CN103007001B - Traditional Chinese medicine preparation for treating sleep disorders and preparation method thereof - Google Patents
Traditional Chinese medicine preparation for treating sleep disorders and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a traditional Chinese medicine preparation for treating sleep disorders and a preparation method thereof. The traditional Chinese medicine preparation is prepared from 8-12 parts by weight of polygala tenuifolia, 13-17 parts by weight of spina date seed (fried), 6-10 parts by weight of gynostemma pentaphylla, 8-12 parts by weight of cynanchum paniculatum, 6-10 parts by weight of daylily flowers and 4-8 parts of valeriana jatamansi. The traditional Chinese medicine preparation disclosed by the invention has remarkable curative effects on insomnia, no toxic as well as side effect and remarkable sedation. According to the preparation method of the traditional Chinese medicine preparation, addition of multiple auxiliaries in the production process of the preparation is unnecessary, and no medicine dosage of a patient and no use cost are added. The traditional Chinese medicine preparation, disclosed by the invention, has very good curative effects on insomnia caused by different syndromes of TCM and different diseases, has no drug tolerance due to successive medication, is safe and effective, and has remarkable curative effects.
Description
Technical field
compound recipe zizyphinine god far away Chinese medicine preparation) and preparation method thereof the present invention relates to a kind of Chinese medicine preparation for the treatment of sleep disorder (trade name:, belong to medicine preparation field.
Background technology
insomnia (insomnia) is the common sympton in nearly hundred kinds of diseases in sleep disorder field, is a kind of subjective experience that sleep quality or quantity do not reach normal demand.Sleep disorder is the simultaneous phenomenon of various diseases, and Chinese traditional treatment sleep disorder is mainly used tranquilizing by nourishing the heart and tranquillization with heavy prescription two class Chinese medicine and compound recipes thereof.The clinical practice of several thousand proves, the curative effect of these Chinese medicines and compound recipe thereof tool uniqueness aspect improvement sleep, raising sleep quality.
existing Chinese medicine and compound preparation thereof, sedation is not obvious, also not remarkable to the curative effect of insomnia, and in the production process of preparation, needs to add multiple auxiliary materials, has increased patient's dosage and use cost.
Summary of the invention
the object of the present invention is to provide a kind of Chinese medicine preparation for the treatment of sleep disorder and preparation method thereof.This Chinese medicine preparation has significant curative effect and has no toxic and side effects and drug resistance insomnia, and sedation is remarkable, and the preparation method of this Chinese medicine preparation without adding multiple auxiliary materials, does not increase patient's dosage and use cost in the production process of preparation.
for solving the problems of the technologies described above, technical scheme provided by the invention is as follows: the Chinese medicine preparation for the treatment of sleep disorder, and this Chinese medicine preparation is by weight by Radix Polygalae 8-12 part, Semen Ziziphi Spinosae (stir-fry) 13-17 part, Herb Gynostemmae Pentaphylli 6-10 part, Radix Cynanchi Paniculati 8-12 part, Hemerocallis fulva L. 6-10 part and Rhizoma valerianae latifoliae 4-8 part are made.
the Chinese medicine preparation of aforesaid treatment sleep disorder, by weight preferably by Radix Polygalae 9-11 part, Semen Ziziphi Spinosae (stir-fry) 14-16 part, Herb Gynostemmae Pentaphylli 7-9 part, Radix Cynanchi Paniculati 9-11 part, Hemerocallis fulva L. 7-9 part and Rhizoma valerianae latifoliae 5-7 part are made.
the Chinese medicine preparation of aforesaid treatment sleep disorder, by weight more preferably by 10 parts of Radix Polygalaes, 15 parts of Semen Ziziphi Spinosaes (stir-fry), 8 parts of Herb Gynostemmae Pentaphylli, 10 parts of Radix Cynanchi Paniculatis, 6 parts of 8 parts of Hemerocallis fulva L.s and Rhizoma valerianae latifoliaes are made.
in the Chinese medicine preparation of aforesaid treatment sleep disorder, described Chinese medicine preparation is any one oral preparations of use clinically.
in the Chinese medicine preparation of aforesaid treatment sleep disorder, described oral medicine is, powder, tablet, granule, capsule, microcapsule, pill, drop pill, oral liquid, soft capsule, syrup, dispersant, thin membrane coated tablet or effervescent tablet.
the method of the Chinese medicine preparation of preparation aforementioned therapies sleep disorder, comprises the following steps:
a. by above-mentioned formula, taking Radix Polygalae, Semen Ziziphi Spinosae (stir-fry), Herb Gynostemmae Pentaphylli, Hemerocallis fulva L. four Chinese medicine material, by 60% ethanol heating extraction 3 times, obtain extracting solution, is A product;
b. A product are crossed to 400 order filter clothes while hot, concentrating under reduced pressure reclaims after ethanol, and obtaining clear paste is B product;
c. B product are placed in to 70 ℃ of baking ovens of decompression or microwave vacuum dryer dry, get dry extract, cross No. five sieve after pulverizing, the powder that gets dry extract is C product;
d. by above-mentioned formula, get Radix Cynanchi Paniculati, Rhizoma valerianae latifoliae two taste medical materials, first clean, dry, sterilizing, then pulverized sieve No. six, and obtaining powder is D product;
e. C product are mixed homogeneously with D product, obtain E product;
f. F product are processed into the Chinese medicine preparation of clinical use.
the method of the Chinese medicine preparation of aforesaid preparation treatment sleep disorder, in steps A, described use 60% ethanol extraction 3 times, be specially, first use 60% ethanol extraction of 9.5 times of amounts once, the time is 1.5 hours, then with 8 times, measures 60% ethanol extractions twice, each time is 1 hour, during extraction with 60 ℃ of-90 ℃ of heating.
the method of the Chinese medicine preparation of aforesaid preparation treatment sleep disorder, in step B, described clear paste, the relative density recording in the time of 20 ℃ is 1.2.
compared with prior art, Chinese medicine preparation of the present invention has significant curative effect and has no toxic and side effects and drug resistance insomnia, sedation is remarkable, and the preparation method of Chinese medicine preparation of the present invention without adding multiple auxiliary materials, does not increase patient's dosage and use cost in the production process of preparation.Chinese medicine preparation of the present invention all has good curative effect to the insomnia due to different TCM Syndrome Type and various disease, and not because successive administration produces drug resistance, safe and effective, evident in efficacy.
medical material in prescription of the present invention all belongs to the categories such as disease of being insomnia due to motherland's medical science " deficiency syndrome ", therefore adopts supplementing QI and nourishing YIN, nourish blood, and mind tranquilizing and the heart calming, the rule for the treatment of that clearing heat and relieving fidgetness is primary disease.This prescription analysis and demonstration are as follows: in side, Radix Polygalae is returned liver, gallbladder, heart channel, and nature and flavor are sweet flat with nourishing liver-YIN, therefore energy tonifying liver, mind tranquilizing and the heart calming, is the key medicine of the irritated sleeplessness for the treatment of blood deficiency; Semen Ziziphi Spinosae GUIXIN, kidney channel, have the Fructus Alpiniae Oxyphyllae of calming the nerves, and falls heart-fire effect; Two medicines share nourishing the liver and kidney blood, and mind calming god, is monarch drug.Be aided with Herb Gynostemmae Pentaphylli, Radix Cynanchi Paniculati supplementing QI and nourishing YIN, promoting the production of body fluid and inducing sedation of the mind.Assistant is with Hemerocallis fulva L., Rhizoma valerianae latifoliae tranquillizing and allaying excitement, wind-expelling pain-stopping.All medicines share, and the blood of conscience kidney nourishes active, plays altogether income gas, nourish blood, and adjust liver nourishing kidney, mind tranquilizing and the heart calming, the relieving restlessness that clears away heart-fire, the effect of pain relieving.
we have done preliminary bioactivity research test, its result shows: the compound extract that above 6 taste medicines form all can significantly reduce the autonomic activities number of mice, can obviously extend pentobarbital sodium in mice length of one's sleep, and can improve the sub-threshold dose pentobarbital sodium mice number of falling asleep, have obvious tranquilizing soporific active.
the inventor has carried out a large amount of experimentatioies to the prescription of crude drug, extraction, moulding process:
(1) research of extraction process
one) screening of prescription
1. the selection of medical material Radix Cynanchi Paniculati and research
medical material Radix Cynanchi Paniculati is that 6g medical material is directly beaten after fine powder (crossing 120 mesh sieves) is mixed homogeneously with the dry cream of extraction of other four Chinese medicine material with the fine powder (120 mesh sieves excessively) of 6g medical material Rhizoma valerianae latifoliae again and used in original prescription.But add crude drug powder can make the dose of prescription increase, also do not meet the requirement of modern Chinese medicine preparation, in order to reduce dose, consider to intend Radix Cynanchi Paniculati medical material to extract.Main chemical compositions in medical material Radix Cynanchi Paniculati is volatile ingredient, has this volatile ingredient of bibliographical information to have the effect of tranquillizing and allaying excitement, therefore adopt steam distillation to extract the volatile ingredient in medical material Radix Cynanchi Paniculati.
the extraction of 1.1 Radix Cynanchi Paniculati medical materials: take medical material Radix Cynanchi Paniculati 50g and be placed in 2000ml round-bottomed flask, the water that adds 20 times of amounts, soak 0.5hr, use extraction by steam distillation 4hr, the about 200ml/hr of the speed that distillates, liquid to be distilled is collected about 800ml in conical flask, adds 10gNaCl, puts into refrigerator and cooled and hides crystallization.Medicinal residues add 5 times of water gagings again and decoct 1 hour, filter, and merge twice filtrate, and dry at 80 ℃ after concentrating under reduced pressure, dry cream is beaten powder, standby.
Table 1 Radix Cynanchi Paniculati medicinal material extract result of the test
1.2 Radix Cynanchi Paniculati medical materials are directly played the comparative study of powder and the calm test of extract
in order to explore the biological activity of medical material Radix Cynanchi Paniculati after extracting and whether directly beat powder variant, therefore medical material Radix Cynanchi Paniculati is directly beaten between powder and extract and carried out the calm parallel comparative study of testing biology.
principle: this test is measured with Multifunctional mouse autonomic activities instrument.By the infrared facility in Multifunctional mouse autonomic activities instrument, measure mice spontaneous activity frequency in instrument, can the neural situation of RC.Record the spontaneous activity number of mouse unit in the time, to evaluate medicine, whether central nervous system is had to inhibitory action.
average-administration class mean is counted in the blank group activity of movable suppression ratio %=()/blank class mean * 100%
1.2.1 the extract of 10g medical material Radix Cynanchi Paniculati and 10g medical material Radix Cynanchi Paniculati are played bioactive comparison between powder
for the comparability between the two, therefore consumption is all designed to 10g medical material, the results are shown in Table 2 and table 3.
