CN103494896B - Cnidium monnieri and rheum officinale vaginal dilation suppository as well as preparation method and detection method thereof - Google Patents

Abstract

The invention relates to a cnidium monnieri and rheum officinale vaginal dilation suppository as well as a preparation method and a detection method thereof. The dilation suppository mainly comprises a Chinese medicine composition, a matrix and a dilation carrier, wherein the Chinese medicine composition is prepared from radix sophorae flavescentis, cnidium monnieri, rheum officinale and ginseng through extracting; a mixture extract of the radix sophorae flavescentis and the cnidium monnieri in the dilation suppository is subjected to micronization, the particle size is controlled within a certain range, and the dissolution rate of the mixture extract is remarkably increased; hydrogenated oil and the micronized extract form a coating, so that the mixing between the micronized extract and other ingredients can be enhanced, and meanwhile, a thickening effect is achieved; a controlled release agent has the functions of prolonging the action time of the medicament on the vagina and prolonging the curative effect; meanwhile, the dilation suppository also employs seven unique advanced technologies and has the beneficial effects of preventing outflow of medicine liquor and preventing secondary infection, and is high in stability, durable in curative effect and the like.

Description

Yellow vaginal expansion plug of Serpentis and preparation method thereof and detection method

Technical field

The invention belongs to vaginal suppository field, particularly yellow vaginal expansion plug of a kind of Serpentis and preparation method thereof and detection method.

Background technology

The yellow bolt of Serpentis, makes primarily of Radix Sophorae Flavescentis 1800g, Fructus Cnidii 2000g, Radix Et Rhizoma Rhei 600g, Radix Ginseng 500g and appropriate semi-synthetic fatty acid glyceride; The yellow bolt curative effect of Serpentis obtains clinical confirmation for many years, is widely used in the secretions increase that female vagina causes, the symptom having the gynaecopathia such as abnormal flavour and pruritus vulvae common; But there are some technical problems in the yellow bolt of described Serpentis always, such as Chinese patent CN1530125 provides a kind of suppository be made up of the substrate such as Chinese medicine composition and semi-synthetic fatty acid glyceride, in described suppository, the dissolubility of each composition there are differences, and causes the bioavailability of medicine to reduce; In order to improve bioavailability and the dissolution of Chinese medicine composition, majority adopts to add the additives such as absorption enhancer, but additives add the character that membership affects substrate, thus cause the application of suppository limited; In prior art, also the character of the not open Chinese medicine composition self by changing the yellow bolt of Serpentis improves the dissolution of suppository and the technical scheme of bioavailability; In addition, the yellow bolt of Serpentis still has following problem to need to solve: the cotton sliver in the yellow bolt of 1, traditional Serpentis is without expansion, or it is unordered to expand, and greatly reduces clinical application; 2, method of quality control is unreliable, causes in actual production process, batch between content, stability, melt become the time limit alter a great deal; 3, multiple compound recipe composition simply mixes, and can not play respective curative effect respectively.

Summary of the invention

In order to solve the problems of the technologies described above, improve the dissolution of the yellow bolt Chinese medicine composition of Serpentis, giving full play to curative effect, the present invention have studied yellow vaginal expansion plug of a kind of Serpentis and preparation method thereof; Additionally provide a kind of science detection method that can control the yellow vaginal expansion plug product quality of above-mentioned Serpentis simultaneously.

The concrete technical scheme of the present invention is as follows:

The invention provides the yellow vaginal expansion plug of a kind of Serpentis, the substrate that described expansible plug comprises Chinese medicine composition that weight portion is 5-40 part, weight portion is 50-220 part and weight portion are the expandable expandable carrier of 50-400 part, described Chinese medicine composition 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 described Chinese medicine composition is prepared from through extracting primarily of the crude drug of following weight portion:

Radix Sophorae Flavescentis 100-300

Fructus Cnidii 120-350

Radix Et Rhizoma Rhei 30-150

Radix Ginseng 20-100

Described substrate comprise in Acrawax, natural acid ester, lipoidis substrate, water-soluble base, gel-type vehicle, 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 glyceride comprises Adeps Solidus, Massa Estarinum A, MassaEstarinum AS, Massa Estarinum B, Massa Estarinum C, MassaEstarinum D, Massa Estarinum E, Massa Estarinum I, Massa EstarinumT, Massa Mf13, Suppository Base W, Suppository Base AB, SuppositoryBase A, Suppository Base B, Suppository Base BC, Suppository BaseBD, Suppository Base BBC, Suppository Base E, Suppository BaseBCF, Suppository Base C, Suppository Base D, Suppository Base299, Wecobee W, Wecobee K, Wecobee S, Wecobee M, Wecobee ES, Massuppol, Massuppol15, Suppocire OSI, Suppocire OSIx SuppocireA, Suppocire B, Suppocire C, Suppocire D, Suppocire DM, SuppocireH, Suppocire L, Tegester Triglyceride Bases-9, TegesterTriglyceride Bases-MA, Tegester Triglyceride Bases-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).

