CN1569205A - Method for preparing and controlling the quality of Chinese medicinal soft capsule - Google Patents
Method for preparing and controlling the quality of Chinese medicinal soft capsule Download PDFInfo
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Abstract
The invention provides a method for preparing and controlling the quality of Chinese medicinal soft capsule, wherein the capsule is prepared from rheum officinale, goldthread root, root of large-flowered skullcap through extracting, ball squeezing, washing and drying.
Description
Invention field
The present invention relates to a kind of preparation method and method of quality control of Chinese medicinal soft capsule preparation, particularly a kind of have heat clearing away, pathogenic fire purging, dampness, Detoxication the preparation method and the method for quality control of pure Chinese medicinal soft capsule preparation, belong to medical technical field.
Background technology
Radix Et Rhizoma Rhei is one of traditional Chinese medical science general medicine, is clinical the most frequently used medicine from ancient times to the present always, and its nature and flavor bitter cold is gone into taste, large intestine, liver, pericardium channel.Once record in the Shennong's Herbal: " main blood stasis, blood down close cold and heat, and broken lump in the abdomen, prolonged fluid-retention dyspepsia are cleansed the intestines and stomach, push away Chen Zhixin, tonneau water paddy, relieving dyspepsia in the accent, peace and the five internal organs ".Ming Dynasty's Li Shizhen (1518-1593 A.D.) is through examination and clinical verification on the spot, the Radix Et Rhizoma Rhei effect carried out replenishing perfect, and points out in Compendium of Material Medica: " main dysentery is red white, pain in the abdomen stomachache, dribbling urination, excess-heat dryness accumulated in the stomach and intestine, hectic fever delirium, all burn of jaundice ".
Rhizoma Coptidis also is one of medicine that from ancient times is celebrated.Good medicine for health tastes bitter to the mouth, is the famous dictum that people know already.Rhizoma Coptidis just has very high medical value just because of it is bitter.Rhizoma Coptidis is the Ranunculaceae herbaceos perennial, and medicinal its root is the Chinese medicine key medicine, in the Shennong's Herbal it is classified as top grade.Rhizoma Coptidis is famous with heat-clearing and toxic substances removing, thereby ancient Chinese medicine doctor all has very high praise to it.As Southern Dynasties's beam, TAO Hong-Jing between neat saying of " obeying long-living for a long time " arranged once.Ming Dynasty's Miao Xiyong has the praise of " elixir of sick wine, the SHENCAO of dysentery ".Because its root is beaded and yellow skin, so the name Rhizoma Coptidis.Again because of geographic Mount Emei, main product Sichuan in history and Hongya one band, and shape such as chicken feet, so titles such as Rhizoma Coptidis, refined company, Rhizoma Coptidis are arranged again.As far back as two do for many years before, Rhizoma Coptidis has gone into medicinal, has now become the rare medicinal herbs of famous China and foreign countries, has heat clearing away, pathogenic fire purging, dampness, a multiple use such as the relieving restlessness of detoxifying, clear away heart-fire.
Radix Scutellariae, bitter in the mouth, cold in nature, go into heart stomach gallbladder large intestine channel.Do not record cloud: " Radix Scutellariae, its property is respectful clearly, and bitter in the mouth is with dampness, and is cold in nature with heat clearing away, the main all heat in side.All hot persons, pathogenic heat and also damp and hot." have the hot dampness that disappears, eliminating fire and detoxication, hemostasis, antiabortive effect.
Burning hot disease is commonly called as " getting angry ", is a kind of very common disease, and generation is all arranged throughout the year.Mainly be that function presents a unusual excited class disease behind the body because paathogenic factor acts on, clinical manifestation is that mouth and nose are given birth to skin ulcer, dry mouth and parching tongue, constipation etc.This disease need be used cold and cool Drug therapy.In " Medical Treasures of the Golden Chamber " " XIEXIN TANG " of record, Radix Et Rhizoma Rhei: purging heat and dredging bowels, removing pathogenic heat from blood and toxic substance from the body, eliminating blood stasis and inducing menstruation; Rhizoma Coptidis: heat clearing away, pathogenic fire purging, dampness, the relieving restlessness of detoxifying, clear away heart-fire; Radix Scutellariae: heat clearing and damp drying, eliminating fire and detoxication, hemostasis, antiabortive.Three kinds of compositions all belong to clearing up internal heat by using drugs of bitter in taste and cold in nature antidote, and these three kinds of compatibility of drugss make that the three warmers excess-fire is hot and suffocating just discharges through two, and are very suitable to all diseases due to the long-pending heat of three warmers.The clinical heat-clearing and toxic substances removing that is applicable to, pathogenic fire purging relieving constipation, eliminating toxin and beautifying the skin.Be used for that mouth and nose give birth to that skin ulcer, swelling throat are closed, tooth pain, dry mouth and parching tongue ， lumps in the chest and abdomen, have a dizzy spell, constipation, yellowish or reddish urine, and various pharyngolaryngitis, tonsillitis, oral ulcer, swelling and aching of gum and acne seat skin ulcer etc. belong to above disease person.But three flavor medicines are the product of bitter cold, make the extremely bitter patient of granule mouthfeel and be difficult for accepting, and dosage is bigger, the easy moisture absorption instability of granule in addition, the destruction that is subjected to moisture, light and oxygen easily; As make capsule, and then exist dose bigger equally, shortcomings such as mouthfeel difference, and be added with adjuvants such as starch, Pulvis Talci and magnesium stearate in the drug extract, disintegration time is long in vivo, absorbs relatively poor.
Summary of the invention
One of purpose of the present invention provides a kind of preparation method of Chinese medicinal soft capsule preparation; Another object of the present invention is to provide a kind of Radix Et Rhizoma Rhei, Rhizoma Coptidis, Radix Scutellariae effective component extracts of containing, and has the preparation method of the pure Chinese medicinal soft capsule preparation of heat clearing away, pathogenic fire purging, dampness, detoxicating functions; The 3rd purpose of the present invention provides a kind of method of quality control of Chinese medicinal soft capsule preparation.
The preparation method of this Chinese medicinal soft capsule preparation is:
Preparation method 1:
Radix Et Rhizoma Rhei, Rhizoma Coptidis, Radix Scutellariae three flavors, be broken into coarse powder, add decocting in water respectively and fry in shallow oil secondary (Radix Scutellariae is in 80-90 ℃ of adding), add 5～15 times of amounts of water for the first time, decocted 1～2 hour, add for the second time 5～15 times of amounts of water, decocted 0.5～1.5 hour, collecting decoction filters, and filtrate decompression is concentrated into 2 ~ 3 times of medical material amount, get supernatant concentration to relative density behind the high speed centrifugation and be about 1.25 (60-80 ℃), be spray dried to dry extract; Above-mentioned extract powder adds 991-999: the PEG400 of 1-9 ratio, polyethylene glycol 6000, and mixing, the shared capsule liquid proportional of medicated powder 36%-45% crosses colloid mill, and through pelleting, drying is washed ball, and operations such as drying promptly get soft capsule.
Preparation method 2:
The extraction of a, Radix Et Rhizoma Rhei:
Radix Et Rhizoma Rhei powder is broken into coarse powder, adds 5～15 times of amounts of 90%～95% ethanol and soaks after 12～36 hours, with ultrasonic Treatment 20～40min of frequency 10～30kHz, filters, and discards medicinal residues, and filtrate is concentrated into relative density and is about 1.10 after high speed centrifuge is centrifugal; Concentrated filtrate is crossed the macropore resin bed and is analysed post, and water and 90%～99% ethanol elution reclaim ethanol elution successively, concentrate spray-dried effective ingredient anthraquinone class, the dianthracene ketone refined powder that obtains Radix Et Rhizoma Rhei.
The extraction of b, Rhizoma Coptidis:
Rhizoma Coptidis powder is broken into coarse powder, adds 10～14 times of water yields, decocts 1～3 hour, decocts 2～4 times, and collecting decoction concentrates after drying, pulverizing.30～50 times of dehydrated alcohol reflux, extract, of reuse 2～4 times, each 20～60 minutes, filtered while hot, filtrate recycling ethanol are filtered after high speed centrifuge is centrifugal, concentrate, concentrated filtrate is crossed the macropore resin bed and is analysed post, and water and 90%～99% ethanol elution reclaim ethanol elution successively, concentrate the spray-dried refined powder that obtains the effective ingredient berberine hydrochloride of Rhizoma Coptidis.
The extraction of c, Radix Scutellariae:
Radix Scutellariae powder is broken into coarse powder, adds 5～15 times of amounts of 90%～95% ethanol and soaks after 12～36 hours, with ultrasonic Treatment 20～40min of frequency 10～30kHz, filters, and discards medicinal residues, and filtrate is concentrated into relative density and is about 1.10 after high speed centrifuge is centrifugal; Concentrated filtrate is crossed the macropore resin bed and is analysed post, and water and 90%～99% ethanol elution reclaim ethanol elution successively, concentrate the spray-dried refined powder that obtains containing baicalin; The refined powder of Radix Et Rhizoma Rhei, Rhizoma Coptidis, Radix Scutellariae three flavor medical materials merges, and adds 991-999: the PEG400 of 1-9 ratio, polyethylene glycol 6000, mixing, the shared capsule liquid proportional of medicated powder 36%-45% crosses colloid mill, through pelleting, drying is washed ball, and operations such as drying promptly get soft capsule.
Soft capsule shell in above-mentioned two kinds of preparation methoies is with gelatin: water: glycerol: the titanium dioxide raw material, and gelatin: water: glycerol: the weight ratio between the titanium dioxide is 1.0: 1.2: 0.3-1.0: 0.01; The shared capsule liquid proportional of medicated powder in above-mentioned two kinds of preparation methoies is 42% or 39%.