The fine powder dosage of table 2 10g medical material Radix Cynanchi Paniculati extract and 10g medical material Radix Cynanchi Paniculati
Note: above-mentioned medicated powder is dissolved in respectively in 10ml distilled water, all amounts to into identical crude drug concentration (containing crude drug 0.2g.ml
-1).
The calm test of table 3 10g medical material Radix Cynanchi Paniculati extract and 10g Radix Cynanchi Paniculati crude drug fine powder comparing data
Note: Radix Cynanchi Paniculati is beaten powder group and the comparison of extract group, p ﹤ 0.01.
result: can be obtained by table 2 and table 3 data: p ﹤ 0.01.Therefore have utmost point significant difference between the extract of 10g medical material Radix Cynanchi Paniculati and 10g medical material Radix Cynanchi Paniculati fine powder, the calm test of medical material fine powder is obviously better than extract.
1.2.2 the comparative study of calm test between the extract of 10g medical material Radix Cynanchi Paniculati and 6g medical material Radix Cynanchi Paniculati fine powder
between 10g medical material Radix Cynanchi Paniculati extract and 10g medical material Radix Cynanchi Paniculati fine powder, there is utmost point significant difference, a recipe quantity of original prescription Chinese crude drug Radix Cynanchi Paniculati is 6g, 10g medical material Radix Cynanchi Paniculati extract and 6g medical material Radix Cynanchi Paniculati fine powder carry out the comparison of calm test again, to determine and to filter out best prescription consumption.
design: beating powder group crude drug concentration is 0.12g/ml, and it is 0.2g/ml that extract group (the dry cream of volatile ingredient+water extraction) is amounted to into crude drug concentration.
The comparing data of calm test between table 4 10g medical material Radix Cynanchi Paniculati extract and 6g medical material Radix Cynanchi Paniculati fine powder
result: can be obtained by table 4 data: p ﹥ 0.05.So there was no significant difference between the extraction of 10g medical material Radix Cynanchi Paniculati and 6g medical material Radix Cynanchi Paniculati fine powder.
1.2.3 this test result analysis and summary
when 1.2.3.1 medical material Radix Cynanchi Paniculati is beaten powder group, extraction group all respectively for 10g crude drug amount, test as every group of 13 mices.The results are shown in Table 5.
The comparing data that table 5 10g medical material Radix Cynanchi Paniculati extract and the calmness of 10g medical material Radix Cynanchi Paniculati fine powder are used as medicine and are tested
| ? | Crude drug concentration (g.ml -1） | Movable number per minute | Movable suppression ratio % |
| Beat powder group | 0.2 | 7.88 | 71.86 |
| Extraction group | 0.2 | 21.11 | 24.61 |
from table 5, the movable number of beating powder group is about extraction group 1/3, and between group, has utmost point significant difference (P ﹤ 0.05, P ﹤ 0.01).
1.2.3.2 6g crude drug is beaten powder group, and 10g crude drug extraction group is tested as every group of 10 mices.The results are shown in Table 6.
The calm test of table 6 10g medical material Radix Cynanchi Paniculati extract and 6g medical material Radix Cynanchi Paniculati fine powder comparing data
| ? | Crude drug concentration (g.ml -1） | Movable number per minute | Suppression ratio % |
| Beat powder group | 0.12 | 17.5 | 49.51 |
| Extraction group | 0.2 | 22.8 | 34.22 |
from table 6, beat powder group and reduced crude drug 40%(minimizing 4g), crude drug concentration ratio extraction group also reduces by 0.4 times, but biological activity is still good than the biological activity of extraction group 10g medical material.
1.2.3.3 medical material Radix Cynanchi Paniculati 10g and 6g play the comparison of powder group, the results are shown in Table 7.
Table 7 Radix Cynanchi Paniculati is directly beaten twice calm test comparing data of powder
| ? | Crude drug concentration (g.ml -1） | Movable number per minute | Crude drug amount (g) |
| Test for the first time | 0.2 | 7.88 | 10 |
| Test for the second time | 0.12 | 17.5 | 6 |
result: test has for the second time reduced medical material Radix Cynanchi Paniculati 40%, and its movable number per minute has approximately increased approximately 1.2 times.Also proved that in this compound recipe, dose-effect relationship has concordance simultaneously
1.2.3.4 the comparison of 10g medicinal substances extract, the results are shown in Table 8.
Twice calm test comparing data of table 8 10g medical material Radix Cynanchi Paniculati extract
| ? | Crude drug concentration (g.ml -1） | Movable number per minute |
| Test for the first time | 0.2 | 21.11 |
| Test for the second time | 0.2 | 22.8 |
from table 8, the movable number close (21.11,22.8) of 10g medicinal material extract group mice per minute in second trial, illustrates the repeatability of this test.
conclusion: to take safety, effectiveness be basis in exploitation according to whole compound drug, and our preparations shaping, dosage the aspect such as need reduce and consider, therefore screening 6g Radix Cynanchi Paniculati crude drug is an amount in prescription, directly beat powder and four Chinese medicine and close and carry after dried cream powder mix homogeneously, there is easy dispersion, the fast feature of proving effective.
2. the STUDY ON SCREENING of medical material Rhizoma valerianae latifoliae
the chemical composition of medical material Rhizoma valerianae latifoliae is very complicated, fragile, chemical constitution is variable, as containing volatile oil, iridoids, terpene acids, alkaloids etc., wherein normal tool carboxyl in the structure of iridoids, aldehyde radical, carbonyl, unsaturated double-bond, together with functional groups such as diether, hemiacetals, therefore chemical property is extremely active, in preparation process, affected by the more violent conditions such as acid, alkali, heat, scission of link, open loop and isomerization easily occur, will produce catabolite.Thies etc. also find no matter Rhizoma valerianae latifoliae is at column chromatography, or when 60 ℃ of distillations, iridoids all can be degraded, and cannot obtain good separating effect.If its preparation dried or storage requirement are improper, can only obtain degraded or the converted product of real effective ingredient.Chapell finds that the suitable baking temperature of Rhizoma valerianae latifoliae is 40 ℃, as temperature risen to 60 ℃ or 120 ℃, will make iridoids lose 30 %-75%.Chapelle etc. find that the placement of Rhizoma valerianae latifoliae dichloromethane extract is after 5 months, the not degraded of only remaining 25% iridoids.
iridoids and volatile oil should be indispensable active component and position in preparation.Literature research also confirms, in the industrial processes of Rhizoma valerianae latifoliae extractum, Aranea aromatin tincture, iridoids extracts not exclusively, and volatile oil loses also more in concentration process.And the PROCESS FOR TREATMENT such as Rhizoma valerianae latifoliae powder un-extracted is concentrated, various compositions still keep its primordial condition, comparatively desirable to guaranteeing curative effect of medication.Therefore English, U.S., Deng developed country pharmacopeia are used as medicine by initial Aranea cus-cus, rhizome, through extractum, fluid extract and tincture, develop into preparation of active ingredient, then returned to again in recent years crude drug in whole powder, it is larger that crude drug powder also has surface area, thereby there is easy dispersion, the fast feature of proving effective.
in sum, intend still being directly used as medicine and being advisable with the fine powder of medical material Rhizoma valerianae latifoliae.
two) investigation of Radix Polygalae, Semen Ziziphi Spinosae, Herb Gynostemmae Pentaphylli, Hemerocallis fulva L. four Chinese medicine ethanol extraction technique
1. in prescription, four Chinese medicine different concentration ethanol reflux, extract, is preferred
investigate index: 1. tenuifolin extracts the rate of transform; 2. total saponins extracted amount; 3. dry cream yield; 4. calm test (mice autonomic activities suppression ratio).
2. the assay of tenuifolin in different concentration ethanol Effect of Alcohol Extracting Procedureto Total
the accurate dried cream powder that takes different concentration ethanol reflux, extract, is each 2 parts respectively, and every part of 450mg, in 250ml boiling flask, obtains test sample, carry out the Content inspect of tenuifolin, measure: get and join solution, the accurate 10 μ l that draw, each repeats sample introduction 2 times, calculates, and the results are shown in Table 9.
the method of the Content inspect of tenuifolin is:
(1) chromatographic condition and system suitability: with octadecylsilane chemically bonded silica, be filler; Mobile phase is methanol and 0.05% phosphoric acid of 55:45; Flow velocity is 1.0ml/min; Column temperature is 30 ℃; Detection wavelength is 202nm, and theoretical cam curve should be not less than 5000 in tenuifolin peak;
(2) preparation of reference substance solution: accurately weighed tenuifolin reference substance 10.00mg, in 10ml volumetric flask, with chromatograph dissolve with methanol standardize solution, shakes up, and obtains the reference substance solution that concentration is 1.00mg/ml;
(3) preparation of need testing solution: add 10%NaOH solution 100ml at test sample, hydrolysis 2h, takes out after hydrolysis, cooling, with hydrochloric acid adjust pH to 4～5, with water saturated n-butanol extraction 4 times, merge n-butanol layer, 80 ℃ of water-baths volatilize, with dissolve with methanol residue and be transferred in 25ml volumetric flask, standardize solution, shakes up, with 0.45 μ m microporous filter membrane, filter, obtain need testing solution
(3) algoscopy: precision is drawn reference substance solution and each 10 μ l of need testing solution respectively, and injection liquid chromatography, measures, and records chromatogram, adopts one point external standard method to carry out cubage to the tenuifolin in preparation by peak area value;
the tenuifolin assay (n=2) that table 9 different concentration ethanol Effect of Alcohol Extracting Procedureto Total is investigated
result:
a. tenuifolin content raises along with the increase of concentration of alcohol, tenuifolin content the highest (1.83%) in the dry cream of 80% ethanol extraction, tenuifolin content minimum (1.33%) in the dry cream of 50% ethanol extraction.
b. dry cream yield presents downward trend along with the increase of concentration of alcohol, the dry cream yield minimum (26.41%) of 50% ﹥ 60% ﹥ 70% ﹥ 80%, 80%, 50% dry cream yield the highest (29.46%).
