CN103520635B - Compound zedoary oil expandable vaginal expansible plug and preparation method thereof and detection method - Google Patents
Compound zedoary oil expandable vaginal expansible plug and preparation method thereof and detection method Download PDFInfo
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Abstract
The present invention relates to a kind of compound zedoary oil expandable vaginal expansible plug and preparation method thereof and detection method; Described expansible plug comprises active component, substrate and expandable carrier, and described active component comprises imidazoles antimicrobial drug and Oleum Curcumae; Can increase dissolubility and the stability of Oleum Curcumae in the pastille substrate of described expansible plug containing polyvidone, described Mentholum can play the effect promoting active ingredient draws; Described compound zedoary oil expandable vaginal expansible plug is the double-deck expansible plug of hollow, and this suppository makes substrate and active component separately, further increases the stability of active component, can prevent the volatilization of Oleum Curcumae simultaneously, thus improves the curative effect of suppository; And described compound zedoary oil expandable vaginal expansible plug have employed six leading technologies of original creation, has and prevents medicinal liquid outflows, and stability is high, evident in efficacy beneficial effect of Denging.
Description
Technical field
The invention belongs to vaginal suppository field, particularly a kind of compound zedoary oil expandable vaginal expansible plug and preparation method thereof and detection method.
Background technology
Imidazoles antimicrobial drug is synthetic antibacterial drug, and the biosynthesis mainly through Antifungi cell membrane ergosterol plays antibacterial action, and described imidazoles antimicrobial drug mainly comprises econazole, metronidazole, clotrimazole or miconazole etc.The preparation of imidazoles antimicrobial drug described clinically at present comprises oral (tablet), injection and suppository etc., described oral and injection ubiquity the untoward reaction such as digestive tract, but described suppository can overcome above-mentioned untoward reaction, and the first pass effect of liver can be avoided.
In order to strengthen the antibacterial action of imidazoles antimicrobial drug further, imidazoles antimicrobial drug and Oleum Curcumae are made compound preparation to strengthen its curative effect by prior art, and described compound preparation is mainly used in treatment trichomonal vaginitis, reads the gynaecopathias such as coccus vulvovaginitis." chemical drugs provincial standard rising national standard " the 16th discloses the compound zedoary oil suppository be made up of econazole nitrate 50g, Oleum Curcumae 210ml and adjuvant; Prior art certain references discloses the suppository of compound zedoary oil in addition, such as, CN1449784 discloses three kinds of suppositorys of compound zedoary oil, comprise the ordinary suppository that the active component that is made up of Oleum Curcumae, econazole nitrate, Borneolum Syntheticum and water-soluble base are made, the capsule suppository that the glue shell be made up of gelatin, glycerol etc. and active component are made, the inclusion suppository be made up of beta-schardinger dextrin-, sorbitan monolaurate and active component; Above-mentioned part suppository solves the volatile feature of Oleum Curcumae, but due to grease nature instability, no matter makes clathrate and mix with substrate or directly mix with substrate, all can affect the stability of Oleum Curcumae.
But prior art is also few to the research of compound zedoary oil suppository, and following problem is had still to need to solve: 1. the cotton sliver in the suppository of traditional compound zedoary oil is without expansion, or it is unordered to expand, and greatly reduces clinical application; 2. release is fast, there is " peak valley " phenomenon; 3. method of quality control is unreliable, causes in actual production process, batch between content, stability, melt become the time limit alter a great deal; 4. the simple mixing of active component and adjuvant, can not give full play to the curative effect etc. of active component.
Summary of the invention
In order to solve the problems of the technologies described above, give full play to the curative effect of active component in compound zedoary oil suppository, the present invention have studied that a kind of stability is high, the compound zedoary oil expandable vaginal expansible plug that Oleum Curcumae can be suppressed to volatilize and preparation method thereof; Additionally provide a kind of science detection method that can control above-mentioned compound zedoary oil expandable vaginal expansible plug product quality simultaneously.
The concrete technical scheme of the present invention is as follows:
The invention provides a kind of compound zedoary oil expandable vaginal expansible plug, described expansible plug comprises active component, substrate and expandable expandable carrier, described active component comprises imidazoles antimicrobial drug and Oleum Curcumae, described active component and substrate formed pastille substrate are coated in expandable carrier surface, the swell value of described expandable carrier after saturated water suction is greater than 1.1, and the parts by weight of each composition of described expansible plug are:
Described substrate comprise in Acrawax, natural acid ester, lipoidis substrate, water-soluble base, gel-type vehicle, hydrogenated oil and fat, glyceride, distillate oil, wax work, stearate or colloidal compound one or more;
Described Acrawax comprise in mixed fatty glycerides, propylene glycol stearate, fixed oil, semi-synthetic fatty acid glyceride, semi-synthetic cocos nucifera oil ester, Witepsol, semi-synthetic Petiolus Trachycarpi grease or semi-synthetic Fructus Litseae ester one or more;
Described natural acid ester comprise in oleum sapii, Oleum Linderae, Fructus Foeniculi fat, Ke Kemu fat or cocoa butter one or more;
Described lipoidis substrate comprises lanoline or lanonol;
Described water-soluble base comprise in PEG400, polyethylene glycol 1500, Macrogol 4000, polyethylene glycol 6000, glycerin gelatine, polysorbate60, polysorbate65, polyethylene oxide condensate Idropostal, polyoxyethylene monostearate or poloxamer one or more;
Described gel-type vehicle comprise in sodium carboxymethyl cellulose, hypromellose, carbomer, alginic acid or sodium alginate one or more;
Described hydrogenated oil and fat comprise in hydrogenated vegetable oil, hydrogenated groundnut, castor oil hydrogenated or cotmar one or more;
Described glyceride comprises AdepsSolidus, MassaEstarinumA, MassaEstarinumAS, MassaEstarinumB, MassaEstarinumC, MassaEstarinumD, MassaEstarinumE, MassaEstarinumI, MassaEstarinumT, MassaMf13, SuppositoryBaseW, SuppositoryBaseAB, SuppositoryBaseA, SuppositoryBaseB, SuppositoryBaseBC, SuppositoryBaseBD, SuppositoryBaseBBC, SuppositoryBaseE, SuppositoryBaseBCF, SuppositoryBaseC, SuppositoryBaseD, SuppositoryBase299, WecobeeW, WecobeeK, WecobeeS, WecobeeM, WecobeeES, Massuppol, Massuppol15, SuppocireOSI, SuppocireOSIxSuppocireA, SuppocireB, SuppocireC, SuppocireD, SuppocireDM, SuppocireH, SuppocireL, TegesterTriglycerideBases-9, TegesterTriglycerideBases-MA, TegesterTriglycerideBases-57, tripalmitin, glycerol tristearate, one or more in Gan You behenic acid ester or lauric acid three ester,
Described distillate oil comprises fractionating palm oil or fractionated coconut oil;
Described wax work comprise in Brazil wax, spermaceti, cationic emulsified wax, Cera Flava or Cera Flava one or more;
Described stearate comprise in xylitan monostearate, stearic acid palm glycerides, polyethylene glycol mono stearate, ethylene glycol monostearate or glyceryl monostearate one or more;
Described colloidal compound comprise in arabic gum, gelatin or pectin one or more.