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 medicated layer, after described expandable carrier expands, medicated layer 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-medicated layer), 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 weight portion of described Chinese medicine composition is 10-25 part, and the weight portion of described substrate is 100-200 part, and the weight portion of described expandable carrier is 100-250 part, prepares the raw materials used parts by weight of described Chinese medicine composition and is:

Radix Sophorae Flavescentis 150-250

Fructus Cnidii 180-300

Radix Et Rhizoma Rhei 50-100

Radix Ginseng 40-80

Described substrate is the mixture of water-soluble base and distillate oil, and the ratio of weight and number of described water-soluble base and distillate oil is 14-19:1.Described mixed-matrix can improve the zest of water-soluble base to vagina, promotes the stripping of Chinese medicine composition simultaneously, makes the whole stripping in 30min of described Chinese medicine composition, melts and becomes time limit shortening.

Further, the PEG400 that described distillate oil is weight portion is the fractionating palm oil of 10 parts, described water-soluble base to be weight portion the be polyethylene glycol 1500 of 75 parts and weight portion are 70 parts; The parts by weight of described Chinese medicine composition are 20 parts, and the weight portion of described expandable carrier is 200 parts, prepare the raw materials used parts by weight of described Chinese medicine composition to be:

Radix Sophorae Flavescentis 180

Fructus Cnidii 200

Radix Et Rhizoma Rhei 60

Radix Ginseng 50

Preferably, Radix Sophorae Flavescentis of the present invention obtains Radix Sophorae Flavescentis extract through water extraction alcohol settling, described Fructus Cnidii obtains Fructus cnidii extract through ethanol extraction, and the mixed extract of described Radix Sophorae Flavescentis extract and Fructus cnidii extract is micronization extract, the d of described micronization extract particle diameter _0.9for 25-100 μm; Wherein " d _0.9for 25-100 μm " refer to that 90% particle size range is 25-100 μm.

Just Chinese medicine composition is made after four taste crude drug in Chinese medicine composition of the present invention are all through extraction, in described Chinese medicine composition, the content of macromole sugar and protein reduces, the gross weight of Chinese medicine composition also reduces, but the parts by weight playing the composition of antibacterial action increase, and the curative effect making suppository also increases thereupon thereupon, in the yellow vaginal expansion plug of described Serpentis, Fructus Cnidii is monarch drug, Radix Sophorae Flavescentis is ministerial drug, by these two kinds of crude drug respectively through after special extraction, preferred Radix Sophorae Flavescentis adopts water extraction ethanol precipitation methods to prepare extract, Fructus Cnidii adopts ethanol extraction to obtain extract, the gross weight that the content of the component of obtained performance antibacterial action accounts for suppository is higher, but the water solublity of described extract is bad, affect its stripping, in order to increase the dissolution of two kinds of main component extracts further, the mixture of Radix Sophorae Flavescentis extract and Fructus cnidii extract is carried out micronization by the present invention, the d of described micronized particle _0.9meet 25-100 μm, the dissolution of the mixture of described Radix Sophorae Flavescentis extract and Fructus cnidii extract increases, show in prior art, particle diameter is less, and the dissolution of described Chinese medicine composition is higher, but the present invention shows through test, after described mixed extract micronization, and the d of particle diameter _0.9when being less than 25 μm, dissolution does not increase thereupon, and particle diameter is less, and technique is more complicated, and production cost increases, and particle diameter meticulous being unfavorable for mixes with other compositions, as the d of particle diameter after described mixed extract micronization _0.9when being greater than 100 μm, dissolution is bad, the micronized particle diameter d of mixed extract of described Radix Sophorae Flavescentis extract and Fructus cnidii extract _0.9control within the scope of 25-100 μm, dissolution is better, and the bioavailability of suppository also increases thereupon, and in addition, micronization extract can prevent the layering of Chinese medicine composition.

Further preferably, described pastille substrate also comprises the hydrogenated oil and fat that weight portion is 5-30 part, described hydrogenated oil and fat and described micronization extract form coated mixture, described hydrogenated oil and fat be selected from hydrogenated groundnut, cotmar, castor oil hydrogenated, hydrogenation coconut palm seed oil or hydrogenated olive oil in one or more.

After hydrogenated oil and fat of the present invention and micronization extract form coated mixture, the stability of suppository can be improved, and the mobility of micronization extract can be increased, be more conducive to and other mixing compositions, play the effect of thickening simultaneously.

In order to the curative effect of further prolong drug, make " prolonged drug layering release ", increase Chinese medicine composition to the action time of vagina, described pastille substrate also comprises the slow releasing agent that weight portion is 1-5 part, described slow releasing agent be selected from polyacrylic acid amide, polymethyl methacrylate or 2-HEMA one or more.

Slow releasing agent of the present invention can extend the action time of Chinese medicine composition to vagina, and extend curative effect, within one day, be administered once, drug effect reaches 24 hours, improves patient compliance; Meanwhile, the slow releasing agent selected by the present invention can play synergism with hydrogenated oil and fat, and the common mixing increasing each composition in suppository, increases denseness, prevent Chinese medicine composition from precipitating from suppository, increases the stability of suppository.