The method of quality control of this composite preparation contains one or more in following discriminating and/or the content assaying method, and discriminating in the method for quality control of the present invention and content assaying method are:
Discrimination method is selected from one or more in the following method:
Represent composition emodin, berberine hydrochloride and baicalin to carry out Study on Identification with it respectively to Radix Et Rhizoma Rhei, Rhizoma Coptidis, Radix Scutellariae three flavor medical materials in the prescription:
A, Radix Et Rhizoma Rhei (emodin):
Get the about 2g of Chinese medicinal soft capsule preparation content, add methanol 50ml, flooded 1.5-3 hour, and jolting constantly, filtering, filtrate is put evaporate to dryness in the water-bath, residue adds water 10ml makes dissolving, add hydrochloric acid 1ml again, put in the water-bath and heated 20-40 minute, immediately cooling, divide 2 extractions with chloroform 20ml, the combined chloroform extracting solution is concentrated into about 1ml, as need testing solution; Other gets the emodin reference substance, and chlorination is copied into the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography (" Chinese pharmacopoeia appendix VIB in 2000) test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; Under 60～90 ℃ of temperature, with 15-18: 6-8: the upper strata liquid of 1 petroleum ether-Ethyl formate-formic acid is developing solvent, launches, smoked method develops the color in the rearmounted ammonia of airing, in the test sample chromatograph, with reference substance chromatograph relevant position on, show the speckle of same color.
B, Rhizoma Coptidis (berberine hydrochloride):
Get the about 2g of Chinese medicinal soft capsule preparation content, add methanol 50ml, flooded 1.5-3 hour, and jolting constantly, filtering, filtrate is put and is concentrated into about 1ml in the water-bath, as need testing solution; Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography (" Chinese pharmacopoeia appendix VIB in 2000) test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; With 10: 6: 1: 1 ethyl acetate-butanone-formic acid-water was developing solvent, launched, and took out, and inspected under the rearmounted uviol lamp of airing (365nm), showed the fluorescence speckle of same color.
C, Radix Scutellariae (baicalin):
Get the about 2g of Chinese medicinal soft capsule preparation content, add methanol 50ml, 4～6 of dripping hydrochloric acid, jolting 15-30 minute, filter, filtrate is put and is concentrated into about 4ml in the water-bath, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography (" Chinese pharmacopoeia appendix VIB in 2000) test, draw each 15 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; With 5-7: 3-4: 1: 1 ethyl acetate-butanone-formic acid-water is developing solvent, launch, spray behind the airing and develop the color with 2% ferric chloride alcoholic solution, in the test sample chromatograph, with reference substance chromatograph relevant position on, the speckle of apparent same color.
Content assaying method is:
Baicalin is the main effective ingredient of Radix Scutellariae in the prescription, so consider to adopt the HPLC method to measure content of baicalin in the soft capsule.
The ODS reversed phase chromatographic column (4.6mm * 150mm, I.D.); With 50: 50 methanol-0.2mol/L phosphate sodium dihydrogen buffer solution (phosphoric acid adjust pH to 2.7) (behind sucking filtration, ultrasonic degas, using) be mobile phase; Flow velocity: 0.8mlmin
-1Detect wavelength: 276nm; Sample size: 10ul; Sensitivity: 0.05AUFS, column temperature: room temperature; The number of theoretical plate at baicalin peak is 3230.
Precision takes by weighing the about 0.6g of this Chinese medicinal soft capsule preparation content, put in the 50ml measuring bottle, add the about 40ml of methanol, ultrasonic 20min, use methanol constant volume, shake up, the accurate absorption in 1ml to the 10ml measuring bottle is diluted to scale with methanol, shake up, centrifugal 10min (15000r/min) divides and gets supernatant, promptly gets need testing solution; Precision takes by weighing 105 ℃ of about 5mg of baicalin reference substance that are dried to constant weight, puts in the 50ml measuring bottle, adds methanol 40ml, ultrasonic 20min, put cold after, use methanol constant volume, shake up, that is, every 1ml contains baicalin and is no less than 100 μ g.
The present invention is refined into three flavor Chinese medicines behind modern extraction process effective component extracting soft capsule (a clear soft capsule), it is fast to have disintegration rate, directly absorbs at intestinal after the disintegrate, need not course of dissolution, absorbs fast; The bioavailability height, taking dose is little; Medicine stability is good, is difficult for the moisture absorption; Good airproof performance has hidden the bad smell of medicine; Taking convenience, advantage such as be easy to carry.
Following experimental example is used to further specify the present invention:
The Study on extraction of test example 1 Radix Et Rhizoma Rhei
The present invention considers to obtain crude extract with the ultrasonic extraction Radix Et Rhizoma Rhei, and the technology of separating purification with the resin chromatographic column is extracted the anthraquinone component in the Radix Et Rhizoma Rhei then.
1. ultrasonic extraction choice of Solvent:
The content of anthraquinone in Radix Et Rhizoma Rhei extract when investigation makes water and Different concentrations of alcohol (80%, 90%, 95%, dehydrated alcohol) as solvent under the different frequency ultrasound wave.The percentage composition of general anthraquinone, dissociated anthraquinone, combined anthraquinone in water and the Different concentrations of alcohol extracting solution has been carried out linear regression to concentration of alcohol.Percentage composition and the concentration of alcohol of finding combined anthraquinone have certain dependency, with the raising of concentration of alcohol the trend of increase are arranged, wherein 95% and dehydrated alcohol extraction liquid in anthraquinone class percentage composition difference do not have significance, so select for use 95% ethanol as solvent.
2. the selection of frequency of ultrasonic:
Frequency of ultrasonic has been investigated 10KHZ respectively, 20KHZ, and 200KHZ, the yield of anthraquinone in the same solvent under the several different frequencies of 600KHZ, wherein the anthraquinone component yield under the 20KHZ frequency is the highest.So select the ultrasound wave of 20KHZ for use.
3. the selection of time of ultrasonic extraction:
In conjunction with above-mentioned alternative condition, investigated supersound extraction respectively 20 minutes, 30 minutes, the percentage composition of anthraquinone in 40 minutes extracting solution, found that increase with the supersound extraction time, the percentage composition of anthraquinone also increases accordingly in the extracting solution, and wherein the yield difference of 30 minutes and 40 minutes does not have significance, so selected supersound extraction for use 30 minutes.
4. the Radix Et Rhizoma Rhei crude extract is refining:
In order to keep effective ingredient to greatest extent, to remove invalid components, the selection supercentrifugal process is tentatively removed the impurity in the medicinal liquid.Supercentrifugal process is to be capital equipment with the centrifuge, by running up of centrifuge, makes centrifugal acceleration surpass hundreds and thousands of times of acceleration of gravity, and sedimentation velocity is increased, with a kind of method of quickening contamination precipitation in the medicinal liquid and removing.Sedimentation-type centrifuge separate medicinal liquid have save time, laborsaving, medicinal liquid reclaims fully, active constituent content height, the characteristics that clarity is high are suitable for separating and contain the suspension that is difficult to filtering fine particles of sedimentation or floccule.Use supercentrifugation, make extracting solution stable, put haze-freely for a long time, avoided medicinal liquid to concentrate, change the molten content that makes effective ingredient caused by heat damage repeatedly simultaneously again and reduced.Said extracted liquid is filtered, merges, and the 2-3 that is evaporated to the medical material amount doubly carries out centrifugally, adopts the high speed tube centrifuge, and rotating speed is more than the 10000r/min.Filtrate decompression after centrifugal is concentrated into relative density is about 1.25 (70 ℃), cross macroporous resin and separate.
Considered to utilize the characteristics of nonpolar and resinene in the macroporous adsorbent resin, free anthraquinone in the Radix Et Rhizoma Rhei extract separated and purification with combined anthraquinone.Select the high-crosslinking-degree polymer resin of P-MA structural type or the resin of styrene type structure for use, have the characteristics of stronger hydrophilic and surface affinity and high hole.Go up the macroporous resin chromatographic column after adjusting about Radix Et Rhizoma Rhei crude extract pH value to 7.5, it is colourless to be eluted to eluent with pure water earlier after application of sample finishes, and uses the high concentration ethanol eluting again instead and can not detect corresponding speckle until alcohol eluen through TLC.Collect alcohol eluen, reclaim ethanol and obtain anthraquinone class refined powder.
TLC serves as to detect index with anthraquinone class emodin, according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000) research experiment.
Get the about 2g of anthraquinone class refined powder, add methanol 50ml, flooded 2 hours, and jolting constantly, filtering, filtrate is put evaporate to dryness in the water-bath, residue adds water 10ml makes dissolving, add hydrochloric acid 1ml again, put in the water-bath and heated 30 minutes, immediately cooling, divide 2 extractions with chloroform 20ml, the combined chloroform extracting solution is concentrated into about 1ml, as need testing solution.Other gets the emodin reference substance, and chlorination is copied into the solution that every 1ml contains 0.5mg, in contrast product solution.Draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; Upper strata liquid with petroleum ether (60～90 ℃)-Ethyl formate-formic acid (15: 7: 1) is that smoked method develops the color in the rearmounted ammonia of developing solvent expansion, airing.
The Study on extraction of test example 2 Rhizoma Coptidis
On the basis that water is carried, refining with alcohol reflux to water extract.
1. the investigation of decocting in water extraction conditions: adopting orthogonal experiment method, is factor with amount of water, extraction time, extraction time, presses L
9(3
4) orthogonal table is tested, and is evaluation index with dried cream yield and effective ingredient, respectively Rhizoma Coptidis decocting in water extraction process is screened.Factor level sees Table 1.
Table 1 factor level table
| Level | Factor | ||
| A amount of water (doubly) | B extraction time (h) | The C extraction time | |
| ????1 ????2 ????3 | ????8 ????10 ????12 | ??0.5(0.5、0.5) ??1.5(1.0、0.5) ??2.0(1.5、1.0) | ????1 ????2 ????3 |
Get Rhizoma Coptidis medical material 40g, be ground into the following fritter of 1cm, soak 30min, test according to table 1.
Berberine hydrochloride is measured assay method: get the about 20mg of berberine hydrochloride reference substance, the accurate title, decide, and adds methanol-hydrochloric acid (100: 1) dissolving back reuse ethanol and make the solution that every 1ml contains 8 μ g approximately, in contrast product solution.In addition precision takes by weighing and makes the about 75mg of dried cream powder, puts in the 50ml measuring bottle, adds methanol-hydrochloric acid (100: 1) and dissolves and be diluted to scale, shakes up.Precision is measured 1ml and is added on (dry column-packing is with ethanol 20ml prewashing) on the 5g neutral alumina post, is eluted in the 50ml measuring bottle with ethanol 25ml, and standardize solution is as need testing solution.Get above-mentioned two kinds of solution and measure trap at the 345nm place, calculate promptly.Result of the test sees Table 2.
