drying to prepare, and said solid hydrophilic dispersion carrier is polyvidone, cyclodextrin, mannitol, lactose or gelatin hydrolysate;
4) said soy isoflavone solid dispersion adopts polishing to prepare, and said solid hydrophilic dispersion carrier is Macrogol 4000, polyethylene glycol 6000, microcrystalline Cellulose PH102, microcrystalline Cellulose PH301, microcrystalline Cellulose PH302, microcrystalline Cellulose PH M06, microcrystalline Cellulose PH M15, microcrystalline Cellulose PH M25, microcrystalline Cellulose PH KG801 and sodium carboxymethyl cellulose RC A591NF, cyclodextrin, 30 POVIDONE K 30 BP/USP 30 or lactose.
2. suppository according to claim 1 is characterized in that: said soy isoflavone vaginal suppository is processed by soy isoflavone solid dispersion and water-soluble base.
3. suppository according to claim 1 and 2 is characterized in that: the mass ratio of soy isoflavone solid dispersion and said water-soluble base described in the said soy isoflavone vaginal suppository is 1: (2-20).
4. suppository according to claim 1 is characterized in that: said water-soluble base is glycerol gelatin matrix, Polyethylene Glycol, polyoxyethylene monostearate or poloxamer.
5. suppository according to claim 4 is characterized in that: said water-soluble base is a glycerol gelatin matrix, and said glycerol gelatin matrix is made up of glycerol, gelatin, water, and wherein the mass ratio of glycerol, gelatin, water is 7: 2: 1.
6. suppository according to claim 1 is characterized in that: the particle diameter of said soy isoflavone solid dispersion is greater than 80 orders.
7. the method for preparing of the described soy isoflavone vaginal suppository of claim 1; Step is following: soy isoflavone solid dispersion is mixed with water-soluble base; Heating makes the mixture fusion, injects the bolt mould that has coated lubricant then, cools off under the room temperature; The demoulding promptly gets said soy isoflavone vaginal suppository;
The mass ratio of said soy isoflavone solid dispersion and said water-soluble base is 1: 2-20;
Said solid hydrophilic dispersion carrier adopts following 1)-4) in any one method prepare:
1) said soy isoflavone solid dispersion adopts solvent method to prepare, and said solid hydrophilic dispersion carrier is the hard ester acid of Polyethylene Glycol, polyvidone, a poloxamer or polyoxyethylene fat;
2) said soy isoflavone solid dispersion adopts fusion method to prepare, and said solid hydrophilic dispersion carrier is Polyethylene Glycol, carbamide, citric acid or succinic acid;
3) said soy isoflavone solid dispersion adopts freeze-drying to prepare, and said solid hydrophilic dispersion carrier is polyvidone, cyclodextrin, mannitol, lactose or gelatin hydrolysate;
4) said soy isoflavone solid dispersion adopts polishing to prepare, and said solid hydrophilic dispersion carrier is Macrogol 4000, polyethylene glycol 6000, microcrystalline Cellulose PH102, microcrystalline Cellulose PH301, microcrystalline Cellulose PH302, microcrystalline Cellulose PH M06, microcrystalline Cellulose PH M15, microcrystalline Cellulose PH M25, microcrystalline Cellulose PH KG801 and sodium carboxymethyl cellulose RC A591NF, cyclodextrin, 30 POVIDONE K 30 BP/USP 30 or lactose.
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| CN103110586B (en) * | 2013-01-17 | 2014-12-03 | 山西医科大学 | Method for preparing farrerol solid dispersion |
| CN106389335A (en) * | 2015-08-03 | 2017-02-15 | 高雄医学大学 | Preparation method of 7,3',4'-soy isoflavone preparation |
| CN111603447A (en) * | 2020-06-17 | 2020-09-01 | 新疆维吾尔自治区药物研究所 | Tilianin solid dispersion and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1233173A (en) * | 1996-08-30 | 1999-10-27 | 诺沃根研究有限公司 | Therapeutic methods and compositions involving isoflavones |
| CN1449763A (en) * | 2003-04-24 | 2003-10-22 | 沈阳药科大学 | Soy daidzin composition and preparation process and use thereof |
| CN1559606A (en) * | 2004-02-19 | 2005-01-05 | 复旦大学 | Cyclosporin A dispersion solid and its preparation method |
| CN1708490A (en) * | 2002-11-01 | 2005-12-14 | 诺沃根研究股份有限公司 | Aminated isoflavonoid derivatives and uses thereof |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1233173A (en) * | 1996-08-30 | 1999-10-27 | 诺沃根研究有限公司 | Therapeutic methods and compositions involving isoflavones |
| CN101006999A (en) * | 1996-08-30 | 2007-08-01 | 诺沃根研究有限公司 | Therapeutic methods and compositions involving isoflavones |
| CN1708490A (en) * | 2002-11-01 | 2005-12-14 | 诺沃根研究股份有限公司 | Aminated isoflavonoid derivatives and uses thereof |
| CN1449763A (en) * | 2003-04-24 | 2003-10-22 | 沈阳药科大学 | Soy daidzin composition and preparation process and use thereof |
| CN1559606A (en) * | 2004-02-19 | 2005-01-05 | 复旦大学 | Cyclosporin A dispersion solid and its preparation method |
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