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 rear end of the expandable carrier of the yellow vaginal expansion plug of Serpentis 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 the yellow vaginal expansion plug of Serpentis 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, can not ensure that the yellow vaginal expansion plug of Serpentis of the present invention is met feature that namely water expand and makes 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 the yellow vaginal expansion plug of Serpentis, described method comprises the steps:

1) preparation of pastille substrate:

A. substrate is placed in water-bath heating and melting, obtained fused mass;

B. take the Fructus Cnidii of recipe quantity, pulverize, add 50-80% ethanol, reflux, extract, twice, first time adds the 5-10 times amount that amount of alcohol is Fructus Cnidii weight, backflow 1-2h, and second time adds the 3-5 times amount that amount of alcohol is Fructus Cnidii weight, backflow 1-2h, filter, filtrate merges, and reclaims ethanol, when being concentrated into 60-70 DEG C, relative density is the clear paste of 1.22-1.26, obtains Fructus cnidii extract;

C. take the Radix Sophorae Flavescentis of recipe quantity, pulverize, decoct with water twice, amount of water is 10-15 times of Radix Sophorae Flavescentis weight for the first time, decoct 1-3h, the second amount of water is 6-10 times of Radix Sophorae Flavescentis weight, decocts 1-2 hour, filter, merging filtrate, when filtrate is concentrated into 60-70 DEG C, relative density is the clear paste of 1.22-1.26; Add 50-90% ethanol, amount of alcohol used is 5-10 times of clear paste weight, leaves standstill and makes precipitation, and get supernatant and reclaim ethanol, being concentrated into 70-80 DEG C of relative density is the thick paste of 1.30-1.32, obtains Radix Sophorae Flavescentis extract;

D. take Radix Et Rhizoma Rhei and the Radix Ginseng of recipe quantity, pulverize, decoct with water twice, amount of water is 10 times of Radix Et Rhizoma Rhei and Radix Ginseng gross weight for the first time, decoct 2h, the second amount of water is 6 times of Radix Et Rhizoma Rhei and Radix Ginseng gross weight, decocts 1 hour, filter, merging filtrate, when filtrate is concentrated into 60-70 DEG C, relative density is the clear paste of 1.22-1.26, obtains Radix Et Rhizoma Rhei and Radix Ginseng extract, described extract is spray dried to fine powder, obtained ginseng rhubarb mixed extract;

E. by Fructus cnidii extract and Radix Sophorae Flavescentis extract mix homogeneously, obtained mixed extract, with spray drying method by mixed extract micronization, obtained micronization extract;

F. hydrogenated oil and fat is placed in water-bath to heat, under stirring, slowly adds micronization extract, continue to stir, be slowly warming up to hydrogenated oil and fat melting, stop heating, cooling, obtained coated mixture;

G. by the ginseng rhubarb mixed extract mix homogeneously of the coated mixture of f step and Step d, obtained compositions;

H. g step compositions and mixing diluents is even, obtained mixture;

I. the fused mass of the mixture of h step with a step is mixed homogeneously, obtained pastille substrate;

2) pour in bolt mould by pastille substrate, insert expandable carrier, cooling and shaping, makes suppository.

The preparation method of the yellow vaginal expansion plug of Serpentis 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 the yellow vaginal expansion plug of described Serpentis 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 the yellow vaginal expansion plug end face of described Serpentis is chosen a bit or some points, measures the initial length H of described expandable carrier;

B., after the saturated water suction of the yellow vaginal expansion plug of described Serpentis, 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;

$p=\frac{h}{H}---\left(I\right)$

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 the yellow vaginal expansion plug of described Serpentis chooses a place or some positions, measures the initial diameter R of described expandable carrier;

B., after the saturated water suction of the yellow vaginal expansion plug of described Serpentis, selected location place expandable carrier expanded diameter r in a step is determined at;

When c. calculating described swell value, calculate by II formula;

$P=\frac{r}{R}---\left(\mathrm{II}\right)$

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 the yellow vaginal expansion plug of described Serpentis, take weight M;

B. the expandable carrier in the yellow vaginal expansion plug of the described Serpentis scraping 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 the yellow vaginal expansion plug of Serpentis 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 the yellow vaginal expansion plug end face of described Serpentis, after measuring the initial length H of described expandable carrier, then different angles of rolling measure several times, and average Hi;

B., after described Serpentis Huang vaginal expansion 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;

$\mathrm{pi}=\frac{\mathrm{hi}}{\mathrm{Hi}}---\left(I\right)$

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 the yellow vaginal expansion plug of described Serpentis, after measuring the initial diameter R of described expandable carrier, then different angles of rolling measure several times, and average Ri;

B., after the yellow vaginal expansion plug of described Serpentis 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;

$P_i=\frac{\mathrm{ri}}{\mathrm{Ri}}---\left(\mathrm{II}\right)$

Wherein, Pi represents the swell value of radial direction, ri represents the rear average diameter that expands, Ri represents average initial diameter.

Wherein said melting becomes time limit assay method (existing Chinese Pharmacopoeia two annex) and comprising: get the yellow vaginal expansion plug 3 of described Serpentis, 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 fix 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 the yellow vaginal expansion plug of described Serpentis, 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 the yellow vaginal expansion plug of Serpentis of the present invention, described expandable carrier is cotton sliver, and described detection method comprises at least one detection method:

1) swell value assay method:

Get the yellow vaginal expansion plug 3 of described Serpentis, 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, the two ends of each cotton sliver and middle three positions are measured with slide gauge, roll after about 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 the yellow vaginal expansion plug 10 of described Serpentis, 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 the yellow vaginal expansion plug of Serpentis 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 yellow vaginal expansion plug of the standard detection Serpentis of the present invention performing state-promulgated pharmacopoeia annex weight differential, 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 VI B tlc determination.