The substrate of English name of the present invention is included in " industrial pharmacy theory and practice " book (L. La Heman, H.A. profit Berman, J.L. card Buddhist nun is uncommon. industrial pharmacy theory and practice, Chemical Industry Press, the second edition: 215-217); The relative density of described Oleum Curcumae is 0.97-0.99.
Present invention employs " the intravaginal sticking type medicine-feeding technology " of original creation, this technology by adding expandable carrier to realize in suppository.Ordinary suppository is due to the relation of gravity, no matter user is standing, under sitting posture or formula position of lying, always there is vagina or lessly can not to touch pastille substrate, after described expandable carrier expands, pastille substrate can contact with vaginal walls in 360 °, abundant administration, administration enlarged areas 6 times, medicine directly attaches to lesions position, makes the position that originally cannot contact medicine also effectively can be attached treatment; And due to the buffer action that stype plays in the middle of vagina, make no longer to contact with each other between wound surface, thus avoid superinfection, make its no longer recurrent exerbation.In addition, the introducing of expandable carrier applies " lateral leakage protection key " design concept, because the expansion of expandable carrier tail end (non-pastille substrate), can be close to vaginal wall, and then prevent the outflow of medicine and substrate, reduce the pollution of medicated clothing and keep the valid density of medicine.And by " inner core coefficient of expansion control technology ", the swell value of expandable carrier after saturated water suction can be made to be greater than 1.1.
Further, the parts by weight of each composition of described expansible plug are:
Described imidazoles antimicrobial drug comprise in econazole nitrate, Metronidazole mononitrate., nitric acid clotrimazole or miconazole nitrate one or more; Described substrate is the mixture of wax work and natural acid ester, and the ratio of weight and number of described wax work and natural acid ester is 1:2-5; The fusing point of described mixed-matrix improves, and improves the technical problem that suppository chance high temperature easily melts, improves the stability of suppository.
Further, described imidazoles antimicrobial drug is econazole nitrate, and described wax work is cationic emulsified wax, and described natural acid ester is cocoa butter, and the parts by weight of each composition of described expansible plug are:
Preferably, the pastille substrate of compound zedoary oil expandable vaginal expansible plug of the present invention also comprises buffer agent, the polyvidone of 15-125 part and the stabilizing agent of 10-50 part that weight portion is 1-20 part, described buffer agent be selected from sodium citrate, sodium citrate or sodium hydrogen phosphate one or more, described stabilizing agent be selected from Emulsifier LM-102, citric acid fatty glyceride or sorbitan monolaurate one or more.
Imidazoles antimicrobial drug of the present invention is strong acid weak base salt, because vagina belongs to weak acid environment, suppository enters intravaginal, the specific weak acid environment of intravaginal can be affected, in order to maintain the itself clean function of vagina, present invention adds a certain amount of buffer agent, it can play the effect maintaining the specific weak acid environment of vagina; Described stabilizing agent not only plays the effect of stabilizing active ingredient, simultaneously can carry active component, play dispersion of active ingredients, make its dispersion in suppository evenly; Described a certain amount of polyvidone can as the carrier of grease Oleum Curcumae, increase the dissolubility of Oleum Curcumae medicine, the effect of stable Oleum Curcumae can also be played simultaneously, and because Oleum Curcumae is that grease is volatile, Oleum Curcumae is carried on polyvidone by the present invention, can be made into powder, decrease the volatilization of Oleum Curcumae.
Further preferably, pastille substrate of the present invention also comprises the Mentholum that weight portion is 10-60 part, and described Mentholum not only can promote the absorption of active component, and can cover the abnormal smells from the patient of Oleum Curcumae.
In prior art, mostly suppository Chinese medicine is mutually to mix with substrate, and there is profit assigning process, release is slow; In order to overcome the problems referred to above, compound zedoary oil expandable vaginal expansible plug is made hollow expansible plug by the present invention, the described pastille substrate being coated in described expandable carrier surface in described hollow expansible plug comprises medicated layer and hypothallus from inside to outside successively, described hypothallus comprises hollow shell and closed matrix layer, and the described expandable carrier part with medicated layer is surrounded by the closed space that described hollow shell and described closed matrix layer are formed; Described hypothallus is made up of substrate; Described medicated layer comprises Oleum Curcumae composition layer and is wrapped in the imidazoles antimicrobial drug composition layer outside Oleum Curcumae composition layer, described Oleum Curcumae composition layer comprises Oleum Curcumae, polyvidone and Mentholum, and described imidazoles antimicrobial drug composition layer comprises imidazoles antimicrobial drug, stabilizing agent, buffer agent and Mentholum.
Further preferred, the ratio of weight and number 8-45:2-15 of Mentholum in described Oleum Curcumae composition layer and imidazoles antimicrobial drug composition layer.
In expansible plug of the present invention, medicine and substrate are separated completely, more stable than ordinary suppository; There is not profit assigning process, drug releasing rate is fast simultaneously; In order to prevent the volatilization of Oleum Curcumae further, Oleum Curcumae is made different layers from imidazoles antimicrobial drug by the present invention respectively, and Oleum Curcumae compositions is positioned at innermost layer, can suppress the volatilization of Oleum Curcumae further; Mentholum is assigned in Oleum Curcumae compositions and imidazoles antimicrobial drug compositions by a certain amount of ratio of weight and number by the present invention, can ensure that vagina has good Absorption to active component in two compositionss.
The swell value of expandable carrier of the present invention after saturated water suction is greater than 1.5, and described swell value is radial swell value; Described expandable carrier includes but not limited to cotton sliver, also can comprise other sterilizable materials that can expand, as non-woven fabrics, elastic fiber etc.
Pastille substrate of the present invention is the 1/5-4/5 place, front end that Semi surrounding type is coated in described expandable carrier, according to " human engineering suppository " shape, is designed to the shapes such as duckbill, spherical, avette or bullet shaped, torpedo, cylindrical, conical or clavate.
