CN1331461C - Chinese medicine preparation for treating gynecopathy and its preparation method - Google Patents
Chinese medicine preparation for treating gynecopathy and its preparation method Download PDFInfo
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Abstract
The present invention relates to a traditional Chinese medicine preparation for treating gynecopathy and a preparation method thereof. The traditional Chinese medicine preparation is prepared from saxifrage, paniculate swallowwort root, cat's-foot and heroubill geranium, and is used for treating gynecopathy usually appearing in females, such as bellyache in menstrual periods, dark menstrual color, blood clots, leucorrhea with reddish discharge, multiple amount of leucorrhea, odoriferous odor, pudendum pruritus, ardor, etc. The present invention has the advantages of rich preparation variety, large crowd application range, high bioavailability, high medicine stability and scientific and reasonable preparation method.
Description
Technical field: the present invention is a kind of Chinese medicine preparation for the treatment of gynecological disease and preparation method thereof, belongs to the technical field of Chinese medicine.
Technical background: gynecological disease such as bellyache in menstrual period, dark through color, clot, leukorrhea with reddish discharge, it is smelly to measure many gas, the scorching hot grade of pudendal pruritus all is to threaten the able-bodied common disease of women in the world today, brought great misery for numerous women, traditional methods for the treatment of mostly is antibiotic or physiotherapy, uses for a long time antibiotic, can make the patient that resistance occurs and easily cause double infection, physiotherapy then makes most of patients not adhere to and TD for a long time. Prevent and treat purpose in order to reach, many inventors and enterprises have been done a large amount of research, and the product of some treatments also is provided; The application number of submitting to such as the applicant is: 02127980.2, to be called " treating gynopathic capsule and preparation technology thereof " be exactly to develop for treating this type of disease to name, but, the medicinal extract hygroscopicity of finding this product in the research that continues is very strong, so that the capsule hygroscopicity is stronger, for a long time storage benefit is rotten, unstable product quality. And the formulation kind is abundant not, applicable crowd's narrow range, and bioavilability, the medicine stability of conventional dosage forms are undesirable, and the problem that especially bioavilability of active ingredient is not high is badly in need of solving; In view of such circumstances, improve the thing that formulation has just become people to be badly in need of solving.
Summary of the invention: the object of the invention is to: a kind of Chinese medicine preparation for the treatment of gynecological disease and preparation method thereof is provided; The present invention is directed to prior art, the micropill that provides, dispersing tablet, disintegrative are good, and bioavilability is high, are particularly suitable for infant, the elderly and swallow tablet or the inconvenient patient of capsule take; Soft capsule preparation provided by the invention forms drug blockage in soft gel coat, solved medicine and met damp and hot unsettled problem, can also cover adverse drug taste, smell, can play the effect that increases stability, improves bioavilability; Particle good mouthfeel provided by the invention does not need disintegration, absorbs soon taking convenience.
The present invention consists of like this: calculate according to weight, it is made into injection with kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g and geranium wilfordii 750g, comprising: all acceptable formulations on parenteral solution, powder pin, freeze-dried powder, tablet, dispersing tablet, capsule, soft capsule, microcapsules, granule, pill, micropill, powder, pill, sustained release preparation, controlled release preparation, gel, oral liquid, soft extract, extract and the film pharmacy. Say accurately: make tablet, dispersing tablet, soft capsule, granule, micropill preparation, gel, oral liquid or pill with kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g and geranium wilfordii 750g.
The preparation method of the Chinese medicine preparation for the treatment of gynecological disease of the present invention: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filters, and filtrate decompression is concentrated, let cool, slowly add ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, then drying makes respectively different preparations.
Granule in the preparation of the present invention prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; It is an amount of to add 2.7% aspartame and dextrin, and mixing is granulated, and be get final product.
Disket in the preparation of the present invention prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; Get PPVP3.5g and lemon yellow mixing, get 1/5 and mix with extract powder, make adhesive with 0.8% K30 anhydrous alcohol solution, 40 orders material processed, whole grain, the mixed powder that remains 4/5PPVP2.8g and lemon yellow mixing is added in the particle that makes, compressing tablet, and get final product.
Micropill preparation in the preparation of the present invention prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; Add an amount of starch, with 75% ethanol and 1.3% soybean oil softwood processed, the softwood that makes micropill mechanism ball, wet feed pushed the 0.8mm sieve aperture, and the wet grain of strip cuts off round as a ball, 50～60 ℃ of drying and mouldings, crossing 16～20 mesh sieves selects ball or merges above-mentioned four kinds of clear cream, spray-drying, wet-milling granulation molding, mould placed add the great achievement ball in the coating pan, medicinal powder: water is 1: 1.3, and the coating pan rotating speed is 30r/min, capping, select ball, and get final product.
Soft capsule in the preparation of the present invention prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; Press medication amount: matrix amount=1: 1.3 adding soybean oil, mixing; The prescription of rubber is gelatin: glycerine: water: titanium dioxide=100g: 40g: 100g: 1g, batchingization adhesive tape part is: weigh batching, in the inputization glue tank, cold soaking is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirred 5 hours and vacuumized simultaneously bubble removing, until the evenly rear blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; The debugging pellet press, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity＜40%, pelleting; Dry adopt the typing of rolling dry with tray dried two step combinations, dry 2 hours of the typing of rolling, 22 ℃ of baking temperatures, dry relative humidity should be lower than 40%, drying time is at 24～48 hours, and get final product.
Pill in the preparation of the present invention prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; Get 1 part of extract powder, PEG40001.5 part and polyoxyl 40 stearate S-401 part mix, and melt in the water-bath, stir evenly, drip and in dimethicone, to become ball, drip apart from 5cm drip footpath 2.5mm/2mm, mix the ointment temperature 70 C, cooling fluid height 70cm, and get final product.
Tablet in the preparation of the present invention prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filter, filtrate decompression is concentrated, lets cool, slowly add ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, and filtered Recycled ethanol, reduced pressure concentration adds above-mentioned paniculate swallowwort fine powder, mixing, drying is pulverized, and adds microcrystalline cellulose 25g, use 85% alcohol granulation, drying, whole grain, add dolomol 2g, mixing, compressing tablet, dressing, and get final product.
Oral liquid in the preparation of the present invention prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, and filtrate decompression is concentrated, let cool, slowly add ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, and filtered Recycled ethanol, reduced pressure concentration adds above-mentioned paniculate swallowwort fine powder, mixing, add distilled water, 3.5% aspartame, sterilization, and get final product.
Vaginal tablets in the preparation of the present invention prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filter, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter, Recycled ethanol, reduced pressure concentration adds above-mentioned paniculate swallowwort fine powder, mixing, dry, add the potassium hydrogen tartrate of 3 times of amounts, the sodium bicarbonate of 2 times of amounts, the silica of 1 times of amount, compressing tablet, and get final product.