Get the yellow vaginal expansion plug 3 of described Serpentis, accurately weighed, heating water 50ml, is stirred to dissolve, put in refrigerator, place and make matrix set in about 15 minutes, incline water intaking liquid, residue reusable heat washes 2 times, each 25ml, merges water lotion, add strong ammonia solution and adjust pH10-11, with chloroform extraction 4 times, each 30ml, merge chloroform extraction liquid, evaporate to dryness, residue chloroform dissolves and is transferred in 5ml measuring bottle, add chloroform and be diluted to scale, shake up, as need testing solution; Separately get matrine reference substance, add chloroform and make every 1ml containing 0.5mg solution, in contrast product solution.Test according to thin layer chromatography (China's coastal port annex VI B), absorb need testing solution 4 μ l, reference substance solution 2 μ l and 4 μ l, put respectively on same silica gel g thin-layer plate, with benzene-acetone and ethyl acetate-strong ammonia solution (2:3:4:0.2) for developing solvent, launch, take out, dry, it is clear to spot development with rare bismuth potassium iodide test solution to spray, take out, lamellae covers onesize glass plate, surrounding immobilization with adhesive tape, place after 2 hours, scan according to thin layer chromatography (China's coastal port annex VI B thin layer chromatography scanning), wavelength: λ s=495nm, λ k=650nm, measure test sample trap integrated value and reference substance trap integrated value, calculate, obtain.

The yellow vaginal expansion plug every of Serpentis of the present invention contains Radix Sophorae Flavescentis with matrine (C ₁₅h ₂₄n ₂o) count, must not 1.10mg be less than.

It is high that the yellow vaginal expansion plug of Serpentis provided by the present invention has curative effect, stability height waits beneficial effect, and the yellow vaginal expansion plug of this Serpentis have employed seven leading technologies of original creation, expandable carrier in the yellow vaginal expansion plug of described Serpentis add " the disposable fill of stype the is integrally formed " technology 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 medicated layer of the yellow vaginal expansion plug of Serpentis fully contact with vaginal walls, and prevent medicinal liquid from outflowing, also there is effect that cleaning vagina prevents superinfection, the present invention, by the mixed extract micronization of Radix Sophorae Flavescentis extract and Fructus cnidii extract in described expansible plug, by micronization size controlling within the specific limits, significantly increases the dissolution of mixed extract, add hydrogenated oil and fat and slow releasing agent in described pastille substrate, described hydrogenated oil and fat and micronization extract form coated mixture, can increase mixing of micronization extract and other compositions, play the effect of thickening simultaneously, technology that described slow releasing agent applies " prolonged drug layering release ", prolong drug is to the action time of vagina, extend curative effect, slow releasing agent selected by the present invention can play synergism with hydrogenated oil and fat, the mixing of each composition in common increase expansible plug, increase denseness, prevent Chinese medicine composition from precipitating from suppository, increase the stability of expansible plug.

Accompanying drawing explanation

The vitro release result of the test of the yellow vaginal expansion plug of Serpentis described in Fig. 1 embodiment 7-9;

The schematic diagram of Fig. 2 and Fig. 3 swell value assay method.

Detailed description of the invention

Embodiment 1

Preparation method:

1) preparation of pastille substrate:

A. fractionating palm oil, polyethylene glycol 1500 and PEG400 are placed in water-bath heating and melting, obtained fused mass;

B. take the Fructus Cnidii of recipe quantity, pulverize, add 50% ethanol, reflux, extract, twice, first time adds 10 times amount that amount of alcohol is Fructus Cnidii weight, backflow 2h, and second time adds 3 times amount that amount of alcohol is Fructus Cnidii weight, backflow 2h, filter, filtrate merges, and reclaims ethanol, when being concentrated into 60 DEG C, relative density is the clear paste of 1.22, obtains Fructus cnidii extract;

C. take the Radix Sophorae Flavescentis of recipe quantity, pulverize, decoct with water twice, amount of water is 15 times of Radix Sophorae Flavescentis weight for the first time, decoct 1h, the second amount of water is 6 times of Radix Sophorae Flavescentis weight, decocts 2 hours, filter, merging filtrate, when filtrate is concentrated into 60 DEG C, relative density is the clear paste of 1.22; Add 50% ethanol, amount of alcohol used is 10 times of clear paste weight, leaves standstill and makes precipitation, and get supernatant and reclaim ethanol, being concentrated into 70 DEG C of relative densities is the thick paste of 1.30, obtains Radix Sophorae Flavescentis extract;

D. take Radix Et Rhizoma Rhei and the Radix Ginseng of recipe quantity, pulverize, decoct with water twice, amount of water is 10 times of Radix Et Rhizoma Rhei and Radix Ginseng gross weight for the first time, decoct 2h, the second amount of water is 6 times of Radix Et Rhizoma Rhei and Radix Ginseng gross weight, decocts 1 hour, filter, merging filtrate, when filtrate is concentrated into 60 DEG C, relative density is the clear paste of 1.22, obtains Radix Et Rhizoma Rhei and Radix Ginseng extract, described extract is spray dried to fine powder, obtained ginseng rhubarb mixed extract;

E. by Fructus cnidii extract, Radix Sophorae Flavescentis extract and ginseng rhubarb mixed extract, mix homogeneously obtains Chinese medicine composition;

F. the fused mass of Chinese medicine composition with a step is mixed homogeneously, obtained pastille substrate;

2) pour in bolt mould by pastille substrate, insert cotton sliver, cooling and shaping, makes 100 pieces of cylindrical suppositorys, every piece of heavily about 3.7g.