3. the assay of total saponins in different concentration ethanol Effect of Alcohol Extracting Procedureto Total
respectively precision parallel take different concentration ethanol reflux, extract, dried cream powder each 2 parts, every part of 55mg is in 10ml volumetric flask, obtain test sample, carry out the Content inspect of total saponins, with the methanol of application of sample not, with method, be prepared as retinue blank, under 544nm, measure, record total saponin content in ginsenoside Rb1.The results are shown in Table 10.
the method of the Content inspect of total saponins is:
condition determination: by colorimetry, 547 ± 2nm is for measuring wavelength, and developer is 5% vanillin-glacial acetic acid solution 0.2ml and 0.8ml perchloric acid;
(2) preparation of reference substance solution: precision takes ginsenoside Rb1's reference substance 10.00mg in 10ml volumetric flask, adds chromatograph dissolve with methanol standardize solution, shakes up and obtain reference substance solution, and its concentration is 1.00mg/ml;
(3) preparation of need testing solution: add 10ml hot distilled water to dissolve in test sample, solution is put in separatory funnel, with same volume defat with petroleum ether 3 times (10ml/ is each), discard petroleum ether layer, water saturated n-butanol extraction 4 times (20ml/ is each) for water layer, merge n-butanol layer in 250ml separatory funnel, with the saturated aqueous solution 80ml of n-butyl alcohol, wash 1 time, discard water layer, n-butanol layer volatilizes in 80 ℃ of water-baths, and residue is with dissolve with methanol and be transferred in 25ml volumetric flask, with methanol, is diluted to scale, shake up, obtain;
(4) algoscopy: accurately pipette 1.5ml solution in color-comparison tube, 70 ℃ of water-baths volatilize methanol, the color comparison tube that volatilizes methanol is accurately added to 5% vanillin-glacial acetic acid solution 0.2ml and 0.8ml perchloric acid solution, after 60 ℃ of airtight colour developing 10min, ice bath 10min, after adding again 5ml glacial acetic acid to shake up, with the methanol of application of sample not, with method, be prepared as retinue blank, according to ultraviolet-visible spectrophotometry of 2010 editions pharmacopeia, under 547 ± 2nm, carry out the mensuration of absorbance, record total saponins absorbance substitution ginsenoside Rb1 regression equation calculation, obtain;
In the investigation of table 10 different concentration ethanol Effect of Alcohol Extracting Procedureto Total, total saponin content is measured (n=2)
Note: 1. total saponins extracted amount=total saponin content * dry cream weight
2. total saponins extracts relative percentage and is up to 100% in total saponins extracted amount in test.
result:
a. total saponin content increases along with the rising of concentration of alcohol, wherein in the dry cream of 50% ethanol extraction total saponin content lower be in the dry cream of 4.95%, 80% ethanol extraction total saponin content higher be 9.60%.
b. in conjunction with dry cream weight, total saponins extracted amount is: 80% ﹥ 70% ﹥ 60% ﹥ 50%, wherein in the dry cream of 50% ethanol extraction total saponins extracted amount lower be 0.5979g, in the dry cream of 80% ethanol extraction total saponin content higher be 1.0396g.
4. the calmness of the dry cream of different concentration ethanol reflux, extract, test (mice autonomic activities number of times)
whether in order to inquire into four concentration ethanol, extract biological activity between dry cream and there are differences, the selection index of final extraction process, therefore the dry cream of four concentration ethanol extraction processes is carried out to the comparison of calm test if take drug effect as main.
average-administration class mean is counted in the blank group activity of movable suppression ratio %=()/blank class mean * 100%, the results are shown in Table 11.
The dry cream mice of table 11 different concentration ethanol reflux, extract, autonomic activities number of times result of the test
Note: between each group, dosage and concentration are identical.
*administration group is compared with blank group, p ﹤ 0.05.
movable suppression ratio power is 60% ﹥ 80% ﹥ 50% ﹥ 70% as seen from Table 11, and positive drug is more weak, is only 10.70%.Wherein 60%, 80% ethanol extraction is compared with blank group, has significant difference.50%, 70% ethanol extraction is compared with blank group, and first there was no significant difference, so give up 50% and 70% these two concentration of alcohol.
60%, 80% ethanol extraction is carried out to t-check analysis again, the results are shown in Table 12.
Table 12 60%, 80% ethanol extraction mice autonomic activities is counted t-check analysis tables of data
by table 12, shown that p ﹥ 0.05 illustrates the affect there was no significant difference of the ethanol extraction of 60%, 80% concentration on mice autonomic activities.
for the reliability of result of the test, the calmness of different concentration ethanol extract test has been done four times, the results are shown in Table 13 and table 14.
The movable suppression ratio of the dry cream mice of four different concentration ethanol reflux, extract, of table 13
| 1 | 2 | 3 | 4 | |
| 50％ | 22.21 | 50.82 | 52.06 | 22.60 |
| 60％ | 52.89 | 61.01 | 66.05 | 36.81 |
| 70％ | 18.07 | 32.88 | 45.63 | 13.62 |
| 80％ | 48.19 | 43.04 | 66.94 | 23.69 |
The movable suppression ratio size of the dry cream mice of four different concentration ethanol reflux, extract, of table 14 relatively
| Test number (TN) | Movable suppression ratio % | Crude drug concentration g.ml -1 | Movable number per minute |
| 1 | 60％﹥80％﹥50％﹥70％ | 0.62 | 23.5～26.4 |
| 2 | 60％﹥50％﹥80％﹥70％ | 0.992 | 13.8～20.5 |
| 3 | 80％﹥60％﹥50％﹥70％ | 1.14 | 11.4～19.3 |
| 4 | 60％﹥80％﹥50％﹥70％ | 1.14 | 12.5～23.6 |
from table 13 and table 14, test for the third time 80% alcohol extraction group ﹥ 60% alcohol extraction group, but the movable suppression ratio that the movable suppression ratio of 80% alcohol extraction group is 66.94%, 60% alcohol extraction group is 66.05%, the two is close, illustrates that this test has repeatability, reliable results.
5. the comparative study of positive control drug and this compound biological activity
with positive drug (compound recipe sedative jujube kernel capsule.Manufacturer: Guizhou Tongjitang Pharmaceutical Co., Ltd; Authentication code: the accurate word Z20010033 of traditional Chinese medicines; Product batch number 20071003) in matched group comparative study, positive drug control group is 10.70% to mice autonomic activities suppression ratio, the 70% ethanol extraction group autonomic activities suppression ratio 18.07% the poorest with biological activity compared, and biological activity still differs approximately 1.8 times.Positive drug control group and 60% ethanol extraction group are carried out to t check analysis, the results are shown in Table 15.
Table 15 positive drug control group and 60% ethanol extraction group mice autonomic activities number of times t check analysis data
Note: 60% ethanol is put forward group and compared with compound recipe sedative jujube kernel capsule group, p ﹤ 0.01.
by table 15, can be seen, p ﹤ 0.01, between positive drug control group and 60% ethanol extraction group there is significant difference in biological activity, 60% ethanol is carried group biological activity and is better than positive controls, illustrated this compound recipe and similar listing kind this test relatively in, this compound recipe sedation is remarkable, becomes the property of medicine good, therefore there is good DEVELOPMENT PROSPECT.
6. the investigation of different concentration ethanol extraction process is summed up
in conjunction with tenuifolin and total saponin content measure, the comparison of biological indicator (calm test), the results are shown in Table 16.
Table 16 different concentration ethanol extraction process is investigated index and result
from table 16:
a. receive cream rate and along with the increase of concentration of alcohol, present downward trend, wherein 80% receipts cream rate is minimum, and 50% receipts cream rate is the highest.
b. tenuifolin content and total saponin content raise along with the increase of concentration of alcohol.
c. mice autonomic activities suppression ratio is: 60% ﹥ 80% ﹥ 50% ﹥ 70%.
in sum, therefore the concentration of alcohol when extracting is defined as 60% alcohol reflux is advisable.
three) orthogonal test of four Chinese medicine extraction process in prescription
1. four Chinese medicine extracts orthogonal test
the principal element that affects 60% alcohol reflux has the quantity of solvent of adding, extraction time, extraction time, therefore respectively get 3 levels, carries out L
9
(3
4
) orthogonal test, design is in Table 17.
Table 17 four Chinese medicine closes puies forward experimental factor and level set
2. take a recipe quantity four Chinese medicine material 41g(Radix Polygalae 10g, Semen Ziziphi Spinosae (stir-fry) 15g, Herb Gynostemmae Pentaphylli 8g, Hemerocallis fulva L. 8g), 60% alcohol reflux is carried out in the requirement in each 9 parts of photograph orthogonal table under each tested number, concentrated, dry, obtain the dry cream under different process, beat powder, put sealing in exsiccator and preserve, standby.
3. evaluation index
(1) by the Content inspect method of tenuifolin, measure the content of leading indicator composition tenuifolin in monarch drug Radix Polygalae.
(2) by the Content inspect method of total saponins, measure the content of large effective constituents total saponins.
(3) dry cream yield.
(4) biological indicator---calm test (mice autonomic activities suppression ratio).
4. comprehensive grading
a. because of monarch drug in the Radix Polygalae side of being, there is the effect of the Fructus Alpiniae Oxyphyllae of calming the nerves.Its saponin component is the important effective ingredient in Radix Polygalae, and tenuifolin is the secondary saponin that Radix Polygalae total saponins basic hydrolysis generates, Radix Polygalae total saponins all can be converted into tenuifolin through basic hydrolysis, pretend and by the Content inspect method of tenuifolin, detect the content of tenuifolin for index composition, the quality of evaluating extraction process with this, weight coefficient is decided to be 0.4.
b. in side, Radix Polygalae, Semen Ziziphi Spinosae and Herb Gynostemmae Pentaphylli etc. all contain tetracyclic triterpene saponins, are the main effective ingredient of tranquillizing and allaying excitement.Therefore in we, total saponins has also been done intensive methodological study as the assay of large constituents, evaluates the quality of extraction process, weight coefficient is decided to be 0.4.
c. this prescription is sedative, adopts mice autonomic activities instrument to test spontaneous activity in mice number, observes its sedation, with pharmacodynamic index, evaluates and screen extraction process, is also an evaluation index with better reference value, therefore weight coefficient is decided to be 0.2.
d. in orthogonal test, dry cream yield impact not obvious between test between each extraction process, therefore do not listed in consideration during weighted scoring.
comprehensive grading=(40/ the highest tenuifolin extracts the rate of transform) * tenuifolin extracts the rate of transform+(40/ the highest total saponins extracted amount) * total saponins extracted amount+(20/ the highest autonomic activities suppression ratio) * autonomic activities suppression ratio
four Chinese medicine reflux, extract, orthogonal test investigate in the assay of tenuifolin and total saponins
5.1 tenuifolin assays and the extraction rate of transform are calculated
precision parallel takes each 2 parts of extract dried cream powders under different extraction processes respectively, every part of 450mg in 250ml boiling flask, the same tenuifolin Content inspect of method method.
measure: get and join solution, the accurate 10 μ l that draw, each repeats sample introduction 2 times, calculates, and the results are shown in Table 18.
Prescription four Chinese medicine of table 18 extracts tenuifolin content and the extraction rate of transform (n=2) in orthogonal test
result: in orthogonal test, extracting the rate of transform the highest (84.80%) to test 3 tenuifolins, is secondly test 7(83.83%), that the tenuifolin extraction rate of transform is minimum is test 1(64.65%).