Suppository in the preparation of the present invention prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; It is an amount of to get distilled water, dropping lactic acid is an amount of, adds extract powder and stirs, and treats dissolve complete, add the glycerine of 10 times of amounts and the gelatin solution of 10 times of amounts, stir evenly, be poured into and sterilized in advance and scribble in the duckbill vaginal plug mould of liquid paraffin, slightly cold after, scrape off and overflow part, after condensation, take out, packing, and get final product.
Cream in the preparation of the present invention prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; With the cetanol of 4 times of amounts, the stearyl alcohol of 2 times of amounts, through 80 ℃ of meltings of water-bath, mix, insulation is as oil phase; Propane diols, the phenmethylol of 1 times of amount, the water of 2 times of amounts are heated to 80 ℃, and dissolving mixes, as water; Oil phase is under agitation slowly added water, stirring and emulsifying, be chilled to 40 ℃ stand-by; The third two ferment of medicinal powder and 1 times of amount are ground to transparence, add in the above-mentioned matrix, mix, and get final product.
Lotion in the preparation of the present invention prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filter, filtrate decompression is concentrated, lets cool, slowly add ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing is dry, adds metronidazole 5g, Sodium Benzoate 2g again and is stirred to moltenly, filters, filtrate is added distilled water to full dose, can, sterilization, and get final product.
Among the we, kiss-me, paniculate swallowwort, Longtube Ground Ivy Herb, geranium wilfordii compatibility are clearing heat and detoxicating, eliminating dampness and arresting leucorrhea, menstruction regulating and pain relieving. Bellyache in menstrual period due to stagnant for the hot malicious stasis of blood, dark through color, clot, leukorrhea with reddish discharge, it is smelly to measure many gas, and pudendal pruritus is scorching hot.
Compared with prior art, micropill disintegrative of the present invention is good, and bioavilability is high, is particularly suitable for the elderly and swallow tablet or the inconvenient patient of capsule take; Medicine tablet formulation provided by the invention, it is more to take mode, can swallow, contain clothes and sucking takes, it is convenient to use more than other oral solid formulations, simultaneously, these product are met water can rapid disintegration form the homodisperse aqueous solution in 3 minutes, solved the not high problem of active ingredient bioavilability; Soft capsule of the present invention is that drug blockage is formed in soft gel coat, has solved medicine and has met damp and hot unsettled problem, can also cover adverse drug taste, smell, plays the effect that increases stability, improves bioavilability; Granule provided by the invention, good mouthfeel absorbs soon simultaneously, and bioavilability is high.
The applicant finds in the process of development granule: granule enters in the body with solution state, compare with oral solid formulation, reduced disintegrating procedue in the body, be conducive to the absorption of this product, greatly shortened onset time, but also there is certain problem in this product granule, is exactly that hygroscopicity is strong, mouthfeel is bitter. The inventor herein intends solving this two problems by adding flavouring with preferred supplementary product kind. Because consider among the applicable crowd diabetic may be arranged, draw up for sugar-free type granular formulation, with high-potency sweetener as flavouring, whole supplementary product consumption is significantly reduced, simultaneously, also need by kind and the technological parameter of strict screening auxiliary material, in the situation that does not increase supplementary product consumption, solve the excessively strong problem of former powder hygroscopicity that exists in the raw material medicinal powder. The applicant finds when the development dispersing tablet, pharmacopeia regulation dispersing tablet must fully disintegration in the 3min in 19 ℃～21 ℃ water, suspension ability, bioavilability, dispersed homogeneous degree etc. are also had higher requirements, and the paste-forming rate of extract of the present invention is very high, viscosity is excessive, hygroscopicity is excessively strong, so that select to require very strict to kind and the consumption of various auxiliary materials in the moulding process prescription, deviation is slightly arranged, will cause product defective.
The diameter of micropill is less than 2.5mm, and class is in particle properties, and bioavilability is high, and the applicant is when development product of the present invention, and maximum difficulty is exactly the strong and poor fluidity of medicinal extract hygroscopicity, and poor plasticity is difficult to moulding and leaches slower.
Soft capsule disintegration in intestines and stomach is fast, and after softgel shell broke, medicine disperseed rapidly, so medicine release stripping is fast, produce effects is rapid, and bioavilability is high; Semi-transparent soft capsule can protect medicine not to be subjected to the effect of oxygen, light in moisture and the air with packaging material preferably, thereby improves the stability of labile element; So the stability of soft capsule itself and moulding process directly affect the stability of product, it is very crucial technology.
In the process of development dripping pill, find, matrix polyethylene glycols commonly used is that esterification forms, the surface-active water-soluble base of a kind of tool (fusing point is 46～51 ℃), solubility to insoluble drug is not good, we add S-40 change polyethylene glycols itself and do not have close ester structure and surface-active character, be conducive to the absorption of medicine, if but the consumption of S-40 is too high, and can cause product to draw moist enhancing.
And the major advantage of vaginal approach administration has: the method for administration that is a Noninvasive; But self administration can prolong holdup time of delivery system; Avoid the first-pass metabolism of liver; Some medicine had higher permeability; In the vagina degraded of enzyme seldom, medicine can be by metabolism and inactivation. But in fact this method of administration also has some shortcomings, poor such as administration inconvenience, the local tolerance of some semi-solid systems, as to be subjected to sexual intercourse interference etc. Can be in order to satisfy different patients' needs, we are except providing oral formulations, and the applicant also provides the products such as emulsifiable paste, suppository, vaginal tablets, lotion, and by rational technique, so that the having good stability of product, excitant are low.
Experimental example 1: Study on Forming
(1) granule Study on Forming
The applicant is in development process, and the greatest problem of finding the agent of this product granulation is exactly that hygroscopicity is strong, mouthfeel is bitter. Because consider applicable crowd, the standby sugar-free type granular formulation of drawing up is so supplementary product consumption is just fewer, and the former powder hygroscopicity of the medicinal extract of this product is very strong, supplementary product consumption can not be too much situation under, must by strict screening and the control of auxiliary material and process conditions, just can address these problems.
(1) supplementary product kind and consumption thereof are investigated
1. flavouring is selected
The function as sweeteners comparison sheet
| Kind | Sucrose | Aspartame | Honey element |
| The security of sugariness flavor quality and price lattice consumption | 1 (standard of comparison) 1 (standard of comparison) unrestricted (but diabetes are avoided usefulness) is good | 200～300 times 80 times unrestricted good | 30 times have the low consumption of metalloid flavor cost limited, generally are no more than 0.1% better |
Through relatively comprehensive, selected aspartame is made the flavouring of this product, and institute's expense per os sense is debugged and got. Screening experiment: get extract powder 40g, be divided into four parts, portion does not add any auxiliary material, and three parts add respectively 2.5%, 2.7%, 3% aspartame mixing in addition, adds an amount of boiling water and takes after mixing it with water, and tastes its flavor through many people, judges the quality of mouthfeel, and it the results are shown in Table.