Embodiment 2

Preparation method: make 100 pieces of torpedo suppositorys by method described in embodiment 1, every piece of heavily about 3.9g.

Embodiment 3

Preparation method:

1) preparation of pastille substrate:

A. mixed fatty glycerides, fixed oil and glycerol tristearate are placed in water-bath heating and melting, obtained fused mass;

B. take the Fructus Cnidii of recipe quantity, pulverize, add 80% ethanol, reflux, extract, twice, first time adds 5 times amount that amount of alcohol is Fructus Cnidii weight, backflow 1h, and second time adds 5 times amount that amount of alcohol is Fructus Cnidii weight, backflow 1h, filter, filtrate merges, and reclaims ethanol, when being concentrated into 70 DEG C, relative density is the clear paste of 1.26, obtains Fructus cnidii extract;

C. take the Radix Sophorae Flavescentis of recipe quantity, pulverize, decoct with water twice, amount of water is 10 times of Radix Sophorae Flavescentis weight for the first time, decoct 3h, the second amount of water is 10 times of Radix Sophorae Flavescentis weight, decocts 1 hour, filter, merging filtrate, when filtrate is concentrated into 70 DEG C, relative density is the clear paste of 1.26; Add 90% ethanol, amount of alcohol used is 5 times of clear paste weight, leaves standstill and makes precipitation, and get supernatant and reclaim ethanol, being concentrated into 80 DEG C of relative densities is the thick paste of 1.32, obtains Radix Sophorae Flavescentis extract;

D. take Radix Et Rhizoma Rhei and the Radix Ginseng of recipe quantity, pulverize, decoct with water twice, amount of water is 10 times of Radix Et Rhizoma Rhei and Radix Ginseng gross weight for the first time, decoct 2h, the second amount of water is 6 times of Radix Et Rhizoma Rhei and Radix Ginseng gross weight, decocts 1 hour, filter, merging filtrate, when filtrate is concentrated into 70 DEG C, relative density is the clear paste of 1.26, obtains Radix Et Rhizoma Rhei and Radix Ginseng extract, described extract is spray dried to fine powder, obtained ginseng rhubarb mixed extract;

E. by Fructus cnidii extract and Radix Sophorae Flavescentis extract mix homogeneously, obtained mixed extract, with spray drying method by mixed extract micronization, obtained micronization extract, the d of described micronization extract particle diameter _0.9it is 25 μm;

F. micronization extract is mixed homogeneously with the ginseng rhubarb mixed extract of Step d, obtained compositions;

G. the fused mass of compositions with a step is mixed homogeneously, obtained pastille substrate;

2) pour in bolt mould by pastille substrate, insert cotton sliver, cooling and shaping, makes 100 pieces of torpedo suppositorys, every piece of heavily about 5.0g.

Embodiment 4

Preparation method: make 100 pieces of spherical suppositorys by embodiment 3 method, every piece of heavily about 3.2g, the d of described micronization extract particle diameter _0.9it is 100 μm.

Embodiment 5

Preparation method:

1) preparation of pastille substrate:

A. poloxamer, polyethylene glycol 6000 and fractionating palm oil are placed in water-bath heating and melting, obtained fused mass;

B. Fructus cnidii extract is prepared by method described in step b in embodiment 1;

C. Radix Sophorae Flavescentis extract is prepared by method described in step c in embodiment 1;

D. ginseng rhubarb mixed extract is prepared by method described in steps d in embodiment 1;

E. by Fructus cnidii extract and Radix Sophorae Flavescentis extract mix homogeneously, obtained mixed extract, with spray drying method by mixed extract micronization, obtained micronization extract, the d of described micronization extract particle diameter _0.9it is 50 μm;

F. castor oil hydrogenated is placed in water-bath to heat, under stirring, slowly adds micronization extract, continue to stir, be slowly warming up to castor oil hydrogenated melting, stop heating, cooling, obtained coated mixture;

G. by the ginseng rhubarb mixed extract mix homogeneously of the coated mixture of f step and Step d, obtained compositions;

H. the fused mass of compositions with a step is mixed homogeneously, obtained pastille substrate;

2) pour in bolt mould by pastille substrate, insert cotton sliver, cooling and shaping, makes 100 pieces of bullet shaped suppositorys, every piece of heavily about 3.7g.

Embodiment 6

Preparation method: make 100 pieces of avette suppositorys by embodiment 5 method, every piece of heavily about 1.1g, the d of described micronization extract particle diameter _0.9it is 75 μm.

Embodiment 7

Preparation method:

1) preparation of pastille substrate:

A. fractionating palm oil, polyethylene glycol 1500 and PEG400 are placed in water-bath heating and melting, obtained fused mass;

B. Fructus cnidii extract is prepared by method described in step b in embodiment 1;

C. Radix Sophorae Flavescentis extract is prepared by method described in step c in embodiment 1;

D. ginseng rhubarb mixed extract is prepared by method described in steps d in embodiment 1;

E. by Fructus cnidii extract and Radix Sophorae Flavescentis extract mix homogeneously, obtained mixed extract, with spray drying method by mixed extract micronization, obtained micronization extract, the d of described micronization extract particle diameter _0.9it is 25 μm;

F. hydrogenation coconut palm seed oil is placed in water-bath to heat, under stirring, slowly adds micronization extract, continue to stir, be slowly warming up to the melting of hydrogenation coconut palm seed oil, stop heating, cooling, obtained coated mixture;

G. by the ginseng rhubarb mixed extract mix homogeneously of the coated mixture of f step and Step d, obtained compositions;

H. g step compositions is mixed homogeneously with polyacrylic acid amide, obtained mixture;

I. the fused mass of the mixture of h step with a step is mixed homogeneously, obtained pastille substrate;

3) pour in bolt mould by pastille substrate, insert cotton sliver, cooling and shaping, makes 100 pieces of conical suppositorys, every piece of heavily about 4.0g.