Table 2 Rhizoma Coptidis is extracted orthogonal test table
| Tested number | ????A | ????B | ????C | D (blank) | Dried cream powder yield (%) | Content of berberine hydrochloride (%) | |
| ????1 ????2 ????3 ????4 ????5 ????6 ????7 ????8 ????9 | ????1 ????1 ????1 ????2 ????2 ????2 ????3 ????3 ????3 | ????1 ????2 ????3 ????1 ????2 ????3 ????1 ????2 ????3 | ????1 ????2 ????3 ????2 ????3 ????1 ????3 ????1 ????2 | ????1 ????2 ????3 ????3 ????1 ????2 ????2 ????3 ????1 | ????6.73 ????5.98 ????20.24 ????8.75 ????15.74 ????8.38 ????11.32 ????8.16 ????8.98 | ????27.24 ????33.23 ????28.91 ????27.98 ????39.26 ????33.31 ????30.28 ????30.39 ????34.20 | |
| Yield of extract (%) | K 1 | ? ??32.95 ??32.87 ??28.46 ??4.49 | ? ??26.80 ??29.88 ??37.60 ??10.80 | ? ??23.27 ??23.71 ??47.30 ??24.03 | ? ???31.45 ???25.68 ???37.15 ???11.47 | ||
| K 2 | |||||||
| K 3 | |||||||
| R | |||||||
| Berberine hydrochloride % | K | ?89.38 ?100.55 ?94.87 ?11.17 | ??85.50 ??102.88 ??96.42 ??17.38 | ??90.94 ??95.41 ??98.45 ??7.51 | ???100.70 ???96.82 ???87.28 ???13.42 | ||
| K 2 | |||||||
| K 3 | |||||||
| R | |||||||
It serves as to investigate index that the result shows with dried cream rate, and best of breed is A
1B
3C
3, C＞B＞A; With the content of berberine hydrochloride is to investigate index, and best of breed is A
2B
2C
3, B＞A＞C, because content's index is even more important, so be evaluated as the master with content, again because in three factors of content, C influences minimum and K
2With K
3Close, consider energy savings in the big production, reduce cost, therefore take all factors into consideration and select C
2, promptly with 10 times of water gagings, extract twice, 1.5 hours for the first time, 1 hour for the second time was best.
Other gets three parts of medical materials and verifies, the results are shown in Table 3.
Table 3 Rhizoma Coptidis is extracted the checking result
| Sequence number | ????1 | ????2 | ????3 |
| Dried cream rate (%) content of berberine hydrochloride (%) | ????10.20 ????38.09 | ????9.24 ????37.38 | ????9.77 ????37.01 |
Result of the test and orthogonal experiments are close, and the result shows that this extraction process by water is stable.
2. the investigation of alcohol reflux condition:
Adopting orthogonal experiment method, is factor with amount of alcohol, concentration of alcohol, return time, backflow number of times, presses L
9(3
4) orthogonal table is tested, and is evaluation index with dried cream yield and effective ingredient, respectively the alcohol reflux process conditions of Rhizoma Coptidis the water extracted immersing paste are screened.Factor level sees Table 4.
Table 4 factor level table
Carry out orthogonal test according to the factor level table, the results are shown in Table 5.
| Level | Factor | |||
| A amount of alcohol (doubly) | B return time (h) | C concentration of alcohol (%) | D backflow number of times | |
| ????1 ????2 ????3 | ????20 ????30 ????40 | ????0.5 ????1.5 ????2.0 | ????90％ ????95％ ????100％ | ????1 ????2 ????3 |
The alcohol reflux orthogonal test table of table 5 Rhizoma Coptidis the water extracted immersing paste
| Tested number A B C D result of the test | |
| 1234 yield of extract (%) quaternary amine total alkalis (%) | |
| ??????????1?????????1?????1?????1????1????5.13??????????????2.50 | |
| ??????????2?????????1?????2?????2????2????8.55??????????????4.86 | |
| ??????????3?????????1?????3?????3????3????10.75?????????????5.82 | |
| ??????????4?????????2?????1?????2????3????5.54??????????????3.00 | |
| ??????????5?????????2?????2?????3????1????8.14??????????????4.00 | |
| ??????????6?????????2?????3?????1????2????8.85??????????????5.33 | |
| ??????????7?????????3?????1?????3????2????6.01??????????????3.66 | |
| ??????????8?????????3?????2?????1????3????8.94??????????????5.53 | |
| ??????????9?????????3?????3?????2????1????9.62??????????????5.56 | |
| Yield of extract (%) | ?K1???24.43?16.68?19.52?22.89 |
| ?K2???22.53?25.63?23.71?23.41 | |
| ?K3???24.57?29.22?24.90?25.23 | |
| ?K1/2?8.14??5.56??6.51??7.63 | |
| ?Kg/3?7.51??8.54??7.90??7.80 | |
| ?K3/3?8.19??9.74??8.30??8.41 | |
| ?R????0.68??4.18??1.79??0.78 | |
| Berberine hydrochloride % | ?K1???13.18?9.16??13.36?12.06 |
| ?K2???12.33?14.39?13.42?13.85 | |
| ?K3???14.75?16.71?13.48?14.35 | |
| ?K1/3??4.39?3.05??4.45??4.02 | |
| ?K2/3??4.11?4.80??4.47??4.62 | |
| ?K3/3??4.92?5.57??4.49??4.78 | |
| ?R?????0.81?2.52??0.04??0.76 | |
The result is the optimum extraction process (A3B3C3D3) that index obtains with the yield of extract, and its yield of extract and content of berberine hydrochloride are all the highest.Confirmatory experiment proves that further this process stabilizing is feasible.Therefore the best reflux technique that obtains of screening is: with 40 times of dehydrated alcohol reflux, extract, 3 times, and 30min at every turn, filtered while hot.The Study on extraction of test example 3 Radix Scutellariaes
Can be because contain in the radix scutellariae medicinal materials with the enzyme of baicalin hydrolysis, for fear of enzyme baicalin is decomposed destruction, technology is considered with ultrasound wave Radix Scutellariae to be extracted, avoid under higher temperature on the one hand, the enzyme that Radix Scutellariae self contains is to the decomposition of baicalin, adopt the ultrasonic extraction baicalin on the other hand, yield is obviously than water-boiling method height.
1. ultrasonic extraction choice of Solvent:
Content of baicalin in Radix Scutellariae extracting solution when investigation makes water and Different concentrations of alcohol (80%, 90%, 95%, dehydrated alcohol) as solvent under the different frequency ultrasound wave.The percentage composition of baicalin in water and the Different concentrations of alcohol extracting solution has been carried out linear regression to concentration of alcohol.Percentage composition and the concentration of alcohol of finding baicalin have certain dependency, with the raising of concentration of alcohol the trend of increase are arranged, wherein 95% and dehydrated alcohol extraction liquid in the percentage composition difference of baicalin do not have significance, so select for use 95% ethanol as solvent.
2. the selection of frequency of ultrasonic:
Frequency of ultrasonic has been investigated 10KHZ respectively, 20KHZ, and 200KHZ, the yield of baicalin in the same solvent under the several different frequencies of 600KHZ, wherein the baicalin composition yield under the 20KHZ frequency is the highest.So select the ultrasound wave of 20KHZ for use.
3. the selection of time of ultrasonic extraction:
In conjunction with above-mentioned alternative condition, investigated supersound extraction respectively 20 minutes, 30 minutes, the percentage composition of baicalin in 40 minutes extracting solution, found that increase with the supersound extraction time, the percentage composition of baicalin also increases accordingly in the extracting solution, and wherein the baicalin yield difference of supersound extraction 30 minutes and 40 minutes does not have significance, so selected supersound extraction for use 30 minutes.
The technical study that test example 4 Radix Et Rhizoma Rhei, Radix Scutellariae two flavor Chinese medicine decocting in water extract
Adopting orthogonal experiment method, is factor with amount of water, extraction time, extraction time, presses L
9(3
4) orthogonal table is tested, and is evaluation index with dried cream yield and effective ingredient, respectively Radix Et Rhizoma Rhei and Radix Scutellariae extraction process in the prescription are screened.Factor level sees Table 6.
Table 6 factor level table
Factor
Level
A amount of water (doubly) B extraction time (h) C extraction time
1????????8????????????0.5(0.5、0.5)??????????1
2????????10???????????1.5(1.0、0.5)??????????2
3????????12???????????2.0(1.5、1.0)??????????3
1. the extraction of Radix Et Rhizoma Rhei:
Getting rhubarb medicinal material 40g, be ground into the following fritter of 1cm, soak 30min, test according to table 6, is evaluation index with dried cream rate and total anthraquinones content.
The general anthraquinone assay method is:
Precision takes by weighing through 105 ℃ and is dried to 1 of constant weight, and 8-dihydroxyanthraquinone 12.6mg puts in the 25ml measuring bottle, adds diethyl ether to make dissolving and be diluted to scale, shake up, and accurate the absorption in 5ml to the 50ml measuring bottle, adding diethyl ether is diluted to scale, shakes up, as storing solution.Each accurate absorption in storing solution 1,2,3,4,5ml to the 10ml measuring bottle, the water bath method ether adds 0.5% magnesium acetate methanol solution to scale, shake up, measure trap in the 508nm place, get regression equation: Y=0.0441X+0.0077, correlation coefficient r=0.9998.
Precision takes by weighing the about 0.4g of dried cream powder and puts in the flask, adds 2.5mol/L sulphuric acid 20ml and refluxes 1.5 hours, and the cold slightly 30ml chloroform that adds again continues to reflux 1 hour, divide and get chloroform layer, reuse chloroform 10ml washs acid solution, combined chloroform liquid, be settled to 50ml, the accurate absorption in 2ml to the 25ml measuring bottle, the water bath method chloroform adds 0.5% magnesium acetate methanol solution to scale, shake up, measure trap in the 508nm place, the substitution regression equation calculates content.Result of the test sees Table 7.