The aspartame scale
| Tested number | 1 | 2 | 3 | 4 |
| The addition mouthfeel | Do not add auxiliary material pained (-) | Add the slightly sweet bitter taste (+) that still has of 2.5% aspartame | Add 2.7% aspartame sugariness moderate (++) | Add 3% aspartame excessively sweet (+++) |
The result shows, adds 2.7% aspartame, and mouthfeel is moderate.
2. wettability test is got two parts of extract powders, a dextrin that adds, and mixing is put respectively in the flat weighing bottle of having weighed, and is accurately weighed, is to measure its hygroscopic capacity under 75.0% condition in 25 ℃ of temperature, relative humidity, the results are shown in Table.
The wettability test result
| Sample | Pure extract powder | Extract powder+dextrin |
| The weighing bottle numbering | 1 | 2 |
| Weight of material (g) | 1.0013 | 0.9965 |
| Moisture absorption blanking time percentage (%) | 1h | 1.48 | 1.19 |
| 2h | 4.45 | 2.37 | |
| 3h | 6.48 | 4.59 | |
| 4h | 8.12 | 6.13 | |
| 6h | 10.16 | 7.26 | |
| 8h | 12.65 | 9.62 | |
| 10h | 15.23 | 11.27 | |
| 12h | 18.45 | 12.11 | |
| 24h | 20.52 | 15.43 | |
| 36h | 25.21 | 18.35 | |
| 48h | 35.13 | 21.46 | |
| 72h | 41.56 | 26.92 | |
| 84h | 42.20 | 32.46 | |
| 96h | 46.17 | 32.77 |
(2) Disket Study on Forming
Dispersing tablet meet water rapidly disintegration form the water dispersion tablet of uniform sticky suspension, it is poor to have solved former formulation disintegrative, stripping is shortcoming slowly, and the dispersing tablet that the applicant makes is fully disintegration in the 3min in 19 ℃～21 ℃ water, and suspension ability is good, bioavilability is high, dispersed homogeneous degree.
1. auxiliary material screening
Prescription PPVP (g) K30 (%) disintegration time/s
Add in adding
1 0.7 2.8 1.0 67
2 1.4 2.1 1.0 75
3 2.1 1.4 0.8 67
4 2.8 0.7 0.8 35
5 3.5 0 1.2 65
6 0 3.5 1.2 44
2. check disintegration time limited
Employing turns the basket method, and lift disintegration tester, tablet are got 6, observes the situation by screen cloth. Percent of pass height then disintegrative is good, more pleasant bulk absorption.
Group disintegration time limited (s)
1 2 3 4 5 6
1 batch 25 28 32 32 27 28 in tablet of the present invention
2 batches 25 29 30 33 29 28 in tablet of the present invention
3 batches 25 28 34 32 28 29 in tablet of the present invention
The result shows, get PPVP3.5g and lemon yellow mixing, getting 1/5 mixes with extract powder, K30 anhydrous alcohol solution with 0.8 % is made adhesive, 40 orders material processed, whole grain, the mixed powder of residue 4/5PPVP2.8g and lemon yellow mixing is added in the particle that makes, compressing tablet, and the dispersing tablet product that obtains is easy to disintegration.
(3) micropill preparation Study on Forming
The micropill diameter is less than 2.5mm, and class is in particle properties, and bioavilability is high, and the applicant is when development product micropill of the present invention, and the greatest difficulty that runs into is exactly the strong and poor fluidity of hygroscopicity, and poor plasticity is difficult to moulding. The micropill manufacturing technology that employing the applicant screening obtains and auxiliary material are so that product is easy to disintegration, and bioavilability is high, and is well-behaved.
1, extrudes-the spheronization pill
(1) supplementary product kind and consumption are selected
Wettability test is got two parts of extract powders, a starch that adds, and mixing is put respectively in the flat weighing bottle of having weighed, and is accurately weighed, is to measure its hygroscopic capacity under 75.0% condition in 25 ℃ of temperature, relative humidity, the results are shown in Table.
The wettability test result
| Sample | Pure extract powder | Extract powder+starch | |
| The weighing bottle numbering | 1 | 2 | |
| Weight of material (g) | 0.9880 | 0.986 | |
| Moisture absorption blanking time percentage (%) | 1h | 1.44 | 1.11 |
| 2h | 4.69 | 2.27 | |
| 3h | 6.70 | 4.58 | |
| 4h | 8.14 | 6.31 | |
| 6h | 10.01 | 7.86 | |
| 8h | 12.46 | 9.60 | |
| 10h | 15.39 | 11.31 | |
| 12h | 17.14 | 13.21 | |
| 24h | 20.21 | 17.32 | |
| 36h | 26.17 | 18.26 | |
| 48h | 34.15 | 22.38 | |
| 72h | 42.89 | 27.32 | |
| 84h | 45.54 | 37.20 | |
| 96h | 46.56 | 39.16 |
The result shows, adopts starch to make the auxiliary material reasonable.
(2) softwood processed
Get medicinal extract fine powder and starch, soybean oil and appropriate amount of ethanol and make softwood with wet granulation process, make it to reach and hold agglomeratingly, that pinches can fall apart, for subsequent use. Research emphasis concentration of alcohol and soybean oil consumption affect pill, and experimental result sees Table.
Concentration of alcohol is investigated
| Tested number | Concentration of alcohol | Softwood situation processed |
| 1 2 3 | 70% ethanol, 75% ethanol, 80% ethanol | The softwood moderate softwood viscosity of softwood that easily bonds is inadequate |
The soybean oil consumption is investigated
| Tested number | The soybean oil consumption | The pill situation |
| 1 2 3 | 75% ethanol, 1.2% soybean oil, 75% ethanol, 1.3% soybean oil, 75% ethanol, 1.5% soybean oil | Softwood viscosity is inadequate, and is can't the pill softwood moderate, and suitable pill softwood easily bonds, the pill difficulty |
The result as seen, it is more satisfactory to adopt 75% ethanol, 1.3% soybean oil to be that binder is granulated, otherwise is difficult to moulding.
(3) pill
The softwood that makes is with micropill mechanism ball, and wet feed pushed the 0.8mm sieve aperture, and the wet grain of strip cuts off round as a ball, and 50～60 ℃ of drying and mouldings are crossed 16～20 mesh sieves and selected ball.
2, general method for making pill
Because the extruding that the humidification of water and coating pan rotate makes medicinal powder be bonded into ball. Because this product viscosity is larger, general when making ball, water spray is fast and to add medicinal powder speed slow, causes that it is bonding closely the time that then prolongs into ball, makes after dry hardly, is unfavorable for the infiltration of moisture and affects and leach and the absorbing of medicine.
| Numbering | Coating pan rotating speed (r/min) | Leach the time (min) | Mouldability |
| 1 2 3 4 5 | 20 30 40 50 60 | 7.11 7.12 10.19 12.35 15.40 | Relatively poor better hard hard |
The result shows that it is optimum value that the coating pan rotating speed is selected 30r/min.