Embodiment 8

Preparation method: make 100 pieces of duckbill suppositorys by embodiment 7 method, every piece of heavily about 2.9g, the d of described micronization extract particle diameter _0.9it is 30 μm.

Embodiment 9

Preparation method: make 100 pieces of clavate suppositorys by embodiment 7 method, every piece of heavily about 4.7g, the d of described micronization extract particle diameter _0.9it is 80 μm.

Test example 1 stability test

1. accelerated test

The yellow vaginal expansion plug of Serpentis described in Example 5-9 and the yellow bolt of common Serpentis, 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 matrine labelled amount (%), melt become the time limit; The accelerated test of the yellow vaginal expansion plug of the Serpentis described in embodiment 5-9 and the yellow bolt of common Serpentis the results are shown in Table 1.

The yellow vaginal expansion plug of Serpentis of table 1 embodiment 5-9 and the accelerated test result of the yellow bolt of Serpentis

The yellow vaginal expansion plug of Serpentis as can be seen from the table described in embodiment of the present invention 5-9, under the environment of constant temperature high humidity, places after 6 months, the color of described expansible plug, the labelled amount containing matrine, melts the change time limit obvious change does not all occur; And the yellow suppository of common Serpentis is placed after 3 months under high humidity, suppository color changes, and speckle appears in suppository surface, part suppository generation fracture phenomena; And in the yellow suppository of described Serpentis, the content of matrine significantly declines, and melts change duration; Show that the yellow vaginal expansion plug of Serpentis of the present invention stability compared with the yellow suppository of Serpentis significantly improves.

2. long term test

The yellow vaginal expansion plug of Serpentis described in Example 5-9 and the yellow bolt of common Serpentis, 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 matrine, 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 yellow vaginal expansion plug of the Serpentis described in embodiment 5-6 is in table 2, the long-term test results of the yellow vaginal expansion plug of the Serpentis described in embodiment 7-9 and the yellow bolt of Serpentis is in table 3.

The long-term test results of the yellow vaginal expansion plug of the Serpentis described in table 2 embodiment 5-6

The yellow vaginal expansion plug of Serpentis of table 3 embodiment 7-9 and the long-term test results of the yellow suppository of Serpentis

The yellow vaginal expansion plug of Serpentis as can be seen from the table described in embodiment 5-9, under the environment of constant temperature high humidity, places after 36 months, the color of described expansible plug, the labelled amount containing matrine, melts the change time limit obvious change does not all occur; And after the yellow suppository of common Serpentis places 9 months, suppository color changes, and speckle appears in suppository surface, and part suppository breaks; And in the yellow suppository of Serpentis, the content of matrine significantly declines, and melts and becomes time limit significant prolongation; Show that the yellow vaginal expansion plug of Serpentis of the present invention stability compared with the yellow suppository of Serpentis significantly improves.

Test example 2 vitro release determination test

The drug release rate of suppository detects: check with reference to 2010 editions " Chinese Pharmacopoeia " annex XIXD vitro drug release degree.

Get the yellow vaginal expansion plug of Serpentis described in above embodiment 7-9 respectively, put in medicament dissolution instrument, sample respectively in 1h, 2h, 4h, 6h, 12h, 16h, 24h, detect stripping percentage rate by high performance liquid chromatography, and calculate the cumulative release percentage rate of medicine, the results are shown in Figure 1.

As can be seen from the figure the yellow vaginal expansion plug medicine of Serpentis described in embodiment 7-9 slow releasing in 24h; Illustrate that slow releasing agent can extend the action time of expansion suppository to vagina, extend curative effect.

Test example 3 swell value measures

Method one

Get the yellow vaginal expansion plug 3 of described Serpentis, 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 change time limit mensuration and take out residue cotton sliver immediately after terminating, 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 about 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 is all greater than 1.5.

The swell value measuring the yellow vaginal expansion plug of Serpentis described in embodiment 1-9 according to above-mentioned swell value assay method is as shown in table 4;

The swell value of the yellow vaginal expansion plug of table 4 embodiment 1-9 Serpentis

Embodiment	Average diameter (mm) before expanding	Average diameter (mm) after expanding	Swell value (doubly)	Result
					Embodiment 1	12.20	21.35	1.75	Qualified
Embodiment 2	12.13	22.56	1.86	Qualified
					Embodiment 3	12.05	22.74	1.89	Qualified
Embodiment 4	11.95	20.18	1.69	Qualified
					Embodiment 5	12.18	22.44	1.84	Qualified
Embodiment 6	12.11	20.98	1.73	Qualified
					Embodiment 7	12.29	21.67	1.76	Qualified
Embodiment 8	12.31	22.38	1.82	Qualified
					Embodiment 9	12.22	22.81	1.87	Qualified

Method two

As shown in Figures 2 and 3:

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;

$\mathrm{pi}=\frac{\mathrm{hi}}{\mathrm{Hi}}---\left(I\right)$

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, asks 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;

$P_i=\frac{\mathrm{ri}}{\mathrm{Ri}}---\left(\mathrm{II}\right)$

Wherein, Pi represents the swell value of radial direction, ri represents the rear average diameter that expands, Ri represents average initial diameter.