Table 7 Radix Et Rhizoma Rhei extracts orthogonal test table
Tested number A B C D (blank) dried cream powder yield (%) general anthraquinone (%)
1????????1?????1?????1?????1???????????3.43????????1.307
2????????1?????2?????2?????2???????????7.84????????1.523
3????????1?????3?????3?????3???????????9.46????????1.179
4????????2?????1?????2?????3???????????8.64????????1.865
5????????2?????2?????3?????1???????????10.32???????1.389
6????????2?????3?????1?????2???????????4.44????????1.297
7????????3?????1?????3?????2???????????10.15???????1.330
8????????3?????2?????1?????3???????????6.50????????1.653
9????????3?????3?????2?????1???????????9.43????????1.419
Do 20.73 22.22 14.37 23.18
Cream K
123.40 24.66 25.91 22.43
Get K
226.08 23.33 29.93 24.60
Powder K
3
Rate R 5.35 2.44 15.56 2.17
％
Total K
14.009 4.502 4.257 4.115
Anthracene K
24.551 4.565 4.807 4.150
Quinone K
34.402 3.895 3.898 4.697
％??R????0.542?0.67??0.909?0.582
It serves as to investigate index that the result shows with dried cream rate, and best of breed is A
3B
2C
3, C＞A＞B; With the total anthraquinones content is to investigate index, and best of breed is A
2B
2C
2, C＞B＞A is evaluated as the master with content, takes all factors into consideration and selects A
2B
2C
2, promptly with 10 times of water gagings, extract twice, 1.5 hours for the first time, 1 hour for the second time.
Get three parts of rhubarb medicinal materials, verify, the results are shown in Table 8.
Table 8 Radix Et Rhizoma Rhei extracts the checking result
Sequence number 123
Dried cream rate (%) 7.75 7.02 8.14
Content (%) 1.827 1.882 1.786
Result of the test and orthogonal experiments are close, and the result shows process stabilizing.
2. the extraction of Radix Scutellariae:
For the extraction of Radix Scutellariae, the enzyme of baicalin hydrolysis can be decomposed destruction for fear of enzyme to baicalin because contain in the radix scutellariae medicinal materials, adopt Radix Scutellariae in 85 ℃ of water, to feed intake.Get radix scutellariae medicinal materials 40g, be ground into the following fritter of 1cm, feed intake for 85 ℃, test according to table 1 in water temperature.
Content of baicalin is measured according to 248 pages of radix scutellariae medicinal materials assays of Chinese Pharmacopoeia version in 2000 and is carried out.
Table 9 Radix Scutellariae extracts orthogonal test table
Tested number A B C D (blank) dried cream powder yield (%) content of baicalin (%)
1?????????1?????1?????1?????1??????????4.30???????????15.62
2?????????1?????2?????2?????2??????????5.77???????????21.54
3?????????1?????3?????3?????3??????????8.60???????????20.09
4?????????2?????1?????2?????3??????????9.33???????????28.30
5?????????2?????2?????3?????1??????????10.20??????????26.72
6?????????2?????3?????1?????2??????????6.05???????????25.18
7?????????3?????1?????3?????2??????????10.64??????????19.90
8?????????3?????2?????1?????3??????????5.86???????????24.48
9?????????3?????3?????2?????1??????????8.20???????????26.93
Do 18.67 24.27 16.21 22.70
Cream K
125.58 21.83 23.30 22.46
Get K
224.70 22.85 29.44 23.79
Powder K
3
Rate R 6.91 2.44 13.23 1.33
％
Yellow K
157.25 63.82 65.28 69.27
A kind of reed mentioned in ancient books K
280.20 72.74 76.77 66.62
Glycosides K
371.31 72.20 66.71 72.87
％??R???22.95?8.92??11.49??6.25
It serves as to investigate index that the result shows with dried cream rate, and best of breed is A
2B
1C
3, C＞A＞B; With the content of baicalin is to investigate index, and best of breed is A
2B
2C
2, A＞C＞B is evaluated as the master with content, takes all factors into consideration and selects A
2B
2C
2, promptly with 10 times of water gagings, extract twice, 1.5 hours for the first time, 1 hour for the second time.
Get three parts of radix scutellariae medicinal materials, verify, the results are shown in Table 10.
Table 10 Radix Scutellariae extracts the checking result
Sequence number 123
Dried cream rate (%) 8.11 9.26 9.79
Content (%) 27.36 28.40 28.85
Result of the test and orthogonal experiments are close, show process stabilizing.
The prescription screening research of test example 5 soft capsule contents:
1. choice of base
The substrate that soft capsule is commonly used has vegetable oil and Polyethylene Glycol (PEG400), consider that PEG400 centering pharmaceutically active ingredient dissolubility is big, except that being applicable to that water soluble drug prepares the soft capsule, be particularly useful for Chinese medicinal soft capsule and quick-acting preparation of soft capsule, therefore select PEG400, PEG6000 as content substrate.
2. the compatibility of medicated powder and substrate test
In order to investigate the compatibility stability of medicated powder and substrate, carried out following test: above-mentioned spray-dired medicated powder is divided into 3 parts, and wherein 2 parts add 1 times and 1.5 times PEG400 and the mixed liquor of PEG6000, mixing respectively, make simulation capsule liquid, carry out TLC and HPLC test.Medicated powder and capsule liquid TLC detect emodin, berberine hydrochloride and baicalin as a result; Capsule liquid and medicated powder HPLC figure detect baicalin, and do not have more impurity peaks, illustrate that substrate is more stable after mixing with medicated powder, do not react mutually, also do not have to destroy effective ingredient wherein.
3. content preparation
The requirement of soft capsule content should be that suspendible is even, and is not stratified, has suitable flowability.According to the Stokes law, reduce particle diameter and increase the disperse medium viscosity and help the stable of suspension, so soft capsule liquid is wanted earlier by colloid mill with further minimizing particle diameter.
Being respectively 30%, 42% and 48% according to the shared capsule liquid proportional of medicated powder has drafted 3 proportionings and has carried out capsule liquid prescription screening.According to aforementioned proportion 3 candidate prescriptions of preparation (respectively adding 0.5% PEG6000),, calculate sedimentation volumn than (F=H/H with 500r/min centrifugation accelerates sedimentation 2 hours
0), observe its stability.The results are shown in Table 11.
Table 11 centrifugal test result
Medicated powder ratio 30% 42% 48%
Sedimentation volumn is than F 0.93 ≈ 11
Conclusion is unstable stable
The result shows that along with the increase of medicated powder ratio, suspension stability increases, 30% instability, and 42% and 48% is stable.Next find too thickness of 48% ratio capsule liquid in the pelleting operation, the leakage ball is many, yield rate is low, the pelleting difficulty; 42% ratio is pelleting smoothly then, and therefore yield rate is taken all factors into consideration more than 90%, selects 42% to be best capsule liquid proportioning.
The formulating of test example 6 softgel shells
Soft capsule shell of the present invention is made up of gelatin, plasticizer, water and additives, and plasticizer is selected glycerol, opacifier titanium dioxide.The ratio of gelatin and plasticizer can determine the hardness of softgel shell in the softgel shell.But the usually bad grasp of proportioning of gelatin and glycerol in the prescription of softgel shell, glycerol too much then softgel shell feel like jelly; Glycerol very little then softgel shell harden.All can influence the quality stability and the disintegration time of soft capsule.About overtesting finds that the proper ratio of gelatin and plasticizer glycerol is 1: 0.3 ~ 0.4.If the ratio of gelatin and glycerol is lower than at 1: 0.3 o'clock, softgel shell hardens, if the ratio of gelatin and glycerol reaches then softgel shell deliquescing in 1: 1.8 o'clock.Through test, the softgel shell ratio is a gelatin: water: glycerol: titanium dioxide (1: 1.2: 0.3: in the time of 0.01), the capsule that suppresses is aesthetic in appearance, neither too hard, nor too soft, and test according to inspection technique disintegration (appendix XIIA of Chinese Pharmacopoeia version in 2000) disintegration, all in 12min.The results are shown in Table 12.
Table 12 softgel shell prescription and disintegration time
| The test index content | Gelatin: 1 water: 1.2 glycerol: 0.1 titanium dioxide: 0.01 | Gelatin: 1 water: 1.2 glycerol: 0.2 titanium dioxide: 0.01 | Gelatin: 1 water: 1.2 glycerol: 0.3 titanium dioxide: 0.01 | Gelatin: 1 water: 1.2 glycerol: 1.4 titanium dioxide: 0.01 | Gelatin: 1 water: 1.2 glycerol: 1.8 titanium dioxide: 0.01 |
| Softgel shell outward appearance and physical property | Too hard, softgel shell is frangible | Too hard, softgel shell is frangible | Outward appearance is bright and clean, soft durometer is suitable | Relatively poor, too soft, the easy moisture absorption of outward appearance fineness | Relatively poor, too soft, the easy moisture absorption of outward appearance fineness |
| Disintegration time (branch) | ????11 | ????12 | ????10 | ????12 | ????12 |
According to above-mentioned test, can reach a conclusion, the prescription of soft capsule shell is with gelatin: water: glycerol: titanium dioxide=1: 1.2: 0.3: 0.01 (weight ratio) is best proportioning.The outward appearance fineness of softgel shell under this proportioning, soft durometer is all moderate, and disintegration time is about 10 minutes.
Developing solvent determines in the discrimination method in test example 7 method of quality control of the present invention
1, Radix Et Rhizoma Rhei (emodin)
Get the about 2g of Chinese medicinal soft capsule preparation content, add methanol 50ml, flooded 2 hours, and jolting constantly, filtering, filtrate is put evaporate to dryness in the water-bath, residue adds water 10ml makes dissolving, add hydrochloric acid 1ml again, put in the water-bath and heated 30 minutes, immediately cooling, divide 2 extractions with chloroform 20ml, the combined chloroform extracting solution is concentrated into about 1ml, as need testing solution; Other gets the emodin reference substance, and chlorination is copied into the solution that every 1ml contains 0.5mg, in contrast product solution; Draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; Develop the color with smoked method in expansion, the rearmounted ammonia of airing.According to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000) research experiment.