(4) soft capsule Study on Forming
Soft capsule disintegration in intestines and stomach is fast, and after softgel shell broke, medicine disperseed rapidly, so medicine release stripping is fast, produce effects is rapid, and bioavilability is high; Semi-transparent soft capsule can protect medicine not to be subjected to the effect of oxygen, light in moisture and the air with packaging material preferably, thereby improves the stability of labile element; So the stability of capsule and moulding process are very crucial technology.
(1) supplementary product kind and consumption are selected
1. decentralized medium (or claiming matrix) is selected
Can mix at fill material and matrix, and under the prerequisite of the unobstructed conveying of energy and pelleting, reduce substrates quantity as far as possible. By test of many times, determine medication amount (g): matrix amount (g)=be advisable at 1: 1.3, experimental result sees Table.
Substrates quantity is investigated
| Medication amount (g): matrix amount (g) | 1∶1.2 | 1∶1.3 | 1∶1.5 |
| Quality of liquid medicine | Viscosity is large, poor fluidity | Viscosity, flowability are all good | Differences in viscosity is mobile large |
2. capsule shells prescription screening
According to the form below proportion scale batching, put into the 500ml bottle,suction, 65 ℃ of water-baths are dissolved, automatic stirring glue, vacuumize simultaneously, about vacuum 0.095Mpa, insulation was placed 1 hour after 5 hours, filtered glue, get a part of glue and measure viscosity and other performance, part glue evenly is paved into skim (smear below first one deck atoleine) on iron plate, be positioned over to observe the rubber performance next day and judge again, with the investigation result of each index by good to poorly using successively " +++", " ++ ", "+", "-" expression
The results are shown in Table.
Rubber batching the selection result
| Prescription | Viscosity (Mpas) | Flexibility | Elasticity | Toughness | Characteristics | Overall merit |
| 1. gelatin 100g: glycerine 35g: water 100g | 3.60 | -- | --- | + | Crisp, hard | Poor |
| 2. gelatin 100g: glycerine 40g: water 100g | 3.35 | + | ++ | +++ | Tough, good film-forming property | Fine |
| 3. gelatin 100g: glycerine 45g: water 100g | 3.61 | + | ++ | + | Good springiness | Generally |
| 4. gelatin 100g: glycerine 40g: water 80g | 3.83 | ++ | ++ | + | Good springiness, viscosity is large | Fine |
| 5. gelatin 100g: glycerine 40g: water 120g | 3.21 | +++ | + | -- | Too soft | Poor |
| 6. gelatin 100g: glycerine 35g: sorbierite 5g: water 100g | 3.45 | -- | + | ++ | Tough | Better |
| 7. gelatin 100g: glycerine 35g: sorbierite 10g: water 100g | 3.46 | + | + | + | It is good to pierce through performance | Fine |
| 8. gelatin 100g: glycerine 40g: sorbierite 5g: water 100g | 3.50 | ++ | + | + | Tough | Better |
| 9. gelatin 100g: glycerine 40g: sorbierite 10g: water 100g | 3.46 | ++ | ++ | - | Soft | Generally |
| 10. gelatin 100g: glycerine 25g: sorbierite 10g: water 100g | 3.61 | + | + | ++ | It is good to pierce through performance | Better |
| 11. gelatin 100g: glycerine 35g: sorbierite 20g: water 90g | 3.52 | + | ++ | + | Tough | Fine |
| 12. gelatin 100g: glycerine 55g: sorbierite 5g: water 90g | 3.33 | ++ | ++ | + | 0.5mm following rubber is easily broken | Better |
| 13. gelatin 84g: glycerine 28g: sorbierite 28g: water 20g | Glue is too thick, can't change glue | |||||
| 14. gelatin 100g: Arabic gum 25g: glycerine 35g: water 100g | 3.46 | - | --- | + | Color is ash partially | Poor |
| 15. gelatin 85g: Arabic gum 15g: glycerine 45g: water 100g | 3.50 | - | + | + | Crisp, the color belt ash | Generally |
| 16. gelatin 85g: Arabic gum 15g: glycerine 60g: sorbierite 10g: water 60g | 3.47 | + | + | ++ | 0.2～0.8mm rubber tearing strength is large | Fine |
| 17. gelatin 50g: Arabic gum 150g: sorbierite 10g: glycerine 60g: water 55g | 3.58 | + | - | -- | Crisp, the color belt ash | Poor |
| 18. gelatin 85g: Arabic gum 15g: glycerine 45g: sorbierite 10g: water 110g | 3.52 | + | + | + | Crisp | Generally |
| 19. gelatin 85g: Arabic gum 15g: glycerine 60g: sorbierite 10g: water 90g | 3.34 | + | + | + | 0.85mm following rubber poor flexibility | Generally |
| 20. gelatin 100g: Arabic gum 25g: glycerine 45g: sorbierite 5g: water 100g | 3.39 | + | -- | + | Color is ash partially | Generally |
Through above screening, overall merit is considered the characteristics of fill material, selects prescription 2, i.e. gelatin 100g: glycerine 40g: water 100g.
3. opacifier is selected
The transparent adhesive tape softgel shell easily causes unstable, so need to add a certain amount of opacifier. Select titanium dioxide (titanium dioxide) to make opacifier through investigation and can reach effective shaded effect, and steady quality, not with rubber cement and fill material generation chemical change. Its consumption is through investigating with gelatin: glycerine: water: titanium dioxide=100g: 40g: 100g: 1g is advisable, and little to the rubber quality influence, the results are shown in Table.
The opacifier consumption is selected
| Usage ratio | The rubber transparency | Rubber cement viscosity (Mpas) | Overall merit |
| Gelatin 100g: glycerine 40g: water 100g: titanium dioxide 0.3g gelatin 100g: glycerine 40g: water 100g: titanium dioxide 0.5g gelatin 100g: glycerine 40g: water 100g: titanium dioxide 1g gelatin 100g: glycerine 40g: water 100g: titanium dioxide 2g | Translucent translucent opaque | 3.14 3.21 3.34 3.55 | The good not viscosity of the inadequate consumption of consumption is larger |
Quality is more stable after adding opacifier in the capsule formula.
(2) molding technological condition is investigated
1. the medicinal extract grinding particle size is investigated
Medicinal extract is pulverized, crossed respectively 60 orders, 80 orders, 100 orders, 120 mesh sieves, press medicinal extract: matrix=1: 1.3 is even through the colloid mill mill, and observation mixing situation the results are shown in Table.