Test example 4 weight differential determination test

Get the yellow vaginal expansion plug 10 of described Serpentis, 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 yellow vaginal expansion plug of Serpentis described in embodiment 1-9, the equal conformance with standard of its weight differential.

Test example 5 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: secretions increase, has abnormal flavour and pruritus vulvae, has more white bean dregs sample leucorrhea, with pudendum burn feeling;

2, gynecologial examination: secretions is abnormal, and secretions is yellow foam or bean dregs sample;

3, lab testing: microscope can be observed infusorian or antibacterial;

(3) case standard is tested

Include case history standard in: in 21-50 year, meet the married woman of bacteriodiagnosis.

(4) Therapeutic Method

1, treatment group: use the yellow vaginal expansion plug of the Serpentis described in the embodiment of the present invention 7 to treat, every day one 7 days is a course for the treatment of.

2, matched group: use the yellow bolt treatment of Serpentis, every day one 7 days is a course for the treatment of.

(5) observation item

Therapeutic is observed

(1) symptom: vaginitis symptom, the amount of secretions, color, abnormal smells from the patient;

(2) gynecologial examination: comprise pudendum and vaginal secretions inspection;

(3) lab testing: under comprising mirror, picture inspection.

(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) therapeutic effect of symptom (symptom such as secretions color, amount, abnormal smells from the patient, pruritus) that causes vaginitis for the treatment of group is in table 5;

Table 5 embodiment of the present invention sample is to the therapeutic outcome of the symptom that vaginitis causes

As can be seen from the table, Serpentis of the present invention yellow vaginal expansion plug vaginitis is caused secretions increase, have the diseases such as abnormal flavour agent pruritus vulvae to have good curative effect; Color and the amount of patients produce's thing are all changing, and are that yellow gradually becomes transparent by the great majority before treating; Pruritus of vagina, vagina stink symptom disappear very soon.

(2) two groups are compared in table 6 to the therapeutic effect of vaginitis total effects;

Table 6 liang group is to the therapeutic effect of vaginitis total effects

Two groups of comparitive study treatment groups are better than matched group.

Three, conclusion

The yellow vaginal expansion plug of Serpentis can be alleviated very soon and treat the per vaginam scorching symptom caused, and reaches 96.4% to the total treated effect of vaginitis patient, 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 (10)

1. the yellow vaginal expansion plug of Serpentis, it is characterized in that, the substrate that described expansible plug comprises Chinese medicine composition that weight portion is 10-25 part, weight portion is 100-200 part and weight portion are the expandable expandable carrier of 100-250 part, described Chinese medicine composition 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 described Chinese medicine composition is prepared from through extracting by the crude drug of following weight portion:

Described substrate is the mixture of water-soluble base and distillate oil, and the ratio of weight and number of described water-soluble base and distillate oil is 14-19:1;

Described water-soluble base comprise in PEG400, polyethylene glycol 1500, Macrogol 4000, polyethylene glycol 6000, glycerin gelatine, polysorbate60, polysorbate65, polyoxyethylene monostearate or poloxamer one or more;

Described distillate oil is fractionating palm oil or fractionated coconut oil.

2. the yellow vaginal expansion plug of Serpentis as claimed in claim 1, is characterized in that, described distillate oil is weight portion is the fractionating palm oil of 10 parts, described water-soluble base to be weight portion the be polyethylene glycol 1500 of 75 parts and weight portion are the PEG400 of 70 parts; The parts by weight of described Chinese medicine composition are 20 parts, and the weight portion of described expandable carrier is 200 parts, prepare the raw materials used parts by weight of described Chinese medicine composition to be:

3. the yellow vaginal expansion plug of Serpentis as claimed in claim 1, it is characterized in that, described Radix Sophorae Flavescentis obtains Radix Sophorae Flavescentis extract through water extraction alcohol settling, described Fructus Cnidii obtains Fructus cnidii extract through ethanol extraction, the mixed extract of described Radix Sophorae Flavescentis extract and Fructus cnidii extract is micronization extract, described micronization extract particle diameter d _0.9for 25-100 μm.

4. the yellow vaginal expansion plug of Serpentis as claimed in claim 3, it is characterized in that, described pastille substrate also comprises the hydrogenated oil and fat that weight portion is 5-30 part, described hydrogenated oil and fat and described micronization extract form coated mixture, described hydrogenated oil and fat be selected from hydrogenated groundnut, cotmar, castor oil hydrogenated, hydrogenation coconut palm seed oil or hydrogenated olive oil in one or more.

5. the yellow vaginal expansion plug of Serpentis as claimed in claim 4, it is characterized in that, described pastille substrate also comprises the slow releasing agent that weight portion is 1-5 part, described slow releasing agent be selected from polyacrylic acid amide, polymethyl methacrylate or HEMA one or more.