For the selection of developing solvent, adopting the upper strata liquid of petroleum ether (60～90 ℃)-Ethyl formate-formic acid (15: 5: 1) earlier is developing solvent, though separating degree is good, clear spot, rounding are that the emodin Rf value is on the low side, and Rf is about 0.2; The back adjusts slightly to above-mentioned developing solvent, and ratio should be 15: 7: 1, obtains separating effect preferably, and the Rf value of emodin increases, and Rf is about 0.4.Through test, all detect emodin in the test agent in three batches, and negative sample is noiseless, illustrates that this discrimination method has specificity.
2, Radix Scutellariae (baicalin)
Get the about 2g of Chinese medicinal soft capsule preparation content, add methanol 50ml, 4～6 of dripping hydrochloric acid, jolting 20 minutes filters, and filtrate is put and is concentrated into about 4ml in the water-bath, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; Draw each 15 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; Develop the color with 2% ferric chloride alcoholic solution to spray behind expansion, the airing.
Selection for developing solvent, earlier with ethyl acetate-butanone-formic acid-water (10: 6: 1: 1) be developing solvent, speckle hangover as a result is serious, separating degree is poor, and through test, adjusting above-mentioned developing solvent ratio is ethyl acetate-butanone-formic acid-water (5: 3: 1: 1), and with glacial acetic acid in the time of saturated in advance 30 minutes, the result obtains good separating effect, clear spot, and Rf value is moderate.Through test, test agent all detects baicalin in three batches, and negative sample is noiseless, illustrates that this discrimination method has specificity.
Measure the selection of wavelength in the content assaying method in test example 8 method of quality control of the present invention
It is an amount of to get the baicalin reference substance, behind the methanol ultrasonic dissolution, make the solution that every 1ml contains 10ug approximately, in the scope of wavelength 200～400 n m, make uv scan, the result shows at the 276nm place maximum absorption wavelength, determines that according to scanning result it detects wavelength is 276nm.
Test example 9 soft capsule Study on Stability
Get the soft capsule sample and carry out temperature, humidity and strong illumination influence factor test by Chinese Pharmacopoeia two appendix XIXC of version in 2000 " medicine stability test guideline ".Damp condition is 92.5%, illumination condition is 4500Lx, temperature conditions is selected 40 ℃ (because the softgel shell gelatin can melt at 60 ℃, gelatinization glue temperature is 60 ℃ in the production).Selecting the high spot reviews project is that character, discriminating, disintegration and content of baicalin are measured.The results are shown in Table 13.
Table 13 soft capsule influence factor result of the test
Test period content disintegration
Character identification
Condition (my god) (min) (mg)
Outward appearance is clean and tidy, and content detects emodin, hydrochloric acid
0?????????????????????????????????????????12????16.70
Even not stratified berberine, baicalin
Temperature profile is clean and tidy, and content detects emodin, hydrochloric acid
5?????????????????????????????????????????13????16.55
(40 ℃) even not stratified berberine, baicalin
Outward appearance is clean and tidy, and content detects emodin, hydrochloric acid
10????????????????????????????????????????13????16.38
Even not stratified berberine, baicalin
The humidity outward appearance is clean and tidy, and content detects emodin, hydrochloric acid
5?????????????????????????????????????????11????16.50
(92.5%) even not stratified berberine, baicalin
Outward appearance is clean and tidy, and content detects emodin, hydrochloric acid
10????????????????????????????????????????13????16.61
Even not stratified berberine, baicalin
Outward appearance is clean and tidy, and content detects emodin, hydrochloric acid
Illumination 5 12 16.86
Even not stratified berberine, baicalin
Outward appearance is clean and tidy, and content detects emodin, hydrochloric acid
(4500L)??10????????????????????????????????????????11????16.53
Even not stratified berberine, baicalin
The result shows that a clear soft capsule sample was placed 10 days under above-mentioned influence factor's condition, compare before its character, discriminating, disintegration and content and the placement to have no significant change, and steady quality illustrates that preparation technology is reasonable, feasible.
Other gets 3 batch samples, pack with the igelite bottle, placed 18 months in room temperature, respectively at 0,3,6,9,12 and sampling in 18 months, detect every index (limit test of microbe when character, discriminating, disintegration, content and off-test detects index as emphasis) by stable high spot reviews project.The results are shown in Table 14.
Table 14 study on the stability test data
| Lot number | Time (moon) | Character | Differentiate | Disintegration (min) | Microbial limit | Content (mg) |
| ? ? ? ? ? ? 020908 ? ? ? ? ? ? | ? ? ? ????0 ????3 ????6 ? ????9 ????12 ????18 ? ? ? | Outward appearance is clean and tidy, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, does not evenly have precipitation | Detect baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride | ? ? ? ????12 ????14 ????18 ? ????21 ????24 ????29 ? ? ? | Up to specification | ? ? ? ????16.70 ????16.88 ????16.51 ? ????16.50 ????16.12 ????15.81 ? ? ? |
| ? ? ? ? ? ? ?020910 ? ? ? ? ? ? | ? ? ? ????0 ????3 ????6 ? ????9 ????12 ????18 ? ? ? | Outward appearance is clean and tidy, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, does not evenly have precipitation | Detect baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride | ? ? ? ????10 ????13 ????16 ? ????19 ????22 ????30 ? ? ? | Up to specification | ? ? ? ????15.82 ????15.58 ????15.27 ? ????14.84 ????15.04 ????14.57 ? ? ? |
| ? ? ? ? ? ? ?020912 ? ? ? ? ? ? ? | ? ? ? ????0 ????3 ????6 ? ????9 ????12 ????18 ? ? ? ? | Outward appearance is clean and tidy, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, it is clean and tidy evenly not have the precipitation outward appearance, content is the dark brown thick liquid, does not evenly have precipitation | Detect baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride detects baicalin, emodin, berberine hydrochloride | ? ? ? ????10 ????12 ????17 ? ????20 ????25 ????31 ? ? ? ? | Up to specification | ? ? ? ????18.15 ????17.95 ????17.46 ? ????17.60 ????17.30 ????16.94 ? ? ? ? |
The result shows: this product was at room temperature placed 18 months, and its outward appearance, discriminating, disintegration, content and limit test of microbe all meet relevant regulations, illustrated that this product has good stability.
Test example 10 soft capsules and capsule disintegration rate contrast test
Measure soft capsule preparation that the present invention makes and obtain through refining the CORK STOPPER FUMIGATED WITH that is equipped with according to conventional water, the results are shown in Table 15.
Table 15 compares disintegration
The result shows: the average disintegration time of the soft capsule preparation that the present invention makes is 11 minutes, and the average disintegration time of capsule of conventional method preparation is 50 minutes.The disintegration rate of the soft capsule preparation that the present invention makes obviously speeds.
Embodiment 1:One clear preparation of soft capsule (water is carried)
Get Rhizoma Coptidis 440g, Radix Et Rhizoma Rhei 1333g, Radix Scutellariae 667g three flavor medical materials, be ground into coarse powder, add decocting in water respectively and fry in shallow oil secondary (Radix Scutellariae is in 85 ℃ of addings), add 10 times of amounts of water for the first time, decocted 1.5 hours, and added 10 times of amounts of water for the second time, decocted 1 hour, collecting decoction filters, filtrate decompression is concentrated into 2 ~ 3 times of medical material amount, and high speed centrifugation (more than 10000 rev/mins) discards precipitation, supernatant concentration to relative density is about 1.25 (70 ℃), is spray dried to dry extract.Above-mentioned extract powder merges the mixture (99.5%PEG400+0.5%PEG6000) that the back adds PEG400 and polyethylene glycol 6000, mixing, the shared capsule liquid proportional 42% of medicated powder, cross colloid mill, through pelleting, drying, wash ball, operations such as drying promptly get 1000 of soft capsules.
Embodiment 2:One clear preparation of soft capsule
Get Rhizoma Coptidis 440g, Radix Et Rhizoma Rhei 1333g, Radix Scutellariae 667g three flavor medical materials, be ground into coarse powder, add decocting in water respectively and fry in shallow oil secondary (Radix Scutellariae is in 82 ℃ of addings), add 12 times of amounts of water for the first time, decocted 2 hours, and added 8 times of amounts of water for the second time, decocted 1.5 hours, collecting decoction filters, filtrate decompression is concentrated into 2 ~ 3 times of medical material amount, and high speed centrifugation (more than 10000 rev/mins) discards precipitation, supernatant concentration to relative density is about 1.25 (75 ℃), is spray dried to dry extract.Above-mentioned extract powder merges the mixture (99.7%PEG400+0.3%PEG6000) that the back adds PEG400 and polyethylene glycol 6000, mixing, the shared capsule liquid proportional 39% of medicated powder, cross colloid mill, through pelleting, drying, wash ball, operations such as drying promptly get 1000 of soft capsules.
Embodiment 3:One clear preparation of soft capsule
The extraction of Radix Et Rhizoma Rhei:
Radix Et Rhizoma Rhei 4000g is ground into coarse powder, add 10 times of amounts of 95% ethanol and soak after 24 hours,, filter with the ultrasonic Treatment 30min of frequency 20kHz, discard medicinal residues, filtrate is concentrated into relative density and is about 1.10 behind high speed centrifuge centrifugal (rotating speed is more than the 10000r/min).
Concentrated filtrate is crossed the macropore resin bed and is analysed post, and it is colourless to be eluted to eluent with pure water earlier, uses 95% ethanol elution again instead and can not detect corresponding speckle until alcohol eluen through TLC.Collect alcohol eluen, reclaim ethanol elution, concentrate the spray-dried effective ingredient anthraquinone class refined powder that obtains Radix Et Rhizoma Rhei.