5.2 total saponin contents are measured and total extracted amount calculates
precision parallel takes each 2 parts of the dry cream of extraction under each extraction process respectively, every part of 45mg is in 10ml volumetric flask, and the same total saponin content of method investigation method, is prepared as retinue with the methanol of application of sample not with method blank, under 544nm, measure, record total saponin content in ginsenoside Rb1.The results are shown in Table 19.
In prescription of table 19, in four Chinese medicine reflux, extract,, total saponin content is measured and total extracted amount (n=2)
Note: it is to test 3 total saponins extracted amounts to be up to 100% that total saponins extracts relative percentage.
result: in orthogonal test technique to test total saponins extracted amount the highest (0.8161g) in 3.Secondly be test 7(0.7698g), minimum is test 1(0.5243g).
5.3 result
(1) tenuifolin extracts the rate of transform: 3. ﹥ 7. ﹥ 5. ﹥ 9. ﹥ 2. ﹥ 4. ﹥ 8. ﹥ 6. ﹥ is 1..
(2) total saponins extracted amount: 3. ﹥ 7. ﹥ 2. ﹥ 5. ﹥ 9. ﹥ 6. ﹥ 4. ﹥ 8. ﹥ is 1..
(3) dry cream yield: 7. ﹥ 5. ﹥ 9. ﹥ 3. ﹥ 4. ﹥ 2. ﹥ 8. ﹥ 6. ﹥ is 1..
the research of calm test in 5.4 orthogonal tests
the results are shown in Table 20.
Table 20 orthogonal test mice autonomic activities is counted data measured
Note: between each group, dosage and concentration are identical.
result: calm strong and weak: 3. ﹥ 9. ﹥ 7. ﹥ 8. ﹥ 4. ﹥ 5. ﹥ 6. ﹥ 2. ﹥ 1., 9 test group movable amplitude are 16.3～28.3 times/min.
Table 21 orthogonal test mice autonomic activities is counted the one factor analysis of variance table of comparison
| Group | Observation number | Summation | On average | Variance |
| One group | 10 | 1353 | 135.3 | 6520.456 |
| Two groups | 10 | 1256 | 125.6 | 4324.489 |
| Three groups | 10 | 815 | 81.5 | 2987.611 |
| Four groups | 10 | 928 | 92.8 | ? 3282.178 |
| Five groups | 10 | 1009 | 100.9 | 3112.322 |
| Six groups | 10 | 1187 | 118.7 | 7988.456 |
| Seven groups | 10 | 1086 | 108.6 | ? 3342.933 |
| Eight groups | 10 | 1110 | 111.0 | 2572.889 |
| Nine groups | 10 | 1050 | 105.0 | 3028.0 |
Table 22 orthogonal test mice autonomic activities is counted the variance analysis of comparison
| Source of error | SS | df | MS | F | P |
| Between group | 21655.16 | 8 | 2706.894 | 0.655611 | 0.728647 |
| In group | 334434.0 | 81 | 4128.815 | ? | ? |
| Amount to | 356089.2 | 89 | ? | ? | ? |
*F
0.05（8，81）＝2.054882；F
0.01（8，81）＝2.738996
result: as table 21 and table 22, by mice autonomic activities number is carried out to one factor analysis of variance demonstration: F ﹤ F0.05, F ﹤ F0.01, P ﹥ 0.05, P ﹥ 0.01, difference that between each group, there are no significant.
the comparison of each evaluation index in 5.5 orthogonal tests
the results are shown in Table 23.
The comparative result of 9 groups of evaluation indexes in table 23 orthogonal test
from table 23, tenuifolin extracts the rate of transform, total saponins extracted amount is higher, and biological activity is better, and amount effect relationship between them also illustrates the correctness of selecting Chemical Evaluation index simultaneously.
5.6 1 recipe quantity four Chinese medicines (Radix Polygalae 10g, Semen Ziziphi Spinosae (stir-fry) 15g, Herb Gynostemmae Pentaphylli 8g, Hemerocallis fulva L. 8g), 60% alcohol reflux orthogonal experiments
shown in table 24.
Prescription four Chinese medicine 60% alcohol reflux L of table 24
9(3
4) orthogonal experiments table
5.7 orthogonal test variance data
(1) in tenuifolin, extract the rate of transform (amount that is equivalent to Polygala tenuifolia 10g in a prescription)
Table 25 tenuifolin extracts rate of transform analysis of variance table
| Source of error | SS | f | MS | F | P *Significance |
| A | 23.3878 | 2 | 11.6939 | 18.4767 | P>0.05 |
| B | 19.3751 | 2 | 9.6875 | 15.3065 | P>0.05 |
| C | 443.5321 | 2 | 221.766 | 350.3966 | P<0.01 *Extremely remarkable |
| Error e | 1.2658 | 2 | 0.6329 | ? | ? |
*F
0.05(2,2)=19.00;?F
0.01(2,2)=99.00
result: as shown in Table 25, relatively the size of each factor extreme difference R value draws, three factors are extraction time (C) > quantity of solvent (A) > extraction time (B) on the impact size of the tenuifolin extraction rate of transform, by analysis of variance table, can be drawn, in quantity of solvent, extraction time, extraction time, only have extraction time to have the impact of highly significant, quantity of solvent and extraction time affect without significance the extraction rate of transform of tenuifolin.By intuitive analysis, it is evaluation index that the tenuifolin of take extracts the rate of transform, and three factors are best with the 3rd level, and optimum extraction process is A
3
b
3
c
3
.
(2) in total saponins extracted amount (amount that contains Herb Gynostemmae Pentaphylli crude drug 8g in a suitable prescription).
Table 26 total saponins extracted amount analysis of variance table
| Source of error | SS | f | MS | F | P |
| A | 0.01021 | 2 | 0.005107 | 1.0786 | P>0.05 |
| B | 0.00340 | 2 | 0.001699 | 0.3588 | P>0.05 |
| C | 0.07273 | 2 | 0.03637 | 7.6811 | P>0.05 |
| Error e | 0.00947 | 2 | 0.004735 | ? | ? |
*F
0.05(2,2)=19.00;?F
0.01(2,2)=99.00
result: shown in table 26, three factors on the size that affects of total saponins extracted amount are: extraction time (C) ﹥ quantity of solvent (A) ﹥ extraction time (B), the result of variance analysis shows, three factors are for the extracted amount of total saponins there are no significant difference, by intuitive analysis, drawn, add quantity of solvent with the first level for well, extraction time and extraction time are best with the 3rd level, optimum extraction process is A
1
b
2
c
3
.
(3) the power of mice autonomic activities suppression ratio is carried out to variance analysis in calmness test
Table 27 mice autonomic activities suppression ratio analysis of variance table
| Source of error | SS | f | MS | F | P |
| A | 458.08 | 2 | 229.04? | 1.039 | P>0.05 |
| B | 115.26 | 2 | 57.63 | 0.26 | P>0.05 |
| C | 509.55 | 2 | 254.77 | 1.156 | P>0.05 |
| Error e | 440.80 | 2 | 220.40 | ? | ? |
*F
0.05(2,2)=19.00;?F
0.01(2,2)=99.00
shown in table 27, in calmness test, each factor affects size to the suppression ratio of mice autonomic activities: quantity of solvent (A) ﹥ extraction time (C) ﹥ extraction time (B), known by variance analysis, three factors for mice autonomic activities suppression ratio all without significant.By intuitive analysis find out suppression ratio the highest for technique 3, be secondly technique 9 and technique 7, the most bad is technique 1.From pharmacodynamics intuitive analysis, see that three factors all take the 3rd level as best, optimum extraction process is A
3
b
3
c
3
.
(4) comprehensive grading result is carried out variance analysis to orthogonal test
The variance analysis of table 28 comprehensive grading result
| Source of error | SS | f | MS | F | P * |
| A | 121.67 | 2 | 60.83 | 1.2877 | P>0.05 |
| B | 75.78 | 2 | 37.89 | 0.8021 | P>0.05 |
| C | 1087.84 | 2 | 543.92 | 11.5140 | P>0.05 * |
| Error e | 94.49 | 2 | 47.24 | ? | ? |
*F
0.05(2,2)=19.00;?F
0.01(2,2)=99.00
shown in table 28, known by comprehensive grading the results of analysis of variance, the impact size of comprehensive grading result is extraction time (C) ﹥ quantity of solvent (A) ﹥ extraction time (B), but three factors there are no significant difference, and three factors all with the 3rd level for being preferably A
3
b
3
c
3
.
5.8 intuitive analysis
relatively the size of each factor extreme difference R value draws: three factors are extracted big or small extraction time (C) > quantity of solvent (A) > extraction time (B) of being of impact of the rate of transform on tenuifolin, three factors are best with the 3rd level, and optimum extraction process is A
3
b
3
c
3
; Three factors on the size that affects of total saponins extracted amount are: extraction time (C) ﹥ quantity of solvent (A) ﹥ extraction time (B), add quantity of solvent with the first level for well, extraction time and extraction time are best with the 3rd level, and optimum extraction process is A
1
b
3
c
3
; In calmness test, each factor affects size to the suppression ratio of mice autonomic activities and is: quantity of solvent (A) ﹥ extraction time (C) ﹥ extraction time (B), and three factors all be take the 3rd level as best, and optimum extraction process is A
3
b
3
c
3
; The impact size of comprehensive grading result is extraction time (C) ﹥ quantity of solvent (A) ﹥ extraction time (B), and three factors all be take the 3rd level as best, i.e. A
3
b
3
c
3
.
5.9 conclusion
quantity of solvent there is no significance impact to extracting, and for cost-saving, quantity of solvent is defined as to 8 times, extraction time can find out that from intuitive analysis each extraction 2 hours is the best, comprehensively by statistical variance, analyze and intuitive analysis, finally draw, optimum extraction process is A
1
b
3
c
3
, with 8 times, measure 60% alcohol reflux 3 times, each 2hr.
because considering extraction time oversize (6hr altogether), in large production, consume the energy and manpower, therefore cost is high.For reducing costs, save man-hour, carried out again the comparison test of time good extraction process.
6. four Chinese medicine (Radix Polygalae 10g, Semen Ziziphi Spinosae (stir-fry) 15g, Herb Gynostemmae Pentaphylli 8g, Hemerocallis fulva L. 8g) extraction process quadrature demonstration test in a prescription
take four Chinese medicine material in a recipe quantity side and be total to 41g, parallel 3 parts, the optimised process A obtaining according to above-mentioned craft screening
1
b
1
c
3
, add 8 times of amount 60% alcohol reflux 3 times, 1.5hr for the first time, rear twice each 1hr, merging filtrate, concentrates, and puts 70 ℃ of oven dryings, gets dry extract, and beats powder standby.
the dry cream yield of 6.1 quadrature demonstration test and determination of water
align and deliver for a check that confirmatory test gets dry extract and the mensuration of moisture, method is by 05 edition < < Chinese Pharmacopoeia > appendix IX H aquametry first method of > (oven drying method), calculate moisture, the results are shown in Table 29.