The expandable carrier rear end of compound zedoary oil expandable vaginal expansible plug of the present invention is connected with bracing wire, stype after expansion, by the rear end bracing wire of tractive expandable carrier, be adsorbed on the virus be killed on expandable carrier, toxin, the dead bark that comes off also pull out external in the lump, change dressings at every turn and just equal to do to vagina once thoroughly to clean, fundamentally prevention of inflammation recurs again, and namely this expansible plug belongs to " the integrated dosage form for the treatment of cleaning ".
In order to reach compound zedoary oil expandable vaginal expansible plug of the present invention meet water can the effect of undergoes rapid expansion, after described expandable carrier water suction, the maximum water absorption of every is not less than 1.5 milliliters.Suitable water absorption, can ensure the swell value be suitable for, too low or too high water absorption, all can cause bad impact.When water absorption is too low, the feature that namely compound zedoary oil expandable vaginal expansible plug of the present invention chance water expand can not be ensured and make expansion insufficient; When water absorption is too high, the absorption ingredient that expandable carrier can be too much and limit its diffusion.Therefore, water absorption is too low or too high, is not the expandable carrier desired by the present invention.
The invention provides the preparation method of compound zedoary oil expandable vaginal expansible plug, described method comprises the steps:
1) preparation of hypothallus: get substrate and be placed in water-bath heating and melting, obtained fused mass, by a part of fused mass injection bolt mould, places, upset bolt mould, the not solidifying fused mass in centre is flowed out, forms cavity;
2) preparation of imidazoles antimicrobial drug composition layer:
A. imidazoles antimicrobial drug is crossed 80-100 mesh sieve, mix homogeneously with buffer agent, stabilizing agent, obtained mixture;
B. Mentholum is placed in water-bath heating and melting, adds the mixture of step a under stirring, mix homogeneously, obtained imidazoles antimicrobial drug compositions;
C. by vertical for duroplasts inserting step 1) cavity in, described imidazoles antimicrobial drug compositions is filled in cavity, cool qualitative after, extract hard plastic charge bar, formed containing the imidazoles antimicrobial drug composition layer of internal cavities;
3) by the internal cavities described in 1/5-4/5 place, expandable carrier front end inserting step c, the cavity containing expandable carrier is formed;
4) preparation of Oleum Curcumae composition layer:
D. polyvidone is mixed homogeneously with Oleum Curcumae, obtained mixture;
E. Mentholum is placed in water-bath heating and melting, adds the mixture of steps d under stirring, mix homogeneously, obtained Oleum Curcumae compositions;
F. the Oleum Curcumae compositions of step e is filled in the cavity containing expandable carrier described in step 3), forms Oleum Curcumae composition layer;
5) another part fused mass sealing by fusing described in afterbody step 1), form closed matrix layer, cooling and shaping, makes suppository.
The preparation method of compound zedoary oil expandable vaginal expansible plug of the present invention have employed " the integrally formed technology of the disposable fill of stype ".
The present invention additionally provides the detection method of described compound zedoary oil expandable vaginal expansible plug on the other hand, and described detection method comprises swell value assay method, weight differential detection method, assay etc.
Wherein said swell value assay method comprises:
A. the radial direction along described compound zedoary oil expandable vaginal expansible plug end face is chosen a bit or some points, measures the initial length H of described expandable carrier;
B., after the saturated water suction of described compound zedoary oil expandable vaginal expansible plug, expandable carrier expansion rear length h in selected location place in a step is determined at;
When c. calculating described swell value, calculate according to I formula;
（I）
Wherein, p represent axial swell value, h represent expand after length, H represent initial length;
Or described swell value assay method is as follows:
A. the axis along described compound zedoary oil expandable vaginal expansible plug chooses a place or some positions, measures the initial diameter R of described expandable carrier;
B., after the saturated water suction of described compound zedoary oil expandable vaginal expansible plug, selected location place expandable carrier expanded diameter r in a step is determined at;
When c. calculating described swell value, calculate by II formula;
（II）
Wherein, P represents the swell value of radial direction, r represents expanded diameter, R represents initial diameter; Described weight differential assay method comprises:
A. get described compound zedoary oil expandable vaginal expansible plug, take weight M;
B. the expandable carrier scraped in the described compound zedoary oil expandable vaginal expansible plug of pastille substrate is got, dry, take weight m, the weight X according to pastille substrate as described in formula III calculating:
X=M-m
（Ⅲ）。
Further, in the detection method of compound zedoary oil expandable vaginal expansible plug of the present invention, after carrying out melting the detection of change time limit, then carry out following at least one detection method:
1) swell value assay method is as follows:
A. first choose a bit or some points along the radial direction of described compound zedoary oil expandable vaginal expansible plug end face, after measuring the initial length H of described expandable carrier, then different angles of rolling measure several times, and average Hi;
B., after described compound zedoary oil expandable vaginal expansible plug carries out melting the detection of change time limit, expandable carrier expansion rear length h in selected location place in a step is determined at; Different angles of rolling again measure several times, ask average length hi after expanding;
When c. calculating described swell value, calculate according to I formula;
（I）
Wherein, pi represent axial swell value, hi represent expand after average length, Hi represent average initial length; Or described swell value assay method is as follows:
A. first choose a place or some positions an angle along the axis of described compound zedoary oil expandable vaginal expansible plug, after measuring the initial diameter R of described expandable carrier, then different angles of rolling measure several times, and average Ri;
B., after described compound zedoary oil expandable vaginal expansible plug carries out melting the detection of change time limit, selected location place expandable carrier expanded diameter r in a step is determined at; Different angles of rolling again measure several times, ask average diameter ri after expanding;
When c. calculating described swell value, calculate by II formula;
（II）
Wherein, Pi represents the swell value of radial direction, ri represents the rear average diameter that expands, Ri represents average initial diameter.
Wherein said melt become time limit assay method (existing Chinese Pharmacopoeia two annex) comprising: get described compound zedoary oil expandable vaginal expansible plug 3, after room temperature places 1 hour, be placed on respectively on lower floor's plectane of 3 metal rack, load in respective sleeve pipe, and fixing with hook.Unless otherwise specified, be dipped vertically into respectively by said apparatus in the container filling 37.0 ± 0.5 DEG C of water being no less than 4L, its upper end position at 90mm place, underwater, should fill a rot, overturn this device in the solution once every 10 minutes in container.Above numerical range should not be construed as limitation of the present invention, and the technical scheme not in above-mentioned numerical range is also in protection scope of the present invention.
2) weight differential assay method:
A. get described compound zedoary oil expandable vaginal expansible plug, take weight M;
B. scrape pastille substrate, expandable carrier is placed in 20-90 DEG C of organic solvent, take out, in 50-150 DEG C of dry 1-10h, take weight m, according to the weight X of pastille substrate as described in III formula calculating
X=M-m（Ⅲ）
Wherein, described organic solvent is selected from one or more in ethanol, methanol or isopropyl alcohol.