The extraction of Rhizoma Coptidis:
Rhizoma Coptidis 1320g is ground into coarse powder, and in addition 10 times of water gagings extract twice, 1.5 hours for the first time, 1 hour for the second time, collecting decoction, after concentrating with extract dry, pulverizing.40 times of dehydrated alcohol reflux, extract, of reuse 3 times, each 30 minutes, filtered while hot, filtrate recycling ethanol is after high speed centrifuge centrifugal (rotating speed is more than the 10000r/min), filter, concentrate, concentrated filtrate is crossed the macropore resin bed and is analysed post, it is colourless earlier to be eluted to eluent with pure water, uses 95% ethanol elution again instead and can not detect corresponding speckle until alcohol eluen through TLC.Collect alcohol eluen, reclaim ethanol elution, concentrate the spray-dried refined powder that obtains the effective ingredient berberine hydrochloride of Rhizoma Coptidis.
The extraction of Radix Scutellariae:
Radix Scutellariae 2000g is ground into coarse powder, add 10 times of amounts of 95% ethanol and soak after 24 hours,, filter with the ultrasonic Treatment 30min of frequency 20kHz, discard medicinal residues, filtrate (rotating speed is more than the 10000r/min) after high speed centrifuge is centrifugal is concentrated into relative density and is about 1.10.
Concentrated filtrate is crossed the macropore resin bed and is analysed post, and it is colourless to be eluted to eluent with pure water earlier, uses 95% ethanol elution again instead and can not detect corresponding speckle until alcohol eluen through TLC.Reclaim ethanol elution, concentrate the spray-dried refined powder that obtains containing baicalin.
The refined powder of above-mentioned Radix Et Rhizoma Rhei, Rhizoma Coptidis, Radix Scutellariae three flavor medical materials, merge the mixture (99.5%PEG400+0.5%PEG6000) that the back adds PEG400 and polyethylene glycol 6000, mixing, the shared capsule liquid proportional 42% of medicated powder, cross colloid mill, through pelleting, drying, wash ball, operations such as drying promptly get 1000 of soft capsules.
Embodiment 4:One clear preparation of soft capsule
The extraction of Radix Et Rhizoma Rhei:
Radix Et Rhizoma Rhei 4000g is ground into coarse powder, add 12 times of amounts of 92% ethanol and soak after 30 hours,, filter with the ultrasonic Treatment 35min of frequency 20kHz, discard medicinal residues, filtrate is concentrated into relative density and is about 1.10 behind high speed centrifuge centrifugal (rotating speed is more than the 10000r/min).
Concentrated filtrate is crossed the macropore resin bed and is analysed post, and it is colourless to be eluted to eluent with pure water earlier, uses 92% ethanol elution again instead and can not detect corresponding speckle until alcohol eluen through TLC.Collect alcohol eluen, reclaim ethanol elution, concentrate the spray-dried effective ingredient anthraquinone class refined powder that obtains Radix Et Rhizoma Rhei.
The extraction of Rhizoma Coptidis:
Rhizoma Coptidis 1320g is ground into coarse powder, and in addition 12 times of water gagings extract twice, 2.5 hours for the first time, 1 hour for the second time, collecting decoction, after concentrating with extract dry, pulverizing.45 times of dehydrated alcohol reflux, extract, of reuse 4 times, each 45 minutes, filtered while hot, filtrate recycling ethanol is after high speed centrifuge centrifugal (rotating speed is more than the 10000r/min), filter, concentrate, concentrated filtrate is crossed the macropore resin bed and is analysed post, it is colourless earlier to be eluted to eluent with pure water, uses 98% ethanol elution again instead and can not detect corresponding speckle until alcohol eluen through TLC.Collect alcohol eluen, reclaim ethanol elution, concentrate the spray-dried refined powder that obtains the effective ingredient berberine hydrochloride of Rhizoma Coptidis.
The extraction of Radix Scutellariae:
Radix Scutellariae 2000g is ground into coarse powder, add 10 times of amounts of 98% ethanol and soak after 18 hours,, filter with the ultrasonic Treatment 25min of frequency 30kHz, discard medicinal residues, filtrate (rotating speed is more than the 10000r/min) after high speed centrifuge is centrifugal is concentrated into relative density and is about 1.10.
Concentrated filtrate is crossed the macropore resin bed and is analysed post, and it is colourless to be eluted to eluent with pure water earlier, uses 96% ethanol elution again instead and can not detect corresponding speckle until alcohol eluen through TLC.Reclaim ethanol elution, concentrate the spray-dried refined powder that obtains containing baicalin.
The refined powder of above-mentioned Radix Et Rhizoma Rhei, Rhizoma Coptidis, Radix Scutellariae three flavor medical materials, merge the mixture (99.7%PEG400+0.3%PEG6000) that the back adds PEG400 and polyethylene glycol 6000, mixing, the shared capsule liquid proportional 39% of medicated powder, cross colloid mill, through pelleting, drying, wash ball, operations such as drying promptly get 1000 of soft capsules.
Embodiment 5:The discrimination method of this Chinese medicinal soft capsule preparation:
Get the about 2g of Chinese medicinal soft capsule preparation content, add methanol 50ml, flooded 2 hours, and jolting constantly, filtering, filtrate is put evaporate to dryness in the water-bath, residue adds water 10ml makes dissolving, add hydrochloric acid 1ml again, put in the water-bath and heated 30 minutes, immediately cooling, divide 2 extractions with chloroform 20ml, the combined chloroform extracting solution is concentrated into about 1ml, as need testing solution; Other gets the emodin reference substance, and chlorination is copied into the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography (" Chinese pharmacopoeia appendix VIB in 2000) test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; Under 60～90 ℃ of temperature, be developing solvent with the upper strata liquid of 15: 5: 1 petroleum ether-Ethyl formate-formic acid, launch, smoked method develops the color in the rearmounted ammonia of airing, in the test sample chromatograph, with reference substance chromatograph relevant position on, show the speckle of same color.
Embodiment 6:The discrimination method of this Chinese medicinal soft capsule preparation:
Get the about 2g of Chinese medicinal soft capsule preparation content, add methanol 50ml, flooded 2 hours, and jolting constantly, filtering, filtrate is put and is concentrated into about 1ml in the water-bath, as need testing solution; Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography (" Chinese pharmacopoeia appendix VIB in 2000) test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; With 10: 6: 1: 1 ethyl acetate-butanone-formic acid-water was developing solvent, launched, and took out, and inspected under the rearmounted uviol lamp of airing (365nm), showed the fluorescence speckle of same color.
Embodiment 7:The discrimination method of this Chinese medicinal soft capsule preparation:
Get the about 2g of Chinese medicinal soft capsule preparation content, add methanol 50ml, 4～6 of dripping hydrochloric acid, jolting 20 minutes filters, and filtrate is put and is concentrated into about 4ml in the water-bath, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography (" Chinese pharmacopoeia appendix VIB in 2000) test, draw each 15 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; With 5: 3: 1: 1 ethyl acetate-butanone-formic acid-water was developing solvent, launch, spray behind the airing and develop the color with 2% ferric chloride alcoholic solution, in the test sample chromatograph, with reference substance chromatograph relevant position on, the speckle of apparent same color.
Embodiment 8:The content assaying method of this Chinese medicinal soft capsule preparation:
The ODS reversed phase chromatographic column (4.6mm * 150mm, I.D.); With 50: 50 methanol-0.2mol/L phosphate sodium dihydrogen buffer solution (phosphoric acid adjust pH to 2.7) (behind sucking filtration, ultrasonic degas, using) be mobile phase; Flow velocity: 0.8mlmin-
1Detect wavelength: 276nm; Sample size: 10ul; Sensitivity: 0.05AUFS, column temperature: room temperature; The number of theoretical plate at baicalin peak is 3230.
Precision takes by weighing the about 0.6g of Chinese medicinal soft capsule preparation content, put in the 50ml measuring bottle, add the about 40ml of methanol, ultrasonic 20min, use methanol constant volume, shake up, the accurate absorption in 1ml to the 10ml measuring bottle is diluted to scale with methanol, shake up, centrifugal 10min (15000r/min) divides and gets supernatant, promptly gets need testing solution; Precision takes by weighing 105 ℃ of about 5mg of baicalin reference substance that are dried to constant weight, puts in the 50ml measuring bottle, adds methanol 40ml, ultrasonic 20min, put cold after, use methanol constant volume, shake up, that is, every 1ml contains baicalin 100 μ g.
Embodiment 9:The discrimination method of this Chinese medicinal soft capsule preparation:
Get the about 2g of Chinese medicinal soft capsule preparation content, add methanol 50ml, flooded 2 hours, and jolting constantly, filtering, filtrate is put evaporate to dryness in the water-bath, residue adds water 10ml makes dissolving, add hydrochloric acid 1ml again, put in the water-bath and heated 30 minutes, immediately cooling, divide 2 extractions with chloroform 20ml, the combined chloroform extracting solution is concentrated into about 1ml, as need testing solution; Other gets the emodin reference substance, and chlorination is copied into the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography (" Chinese pharmacopoeia appendix VIB in 2000) test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; Under 60～90 ℃ of temperature, be developing solvent with the upper strata liquid of 15: 5: 1 petroleum ether-Ethyl formate-formic acid, launch, smoked method develops the color in the rearmounted ammonia of airing, in the test sample chromatograph, with reference substance chromatograph relevant position on, show the speckle of same color.
Get the about 2g of Chinese medicinal soft capsule preparation content, add methanol 50ml, flooded 2 hours, and jolting constantly, filtering, filtrate is put and is concentrated into about 1ml in the water-bath, as need testing solution; Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography (" Chinese pharmacopoeia appendix VIB in 2000) test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; With 10: 6: 1: 1 ethyl acetate-butanone-formic acid-water was developing solvent, launched, and took out, and inspected under the rearmounted uviol lamp of airing (365nm), showed the fluorescence speckle of same color.
Get the about 2g of Chinese medicinal soft capsule preparation content, add methanol 50ml, 4～6 of dripping hydrochloric acid, jolting 20 minutes filters, and filtrate is put and is concentrated into about 4ml in the water-bath, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography (" Chinese pharmacopoeia appendix VIB in 2000) test, draw each 15 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; With 5: 3: 1: 1 ethyl acetate-butanone-formic acid-water was developing solvent, launch, spray behind the airing and develop the color with 2% ferric chloride alcoholic solution, in the test sample chromatograph, with reference substance chromatograph relevant position on, the speckle of apparent same color.