The dry cream yield of table 29 quadrature demonstration test and moisture determination data
| Sample | Moisture (%) | Dry cream heavy (g) | Dry cream yield (%) |
| 1 | 6.32 | 12.0433 | 29.37 |
| 2 | 7.21 | 11.7866 | 28.75 |
| 3 | 7.16 | 12.0277 | 29.34 |
in the dry cream of 6.2 3 parts of quadrature demonstration tests, tenuifolin and total saponin content are measured
6.2.1 tenuifolin assay and the rate of transform are calculated
precision parallel takes 2 parts, 3 parts of dried cream powders of quadrature demonstration test end respectively, every part of 450mg in 250ml boiling flask, the same tenuifolin Content inspect of method method.
measure: get and join solution, the accurate 10 μ l that draw, each repeats sample introduction 2 times, calculates.Result is shown in table 30.
Tenuifolin assay result (n=2) in 3 parts of dry cream of table 30 quadrature demonstration test
Note: in Polygala tenuifolia, tenuifolin counts 2.11% with dry product.
6.2.2 total saponin content is measured and total extracted amount calculating
precision parallel takes each 2 parts, 3 parts of dried cream powder ends of quadrature demonstration test respectively, every part of 45mg is in 10ml volumetric flask, and the method that the same total saponin content of method is investigated, is prepared as retinue with the methanol of application of sample not with method blank, under 544nm, measure, record total saponin content in ginsenoside Rb1.Result following table 31.
Total saponin content measurement result (n=2) in 3 parts of dry cream of table 31 quadrature demonstration test
| Tested number | Sample weighting amount (mg) | Absorption of sample value A | Dry cream heavy (g) | Content (%) is (with ginsenoside Rb 1Meter) | Average content (%) | Total extracted amount is (with ginsenoside Rb 1Meter) (g) | Extract relative percentage (%) |
| 1 | 45.5 | 0.3806 | 12.0433 | 6.96 | 6.95 | 0.8370 | 98.15 |
| ? | ? | 0.3780 | ? | ? | ? | ? | ? |
| ? | 45.1 | 0.3776 | ? | 6.94 | ? | ? | ? |
| ? | ? | 0.3723 | ? | ? | ? | ? | ? |
| 2 | 45.9 | 0.3879 | 11.7866 | 7.01 | 7.05 | 0.8310 | 97.44 |
| ? | ? | 0.3852 | ? | ? | ? | ? | ? |
| ? | 46.8 | 0.3983 | ? | 7.09 | ? | ? | ? |
| ? | ? | 0.3972 | ? | ? | ? | ? | ? |
| 3 | 46.4 | 0.3956 | 12.0277 | 7.09 | 7.09 | 0.8528 | 100 |
| ? | ? | 0.3932 | ? | ? | ? | ? | ? |
| ? | 46.2 | 0.3931 | ? | 7.09 | ? | ? | ? |
| ? | ? | 0.3924 | ? | ? | ? | ? | ? |
Note: extracting relative percentage is to be up to 100% in total saponin content.
6.2.3 3 demonstration test comparisons of quadrature
Table 32 quadrature demonstration test is received cream rate, tenuifolin and total saponin content and is measured
from table 32, in three demonstration tests, receive cream rate, the tenuifolin extraction rate of transform and the equal zero difference of total saponins extracted amount, RSD% ﹤ 1.2%, therefore the extraction process conditional stability of institute's screening and optimizing is feasible.
four) investigation of impurity removal process
1. evaluation index
a. tenuifolin retention rate.B. total saponins retention rate.C. solid content yield.
2. the technical study of each impurity-removing method
three kinds of remove impurity make use of physics methods methods have been chosen in this test, are filter-cloth filtering, naturally standing (12hr, 24hr) and centrifugal remove impurity (2800r/min, 15min), and take solid content yield and tenuifolin retention rate, total saponins retention rate is evaluation index.
3. the preparation of herbal extract takes Radix Polygalae 300g, Semen Ziziphi Spinosae 450g, Herb Gynostemmae Pentaphylli 240g, Hemerocallis fulva L. 240g in prescription ratio, be total to 1230g(30 recipe quantity), by the four Chinese medicine of a recipe quantity, close and carry definite optimum extraction process and extract, extracting solution is crossed 200 mesh sieves, and 70 ℃ of filtrates are evaporated to 5000ml (1ml medicinal liquid is equivalent to 0.246g prescription medical material).
(1) four Chinese medicine closes and proposes the research of different meshes filter-cloth filtering impurity removal process
1. extracting solution 800ml is got in sample liquid preparation, crosses 200,400 order filter clothes after heating, and 70 ℃ of filtrates are evaporated to 100ml, puts in 70 ℃ of baking ovens dryly, gets dry extract, and beats powder standby.
2. the accurate concentrated solution 10ml that draws of solid content yield assay method is in constant weight the evaporating dish of weighing, water bath method, and 105 ℃ of baking ovens dry 3hr to constant weight.Take out, put rapidly in exsiccator coolingly, weigh.Repeat 3 times, calculating solid content yield is 26.56%.
3. tenuifolin assay precision takes 2 parts of dried cream powders, every part of 450mg, and in 250ml boiling flask, the same tenuifolin Content inspect of method method.Result is as shown in table 33-table 36.
Table 33 tenuifolin four Chinese medicine closes puies forward 200 order filter-cloth filtering remove impurity investigation results (n=2)
Table 34 total saponins four Chinese medicine closes the investigation result (n=2) of proposing 200 order filter-cloth filtering remove impurity tests
Table 35 tenuifolin four Chinese medicine closes puies forward 400 order filter-cloth filtering remove impurity investigation results (n=2)
Note: tenuifolin retention rate (%): be to take 200 order filter-cloth filtering technique gained tenuifolins to extract the rates of transform be radix, other technique gained tenuifolins are extracted to rates of transform gained in contrast.
The tenuifolin extraction rate of transform and tenuifolin retention rate are all to contain Polygala tenuifolia 10g in a recipe quantity.
Table 36 total saponins four Chinese medicine closes the investigation result (n=2) of proposing 400 order filter-cloth filtering remove impurity tests
Note: total saponins retention rate (%): be to using 200 order filter-cloth filtering gained total saponins extracted amounts as radix, by other technique gained total saponins extracted amounts gained in contrast.
1. in prescription, four Chinese medicine closes the Test Summary of proposing filter cloth remove impurity
as show as shown in 33-table 36, by filter-cloth filtering (200 orders or 400 orders), the four Chinese medicine extraction process in prescription is investigated, illustrate while adopting filter-cloth filtering remove impurity, active ingredient index (tenuifolin retention rate and total saponins retention rate) is had no to obvious impact, and remove impurity does not have good effect yet, because 400 order filter-cloth filtering solid content yields reduce not quite, be only 2.2%.
(2) four Chinese medicine closes and proposes the standing impurity removal process research of nature
1. sample liquid preparation
get 2 parts of extracting solution, every part of 800ml, standing 12hr and 24hr, get supernatant concentrating under reduced pressure respectively, puts in 70 ℃ of baking ovens and be dried, and gets dry extract, and beats powder standby.
2. the accurate concentrated solution 10ml that draws of solid content yield assay method is in constant weight the evaporating dish of weighing, water bath method, and 105 ℃ of baking ovens dry 3hr to constant weight.Take out, be placed in rapidly exsiccator cooling, weigh.Repeat 3 times, calculating the solid content yield that solid content yield is standing 12hr is 26.59%, and the solid content yield of standing 24hr is 26.38%.
tenuifolin assay precision take standing 12hr and 24hr dried cream powder each 2 parts, every part of 450mg, in 250ml boiling flask, the same tenuifolin Content inspect of method method.Result is as shown in table 37 and table 38.
Table 37 tenuifolin four Chinese medicine closes puies forward the standing remove impurity investigation of nature result (n=2)
Note: tenuifolin retention rate (%): be to take 200 order filter-cloth filtering technique gained tenuifolins to extract the rates of transform be radix, other technique gained tenuifolins are extracted to rates of transform gained in contrast.
The tenuifolin extraction rate of transform and tenuifolin retention rate are all to contain Polygala tenuifolia 10g in a recipe quantity.
Table 38 total saponins four Chinese medicine closes the investigation result (n=2) of proposing the standing remove impurity test of nature
Note: total saponins retention rate (%): be to using 200 order filter-cloth filtering gained total saponins extracted amounts as radix, by other technique gained total saponins extracted amounts gained in contrast.
4. in prescription, four Chinese medicine closes the Test Summary of proposing the standing remove impurity of nature
as shown in table 37 and table 38, by naturally standing, four Chinese medicine extraction process in prescription is investigated, illustrate while adopting the standing remove impurity of nature, active ingredient index (tenuifolin retention rate and total saponins retention rate) is had no to obvious impact, and remove impurity does not have good effect yet, the solid content yield of standing 24hr slightly reduces, and is only still 2.4%.
(3) four Chinese medicine closes and lifts from the research of heart impurity removal process
1. sample liquid preparation
get extracting solution 800ml and put into the centrifugal 15min of centrifuge (2800r/min), get 70 ℃ of concentrating under reduced pressure of supernatant, put in 70 ℃ of baking ovens and be dried, get dry extract, beat powder standby.
2. solid content yield assay method
the accurate concentrated solution 10ml that draws in constant weight the evaporating dish of weighing, water bath method, 105 ℃ of baking ovens dry 3hr to constant weight.Take out, put rapidly in exsiccator coolingly, weigh.Repeat 3 times, calculating solid content yield is 26.81%.
3. tenuifolin assay
precision takes 2 parts of dried cream powders, every part of 450mg, and in 250ml boiling flask, the same tenuifolin Content inspect of method method.Result is shown in table 39.
Table 39 tenuifolin four Chinese medicine closes lifts from heart remove impurity investigation result (n=2)
Note: tenuifolin retention rate (%): be to take 200 order filter-cloth filtering technique gained tenuifolins to extract the rates of transform be radix, other technique gained tenuifolins are extracted to rates of transform gained in contrast.The tenuifolin extraction rate of transform and tenuifolin retention rate are all to contain Polygala tenuifolia 10g in a recipe quantity.
4. total saponin content is measured: precision takes 2 parts of dried cream powders, and every part of 45mg is in 10ml volumetric flask, and the same total saponin content of the method method of investigationing, is prepared as retinue blank with the methanol of application of sample not with method, under 544nm, measures.The results are shown in Table 40.