The medicinal extract grinding particle size is investigated
| Granularity (order) | 60 | 80 | 100 | 120 |
| The mixing situation | Can not mixing, high speed centrifugation (10000/min) 30min layering | The energy mixing, 30min is not stratified for high speed centrifugation (10000/min) | The energy mixing, 30min is not stratified for high speed centrifugation (10000/min) | The energy mixing, 30min is not stratified for high speed centrifugation (10000/min) |
As seen from the above table, medicinal extract was pulverized just energy mixing of 80 mesh sieves, therefore, selected medicinal extract to pulverize 80 mesh sieves.
2. fill material mixes
The laboratory is got medicinal extract and was pulverized 80 mesh sieves, presses medicinal extract: matrix=add soybean oil at 1: 1.2, use the colloid mill mixing, and vacuumize bubble removing, for subsequent use.
3. batchingization glue is investigated
Be gelatin by aforementioned preferred prescription: glycerine: water: titanium dioxide=1 00g: 40g: 100g: the 1g weigh batching with different temperatures glue, the results are shown in Table.
Changing the glue temperature investigates
| Temperature (℃) | Change the glue time (H) | The rubber quality |
| 50 60 70 80 90 | 6 5 5 5 4 | Good have bubble than the ebonite skin carefully, hard |
By the table prompting, it is the most suitable with 60～70 ℃ to change the glue temperature. So batchingization adhesive tape part is: weigh batching, in the inputization glue tank, cold soaking is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirs 5 hours and vacuumized simultaneously bubble removing, until the evenly rear blowing of sizing material, incapsulates after the filtration in the sizing material bucket of machine.
4. pelleting: sizing material bucket and the spice bucket of normal temperature of insulation are delivered to the capsule machine top, be connected with machine, debug pellet press, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity＜40%. Regulating ball content loading amount after the pellet press debugging is the 400mg/ grain. Survey loading amount once every half an hour in the pelleting process.
5. dry:
The dry soft capsule through pellet press extrusions of typing is in conveyer belt is delivered to rotating cage, and rotating cage is blown a cold wind over while rotating, rotates about 2 hours of the drying of finalizing the design.
Tray dried capsule and pill of cold air drying in rotating cage is contained in clean stainless steel charging tray splendid attire, moves to about 22 ℃ of temperature, and airing is 48 hours in the hothouse of relative humidity below 40%, and constantly stirs, and surveys capsule moisture and is being dry suiting below 10%.
Dry lime light: drying adopts the dry and tray dried two step combinations of the typing of rolling, and the typing of rolling is dry is advisable with two hours through investigation, and overlong time is then rough; Baking temperature is advisable about investigating with 22 ℃, and it is long that it's low drying time is past temperature, though increase in temperature can shorten drying time, easily produces to capsule surface and chaps; Dry relative humidity should be lower than 40% through investigating, otherwise is difficult for dry; Got final product below 10% with control moisture drying time about 24～48 hours.
(5) dripping pill moulding process
(1) screening of matrix
The fusion situation of matrix and main ingredient relatively
| The prescription number | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 | Prescription 6 | Prescription 7 | Prescription 8 |
| Medicine (g) | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
| PEG400 D (g) | 10 | 15 | 15 | 20 | ----20---- | -----30----- | ------------ | ------------ |
| Macrogol 6000 (g) | ------------ | ------------ | ------------ | 20 | 30 | 35 | 40 | 45 |
| S-40 | 10 | 10 | 10 | |||||
| The fusion situation of main ingredient and matrix | Main ingredient can merge with matrix, but system is without flowability | Main ingredient can merge with matrix, and system is better mobile | Main ingredient can merge with matrix, and the system flowability is fine | Main ingredient can merge with matrix, and the system flowability is fine | Main ingredient and matrix merge relatively poor | Main ingredient can merge with matrix, but system is without flowability | Main ingredient can merge with matrix, and the system flowability is relatively poor | Main ingredient can merge with matrix, and system is better mobile |
| The dripping pill outward appearance | ----------- | Roundness is poor, hangover | Smooth, roundness is good | Smooth, roundness is good | ------------ | Roundness is poor, hangover | -roundness is slightly poor. Hangover is slightly arranged | ------------ |
| Dripping pill hardness | ----------- | Hardness is little | Hardness is better | Hardness is better | ------------ | ------------ | Hardness is better | Hardness is better |
| The ball method of double differences is different | 20％ | 8.0％ | 13.5％ | ------------ | 18％ | 20％ | ||
| Dissolve scattered time limit (min) | ----------- | 7～8 | 4～5 | 9～10 | ------------ | ------------ | 6～8 | 6～8 |
The result shows, the dripping pill stripping that composite interstitial substance makes is very fast, because the esterification of polyethylene glycols matrix forms, the surface-active water-soluble base of a kind of tool (fusing point is 46～51 ℃), S-40 has changed polyethylene glycols itself and has not had close ester structure and surface-active character, improve the solubility of insoluble drug, be conducive to the absorption of medicine.
2. drip distance, drip selection fast, temperature
Drip distance, drip selection fast, temperature: the internal-and external diameter of drip is fixed as 4.1,6.1mm. Evaluation index: the heavy qualification rate of ball is by mass discrepancy requirement of Pharmacopoeia of the People's Republic of China version in 2000: meet ± 7.5% within.
| Group | Temperature/℃ | Drip distance/cm | Cooling fluid height/cm | Heavy qualification rate/the % of ball |
| 1 | 90 | 5 | 50 | 76.2 |
| 2 | 90 | 4 | 60 | 84.3 |
| 3 | 90 | 6 | 70 | 82.1 |
| 4 | 80 | 5 | 60 | 90.3 |
| 5 | 80 | 4 | 70 | 84.2 |
| 6 | 80 | 6 | 50 | 90.0 |
| 7 | 70 | 5 | 70 | 94.2 |
| 8 | 70 | 4 | 50 | 88.1 |
| 9 | 70 | 6 | 60 | 85.3 |
The result shows, the optimum condition of preparation dripping pill of the present invention: drip to become ball in dimethicone, drip apart from 5cm drip footpath 2.5mm/2mm, mix the ointment temperature 70 C, cooling fluid height 70cm.
(6) bioavilability relatively
The SD rat, body weight 250～280g, male and female half and half, fasting overnight (can't help water), next day gastric infusion, dosage is 3.8g/kg. Before administration and heart blood sampling after the administration, each blood sample point is with 6 rats. Blood sample is put the anticoagulant heparin pipe, the centrifugal 5min of 3000r/min, and separated plasma is put-30 ° and is saved to analysis. High performance liquid chromatograph is by the M510 pump, the U6K injector, and M490 variable-wavelenght detector and 810 chromatographic data treating stations form (Waters, the U.S.). Analytical column is μ BondpakaC18(0.45mm * 25cm); Mobile phase is methyl alcohol: water=6: 4; Flow velocity: 0.8mL/min; Detect wavelength: λ=230nm. Bergenin extracts in the blood plasma: get 0.5mL blood plasma, add 5mLCHCl3, interior mark 50 μ L, test tube is done 30 ° and is favoured the horizontal direction rocker, and 15min is extracted in jolting, centrifugal (3000r/min) 10min, aqueous phase discarded, the accurate 4mL organic phase of drawing is in a clean tube, at 37 ℃ of water-baths, N2Dry up under the air-flow, residue dissolves the sample introduction analysis again with 200 μ L mobile phases.