The ODS reversed phase chromatographic column (4.6mm * 150mm, I.D.); With 50: 50 methanol-0.2mol/L phosphate sodium dihydrogen buffer solution (phosphoric acid adjust pH to 2.7) (behind sucking filtration, ultrasonic degas, using) be mobile phase; Flow velocity: 0.8mlmin
-1Detect wavelength: 276nm; Sample size: 10ul; Sensitivity: 0.05AUFS, column temperature: room temperature; The number of theoretical plate at baicalin peak is 3230.
Precision takes by weighing the about 0.6g of Chinese medicinal soft capsule preparation content, put in the 50ml measuring bottle, add the about 40ml of methanol, ultrasonic 20min, use methanol constant volume, shake up, the accurate absorption in 1ml to the 10ml measuring bottle is diluted to scale with methanol, shake up, centrifugal 10min (15000r/min) divides and gets supernatant, promptly gets need testing solution; Precision takes by weighing 105 ℃ of about 5mg of baicalin reference substance that are dried to constant weight, puts in the 50ml measuring bottle, adds methanol 40ml, ultrasonic 20min, put cold after, use methanol constant volume, shake up, that is, every 1ml contains baicalin 100 μ g.
Claims (11)
1, a kind of preparation method of Chinese medicinal soft capsule preparation is characterized in that this method is:
Radix Et Rhizoma Rhei, Rhizoma Coptidis, Radix Scutellariae three flavors are broken into coarse powder, add decocting in water respectively and fry in shallow oil secondary, and Radix Scutellariae adds 5～15 times of amounts of water for the first time in 80-90 ℃ of adding, decocts 1～2 hour, adds 5～15 times of amounts of water for the second time, decocts 0.5～1.5 hour; Collecting decoction filters, and filtrate decompression is concentrated into 2～3 times of medical material amount, gets supernatant behind the high speed centrifugation and is concentrated into relative density is about 1.25 in the time of 60-80 ℃, is spray dried to dry extract; Above-mentioned extract powder adds 991-999: the PEG400 of 1-9 ratio, polyethylene glycol 6000, and mixing, the shared capsule liquid proportional of medicated powder 36%-45% crosses colloid mill, and through pelleting, drying is washed ball, is drying to obtain soft capsule.
2, the preparation method of Chinese medicinal soft capsule preparation as claimed in claim 1 is characterized in that this method is:
Get Rhizoma Coptidis, Radix Et Rhizoma Rhei, Radix Scutellariae three flavor medical materials, be ground into coarse powder, add decocting in water respectively and fry in shallow oil secondary, Radix Scutellariae adds 10 times of amounts of water for the first time in 85 ℃ of addings, decocts 1.5 hours, add for the second time 10 times of amounts of water, decocted 1 hour, collecting decoction filters, and filtrate decompression is concentrated into 2～3 times of medical material amount, high speed centrifugation more than 10000 rev/mins, discard precipitation, supernatant is concentrated into relative density at 70 ℃ and is about 1.25, is spray dried to dry extract; Above-mentioned extract powder merges the mixture that the back adds 99.5% PEG400 and 0.5% polyethylene glycol 6000, mixing, and the shared capsule liquid proportional 42% of medicated powder is crossed colloid mill, and through pelleting, drying is washed ball, is drying to obtain soft capsule.
3, the preparation method of Chinese medicinal soft capsule preparation as claimed in claim 1 is characterized in that this method is:
Get Rhizoma Coptidis, Radix Et Rhizoma Rhei, Radix Scutellariae three flavor medical materials, be ground into coarse powder, add decocting in water respectively and fry in shallow oil secondary, Radix Scutellariae adds 12 times of amounts of water for the first time in 82 ℃ of addings, decocts 2 hours, add for the second time 8 times of amounts of water, decocted 1.5 hours, collecting decoction filters, and filtrate decompression is concentrated into 2～3 times of medical material amount, high speed centrifugation, discard precipitation, dense the contracting to relative density at 75 ℃ of supernatant is about 1.25, is spray dried to dry extract; Above-mentioned extract powder adds PEG400, the polyethylene glycol 6000 of 997: 3 ratios, mixing, and the shared capsule liquid proportional 39% of medicated powder is crossed colloid mill, and through pelleting, drying is washed ball, and operations such as drying promptly get soft capsule.
4, a kind of preparation method of Chinese medicinal soft capsule preparation is characterized in that this method is:
The extraction of a, Radix Et Rhizoma Rhei: Radix Et Rhizoma Rhei powder is broken into coarse powder, add 5～15 times of amounts of 90%～95% ethanol and soak after 12～36 hours,, filter with ultrasonic Treatment 20～40min of frequency 10～30kHz, discard medicinal residues, filtrate is concentrated into relative density and is about 1.10 after high speed centrifuge is centrifugal; Concentrated filtrate is crossed the macropore resin bed and is analysed post, and water and 90%～99% ethanol elution reclaim ethanol elution successively, concentrate spray-dried effective ingredient anthraquinone class, the dianthracene ketone refined powder that obtains Radix Et Rhizoma Rhei;
The extraction of b, Rhizoma Coptidis: Rhizoma Coptidis powder is broken into coarse powder, adds 10～14 times of water yields, decocts 1～3 hour, decocts 2～4 times, and collecting decoction concentrates after drying, pulverizing; 30～50 times of dehydrated alcohol reflux, extract, of reuse 2～4 times, each 20～60 minutes, filtered while hot, filtrate recycling ethanol are filtered after high speed centrifuge is centrifugal, concentrate, concentrated filtrate is crossed the macropore resin bed and is analysed post, and water and 90%～99% ethanol elution reclaim ethanol elution successively, concentrate the spray-dried refined powder that obtains the effective ingredient berberine hydrochloride of Rhizoma Coptidis;
The extraction of c, Radix Scutellariae: Radix Scutellariae powder is broken into coarse powder, add 5～15 times of amounts of 90%～95% ethanol and soak after 12～36 hours,, filter with ultrasonic Treatment 20～40min of frequency 10～30kHz, discard medicinal residues, filtrate is concentrated into relative density and is about 1.10 after high speed centrifuge is centrifugal; Concentrated filtrate is crossed the macropore resin bed and is analysed post, and water and 90%～99% ethanol elution reclaim ethanol elution successively, concentrate the spray-dried refined powder that obtains containing baicalin;
The refined powder of above-mentioned Radix Et Rhizoma Rhei, Rhizoma Coptidis, Radix Scutellariae three flavor medical materials merges the back and adds 991-999: the PEG400 of 1-9 ratio, polyethylene glycol 6000, mixing, the shared capsule liquid proportional of medicated powder 36%-45% crosses colloid mill, through pelleting, drying is washed ball, and operations such as drying promptly get soft capsule.
5, the preparation method of Chinese medicinal soft capsule preparation as claimed in claim 4 is characterized in that this method is:
The extraction of a, Radix Et Rhizoma Rhei: Radix Et Rhizoma Rhei powder is broken into coarse powder, adds 10 times of amounts of 95% ethanol and soaks after 24 hours, with the ultrasonic Treatment 30min of frequency 20kHz, filters, and discards medicinal residues, and filtrate is concentrated into relative density and is about 1.10 after high speed centrifuge is centrifugal; Concentrated filtrate is crossed the macropore resin bed and is analysed post, and it is colourless to be eluted to eluent with pure water earlier, uses 95% ethanol elution again instead and can not detect corresponding speckle until alcohol eluen through TLC; Collect alcohol eluen, reclaim ethanol elution, concentrate the spray-dried effective ingredient anthraquinone class refined powder that obtains Radix Et Rhizoma Rhei;
The extraction of b, Rhizoma Coptidis: Rhizoma Coptidis powder is broken into coarse powder, and in addition 10 times of water gagings extract twice, 1.5 hours for the first time, 1 hour for the second time, collecting decoction, after concentrating with extract dry, pulverizing; 40 times of dehydrated alcohol reflux, extract, of reuse 3 times, each 30 minutes, filtered while hot, filtrate recycling ethanol is after high speed centrifuge is centrifugal, filter, concentrate, concentrated filtrate is crossed the macropore resin bed and is analysed post, it is colourless earlier to be eluted to eluent with pure water, uses 95% ethanol elution again instead and can not detect corresponding speckle until alcohol eluen through TLC; Collect alcohol eluen, reclaim ethanol elution, concentrate the spray-dried refined powder that obtains the effective ingredient berberine hydrochloride of Rhizoma Coptidis;
The extraction of c, Radix Scutellariae: Radix Scutellariae 2000 parts by weight of crushed become coarse powder, add 10 times of amounts of 95% ethanol and soak after 24 hours, with the ultrasonic Treatment 30min of frequency 20kHz, filter, and discard medicinal residues, and filtrate is concentrated into relative density and is about 1.10 after high speed centrifuge is centrifugal; Concentrated filtrate is crossed the macropore resin bed and is analysed post, and it is colourless to be eluted to eluent with pure water earlier, uses 95% ethanol elution again instead and can not detect corresponding speckle until alcohol eluen through TLC; Reclaim ethanol elution, concentrate the spray-dried refined powder that obtains containing baicalin;
The refined powder of above-mentioned Radix Et Rhizoma Rhei, Rhizoma Coptidis, Radix Scutellariae three flavor medical materials merges the mixture that the back adds 99.5% PEG400 and 0.5% polyethylene glycol 6000, mixing, the shared capsule liquid proportional 42% of medicated powder is crossed colloid mill, through pelleting, drying is washed ball, and drying process promptly gets soft capsule.