Further, in the detection method of compound zedoary oil expandable vaginal expansible plug of the present invention, described expandable carrier is cotton sliver, and described detection method comprises following at least one method:
1) swell value assay method:
Get described compound zedoary oil expandable vaginal expansible plug 3, survey its afterbody cotton sliver diameter with slide gauge, roll about 90 ° and survey once again, survey twice for every, obtain every 2 meansigma methods Ri measured; Above-mentioned 3 bolts are used for melt and become after the time limit measures and terminate, take out residue cotton sliver immediately, treat that water is disconnected to drip, all gently be placed on glass plate, measure the two ends of each cotton sliver and middle three positions with slide gauge, roll after about 90 ° and measure three positions again, each cotton sliver obtains six data altogether, obtain 6 meansigma methods ri of mensuration, calculate the swell value Pi of every, the swell value of three bolts all should be greater than 1.5.
2) weight differential assay method:
Get described compound zedoary oil expandable vaginal expansible plug 10, accurately weighed weight respectively, gently scrape pastille substrate (cotton sliver must not be lost), cotton sliver is placed in the 200-400ml ethanol of 50-80 DEG C, preferably, cotton sliver is placed in the 300ml ethanol of 60-70 DEG C, and clean 5 minutes at 80khz frequency ultrasound, the stromatolysis of cotton sliver surface residual is removed, take out cotton sliver firmly to extract, 3 times are inhaled again with filter paper, in 105 DEG C of dryings 2 hours, take out, after room temperature places 1 hour, accurately weighed cotton sliver weight respectively, obtain every pastille matrix weight and average pastille matrix weight, every pastille matrix weight compares with average pastille matrix weight, what exceed average pastille matrix weight ± 10% must not more than 2, and 1 overrun 1 times must not be had.
The assay method of the swell value of compound zedoary oil expandable vaginal expansible plug provided by the present invention adopts multi-angle repetitive measurement method, improves the accuracy of measurement, adds the operability of mensuration, and method is easier to judge; When the standard detection performing state-promulgated pharmacopoeia annex weight differential compound zedoary oil expandable vaginal expansible plug of the present invention, substrate need be scraped off, the scraping degree grasped due to operator is different, cause every scraping degree difference comparatively large, so the present invention adopts the substrate on dissolution with solvents expansible plug surface, through verification experimental verification, when adopting the substrate on hot ethanol cleaning expansible plug surface, result is better, and repeatability is higher, and described weight differential assay method is more convenient stable.
Described content assaying method is according to Chinese Pharmacopoeia annex V D high effective liquid chromatography for measuring.
Chromatographic condition and system suitability octadecylsilane chemically bonded silica are filler; So that Spirit of Mindererus. (get ammonium acetate 0.77g, the l000ml that adds water makes dissolving)-second eyeball (25:75) is mobile phase; Determined wavelength is 210nm.Manage the plate number that falls and be not less than 4000 by the calculating of imidazoles antimicrobial drug peak, the separating degree of imidazoles antimicrobial drug peak, Mang cattle ketone peak and adjacent peak should meet the requirements.
Algoscopy gets described compound zedoary oil expandable vaginal expansible plug 10, accurately weighed, chopping, mixing, precision takes in right amount (being about equivalent to imidazoles antimicrobial drug 50mg), puts in 50m1 measuring bottle. and add methanol appropriate, ultrasonic imidazoles antimicrobial drug and the Mang cattle ketone of making dissolves and is diluted to scale, shake up (if any precipitation, filter. get subsequent filtrate); Precision measures 5m1, puts in 50m1 measuring bottle, is diluted to scale with mobile phase, shake up; Precision measures 20 μ l, injection liquid chromatography, record chromatogram.Get imidazoles antimicrobial drug reference substance 25mg and Mang cattle ketone reference substance is about l0mg, accurately weighed, put in 50ml measuring bottle, add that first is liquor-saturated to be made dissolving and be diluted to scale, shake up, precision measures 5m1, puts in 25m1 measuring bottle, is diluted to scale with mobile phase, shake up, be measured in the same method.By external standard method with calculated by peak area, to obtain final product.
Compound zedoary oil expandable vaginal expansible plug provided by the present invention has stability height and waits beneficial effect; " the disposable fill of stype the is integrally formed " technology the adding of expandable carrier in described compound zedoary oil expandable vaginal expansible plug applying original creation, " control of the inner core coefficient of expansion " technology, " human engineering bolt type " technology, " the clean integration for the treatment of " dosage form, " administration of intravaginal sticking type " technology, " design of lateral leakage protection key " six technology, this expandable carrier can make the pastille substrate of compound zedoary oil expandable vaginal expansible plug fully contact with vaginal walls, and prevents medicinal liquid from outflowing; Also there is effect that cleaning vagina prevents superinfection; The buffer agent added in compound zedoary oil expandable vaginal expansible plug of the present invention can play the effect of buffering intravaginal pH value, keeps the specific acid environment of intravaginal; Described polyvidone can promote the volatilization of Oleum Curcumae, increases stability and the dissolubility of Oleum Curcumae; Described Mentholum can promote that vagina is to the absorption of active component, increases the curative effect of suppository; The double-deck expansible plug of described hollow can increase the stability of suppository further, prevents the volatilization of Oleum Curcumae.
Accompanying drawing explanation
The schematic diagram of Fig. 1 and Fig. 2 swell value assay method;
The structural representation of Fig. 3 hollow vaginal expansion plug;
1-hollow shell 2-closed matrix layer 3-medicated layer 4-expandable carrier 5-bracing wire
Detailed description of the invention
Embodiment 1
Preparation method:
1) preparation of pastille substrate:
A. polyoxyethylene monostearate and polysorbate60 are placed in water-bath heating and melting;
B. econazole nitrate is crossed 80 mesh sieves, mix homogeneously with Oleum Curcumae, obtained mixture;
C. the mixture of b step is added in a step, mix homogeneously, obtained pastille substrate;
2) pour in bolt film by pastille substrate, insert cotton sliver, cooling and shaping, makes 100 pieces of spherical suppositorys, every piece of heavily about 2.2g.
Embodiment 2
Preparation method: make 100 pieces of torpedo suppositorys by embodiment 1 method, every piece of heavily about 3.7g.