Rat plasma Bergenin change in concentration (N=6)
Time/h blood plasma Bergenin concentration/(mgL-1)
Dispersing tablet of the present invention gel of the present invention micropill of the present invention soft capsule of the present invention particle JINGDAINING JIAONANG of the present invention dripping pill of the present invention
0 - - - - - - -
0.25 1.68±0.41 1.62±0.14 1.63±0.12 1.70±0.28 1.69±0.13 0.73±0.18 1.71±0.12
0.50 3.59±1.20 3.57±0.58 3.49±1.14 3.36±1.12 3.61±1.04 1.02±0.33 3.72±0.15
0.85 2.32±0.28 2.48±0.73 2.27±0.38 2.51±0.20 2.23±0.36 1.92±0.56 2.34±0.16
1.35 1.64±0.43 1.68±0.46 1.65±0.57 1.74±0.46 1.66±0.42 1.36±0.25 1.68±0.21
2.00 1.31±0.16 1.45±0.33 1.40±0.25 1.38±0.23 1.32±0.23 1.04±0.02 1.32±0.12
3.00 1.05±0.26 1.25±0.27 1.07±0.12 1.02±0.18 1.07±0.11 0.75±0.21 1.04±0.23
4.00 0.81±0.29 0.78±0.15 0.82±0.28 0.83±0.12 0.86±0.20 0.48±0.03 0.81±0.28
6.00 0.46±0.17 0.47±0.12 0.48±0.17 0.46±0.25 0.34±0.12 0.23±0.03 0.41±0.34
8.00 0.24±0.11 0.19±0.02 0.25±0.21 0.24±0.13 0.26±0.06 0.11±0.14 0.26±0.23
The result shows that the bioavilability of product of the present invention is greater than capsule.
(7) anti-inflammatory and antalgic reaches the pharmacological research to the uterus effect of contraction
(1) antiinflammatory action
1. the impact of paraxylene induced mice auricle edema
Experimental technique before use with dispersing tablet of the present invention, micropill, that soft capsule is mixed with the 0.10g/ml suspension with 0.5% sodium cellulose glycolate (CMC-Na) is for subsequent use, the healthy Kunming mouse of animal, body weight 20 grams. Mouse is divided into 7 groups (control group physiological saline) at random, the gavage volume is 20ml/kg, continuous two weeks of gavage, once a day, the last administration after 30 minutes with micro syringe with 0.05ml/ only, dimethylbenzene is applied to mouse right ear, put to death mouse after 15 minutes, cut two ears along the auricle baseline, lay round auricle in left and right sides auricle same area respectively with 8mm diameter steel drift, weighing scale to test twisting force claims two auricle weight in wet bases, with two auricle weight differences as the swelling level index. Inhibitory rate of intumesce equals the difference of the average swelling of control group and the average swelling of administration group and takes advantage of 100% divided by the average swelling of control group again.
Average swelling (mg) inhibiting rate (%) of group dosage (g/kg) animal (only)
Control group 20ml/kg 8 22.32 ± 1.44
Hydrocortisone group 0.04 8 7.12 ± 2.54 70.19
JINGDAINING JIAONANG group 2.0 8 15.23 ± 1.30 30.21
Dispersing tablet group 2.0 8 14.26 of the present invention ± 4.21 32.10
Micropill group 2.0 8 13.45 of the present invention ± 2.18 33.12
Soft capsule group 2.0 8 13.61 of the present invention ± 3.21 33.36
The result shows that preparation of the present invention has good antiinflammatory action, and effect is better than the JINGDAINING JIAONANG group.
2. on the impact of rat uterus inflammation
Experimental technique: animal is selected the female big white mouse of SD kind, about 200 grams of body weight. Animal is divided 7 groups, each treated animal under etherization cuts off the lower abdomen hair, rear long mouthful of the 2cm that cuts in the abdomen center of sterilization, expose the uterus, make a kerf along 1cm place on the angle, left side, uterus, with a plastic hoop (caliber 2cm, long 0.5cm, heavy 2mg, alcohol disinfecting) is positioned in the uterus, sews up with uterine incision and fix, postoperative beginning in 2 hours administration, once a day, the administration volume is the 20ml/kg body weight, puts to death animal after 7 days, takes out the uterus, both sides, except degrease, assay balance is weighed, and left side, every mouse uterus is inflammation swelling degree with the difference on right side, calculates swelling rate and the inhibiting rate of administration group. Swelling rate equals to cause scorching uterus average weight and not multiply by 100% with the difference that does not cause scorching uterus average weight divided by causing scorching uterus average weight, and the difference that inhibiting rate equals the average swelling rate of the average swelling rate in control group uterus and administration group uterus multiply by 100% divided by the average swelling rate in control group uterus.
Group dosage (g/kg) animal (only) swelling rate (%) inhibiting rate (%)
Control group 20ml/kg 10 201.32
Hydrocortisone group 0.04 10 6.73 94.14
JINGDAINING JIAONANG group 2.0 10 18.24 90.78
Dispersing tablet group 2.0 10 15.30 91.12 of the present invention
Dripping pill group 2.0 10 15.32 91.23 of the present invention
Gel group 2.0 10 15.15 91.26 of the present invention
The result shows that preparation of the present invention has good anti-uterus inflammatory effect, and effect is better than the JINGDAINING JIAONANG group.
(2) analgesic activity
Inhibitory action to the mouse writhing reaction
Experimental technique: mouse is divided into 7 groups at random, and continuously gavage is 8 days, the last administration after 90 minutes mouse peritoneal inject 0.7% glacial acetic acid 0.1ml/10 gram body weight, observe writhing number of times in the counting mouse 15 minutes.
Group dosage (g/kg) animal (only) writhing number of times inhibiting rate (%)
Control group 20ml/kg 10 33.0 ± 6.1
Hydrocortisone group 0.04 10 10.2 ± 3.5 68.17
JINGDAINING JIAONANG group 2.0 10 22.3 ± 2.3 26.03
Granule group 2.0 10 18.1 of the present invention ± 3.1 26.18
Micropill group 2.0 10 18.2 of the present invention ± 2.0 27.23
Soft capsule group 2.0 10 18.4 of the present invention ± 3.2 27.19
The result shows that preparation of the present invention has the reagentia of obvious inhibition mouse writhing, illustrates that it has good analgesic activity, and effect is better than commercially available JINGDAINING JIAONANG group.