Table 40 total saponins four Chinese medicine closes the investigation result (n=2) of lifting from heart remove impurity test
Note: total saponins retention rate (%): be to using 200 order filter-cloth filtering gained total saponins extracted amounts as radix, by other technique gained total saponins extracted amounts gained in contrast.
5. in prescription, four Chinese medicine closes the Test Summary of lifting from heart remove impurity
by centrifuging process, the four Chinese medicine extraction process in prescription is investigated, illustrate while adopting centrifugal remove impurity, index sexual element index tenuifolin retention rate is had no to obvious impact, total saponins retention rate has a certain impact, and remove impurity does not have good effect to solid content yield, solid content yield does not have obvious reduction.
(4) the remove impurity make use of physics methods research in extraction process is carried out to data analysis and brief summary
by this to crossing 400 order filter clothes, standing 12hr, standing 24hr and centrifugal four kinds of impurity removal process are investigated test, the results are shown in Table 41.
The result that three kinds of impurity removal process of table 41 are investigated
| Impurity-removing method | Solid content yield (%) | Tenuifolin retention rate (%) | Total saponins retention rate (%) |
| Cross 400 order filter clothes | 26.56 | 93.89 | 93.75 |
| Naturally standing (12hr) | 26.59 | 99.98 | 97.91 |
| Naturally standing (24hr) | 26.38 | 96.22 | 96.41 |
| Centrifugal remove impurity | 26.81 | 98.54 | 92.74 |
analyze:
1. solid content yield
three kinds of impurity-removing method gained solid content yields are basically identical, are all about 26%, and with the dephasign ratio that do not eliminate, three kinds of impurity-removing methods have all reduced less than 3% the yield of solid content, and its reduction amplitude is little, therefore without too large impact.
2. tenuifolin retention rate
three kinds of impurity-removing methods are little to the basic difference of retention rate impact effect of tenuifolin, and its retention rate, all more than 90%, for the highest, is secondly centrifugal remove impurity with naturally standing (12hr), and retention rate is minimum was 400 order filter cloth impurity removal process.
3. total saponins retention rate
three kinds of impurity-removing methods are also little to the retention rate impact effect difference of total saponins, and its retention rate, all more than 90%, for the highest, is secondly nature standing (24hr) with naturally standing (12hr), and minimum is centrifugal impurity removal process.
known by data, four kinds of impurity-removing methods are to solid content yield, the retention rate of tenuifolin, the retention rate three aspects: of total saponins is all without marked difference, but because the standing used time is longer, and in batch production large-scale production process complex operation, in addition, centrifuging process wastes energy again, and total saponins retention rate declines 7.3%.Therefore consider operability and actual property in industrialized great production, and consider from aspects such as cost-saving and times, selected 400 order filter clothes as best impurity removal process, this impurity-removing method is easy, extracting solution easily filters, so select optimum extraction process gained extracting solution to cross while hot 400 order filter clothes, carries out remove impurity.
five) research of drying process
for the medicine in this study of compound prescription, multiformity due to its effective ingredient, some composition is volatile or decompose, can be because high temperature destruction, loss etc. cause the aspects such as reduction of drug effect to consider when dry, its drying mode is investigated, to determine in technique, use rational baking temperature, when guaranteeing efficacy stability, also will consider dry consuming time and extend technological process and complex process equipment etc.At present more conventional drying mode has constant pressure and dry, drying under reduced pressure, spraying is dry and microwave drying etc., according to existence conditions, has selected 60 ℃, 70 ℃, 80 ℃ of 60 ℃ of normal pressures, 70 ℃, 80 ℃, decompression and the investigation method of microwave vacuum drying as drying process.
1. evaluation index
a. tenuifolin content b. total saponin content c. moisture
2. test method
with four Chinese medicine, close and carry definite optimum extraction process and extract 50 recipe quantity medical materials respectively, extracting solution is crossed 400 order filter clothes, while being evaporated to relative density 1.2(20 ℃, survey), respectively getting a recipe quantity concentrated solution puts respectively in the baking oven of 60 ℃, 70 ℃, 80 ℃ of 60 ℃ of normal pressures, 70 ℃, 80 ℃ and decompressions and is dried, separately get 42 recipe quantity concentrated solutions dry in microwave vacuum dryer, get dry extract, beat powder standby.Result is shown in table 42.
The result of the test of different dry drying method in table 42 four Chinese medicine extraction process
| Sample | The heavy g of dry cream | Moisture % | Dry cream yield % | Drying time hr | Dried cream powder end character |
| 60 ℃ of normal pressures | 12.033 | 7.59 | 29.35 | 26.5 | Pale yellow |
| 70 ℃ of normal pressures | 12.0536 | 7.29 | 29.40 | 24 | Pale yellow |
| 80 ℃ of normal pressures | 12.0452 | 4.46 | 29.38 | 24 | Deep yellow (slightly taupe) |
| Reduce pressure 60 ℃ | 12.0727 | 8.36 | 29.45 | 21 | Yellow |
| Reduce pressure 70 ℃ | 12.0636 | 10.0 | 29.42 | 21 | Brown color |
| Reduce pressure 80 ℃ | 12.0574 | 6.608 | 29.41 | 21 | Brown color |
| Microwave vacuum drying | 12.0211 | 9.137 | 29.32 | 3.5 | Yellow is loose |
from table 42:
lower moisture content that gets dry extract of 2.1 each drying processes differs greatly, and wherein 80 ℃ of dry dry cream moisture content of normal pressure are minimum, and the 70 ℃ of dry dry cream moisture content of reducing pressure the highest (while beating powder humidity large due to) is about dry 2 times of 80 ℃ of normal pressures.The different reason of water content is a. difference of drying time, the impact of b. temperature.
2.2 four Chinese medicine extraction processes institute's yield difference that gets dry extract after different dry drying method is not remarkable.
the color getting dry extract under 2.3 each drying processes is also distinguishing.Wherein the dry cream color of 80 ℃ of normal pressures is the darkest, occurs taupe fritter (having insoluble matter during hot water dissolving).
3. the assay of tenuifolin under different dry drying process
Tenuifolin assay result (n=2) under table 43 different dry drying process
Note: content relative percentage be the tenuifolin content in 70 ℃ of gained dried cream powders that reduces pressure be 100%, other content is gained in contrast.
result: shown in table 43, different dry drying process is larger to tenuifolin content influence difference on effect, wherein tenuifolin content (removing moisture effects) height is respectively: reduce pressure 80 ℃ of 60 ℃ of ﹥ normal pressures of the 60 ℃ of ﹥ of 70 ℃ of 70 ℃ of ﹥ normal pressures of ﹥ microwave vacuum drying ﹥ 80 ℃ of ﹥ normal pressures of decompression that reduce pressures, the tenuifolin content in dry cream of reducing pressure at 70 ℃ is at 80 ℃ of normal pressures in dry cream 1.5 times of tenuifolin content.
4. the assay of total saponins under different dry drying process
Total saponin content measurement result (n=2) in dry cream under table 44 different dry drying process
result: shown in table 44, different dry drying process is not remarkable to total saponin content impact effect difference, remove moisture after total saponin content be: 70 ℃ of 60 ℃ of ﹥ normal pressures of 60 ℃ of ﹥ microwave vacuum drying ﹥ decompression 80 ℃ of ﹥ normal pressures of 80 ℃ of ﹥ normal pressures of 70 ℃ of ﹥ decompression reduce pressure.Reduce pressure the total saponin content of 70 ℃ than 70 ℃ high 1.18 times of normal pressures.
5. drying process brief summary
pass through data analysis 5.1 drying times, drying time: 60 ℃ of 70 ℃ of ﹤ normal pressures of microwave vacuum drying ﹤ decompression 80 ℃ of ﹤ normal pressures of 60 ℃, 70 ℃, 80 ℃ ﹤ normal pressures, wherein medical material is 1.722kg(42 recipe quantity during microwave vacuum drying) concentrated solution of medicinal material extract, but drying time, only 3.5h(moisture was larger, it is former because medical material concentrated solution is less, in dry run, there is coking, therefore due to not being dried thoroughly).Because whether extractum dries by artificially judging, subjectivity is too large, therefore can only also need moisture and combine analysis drying time drying time as auxiliary reference index, draws optimum.
80 ℃ of 80 ℃ of > normal pressures of 70 ℃ of > decompressions of 60 ℃ of > normal pressures of 5.2 70 ℃ of moisture decompressions > microwave vacuum drying > 60 ℃ of > normal pressures of decompression.80 ℃ of dry cream moisture of normal pressure are half of 70 ℃ of dry cream moisture of decompression.Its Yugan cream moisture is basically identical.
5.3 dry cream yields
different dry drying method is substantially little on dry cream yield impact.
5.4 tenuifolin content
different dry drying process is larger to tenuifolin content influence difference on effect, wherein tenuifolin content (removing moisture effects) height is respectively: reduce pressure 80 ℃ of 60 ℃ of ﹥ normal pressures of the 60 ℃ of ﹥ of 70 ℃ of 70 ℃ of ﹥ normal pressures of ﹥ microwave vacuum drying ﹥ 80 ℃ of ﹥ normal pressures of decompression that reduce pressures, the tenuifolin content in dry cream of reducing pressure at 70 ℃ is at 80 ℃ of normal pressures in dry cream 1.5 times of tenuifolin content.
5.5 total saponin content
after removing moisture content, total saponin content is: 70 ℃ of 60 ℃ of ﹥ normal pressures of 60 ℃ of ﹥ microwave vacuum drying ﹥ decompression 80 ℃ of ﹥ normal pressures of 80 ℃ of ﹥ normal pressures of 70 ℃ of ﹥ decompression reduce pressure.Reduce pressure the total saponin content of 70 ℃ than 70 ℃ high 1.18 times of normal pressures.From data, different dry drying method is not remarkable to total saponins extracted amount impact effect.
conclusion: comprehensive above data, the 70 ℃ of drought index component contents that reduce pressure are the highest, and drying time is shorter; Vacuum microwave drying index component content occupies the second, and drying time the shortest (only 3.5hr), the two all has drying time short, and the advantage little to limited composition influence all can be used as the drying condition of this extraction process.
below by out-patient department of No.1 Hospital of Guiyang Traditional Chinese Medicine College insomnia training, adopt 35 routine clinical summaries of capsule Cure for insomnia of the present invention to report and further set forth beneficial effect of the present invention.
general clinical data:
random 35 routine insomniac's cases of selecting all derive from No.1 Hospital of Guiyang Traditional Chinese Medicine College's outpatient service insomnia training.The frequent insomnia and dreamful sleep of patient, the length of one's sleep is short, within 2-3 hours, wakes up, after waking up, have difficulty in going to sleep, 21～62 years old age, average 40 years old.Type of deficiency of both the heart and spleen 8 examples, type of failure of the heart and kidney integrating 7 examples, type of hyperactivity of heart-fire 6 examples, type of hyperactivity of fire caused by deficiency of YIN 5 examples, type of deficiency of heart-QI and gallbladder-QI 4 examples, caused by hepatic stagnation qi stagnation 5 examples.Daytime is all with lassitude, pale complexion, headache, cardiopalmus, forgetful, irritable feverish sensation in the chest, soreness of waist and knee, red tongue, thready and weak pulse or count accurately as cardinal symptom, the course of disease take 60 days～2 years be object of study.