Embodiment 3
Preparation method:
1) preparation of pastille substrate:
A. taking polyethylene glycol 4000, polyethylene glycol 6000 and castor oil hydrogenated are placed in water-bath heating and melting, obtained fused mass;
B. econazole nitrate is crossed 100 mesh sieves, mix homogeneously with sodium citrate and Emulsifier LM-102, obtained econazole nitrate compositions;
C. polyvidone is mixed homogeneously with Oleum Curcumae, obtained Oleum Curcumae compositions;
D. by econazole nitrate compositions and Oleum Curcumae compositions mix homogeneously, under stirring, a is added
In fused mass described in step, mix homogeneously, obtained pastille substrate;
2) pastille substrate is poured in bolt mould, cool qualitative, obtained cylindrical 100 pieces of cylindrical suppositorys, every piece of heavily about 4.7g.
Embodiment 4
Preparation method: make 100 pieces of avette suppositorys by embodiment 3 method, every piece of heavily about 5.0g.
Embodiment 5
Preparation method:
1) preparation of pastille substrate:
A. get mixed fatty glycerides, lanoline and propylene glycol stearate and be placed in water-bath heating and melting, obtained fused mass;
B. econazole nitrate is crossed 80 mesh sieves, mix homogeneously with sodium hydrogen phosphate and citric acid fatty glyceride, sorbitan monolaurate, obtained econazole nitrate compositions;
C. polyvidone is mixed homogeneously with Oleum Curcumae, obtained Oleum Curcumae compositions;
D. Mentholum is placed in water-bath heating and melting, adds econazole nitrate compositions and Oleum Curcumae compositions under stirring, mix homogeneously, obtained mixture;
E. add in fused mass described in step a under steps d mixture being stirred, mix homogeneously, obtained pastille substrate;
2) pastille substrate is poured in bolt mould, cool qualitative, obtained cylindrical 100 pieces of bullet shaped suppositorys, every piece of heavily about 3.5g.
Embodiment 6
Preparation method: make 100 pieces of clavate suppositorys by embodiment 5 method, every piece of heavily about 3.6g.
Embodiment 7
Preparation method:
1) preparation of hypothallus: get cationic emulsified wax and cocoa butter and be placed in water-bath and add hot melt
Melt, obtained fused mass, by a part of fused mass injection bolt mould, place, upset bolt mould,
The not solidifying fused mass in centre is flowed out, forms cavity;
2) preparation of imidazoles antimicrobial drug composition layer:
A. econazole nitrate is crossed 80 mesh sieves, mix homogeneously with sodium citrate, citric acid fatty glyceride, obtained mixture;
B. Mentholum is placed in water-bath heating and melting, adds the mixture of step a under stirring, mix homogeneously, obtained econazole nitrate compositions;
C. by vertical for duroplasts inserting step 1) cavity in, described econazole nitrate compositions is filled in cavity, cool qualitative after, extract hard plastic charge bar, formed containing the econazole nitrate composition layer of internal cavities;
3) by the internal cavities described in 1/5-4/5 place, expandable carrier front end inserting step c, the cavity containing expandable carrier is formed;
4) preparation of Oleum Curcumae composition layer:
D. polyvidone is mixed homogeneously with Oleum Curcumae, obtained mixture;
E. Mentholum is placed in water-bath heating and melting, adds the mixture of steps d under stirring, mix homogeneously, obtained Oleum Curcumae compositions;
F. the Oleum Curcumae compositions of step e is filled in the cavity containing expandable carrier described in step 3), forms Oleum Curcumae composition layer;
5) another part fused mass sealing by fusing described in afterbody step 1), forms closed matrix layer, cooling and shaping, obtained 100 pieces of duckbill suppositorys, every piece of heavily about 3.8g.
Embodiment 8
Preparation method: make 100 pieces of torpedo suppositorys by embodiment 7 method, every piece of heavily about 4.4g.
Embodiment 9
Preparation method: make 100 pieces of conical suppositorys by embodiment 7 method, every piece of heavily about 1.3g.
Test example 1 stability test
1. accelerated test
Compound zedoary oil expandable vaginal expansible plug described in Example 2-9 and common Compound Zedoary Turmeric Oil Suppositories, all at constant temperature 30 DEG C ± 2 DEG C, relative humidity is place 6 months under the constant humidity condition of 65% ± 5%, sample respectively once 1 month, 2 months, 3 months, 6 the end of month at duration of test, by the regulation in Chinese Pharmacopoeia, detect expansible plug character, containing imidazoles antimicrobial drug labelled amount (%), melt become the time limit; The accelerated test of the compound zedoary oil expandable vaginal expansible plug described in embodiment 2-8 the results are shown in Table 1, and the compound zedoary oil expandable vaginal expansible plug described in embodiment 9 and the accelerated test of common Compound Zedoary Turmeric Oil Suppositories the results are shown in Table 2.
The accelerated test result of the compound zedoary oil expandable vaginal expansible plug of table 1 embodiment 2-8
The compound zedoary oil expandable vaginal expansible plug of table 2 embodiment 9 and the accelerated test result of Compound Zedoary Turmeric Oil Suppositories
Compound zedoary oil expandable vaginal expansible plug as can be seen from the table described in embodiment of the present invention 2-9, under the environment of constant temperature high humidity, places after 6 months, the color of described expansible plug, the labelled amount containing imidazoles antimicrobial drug, melt become the time limit all there is not obvious change; And common compound zedoary oil suppository is placed after 3 months under high humidity, suppository color changes, and speckle appears in suppository surface, part suppository generation fracture phenomena; And in described compound zedoary oil suppository, the content of imidazoles antimicrobial drug significantly declines, and melts change duration; Show that compound zedoary oil expandable vaginal expansible plug of the present invention stability compared with compound zedoary oil suppository significantly improves.
2. long term test
Compound zedoary oil expandable vaginal expansible plug described in Example 2-9 and common Compound Zedoary Turmeric Oil Suppositories, at temperature 25 DEG C ± 2 DEG C, relative humidity is place 36 months under the condition of 60% ± 10%, sampling in every 3 months once, respectively at 0 month, 3 months, 6 months, 9 months, sampling in 12 months, detect the character of expansible plug, containing the labelled amount (%) of imidazoles antimicrobial drug, melt and become the time limit, after 12 months, still need to continue to investigate index of correlation, respectively at 18 months, 24 months, sampling in 36 months detects, and testing result compared with 0 month, the long-term test results of the compound zedoary oil expandable vaginal expansible plug described in embodiment 2-5 is in table 3, the long-term test results of the compound zedoary oil expandable vaginal expansible plug described in embodiment 6-8 is in table 4, compound zedoary oil expandable vaginal expansible plug described in described 9 and the long-term test results of Compound Zedoary Turmeric Oil Suppositories are in table 5,
The long-term test results of the compound zedoary oil expandable vaginal expansible plug described in table 3 embodiment 2-5
The long-term test results of the compound zedoary oil expandable vaginal expansible plug of table 4 embodiment 6-8
The compound zedoary oil expandable vaginal expansible plug of table 5 embodiment 9 and the long-term test results of Compound Zedoary Turmeric Oil Suppositories
Compound zedoary oil expandable vaginal expansible plug as can be seen from the table described in embodiment 2-9, under the environment of constant temperature high humidity, places after 36 months, the color of described expansible plug, the labelled amount containing imidazoles antimicrobial drug, melt become the time limit all there is not obvious change; And after common compound zedoary oil suppository places 9 months, suppository color changes, and speckle appears in suppository surface, and part suppository breaks; And the content of imidazoles antimicrobial drug significantly declines in compound zedoary oil suppository, melt and become time limit significant prolongation; Show that compound zedoary oil expandable vaginal expansible plug of the present invention stability compared with compound zedoary oil suppository significantly improves.