6. the yellow vaginal expansion plug of the Serpentis as described in as arbitrary in claim 1-5, 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 expansible plug comprises following at least one method:

1) swell value assay method is as follows:

A. the radial direction along the yellow vaginal expansion plug end face of described Serpentis is chosen a bit or some points, measures the initial length H of described expandable carrier;

B., after the saturated water suction of the yellow vaginal expansion plug of described Serpentis, 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;

$p=\frac{h}{H}$

(I)

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 the yellow vaginal expansion plug of described Serpentis chooses a place or some positions, measures the initial diameter R of described expandable carrier;

B., after the saturated water suction of the yellow vaginal expansion plug of described Serpentis, selected location place expandable carrier expanded diameter r in a step is determined at;

When c. calculating described swell value, calculate by II formula;

$P=\frac{r}{R}$

(II)

Wherein, P represents the swell value of radial direction, r represents expanded diameter, R represents initial diameter;

2) weight differential assay method:

A. get the yellow vaginal expansion plug of described Serpentis, take weight M;

B. the expandable carrier in the yellow vaginal expansion plug of the described Serpentis scraping 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)。

7. the yellow vaginal expansion plug of Serpentis as claimed in claim 6, it is characterized in that, described detection method comprises following at least one method:

1) swell value assay method is as follows:

A. first choose a bit or some points along the radial direction of the yellow vaginal expansion plug end face of described Serpentis, after measuring the initial length H of described expandable carrier, then different angles of rolling measure several times, and average Hi;

B., after described Serpentis Huang vaginal expansion 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;

$\mathrm{pi}=\frac{\mathrm{hi}}{\mathrm{Hi}}$

(I)

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 the yellow vaginal expansion plug of described Serpentis, after measuring the initial diameter R of described expandable carrier, then different angles of rolling measure several times, and average Ri;

B., after the yellow vaginal expansion plug of described Serpentis 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;

$P_i=\frac{\mathrm{ri}}{\mathrm{Ri}}$

(II)

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 the yellow vaginal expansion plug of described Serpentis, 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. the yellow vaginal expansion plug of Serpentis as claimed in claim 7, it is characterized in that, described expandable carrier is cotton sliver, and described detection method comprises following at least one method:

1) swell value assay method:

Get the yellow vaginal expansion plug 3 of described Serpentis, 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 the yellow vaginal expansion plug 10 of described Serpentis, 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. the yellow vaginal expansion plug of Serpentis as claimed in claim 8, is characterized in that, cotton sliver is placed in the 300ml ethanol of 60-70 DEG C.

10. the preparation method of the yellow vaginal expansion plug of Serpentis as claimed in claim 5, it is characterized in that, described method comprises the steps:

1) preparation of pastille substrate:

A. substrate is placed in water-bath heating and melting, obtained fused mass;

B. take the Fructus Cnidii of recipe quantity, pulverize, add 50-80% ethanol, reflux, extract, twice, first time adds the 5-10 times amount that amount of alcohol is Fructus Cnidii weight, backflow 1-2h, and second time adds the 3-5 times amount that amount of alcohol is Fructus Cnidii weight, backflow 1-2h, filter, filtrate merges, and reclaims ethanol, when being concentrated into 60-70 DEG C, relative density is the clear paste of 1.22-1.26, obtains Fructus cnidii extract;

C. the Radix Sophorae Flavescentis of recipe quantity is taken, pulverize, decoct with water twice, amount of water is 10-15 times of Radix Sophorae Flavescentis weight for the first time, decocts 1-3h, and second time amount of water is 6-10 times of Radix Sophorae Flavescentis weight, decoct 1-2 hour, filter, merging filtrate, when filtrate is concentrated into 60-70 DEG C, relative density is the clear paste of 1.22-1.26; Add 50-90% ethanol, amount of alcohol used is 5-10 times of clear paste weight, leaves standstill and makes precipitation, and get supernatant and reclaim ethanol, being concentrated into 70-80 DEG C of relative density is the thick paste of 1.30-1.32, obtains Radix Sophorae Flavescentis extract;

D. take Radix Et Rhizoma Rhei and the Radix Ginseng of recipe quantity, pulverize, decoct with water twice, amount of water is 10 times of Radix Et Rhizoma Rhei and Radix Ginseng gross weight for the first time, decoct 2h, second time amount of water is 6 times of Radix Et Rhizoma Rhei and Radix Ginseng gross weight, decocts 1 hour, filter, merging filtrate, when filtrate is concentrated into 60-70 DEG C, relative density is the clear paste of 1.22-1.26, obtains Radix Et Rhizoma Rhei and Radix Ginseng extract, described extract is spray dried to fine powder, obtained ginseng rhubarb mixed extract;

E. by Fructus cnidii extract and Radix Sophorae Flavescentis extract mix homogeneously, obtained mixed extract, with spray drying method by mixed extract micronization, obtained particle diameter d0.9 is the micronization extract of 25-100 μm;

F. hydrogenated oil and fat is placed in water-bath to heat, under stirring, slowly adds micronization extract, continue to stir, be slowly warming up to hydrogenated oil and fat melting, stop heating, cooling, obtained coated mixture;

G. by the ginseng rhubarb mixed extract mix homogeneously of the coated mixture of f step and Step d, obtained compositions;

H. g step compositions is mixed homogeneously with slow releasing agent, obtained mixture;

I. the fused mass of the mixture of h step with a step is mixed homogeneously, obtained pastille substrate;

2) pour in bolt mould by pastille substrate, insert expandable carrier, cooling and shaping, makes suppository.