2. tcm diagnosis standard:
in the < < traditional Chinese medical science disease Standardization of diagnosis and curative effect > > that diagnostic criteria is formulated with reference to State Administration of Traditional Chinese Medicine, the diagnostic criteria of deficiency syndrome, excess syndrome institute induced insomnia is drafted.
all diseases are seen the lighter's difficulty of falling asleep or sleep but easy to wake, after waking up, are insomnia, and severe one is lain awake all night, and with headache and dizziness, palpitation and amnesia, the diseases such as dreaminess are main clinical manifestation person.
3. medicine and Therapeutic Method:
3.1 medicines:
capsule of the present invention.
therapeutic Method:
all patients receive treatment and cut out any medicine with soporific function in first 3 days, and take capsule of the present invention, every day 1 time, within 1 hour just before going to bed, take 5; Take every day continuously, within 7 days, is a course for the treatment of.
4. curative effect determinate standard:
diagnostic criteria is drafted by the standard of " guideline of clinical investigations of new Chinese medicine Cure for insomnia " in < < new Chinese medicine guideline of clinical investigations > >.
clinical recovery: fall asleep smoothly, recover normal the length of one's sleep, or the length of one's sleep more than 6hr, sleep deep, its clinical symptoms disappears substantially.Effective: sleep is clearly better, more than increasing 3hr the length of one's sleep, Depth of sleep increases, and clinical symptoms makes moderate progress.Effective: symptom alleviates, the length of one's sleep is the not enough 3hr of front increase.Invalid: after treatment, insomnia is not improved or the anti-severe one that adds, and clinical symptoms is also not improved.
5. therapeutic outcome:
in 35 routine patients, clinical recovery is 8 examples (22.9%), and effective is 18 examples (51.4%), effective 6 examples (17.1%), and 2 examples invalid (5.7%), 1 example loses contact (2.9%) midway, and total effective rate reaches 91.4 %.Certainly Most patients general treatment obtains effect after 1～2 course for the treatment of, all can obviously improve sleep.In therapeutic process there are no any stimulation and toxicity.
below in conjunction with embodiment, the present invention is further illustrated.
embodiment 1:
the Chinese medicine preparation (tablet) for the treatment of sleep disorder, this Chinese medicine preparation is by weight by Radix Polygalae 1.0Kg, Semen Ziziphi Spinosae (stir-fry) 1.5Kg, Herb Gynostemmae Pentaphylli 0.8Kg, Radix Cynanchi Paniculati 1.0Kg, Hemerocallis fulva L. 0.8Kg and Rhizoma valerianae latifoliae 0.6Kg make 5500.Oral, once-a-day, within 1 hour just before going to bed, take, one time 5.
the method of the Chinese medicine preparation of aforementioned therapies sleep disorder (tablet): comprise the following steps:
a. by above-mentioned formula, taking Radix Polygalae, Semen Ziziphi Spinosae (stir-fry), Herb Gynostemmae Pentaphylli, Hemerocallis fulva L. four Chinese medicine material, by 60% ethanol heating extraction 3 times, obtain extracting solution, is A product; Described use 60% ethanol extraction 3 times, is specially, and first uses 60% ethanol extraction of 9.5 times of amounts once, and the time is 1.5 hours, and then, with 8 times of amount 60% ethanol extractions twice, each time is 1 hour, during extraction with 60 ℃ of heating;
b. A product are crossed to 400 order filter clothes while hot, concentrating under reduced pressure reclaims after ethanol, and obtaining clear paste is B product; Described clear paste, the relative density recording in the time of 20 ℃ is 1.2;
c. B product are placed in to 70 ℃ of baking ovens of decompression or microwave vacuum dryer dry, get dry extract, cross No. five sieve after pulverizing, the powder that gets dry extract is C product;
d. by above-mentioned formula, get Radix Cynanchi Paniculati, Rhizoma valerianae latifoliae two taste medical materials, first clean, dry, sterilizing, then pulverized sieve No. six, and obtaining powder is D product;
e. C product are mixed homogeneously with D product, obtain E product;
f. F product are processed into the Chinese medicinal tablet of clinical use.
embodiment 2:
the Chinese medicine preparation (capsule) for the treatment of sleep disorder, this Chinese medicine preparation is by weight by Radix Polygalae 0.9Kg, Semen Ziziphi Spinosae (stir-fry) 1.4Kg, Herb Gynostemmae Pentaphylli 0.7Kg, Radix Cynanchi Paniculati 0.9Kg, Hemerocallis fulva L. 0.7Kg and Rhizoma valerianae latifoliae 0.5Kg make 5000.Oral, once-a-day, within 1 hour just before going to bed, take, one time 5.
the method of the Chinese medicine preparation of aforementioned therapies sleep disorder (capsule): comprise the following steps:
a. by above-mentioned formula, taking Radix Polygalae, Semen Ziziphi Spinosae (stir-fry), Herb Gynostemmae Pentaphylli, Hemerocallis fulva L. four Chinese medicine material, by 60% ethanol heating extraction 3 times, obtain extracting solution, is A product; Described use 60% ethanol extraction 3 times, is specially, and first uses 60% ethanol extraction of 9.5 times of amounts once, and the time is 1.5 hours, and then, with 8 times of amount 60% ethanol extractions twice, each time is 1 hour, during extraction with 90 ℃ of heating;
b. A product are crossed to 400 order filter clothes while hot, concentrating under reduced pressure reclaims after ethanol, and obtaining clear paste is B product; Described clear paste, the relative density recording in the time of 20 ℃ is 1.2;
c. B product are placed in to 70 ℃ of baking ovens of decompression or microwave vacuum dryer dry, get dry extract, cross No. five sieve after pulverizing, the powder that gets dry extract is C product;
d. by above-mentioned formula, get Radix Cynanchi Paniculati, Rhizoma valerianae latifoliae two taste medical materials, first clean, dry, sterilizing, then pulverized sieve No. six, and obtaining powder is D product;
e. C product are mixed homogeneously with D product, obtain E product;
f. F product are processed into the Chinese medicine capsules of clinical use.
embodiment 3:
the Chinese medicine preparation (soft capsule) for the treatment of sleep disorder, this Chinese medicine preparation is by weight by Radix Polygalae 0.8Kg, Semen Ziziphi Spinosae (stir-fry) 1.3Kg, Herb Gynostemmae Pentaphylli 0.6Kg, Radix Cynanchi Paniculati 0.8Kg, Hemerocallis fulva L. 0.6Kg and Rhizoma valerianae latifoliae 0.4Kg make 5000.Oral, once-a-day, within 1 hour just before going to bed, take, one time 5.
the method of the Chinese medicine preparation of aforementioned therapies sleep disorder (soft capsule): comprise the following steps:
a. by above-mentioned formula, taking Radix Polygalae, Semen Ziziphi Spinosae (stir-fry), Herb Gynostemmae Pentaphylli, Hemerocallis fulva L. four Chinese medicine material, by 60% ethanol heating extraction 3 times, obtain extracting solution, is A product; Described use 60% ethanol extraction 3 times, is specially, and first uses 60% ethanol extraction of 9.5 times of amounts once, and the time is 1.5 hours, and then, with 8 times of amount 60% ethanol extractions twice, each time is 1 hour, during extraction with 60 ℃ of heating;
b. A product are crossed to 400 order filter clothes while hot, concentrating under reduced pressure reclaims after ethanol, and obtaining clear paste is B product; Described clear paste, the relative density recording in the time of 20 ℃ is 1.2;
c. B product are placed in to 70 ℃ of baking ovens of decompression or microwave vacuum dryer dry, get dry extract, cross No. five sieve after pulverizing, the powder that gets dry extract is C product;
d. by above-mentioned formula, get Radix Cynanchi Paniculati, Rhizoma valerianae latifoliae two taste medical materials, first clean, dry, sterilizing, then pulverized sieve No. six, and obtaining powder is D product;
e. C product are mixed homogeneously with D product, obtain E product;
f. F product are processed into the Chinese medicinal soft capsule of clinical use.
embodiment 4:
the Chinese medicine preparation (powder) for the treatment of sleep disorder, this Chinese medicine preparation is by weight by Radix Polygalae 1.1Kg, Semen Ziziphi Spinosae (stir-fry) 1.6Kg, Herb Gynostemmae Pentaphylli 0.9Kg, Radix Cynanchi Paniculati 1.1Kg, Hemerocallis fulva L. 0.9Kg and Rhizoma valerianae latifoliae 0.7Kg make 3000g powder.1.35g powder is one bag.Oral, once-a-day, within 1 hour just before going to bed, take, one time 1 bag.
the method of the Chinese medicine preparation of aforementioned therapies sleep disorder (powder): comprise the following steps:
a. by above-mentioned formula, taking Radix Polygalae, Semen Ziziphi Spinosae (stir-fry), Herb Gynostemmae Pentaphylli, Hemerocallis fulva L. four Chinese medicine material, by 60% ethanol heating extraction 3 times, obtain extracting solution, is A product; Described use 60% ethanol extraction 3 times, is specially, and first uses 60% ethanol extraction of 9.5 times of amounts once, and the time is 1.5 hours, and then, with 8 times of amount 60% ethanol extractions twice, each time is 1 hour, during extraction with 90 ℃ of heating;
b. A product are crossed to 400 order filter clothes while hot, concentrating under reduced pressure reclaims after ethanol, and obtaining clear paste is B product; Described clear paste, the relative density recording in the time of 20 ℃ is 1.2;
c. B product are placed in to 70 ℃ of baking ovens of decompression or microwave vacuum dryer dry, get dry extract, cross No. five sieve after pulverizing, the powder that gets dry extract is C product;
d. by above-mentioned formula, get Radix Cynanchi Paniculati, Rhizoma valerianae latifoliae two taste medical materials, first clean, dry, sterilizing, then pulverized sieve No. six, and obtaining powder is D product;
e. C product are mixed homogeneously with D product, obtain E product;
f. F product are processed into the Chinese powder medicine of clinical use.