(8) stability
Testing result to stability of cream
Time outward appearance water-oil separating granularity pH catabolite
0 day light yellow without uniform and smooth 7 nothings
5 days light yellow has an impure point without unchanged 7
Yellow had an impure point without unchanged 7 in 10 days
The suppository stability experiment
Acceleration by light test is sealed in this product in the colourless neutral density glass vessel, puts that (2500～4000lx) strong illuminations keep 37 ℃, investigate proterties, color and luster, content equistability index in 1,5,9,12,15d sampling. Found that this product proterties does not become, and color and luster is deepened gradually, content is gradually low. Show this product to photaesthesia, should keep in Dark Place.
The vaginal plug that humid test will be made 5 batches of unlaps by oneself places 37 ℃, under the constant humidity condition of relative humidity 25%, and the 90d that keeps in Dark Place, its proterties, color and luster content equistability index are investigated in sampling. Found that all and to show that without marked change this product is to thermally-stabilised.
The humidity accelerated test is under 37 ℃ of constant temperature, the vaginal plug lucifuge of 5 batches of unlaps of self-control is placed under the constant humidity condition of relative humidity 90%, place 90d, its proterties, color and luster, content equistability index are investigated in sampling when 30d, indices does not all meet quality standard as a result, shows not moisture-proof of this product. Should seal and place the preservation of dry place.
Reserved sample observing is got 5 batches of homemade vaginal plugs, and lucifuge packs; Place reserved sample observing 180d under the room temperature of low humidity and constant humidity, investigate its stability, find to change without conspicuousness. The long-time stability of this product are still needed and will further be investigated.
The lotion study on the stability
3 batches of this product were placed 1 year under room temperature, respectively at 0 month, 3 months, 6 months, 9 months, carried out proterties, pH value and limit test of microbe, and investigated proterties, the variation of ph, microorganism checking in 12 months. The result shows that indices has no significant change.
(9) vaginal tablets is to the experimental study of vaginal irritation reaction
Test grouping: 30 rabbit are divided into 5 groups at random, 6 every group, i.e. blank group; Vehicle group (50mg sheet-1); High dose group (25mg sheet-1,50mg sheet-1 and 100mg sheet-1) during vaginal tablets of the present invention is low.
Medication: rabbit by only lying on the back in the rabbit plate, after the introitus sterilization, is placed the vagina middle-end with each group reagent, raise buttocks, behind the 5h rabbit put back in the cage and raise administration every day 1 time, altogether 7d. During the medication, observe overall health of patients and the local reaction of rabbit every day, 24h after last 1 administration puts to death rabbit, takes out vagina tissue, and visually observing vaginal mucosa has non-stimulated performance, then puts into the fixing rear censorship of 10% formalin that configures.
The result: during the medication, all without unusual, introitus also has no redness and the abnormal secretion logistics goes out, with the control group indistinction for vehicle group and vaginal tablets group overall health of patients of the present invention; Visually observe the vagina tissue of taking-up, each group is showed no vaginal mucosa obvious hyperemia, oedema, erosion, ulcer and blutpunkte. See the slight kitchen range cell infiltration of small dose group 1 routine vagina epithelium lower floor under the mirror; Vehicle group 1 routine vagina epithelium focal degeneration, necrosis, come off, upper subcutaneous connective tissue oedema, shallow-layer have the acute and chronic cell infiltration; The routine local vaginal mucosa epithelium distortion of control group 1, downright bad, come off. Upper subcutaneous connective tissue shallow-layer has the impatient chronic inflammation cellular infiltration of kitchen range, remaining no abnormality seen.
(10) minimum inhibitory concentration (MIC) of the common saccharomycete flora of In Vitro Anti vagina is measured
Experimental technique: agar dilution (test tube method) is specifically published " new drug (Western medicine) preclinical study guideline (pharmacy, pharmacology, toxicology) " about the method for antifungal drug pharmacodynamic experiment research institute regulation by bureau of drug administration of Ministry of Health of the People's Republic of China.
By belonging to 9 kind of 49 fungal strain to carried out the mensuration of minimum inhibitory concentration (MIC) by suppository of the present invention, lotion, vaginal tablets, cream extract with the common saccharomycete flora 3 of vagina, its MIC scope sees that to vagina the saccharomycete flora is effective at 3.135-12.7 μ g/ml as a result.
Concrete embodiment:
Embodiments of the invention 1: kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g, geranium wilfordii 750g, get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; It is an amount of to add 2.7% aspartame and dextrin, and mixing is granulated, and namely gets granule, and three times on the one, a 10g.
Embodiments of the invention 2: kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g, geranium wilfordii 750g, get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; Get PPVP3.5g and lemon yellow mixing, get 1/5 and mix with extract powder, make adhesive with 0.8% K30 anhydrous alcohol solution, 40 orders material processed, whole grain, the mixed powder of residue 4/5PPVP2.8g and lemon yellow mixing is added in the particle that makes, and compressing tablet namely gets dispersing tablet.
Embodiments of the invention 3: kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g, geranium wilfordii 750g, get paniculate swallowwort 133g, be ground into fine powder, remaining Xu long namely with Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; Add an amount of starch, with 75% ethanol and 1.3% soybean oil softwood processed, the softwood that makes micropill mechanism ball, wet feed pushed the 0.8mm sieve aperture, and the wet grain of strip cuts off round as a ball, 50～60 ℃ of drying and mouldings, crossing 16～20 mesh sieves selects ball or merges above-mentioned four kinds of clear cream, spray-drying, wet-milling granulation molding, mould placed add the great achievement ball in the coating pan, medicinal powder: water is 1: 1.3, and the coating pan rotating speed is 30r/min, capping, select ball, namely get micropill preparation.
Embodiments of the invention 4: kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g, geranium wilfordii 750g, get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; Press medication amount: matrix amount=1: 1.3 adding soybean oil, mixing; The prescription of rubber is gelatin: glycerine: water: titanium dioxide=100g: 40g: 100g: 1g, batchingization adhesive tape part is: weigh batching, in the inputization glue tank, cold soaking is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirred 5 hours and vacuumized simultaneously bubble removing, until the evenly rear blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; The debugging pellet press, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity＜40%, pelleting; Dry employing is rolled, and typing is dry to go on foot combinations with tray dried two, dry 2 hours of the typing of rolling, and 22 ℃ of baking temperatures, dry relative humidity should be lower than 40%, and namely got soft capsule at 24～48 hours drying time.
Embodiments of the invention 5: kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g, geranium wilfordii 750g, get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; Get 1 part of extract powder, PEG40001.5 part and polyoxyl 40 stearate S-401 part mix, and melt in the water-bath, stir evenly, drip and in dimethicone, to become ball, drip apart from 5cm drip footpath 2.5mm/2mm, mix the ointment temperature 70 C, cooling fluid height 70cm namely gets pill.
Embodiments of the invention 6: kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g, geranium wilfordii 750g, get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filters, and filtrate decompression is concentrated, let cool, slowly add ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter, Recycled ethanol, reduced pressure concentration adds above-mentioned paniculate swallowwort fine powder, mixing, drying is pulverized, add microcrystalline cellulose 25g, use 85% alcohol granulation, drying, whole grain adds dolomol 2g, mixing, compressing tablet, dressing namely gets tablet.