6, the preparation method of Chinese medicinal soft capsule preparation as claimed in claim 4 is characterized in that this method is:
The extraction of a, Radix Et Rhizoma Rhei: Radix Et Rhizoma Rhei powder is broken into coarse powder, adds 12 times of amounts of 92% ethanol and soaks after 30 hours, with the ultrasonic Treatment 35min of frequency 20kHz, filters, and discards medicinal residues, and filtrate is concentrated into relative density and is about 1.10 after high speed centrifuge is centrifugal; Concentrated filtrate is crossed the macropore resin bed and is analysed post, and it is colourless to be eluted to eluent with pure water earlier, uses 92% ethanol elution again instead and can not detect corresponding speckle until alcohol eluen through TLC; Collect alcohol eluen, reclaim ethanol elution, concentrate the spray-dried effective ingredient anthraquinone class refined powder that obtains Radix Et Rhizoma Rhei;
The extraction of b, Rhizoma Coptidis: Rhizoma Coptidis powder is broken into coarse powder, and in addition 12 times of water gagings extract twice, 2.5 hours for the first time, 1 hour for the second time, collecting decoction, after concentrating with extract dry, pulverizing; 45 times of dehydrated alcohol reflux, extract, of reuse 4 times, each 45 minutes, filtered while hot, filtrate recycling ethanol is after high speed centrifuge is centrifugal, filter, concentrate, concentrated filtrate is crossed the macropore resin bed and is analysed post, it is colourless earlier to be eluted to eluent with pure water, uses 98% ethanol elution again instead and can not detect corresponding speckle until alcohol eluen through TLC; Collect alcohol eluen, reclaim ethanol elution, concentrate the spray-dried refined powder that obtains the effective ingredient berberine hydrochloride of Rhizoma Coptidis;
The extraction of c, Radix Scutellariae: Radix Scutellariae powder is broken into coarse powder, adds 10 times of amounts of 98% ethanol and soaks after 18 hours, with the ultrasonic Treatment 25min of frequency 30kHz, filters, and discards medicinal residues, and filtrate is concentrated into relative density and is about 1.10 after high speed centrifuge is centrifugal; Concentrated filtrate is crossed the macropore resin bed and is analysed post, and it is colourless to be eluted to eluent with pure water earlier, uses 96% ethanol elution again instead and can not detect corresponding speckle until alcohol eluen through TLC; Reclaim ethanol elution, concentrate the spray-dried refined powder that obtains containing baicalin;
The refined powder of above-mentioned Radix Et Rhizoma Rhei, Rhizoma Coptidis, Radix Scutellariae three flavor medical materials merges the mixture that the back adds 99.7% PEG400 and 0.3% polyethylene glycol 6000, mixing, the shared capsule liquid proportional 39% of medicated powder is crossed colloid mill, through pelleting, drying is washed ball, and operations such as drying promptly get soft capsule.
7, as the preparation method of claim 1,2,3,4,5 or 6 described Chinese medicinal soft capsule preparations, it is characterized in that soft capsule shell in this method with gelatin, water, glycerol, titanium dioxide raw material, the weight ratio between gelatin, water, glycerol, the titanium dioxide is 1.0: 1.2: 0.3-1.0: 0.01.
8, as the preparation method of claim 1,2,3,4,5 or 6 described Chinese medicinal soft capsule preparations, it is characterized in that soft capsule shell in this method with gelatin, water, glycerol, titanium dioxide raw material, the weight ratio between gelatin, water, glycerol, the titanium dioxide is 1.0: 1.2: 0.3: 0.01.
9, a kind of method of quality control of Chinese medicinal soft capsule preparation is characterized in that comprising in this method in the following discrimination method one or more:
A, emodin: get the about 2g of this Chinese medicinal soft capsule preparation content, add methanol 50ml, flooded 1.5-3 hour, and jolting constantly, filtering, filtrate is put evaporate to dryness in the water-bath, residue adds water 10ml makes dissolving, add hydrochloric acid 1ml again, put in the water-bath and heated 20-40 minute, immediately cooling, divide 2 extractions with chloroform 20ml, the combined chloroform extracting solution is concentrated into about 1ml, as need testing solution; Other gets the emodin reference substance, and chlorination is copied into the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; Under 60～90 ℃ of temperature, with 15-18: 6-8: the upper strata liquid of 1 petroleum ether-Ethyl formate-formic acid is developing solvent, launches, smoked method develops the color in the rearmounted ammonia of airing, in the test sample chromatograph, with reference substance chromatograph relevant position on, show the speckle of same color;
B, berberine hydrochloride: get the about 2g of this Chinese medicinal soft capsule preparation content, add methanol 50ml, flooded 1.5-3 hour, and jolting constantly, filtering, filtrate is put and is concentrated into about 1ml in the water-bath, as need testing solution; Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; With 10: 6: 1: 1 ethyl acetate-butanone-formic acid-water was developing solvent, launched, and took out, and inspected under the rearmounted 365nm uviol lamp of airing, showed the fluorescence speckle of same color;
C, baicalin: get the about 2g of this Chinese medicinal soft capsule preparation content, add methanol 50ml, 4～6 of dripping hydrochloric acid, jolting 15-30 minute, filter, filtrate is put and is concentrated into about 4ml in the water-bath, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography test, draw each 15 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; With 5-7: 3-4: 1: 1 ethyl acetate-butanone-formic acid-water is developing solvent, launch, spray behind the airing and develop the color with 2% ferric chloride alcoholic solution, in the test sample chromatograph, with reference substance chromatograph relevant position on, the speckle of apparent same color.
10, the method for quality control of Chinese medicinal soft capsule preparation as claimed in claim 9 is characterized in that comprising in this method in the following discrimination method one or more:
A, emodin: get the about 2g of content of the present invention, add methanol 50ml, flooded 2 hours, and jolting constantly, filtering, filtrate is put evaporate to dryness in the water-bath, residue adds water 10ml makes dissolving, add hydrochloric acid 1ml again, put in the water-bath and heated 30 minutes, immediately cooling, divide 2 extractions with chloroform 20ml, the combined chloroform extracting solution is concentrated into about 1ml, as need testing solution; Other gets the emodin reference substance, and chlorination is copied into the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; Under 60～90 ℃ of temperature, be developing solvent with the upper strata liquid of 15: 5: 1 petroleum ether-Ethyl formate-formic acid, launch, smoked method develops the color in the rearmounted ammonia of airing, in the test sample chromatograph, with reference substance chromatograph relevant position on, show the speckle of same color;
B, berberine hydrochloride: get the about 2g of content of the present invention, add methanol 50ml, flooded 2 hours, and jolting constantly, filtering, filtrate is put and is concentrated into about 1ml in the water-bath, as need testing solution; Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; With 10: 6: 1: 1 ethyl acetate-butanone-formic acid-water was developing solvent, launched, and took out, and inspected under the rearmounted 365nm uviol lamp of airing, showed the fluorescence speckle of same color;
C, baicalin: get the about 2g of content of the present invention, add methanol 50ml, 4～6 of dripping hydrochloric acid, jolting 20 minutes filters, and filtrate is put and is concentrated into about 4ml in the water-bath, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography test, draw each 15 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose; With 5: 3: 1: 1 ethyl acetate-butanone-formic acid-water was developing solvent, launch, spray behind the airing and develop the color with 2% ferric chloride alcoholic solution, in the test sample chromatograph, with reference substance chromatograph relevant position on, the speckle of apparent same color.
11, a kind of method of quality control of Chinese medicinal soft capsule preparation is characterized in that comprising in this method following content assaying method:
Adopt the ODS reversed phase chromatographic column; With 50: 50 methanol-0.2mol/L phosphate sodium dihydrogen buffer solutions was mobile phase, phosphoric acid adjust pH to 2.7; The detection wavelength is 276nm; The number of theoretical plate at baicalin peak is no less than 3230; Precision takes by weighing the about 0.6g of content, puts in the 50ml measuring bottle, adds the about 40ml of methanol, and ultrasonic 20min uses methanol constant volume, shakes up, and accurate the absorption in 1ml to the 10ml measuring bottle is diluted to scale with methanol, shakes up, and centrifugal 10min divides and gets supernatant, promptly gets need testing solution; Precision takes by weighing 105 ℃ of about 5mg of baicalin reference substance that are dried to constant weight, puts in the 50ml measuring bottle, adds methanol 40ml, ultrasonic 20min, put cold after, use methanol constant volume, shake up, that is, every 1ml contains baicalin and is no less than 100 μ g.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100333746C (en) * | 2005-02-23 | 2007-08-29 | 上海中医药大学附属曙光医院 | Method for preparing Chinese medicine preparation for treating chronic conjestive heart-failure |
| CN101711808B (en) * | 2009-09-11 | 2011-08-24 | 海南海神同洲制药有限公司 | Soft capsule used for clearing away heat and toxic materials and preparation method thereof |
| CN103063798A (en) * | 2013-01-01 | 2013-04-24 | 吉林紫鑫药业股份有限公司 | Novel method for detecting Longdan Xiegan particles |
| CN103063799A (en) * | 2013-01-01 | 2013-04-24 | 吉林紫鑫药业股份有限公司 | Method for comprehensively detecting active ingredients of Longdan Xiegan particles |
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100353990C (en) * | 2005-12-29 | 2007-12-12 | 贵州益佰制药股份有限公司 | Quelity control method of Chinese medicinal preparation for hepatatitis toxin resolving |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100333746C (en) * | 2005-02-23 | 2007-08-29 | 上海中医药大学附属曙光医院 | Method for preparing Chinese medicine preparation for treating chronic conjestive heart-failure |
| CN101711808B (en) * | 2009-09-11 | 2011-08-24 | 海南海神同洲制药有限公司 | Soft capsule used for clearing away heat and toxic materials and preparation method thereof |
| CN103063798A (en) * | 2013-01-01 | 2013-04-24 | 吉林紫鑫药业股份有限公司 | Novel method for detecting Longdan Xiegan particles |
| CN103063799A (en) * | 2013-01-01 | 2013-04-24 | 吉林紫鑫药业股份有限公司 | Method for comprehensively detecting active ingredients of Longdan Xiegan particles |
| CN114569692A (en) * | 2021-08-23 | 2022-06-03 | 杭州市红十字会医院 | Anti-infection traditional Chinese medicine composition and dressing for wound treatment and preparation method thereof |
| CN114569692B (en) * | 2021-08-23 | 2023-06-20 | 杭州市红十字会医院 | Anti-infection traditional Chinese medicine composition and dressing for wound surface treatment and preparation method thereof |
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