Test example 2 swell value determination test
Method one
Get described compound zedoary oil expandable vaginal expansible plug 3, survey its afterbody cotton sliver diameter with slide gauge, roll about 90 ° and survey once again, survey twice for every, obtain every 2 meansigma methods Ri measured; Above-mentioned 3 bolts are used for melt and become after the time limit measures and terminate, take out residue cotton sliver immediately, treat that water is disconnected to drip, all gently be placed on glass plate, measure the two ends of each cotton sliver and middle three positions with slide gauge, roll after about 90 ° and measure three positions again, each cotton sliver obtains six data altogether, obtain 6 meansigma methods ri of mensuration, calculate the swell value Pi of every, the swell value of three bolts is all greater than 1.5.
The swell value of compound zedoary oil expandable vaginal expansible plug described in embodiment 1-8 is measured according to above-mentioned swell value assay method, as shown in table 6;
The swell value of table 6 embodiment 1-9 compound zedoary oil expandable vaginal expansible plug
Method two
As depicted in figs. 1 and 2:
1) swell value assay method:
A. first C1, C2, C3 tri-points are chosen along the radial direction of described vaginal expansion plug end face, measure initial length H1, H2, H3 of described expandable carrier with slide gauge after, roll again 90 ° and measure, choose after C1, C4, C5 tri-some slide gaugies measure initial length H4, H5, H6 of described expandable carrier along the radial direction of described vaginal expansion plug end face, ask the meansigma methods Hi of H1, H2, H3, H4, H5 and H6;
B., after described vaginal expansion plug carries out melting the detection of change time limit, C1, C2, C3 selected in a step tri-rear length h1 of position expandable carrier expansion, h2, h3 is determined at slide gauge; Roll 90 ° again, be determined at C1, C4, C5 selected in a step tri-rear length h4 of position expandable carrier expansion, h5, h6 with slide gauge, ask the average length of h1, h2, h3, h4, h5 and h6, be average length hi after expanding;
When c. calculating described swell value, calculate according to I formula;
（I）
Wherein, pi represent axial swell value, hi represent expand after average length, Hi represent average initial length;
Or, swell value assay method:
D. first A1, A2 and A3 tri-points are chosen an angle along the axis of described vaginal expansion plug, measure initial diameter R1, R2 and R3 of described expandable carrier with slide gauge after, roll 90 ° again, axis along described vaginal expansion plug chooses B1, B2 and B3 tri-points, measure initial diameter R4, R5 and R6 of described expandable carrier with slide gauge after, ask the meansigma methods Ri of R1, R2, R3, R4, R5 and R6 six initial diameters;
E. after described vaginal expansion plug carries out melting the detection of change time limit, be determined at selected A1, A2 and A3 position expandable carrier expanded diameter in d step and be respectively r1, r2 and r3, B1, B2 and B3 position expandable carrier expanded diameter measured selected by d step that rolls again 90 ° is respectively r4, r5 and r6, ask the meansigma methods of r1, r2, r3, r4, r5 and r6, average diameter ri after must expanding;
When f. calculating described swell value, calculate by II formula;
（II）
Wherein, Pi represents the swell value of radial direction, ri represents the rear average diameter that expands, Ri represents flat
Equal initial diameter.
Test example 3 weight differential determination test
Get described compound zedoary oil expandable vaginal expansible plug 10, accurately weighed weight respectively, gently scrape pastille substrate (cotton sliver must not be lost), cotton sliver is placed in the 300ml ethanol of 60-70 DEG C, and clean 5 minutes at 80khz frequency ultrasound, the stromatolysis of cotton sliver surface residual is removed, take out cotton sliver firmly to extract, 3 times are inhaled again with filter paper, in 105 DEG C of dryings 2 hours, take out, after room temperature places 1 hour, accurately weighed cotton sliver weight respectively, obtain every pastille matrix weight and average pastille matrix weight, every pastille matrix weight compares with average pastille matrix weight, what exceed average pastille matrix weight ± 10% must not more than 2, and 1 overrun 1 times must not be had.
Repeat aforesaid operations, detect the compound zedoary oil expandable vaginal expansible plug described in embodiment 1-9, the equal conformance with standard of its weight differential.
Test example 4: clinical trial
One, research method
(1) research approach is formulated about " clinical verification of department of obstetrics and gynecology urogenital tract infection local application " content with reference to Ministry of Health of the People's Republic of China's new drug clinical guidance principle.
(2) diagnostic criteria
1, symptom: mainly thin cystose leucorrhoea grow in quantity or have more white bean dregs sample leucorrhea and pruritus vulvae, with burn feeling, pain, can have abnormal flavour, urgent micturition, dysurea;
2, gynecologial examination: the foam sample of itching of vulva, volume or bean dregs sample vaginal secretions, find vaginal mucosa and ectocervical obviously congested, and having petechia, intravaginal has a large amount of leucorrhea, in canescence, lark thin foam sample liquid body or be yellow green purulent secretion; Swelling of external genitals, epidermis can strip off, and can have scratch;
3. lab testing: vaginal secretions checked under the microscope, visible infusorian or do vaginal secretions plate coating checking, sees that spore and the pseudohypha rate of being positive can reach more than 60%.
(3) case standard is tested
Include case history standard in: 20-60 year, meet gynaecopathia diagnosis married woman.
(4) Therapeutic Method
1, treatment group: use the compound zedoary oil expandable vaginal expansible plug described in embodiment 7, every day one, being used in conjunction 6 days is a course for the treatment of, adheres to 2 courses for the treatment of;
2, matched group: use Compound Zedoary Turmeric Oil Suppositories treatment, every day one, being used in conjunction 6 days is a course for the treatment of, adheres to 2 courses for the treatment of.