Embodiments of the invention 7: kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g, geranium wilfordii 750g, get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filter, filtrate decompression is concentrated, lets cool, slowly add ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter, Recycled ethanol, reduced pressure concentration adds above-mentioned paniculate swallowwort fine powder, mixing, add distilled water, 3.5% aspartame, sterilization namely gets oral liquid.
Embodiments of the invention 8: kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g, geranium wilfordii 750g, get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filters, and filtrate decompression is concentrated, let cool, slowly add ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, and filtered Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing is got carbomer and is made 0.5% glue 1000ml, fully add the medicine thick paste after the dissolving, stir fully lentamente, then set low the lower rapid condensation of temperature, and get final product.
Embodiments of the invention 9: kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g, geranium wilfordii 750g, get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filters, and filtrate decompression is concentrated, let cool, slowly add ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying adds the potassium hydrogen tartrate of 3 times of amounts, the sodium bicarbonate of 2 times of amounts, the silica of 1 times of amount, compressing tablet namely gets vaginal tablets.
Embodiments of the invention 10: kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g, geranium wilfordii 750g, get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; It is an amount of to get distilled water, dropping lactic acid is an amount of, adds extract powder and stirs, and treats dissolve complete, add the glycerine of 10 times of amounts and the gelatin solution of 10 times of amounts, stir evenly, be poured into and sterilized in advance and scribble in the duckbill vaginal plug mould of liquid paraffin, slightly cold after, scrape off and overflow part, take out after condensation, packing namely gets suppository.
Embodiments of the invention 11: kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g, geranium wilfordii 750g, get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; With the cetanol of 4 times of amounts, the stearyl alcohol of 2 times of amounts, through 80 ℃ of meltings of water-bath, mix, insulation is as oil phase; Propane diols, the phenmethylol of 1 times of amount, the water of 2 times of amounts are heated to 80 ℃, and dissolving mixes, as water; Oil phase is under agitation slowly added water, stirring and emulsifying, be chilled to 40 ℃ stand-by; The third two ferment of medicinal powder and 1 times of amount are ground to transparence, add in the above-mentioned matrix, mix, namely get cream.
Embodiments of the invention 11: kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g, geranium wilfordii 750g, get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filters, and filtrate decompression is concentrated, let cool, slowly add ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter, Recycled ethanol, reduced pressure concentration adds above-mentioned paniculate swallowwort fine powder, and mixing is dry, add again metronidazole 5g, Sodium Benzoate 2g is stirred to molten, filter, filtrate is added distilled water to full dose, can, sterilization namely gets lotion.
Claims (5)
1, a kind of Chinese medicine preparation for the treatment of gynecological disease calculates according to weight, and it is made of kiss-me 1500g, paniculate swallowwort 800g, Longtube Ground Ivy Herb 750g and geranium wilfordii 750g; Get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, and filtrate decompression is concentrated, let cool, slowly add ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter, Recycled ethanol, reduced pressure concentration adds above-mentioned paniculate swallowwort fine powder, mixing, then drying makes respectively dispersing tablet, soft capsule, granule, micropill preparation or pill; It is characterized in that: granule prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, lets cool, and slowly adds ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, filter Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; It is an amount of to add 2.7% aspartame and dextrin, and mixing is granulated, and be get final product.
2, according to the preparation method of the Chinese medicine preparation for the treatment of gynecological disease claimed in claim 1, it is characterized in that: Disket prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, let cool, slowly add ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, and filtered Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; Get PPVP3.5g and lemon yellow mixing, get 1/5 and mix with extract powder, make adhesive with 0.8% K30 anhydrous alcohol solution, 40 orders material processed, whole grain, the mixed powder that remains 4/5PPVP2.8g and lemon yellow mixing is added in the particle that makes, compressing tablet, and get final product.
3, according to the preparation method of the Chinese medicine preparation for the treatment of gynecological disease claimed in claim 1, it is characterized in that: micropill preparation prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, let cool, slowly add ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, and filtered Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; Add an amount of starch, with 75% ethanol and 1.3% soybean oil softwood processed, the softwood that makes micropill mechanism ball, wet feed pushed the 0.8mm sieve aperture, and the wet grain of strip cuts off round as a ball, 50～60 ℃ of drying and mouldings, crossing 16～20 mesh sieves selects ball or merges above-mentioned four kinds of clear cream, spray-drying, wet-milling granulation molding, mould placed add the great achievement ball in the coating pan, medicinal powder: water is 1: 1.3, and the coating pan rotating speed is 30r/min, capping, select ball, and get final product.
4, according to the preparation method of the Chinese medicine preparation for the treatment of gynecological disease claimed in claim 1, it is characterized in that: soft capsule prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, let cool, slowly add ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, and filtered Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; Press medication amount: matrix amount=1: 1.3 adding soybean oil, mixing; The prescription of rubber is gelatin: glycerine: water: titanium dioxide=100g: 40g: 100g: 1g, batchingization adhesive tape part is: weigh batching, in the inputization glue tank, cold soaking is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirred 5 hours and vacuumized simultaneously bubble removing, until the evenly rear blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; The debugging pellet press, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity＜40%, pelleting; Dry adopt the typing of rolling dry with tray dried two step combinations, dry 2 hours of the typing of rolling, 22 ℃ of baking temperatures, dry relative humidity should be lower than 40%, drying time is at 24～48 hours, and get final product.
5, according to the preparation method of the Chinese medicine preparation for the treatment of gynecological disease claimed in claim 1, it is characterized in that: pill prepares like this: get paniculate swallowwort 133g, be ground into fine powder, remaining paniculate swallowwort and Longtube Ground Ivy Herb, kiss-me, geranium wilfordii boiling secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, filtrate decompression is concentrated, let cool, slowly add ethanol, make that to contain alcohol amount be 65%, stir evenly, left standstill 24 hours, and filtered Recycled ethanol, reduced pressure concentration, add above-mentioned paniculate swallowwort fine powder, mixing, drying; Get 1 part of extract powder, PEG40001.5 part and polyoxyl 40 stearate S-40 are a, mix, and melt in the water-bath, stir evenly, drip and in dimethicone, to become ball, drip apart from 5cm drip footpath 2.5mm/2mm, mix the ointment temperature 70 C, cooling fluid height 70cm, and get final product.
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| CNB2005100031528A CN1331461C (en) | 2005-08-03 | 2005-08-03 | Chinese medicine preparation for treating gynecopathy and its preparation method |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1418657A (en) * | 2002-11-26 | 2003-05-21 | 吴传喜 | Capsule for treating gynae cological disease and its prepn. process |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1418657A (en) * | 2002-11-26 | 2003-05-21 | 吴传喜 | Capsule for treating gynae cological disease and its prepn. process |
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