(5) observation item
Therapeutic is observed
(1) symptom: whether take a turn for the better or disappear;
(2) gynecologial examination: comprise pudendum, vagina, cervix uteri and vaginal secretions inspection;
(3) lab testing: to vaginal secretions inspection, under comprising mirror, smear.
(6) curative effect determinate standard
1, fully recover: transference cure, gynecologial examination and lab testing normal;
2, effective: symptom obviously alleviates, gynecologial examination and lab testing are clearly better;
3, effective: symptom alleviates to some extent, gynecologial examination and lab testing take a turn for the better;
4, invalid: unchanged before and after treatment.
Two, therapeutic outcome
(1) two group is compared in table 7 to the therapeutic effect of trichomonal vaginitis;
Table 7 liang group is to the therapeutic effect of trichomonal vaginitis
Two groups of comparitive study treatment groups are better than matched group.
(2) two groups are compared in table 8 to the therapeutic effect reading coccus vulvovaginitis;
Table 8 liang group is to the therapeutic effect reading coccus vulvovaginitis
Two groups of comparitive study treatment groups are better than matched group.
Three, conclusion
Compound zedoary oil expandable vaginal expansible plug has good therapeutic effect to trichomonal vaginitis and the coccus vulvovaginitis of thought, and effective percentage all reaches more than 95%, and curative effect is better than matched group; In its curative effect process of checking, do not find toxic and side effects, safe and reliable, evident in efficacy.
Claims (9)
1. a compound zedoary oil expandable vaginal expansible plug, it is characterized in that, described expansible plug comprises active component, substrate and expandable expandable carrier, described active component comprises imidazoles antimicrobial drug and Oleum Curcumae, described active component and substrate formed pastille substrate are coated in expandable carrier surface, the swell value of described expandable carrier after saturated water suction is greater than 1.1, and the parts by weight of each composition of described expansible plug are:
Described substrate be selected from Acrawax, natural acid ester, lipoidis substrate, water-soluble base, hydrogenated oil and fat, distillate oil, wax work or colloidal compound one or more;
Described Acrawax be selected from mixed fatty glycerides, propylene glycol stearate, fixed oil, semi-synthetic fatty acid glyceride, semi-synthetic cocos nucifera oil ester, semi-synthetic Petiolus Trachycarpi grease or semi-synthetic Fructus Litseae ester one or more;
Described natural acid ester be selected from oleum sapii, Oleum Linderae, Fructus Foeniculi fat, Ke Kemu fat or cocoa butter one or more;
Described lipoidis substrate is selected from lanoline or lanonol;
Described water-soluble base be selected from PEG400, polyethylene glycol 1500, Macrogol 4000, polyethylene glycol 6000, glycerin gelatine, polysorbate60, polysorbate65, polyoxyethylene monostearate or poloxamer one or more;
Described hydrogenated oil and fat be selected from hydrogenated vegetable oil, hydrogenated groundnut, castor oil hydrogenated or cotmar one or more;
Described distillate oil is selected from fractionating palm oil or fractionated coconut oil;
Described wax work be selected from Brazil wax, spermaceti, cationic emulsified wax, Cera Flava or Cera Flava one or more;
Described pastille substrate also comprises buffer agent, the polyvidone of 15-125 part and the stabilizing agent of 10-50 part that weight portion is 1-20 part; Described buffer agent be selected from sodium citrate, sodium citrate or sodium hydrogen phosphate one or more, described stabilizing agent be selected from Emulsifier LM-102, citric acid fatty glyceride or sorbitan monolaurate one or more;
Described pastille substrate also comprises the Mentholum that weight portion is 10-60 part;
The described pastille substrate being coated in described expandable carrier surface comprises medicated layer and hypothallus from inside to outside successively, described hypothallus comprises hollow shell and closed matrix layer, and the described expandable carrier part with medicated layer is surrounded by the closed space that described hollow shell and described closed matrix layer are formed; Described hypothallus is made up of substrate; Described medicated layer comprises Oleum Curcumae composition layer and is wrapped in the imidazoles antimicrobial drug composition layer outside Oleum Curcumae composition layer, described Oleum Curcumae composition layer comprises Oleum Curcumae, polyvidone and Mentholum, and described imidazoles antimicrobial drug composition layer comprises imidazoles antimicrobial drug, stabilizing agent, buffer agent and Mentholum.
2. compound zedoary oil expandable vaginal expansible plug as claimed in claim 1, it is characterized in that, the parts by weight of each composition of described expansible plug are:
Described imidazoles antimicrobial drug comprise in econazole nitrate, Metronidazole mononitrate., nitric acid clotrimazole or miconazole nitrate one or more; Described substrate is the mixture of wax work and natural acid ester, and the ratio of weight and number of described wax work and natural acid ester is 1:2-5.
3. compound zedoary oil expandable vaginal expansible plug as claimed in claim 2, it is characterized in that, described imidazoles antimicrobial drug is econazole nitrate, and described wax work is cationic emulsified wax, described natural acid ester is cocoa butter, and the parts by weight of each composition of described expansible plug are:
4. compound zedoary oil expandable vaginal expansible plug as claimed in claim 1, is characterized in that, in described Oleum Curcumae composition layer and imidazoles antimicrobial drug composition layer, the ratio of weight and number of Mentholum is 8-45:2-15.
5. the compound zedoary oil expandable vaginal expansible plug as described in as arbitrary in claim 1-4, it is characterized in that, the swell value of described expandable carrier after saturated water suction is greater than 1.5, and described swell value is radial swell value; Described expandable carrier is cotton sliver; Described pastille substrate is the 1/5-4/5 place, front end that Semi surrounding type is coated in described expandable carrier, and the rear end of described expandable carrier is connected with bracing wire; After described expandable carrier water suction, the maximum water absorption of every is not less than 1.5 milliliters; The detection method of described compound zedoary oil expandable vaginal expansible plug comprises following at least one method:
1) swell value assay method is as follows:
A. the radial direction along described compound zedoary oil expandable vaginal expansible plug end face is chosen a bit or some points, measures the initial length H of described expandable carrier;
B., after the saturated water suction of described compound zedoary oil expandable vaginal expansible plug, expandable carrier expansion rear length h in selected location place in a step is determined at;
When c. calculating described swell value, calculate according to I formula;
Wherein, p represent axial swell value, h represent expand after length, H represent initial length; Or swell value assay method is as follows:
A. the axis along described compound zedoary oil expandable vaginal expansible plug chooses a place or some positions, measures the initial diameter R of described expandable carrier;
B., after the saturated water suction of described compound zedoary oil expandable vaginal expansible plug, selected location place expandable carrier expanded diameter r in a step is determined at;
When c. calculating described swell value, calculate by II formula;
Wherein, P represents the swell value of radial direction, r represents expanded diameter, R represents initial diameter;
2) weight differential assay method:
A. get described compound zedoary oil expandable vaginal expansible plug, take weight M;
B. the expandable carrier scraped in the described compound zedoary oil expandable vaginal expansible plug of pastille substrate is got, dry, take weight m, the weight X according to pastille substrate as described in formula III calculating:
X＝M-m
(Ⅲ)。
6. the preparation method of compound zedoary oil expandable vaginal expansible plug as claimed in claim 4, it is characterized in that, described method comprises the steps:
1) preparation of hypothallus: get substrate and be placed in water-bath heating and melting, obtained fused mass, by a part of fused mass injection bolt mould, places, upset bolt mould, the not solidifying fused mass in centre is flowed out, forms cavity;
2) preparation of imidazoles antimicrobial drug composition layer:
A. imidazoles antimicrobial drug is crossed 80-100 mesh sieve, mix homogeneously with buffer agent, stabilizing agent, obtained mixture;
B. Mentholum is placed in water-bath heating and melting, adds the mixture of step a under stirring, mix homogeneously, obtained imidazoles antimicrobial drug compositions;
C. by vertical for duroplasts inserting step 1) cavity in, described imidazoles antimicrobial drug compositions is filled in cavity, cool qualitative after, extract hard plastic charge bar, formed containing the imidazoles antimicrobial drug composition layer of internal cavities;
3) by the internal cavities described in 1/5-4/5 place, expandable carrier front end inserting step c, the cavity containing expandable carrier is formed;
4) preparation of Oleum Curcumae composition layer:
D. polyvidone is mixed homogeneously with Oleum Curcumae, obtained mixture;
E. Mentholum is placed in water-bath heating and melting, adds the mixture of steps d under stirring, mix homogeneously, obtained Oleum Curcumae compositions;
F. the Oleum Curcumae compositions of step e is filled into step 3) described in containing in the cavity of expandable carrier, form Oleum Curcumae composition layer;
5) afterbody step 1) described in another part fused mass sealing by fusing, form closed matrix layer, cooling and shaping, makes suppository.
7. compound zedoary oil expandable vaginal expansible plug as claimed in claim 5, is characterized in that, after carrying out melting the detection of change time limit, then carries out following at least one detection method:
1) swell value assay method is as follows:
A. first choose a bit or some points along the radial direction of described compound zedoary oil expandable vaginal expansible plug end face, after measuring the initial length H of described expandable carrier, then different angles of rolling measure several times, and average Hi;
B., after described compound zedoary oil expandable vaginal expansible plug carries out melting the detection of change time limit, expandable carrier expansion rear length h in selected location place in a step is determined at; Different angles of rolling again measure several times, ask average length hi after expanding;
When c. calculating described swell value, calculate according to I formula;
Wherein, pi represent axial swell value, hi represent expand after average length, Hi represent average initial length;
Or swell value assay method is as follows:
A. first choose a place or some positions an angle along the axis of described compound zedoary oil expandable vaginal expansible plug, after measuring the initial diameter R of described expandable carrier, then different angles of rolling measure several times, and average Ri;
B., after described compound zedoary oil expandable vaginal expansible plug carries out melting the detection of change time limit, selected location place expandable carrier expanded diameter r in a step is determined at; Different angles of rolling again measure several times, ask average diameter ri after expanding;
When c. calculating described swell value, calculate by II formula;
Wherein, Pi represents the swell value of radial direction, ri represents the rear average diameter that expands, Ri represents average initial diameter;
2) weight differential assay method:
A. get described compound zedoary oil expandable vaginal expansible plug, take weight M;
B. scrape pastille substrate, expandable carrier is placed in 20-90 DEG C of organic solvent, take out, in 50-150 DEG C of dry 1-10h, take weight m, according to the weight X of pastille substrate as described in III formula calculating
X＝M-m(Ⅲ)
Wherein, described organic solvent is selected from one or more in ethanol, methanol or isopropyl alcohol.
8. compound zedoary oil expandable vaginal expansible plug as claimed in claim 7, it is characterized in that, described expandable carrier is cotton sliver, and described detection comprises following at least one method:
1) swell value assay method:
Get described compound zedoary oil expandable vaginal expansible plug 3, survey its afterbody cotton sliver diameter with slide gauge, roll 90 ° and survey again once, survey twice for every, obtain every 2 meansigma methods Ri measured; Above-mentioned 3 bolts are used for melt and become after the time limit measures and terminate, take out residue cotton sliver immediately, treat that water is disconnected to drip, all gently be placed on glass plate, the two ends of each cotton sliver and middle three positions are measured with slide gauge, roll after 90 ° and measure three positions again, each cotton sliver obtains six data altogether, obtains 6 meansigma methods r of mensuration
i, calculate the swell value P of every
i, the swell value of three bolts all should be greater than 1.5;
2) weight differential assay method:
Get described compound zedoary oil expandable vaginal expansible plug 10, accurately weighed weight respectively, gently scrape pastille substrate, cotton sliver must not be lost, cotton sliver is placed in the 200-400ml ethanol of 50-80 DEG C, and clean 5 minutes at 80khz frequency ultrasound, the stromatolysis of cotton sliver surface residual is removed, take out cotton sliver firmly to extract, 3 times are inhaled again with filter paper, in 105 DEG C of dryings 2 hours, take out, after room temperature places 1 hour, accurately weighed cotton sliver weight respectively, obtain every pastille matrix weight and average pastille matrix weight, every pastille matrix weight compares with average pastille matrix weight, what exceed average pastille matrix weight ± 10% must not more than 2, and 1 overrun 1 times must not be had.
9. compound zedoary oil expandable vaginal expansible plug as claimed in claim 8, is characterized in that, cotton sliver is placed in the 300ml ethanol of 60-70 DEG C.
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| CN1449784A (en) * | 2003-04-18 | 2003-10-22 | 太阳石（唐山）药业有限公司 | Compound Zedoary Turmeric oil preparation and process for making same |
| CN103181889A (en) * | 2012-11-29 | 2013-07-03 | 哈尔滨欧替药业有限公司 | Expandable vaginal suppository |
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| CN1449784A (en) * | 2003-04-18 | 2003-10-22 | 太阳石（唐山）药业有限公司 | Compound Zedoary Turmeric oil preparation and process for making same |
| CN103181889A (en) * | 2012-11-29 | 2013-07-03 | 哈尔滨欧替药业有限公司 | Expandable vaginal suppository |
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