embodiment 5:
the Chinese medicine preparation (pill) for the treatment of sleep disorder, this Chinese medicine preparation is by weight by Radix Polygalae 1.2Kg, Semen Ziziphi Spinosae (stir-fry) 1.7Kg, Herb Gynostemmae Pentaphylli 1.0Kg, Radix Cynanchi Paniculati 1.2Kg, Hemerocallis fulva L. 1.0Kg and Rhizoma valerianae latifoliae 0.8Kg make 6500 pieces.Oral, once-a-day, within 1 hour just before going to bed, take, one time 5 pieces.
the method of the Chinese medicine preparation of aforementioned therapies sleep disorder (pill): comprise the following steps:
a. by above-mentioned formula, taking Radix Polygalae, Semen Ziziphi Spinosae (stir-fry), Herb Gynostemmae Pentaphylli, Hemerocallis fulva L. four Chinese medicine material, by 60% ethanol heating extraction 3 times, obtain extracting solution, is A product; Described use 60% ethanol extraction 3 times, is specially, and first uses 60% ethanol extraction of 9.5 times of amounts once, and the time is 1.5 hours, and then, with 8 times of amount 60% ethanol extractions twice, each time is 1 hour, during extraction with 75 ℃ of heating;
b. A product are crossed to 400 order filter clothes while hot, concentrating under reduced pressure reclaims after ethanol, and obtaining clear paste is B product; Described clear paste, the relative density recording in the time of 20 ℃ is 1.2;
c. B product are placed in to 70 ℃ of baking ovens of decompression or microwave vacuum dryer dry, get dry extract, cross No. five sieve after pulverizing, the powder that gets dry extract is C product;
d. by above-mentioned formula, get Radix Cynanchi Paniculati, Rhizoma valerianae latifoliae two taste medical materials, first clean, dry, sterilizing, then pulverized sieve No. six, and obtaining powder is D product;
e. C product are mixed homogeneously with D product, obtain E product;
f. F product are processed into the medicine pill of clinical use.
embodiment 6:
the Chinese medicine preparation (oral liquid) for the treatment of sleep disorder, this Chinese medicine preparation is by weight by Radix Polygalae 1.0Kg, Semen Ziziphi Spinosae (stir-fry) 1.5Kg, Herb Gynostemmae Pentaphylli 0.8Kg, Radix Cynanchi Paniculati 1.0Kg, Hemerocallis fulva L. 0.8Kg and Rhizoma valerianae latifoliae 0.6Kg make 1200 bottles.Oral, once-a-day, within 1 hour just before going to bed, take, one time 1 bottle.
the method of the Chinese medicine preparation of aforementioned therapies sleep disorder (oral liquid): comprise the following steps:
a. by above-mentioned formula, taking Radix Polygalae, Semen Ziziphi Spinosae (stir-fry), Herb Gynostemmae Pentaphylli, Hemerocallis fulva L. four Chinese medicine material, by 60% ethanol heating extraction 3 times, obtain extracting solution, is A product; Described use 60% ethanol extraction 3 times, is specially, and first uses 60% ethanol extraction of 9.5 times of amounts once, and the time is 1.5 hours, and then, with 8 times of amount 60% ethanol extractions twice, each time is 1 hour, during extraction with 85 ℃ of heating;
b. A product are crossed to 400 order filter clothes while hot, concentrating under reduced pressure reclaims after ethanol, and obtaining clear paste is B product; Described clear paste, the relative density recording in the time of 20 ℃ is 1.2;
c. B product are placed in to 70 ℃ of baking ovens of decompression or microwave vacuum dryer dry, get dry extract, cross No. five sieve after pulverizing, the powder that gets dry extract is C product;
d. by above-mentioned formula, get Radix Cynanchi Paniculati, Rhizoma valerianae latifoliae two taste medical materials, first clean, dry, sterilizing, then pulverized sieve No. six, and obtaining powder is D product;
e. C product are mixed homogeneously with D product, obtain E product;
f. F product are processed into the Chinese medicine oral liquid of clinical use.
embodiment 7
the Chinese medicine preparation (thin membrane coated tablet) for the treatment of sleep disorder, this Chinese medicine preparation is by weight by Radix Polygalae 1.0Kg, Semen Ziziphi Spinosae (stir-fry) 1.5Kg, Herb Gynostemmae Pentaphylli 0.8Kg, Radix Cynanchi Paniculati 1.0Kg, Hemerocallis fulva L. 0.8Kg and Rhizoma valerianae latifoliae 0.6Kg make 5500.Oral, once-a-day, within 1 hour just before going to bed, take, one time 5.
the method of the Chinese medicine preparation of aforementioned therapies sleep disorder (thin membrane coated tablet): comprise the following steps:
a. by above-mentioned formula, taking Radix Polygalae, Semen Ziziphi Spinosae (stir-fry), Herb Gynostemmae Pentaphylli, Hemerocallis fulva L. four Chinese medicine material, by 60% ethanol heating extraction 3 times, obtain extracting solution, is A product; Described use 60% ethanol extraction 3 times, is specially, and first uses 60% ethanol extraction of 9.5 times of amounts once, and the time is 1.5 hours, and then, with 8 times of amount 60% ethanol extractions twice, each time is 1 hour, during extraction with 60 ℃ of heating;
b. A product are crossed to 400 order filter clothes while hot, concentrating under reduced pressure reclaims after ethanol, and obtaining clear paste is B product; Described clear paste, the relative density recording in the time of 20 ℃ is 1.2;
c. B product are placed in to 70 ℃ of baking ovens of decompression or microwave vacuum dryer dry, get dry extract, cross No. five sieve after pulverizing, the powder that gets dry extract is C product;
d. by above-mentioned formula, get Radix Cynanchi Paniculati, Rhizoma valerianae latifoliae two taste medical materials, first clean, dry, sterilizing, then pulverized sieve No. six, and obtaining powder is D product;
e. C product are mixed homogeneously with D product, obtain E product;
f. F product are processed into the thin membrane coated tablet of clinical use.
Claims (8)
1. treat the Chinese medicine preparation of sleep disorder, it is characterized in that: calculate by weight, by following methods, be prepared from:
A. taking Radix Polygalae 8-12 part, Semen Ziziphi Spinosae (parched) 13-17 part, Herb Gynostemmae Pentaphylli 6-10 part, Hemerocallis fulva L. 6-10 part four Chinese medicine material, by 60% ethanol heating extraction 3 times, obtain extracting solution, is A product;
B. A product are crossed to 400 order filter clothes while hot, concentrating under reduced pressure reclaims after ethanol, and obtaining clear paste is B product;
C. B product are placed in to 70 ℃ of baking ovens of decompression or microwave vacuum dryer dry, get dry extract, cross No. five sieve after pulverizing, the powder that gets dry extract is C product;
D. get Radix Cynanchi Paniculati 8-12 part, Rhizoma valerianae latifoliae 4-8 part two taste medical materials, first clean, dry, sterilizing, then pulverized sieve No. six, and obtaining powder is D product;
E. C product are mixed homogeneously with D product, obtain E product;
F. E product are processed into the Chinese medicine preparation of clinical use.
2. the Chinese medicine preparation for the treatment of sleep disorder according to claim 1, is characterized in that: calculate by weight, by following methods, be prepared from:
A. taking Radix Polygalae 9-11 part, Semen Ziziphi Spinosae (parched) 14-16 part, Herb Gynostemmae Pentaphylli 7-9 part, Hemerocallis fulva L. 7-9 part four Chinese medicine material, by 60% ethanol heating extraction 3 times, obtain extracting solution, is A product;
B. A product are crossed to 400 order filter clothes while hot, concentrating under reduced pressure reclaims after ethanol, and obtaining clear paste is B product;
C. B product are placed in to 70 ℃ of baking ovens of decompression or microwave vacuum dryer dry, get dry extract, cross No. five sieve after pulverizing, the powder that gets dry extract is C product;
D. get Radix Cynanchi Paniculati 9-11 part, Rhizoma valerianae latifoliae 5-7 part two taste medical materials, first clean, dry, sterilizing, then pulverized sieve No. six, and obtaining powder is D product;
E. C product are mixed homogeneously with D product, obtain E product;
F. E product are processed into the Chinese medicine preparation of clinical use.
3. the Chinese medicine preparation for the treatment of sleep disorder according to claim 1, is characterized in that: calculate by weight, by following methods, be prepared from:
A. taking 10 parts of Radix Polygalaes, 15 parts of Semen Ziziphi Spinosae (parched)s, 8 parts of Herb Gynostemmae Pentaphylli, 8 parts of four Chinese medicine materials of Hemerocallis fulva L., by 60% ethanol heating extraction 3 times, obtain extracting solution, is A product;
B. A product are crossed to 400 order filter clothes while hot, concentrating under reduced pressure reclaims after ethanol, and obtaining clear paste is B product;
C. B product are placed in to 70 ℃ of baking ovens of decompression or microwave vacuum dryer dry, get dry extract, cross No. five sieve after pulverizing, the powder that gets dry extract is C product;
D. get 10 parts of Radix Cynanchi Paniculatis, 6 part of two taste medical material of Rhizoma valerianae latifoliae, first clean, dry, sterilizing, then pulverized sieve No. six, and obtaining powder is D product;
E. C product are mixed homogeneously with D product, obtain E product;
F. E product are processed into the Chinese medicine preparation of clinical use.
4. according to the Chinese medicine preparation of the treatment sleep disorder described in claim 1,2 or 3, it is characterized in that: described Chinese medicine preparation is any one oral preparations of use clinically.
5. the Chinese medicine preparation for the treatment of sleep disorder according to claim 4, is characterized in that: described oral medicine is, powder, tablet, granule, capsule, microcapsule, pill, drop pill, oral liquid, syrup or dispersant.
6. described in the arbitrary claim of preparation claim 1 to 5, treat the method for the Chinese medicine preparation of sleep disorder, it is characterized in that: comprise the following steps:
A. by above-mentioned formula, taking Radix Polygalae, Semen Ziziphi Spinosae (parched), Herb Gynostemmae Pentaphylli, Hemerocallis fulva L. four Chinese medicine material, by 60% ethanol heating extraction 3 times, obtain extracting solution, is A product;
B. A product are crossed to 400 order filter clothes while hot, concentrating under reduced pressure reclaims after ethanol, and obtaining clear paste is B product;
C. B product are placed in to 70 ℃ of baking ovens of decompression or microwave vacuum dryer dry, get dry extract, cross No. five sieve after pulverizing, the powder that gets dry extract is C product;
D. by above-mentioned formula, get Radix Cynanchi Paniculati, Rhizoma valerianae latifoliae two taste medical materials, first clean, dry, sterilizing, then pulverized sieve No. six, and obtaining powder is D product;
E. C product are mixed homogeneously with D product, obtain E product;
F. E product are processed into the Chinese medicine preparation of clinical use.
7. the method for the Chinese medicine preparation of sleep disorder is treated in preparation according to claim 6, it is characterized in that: in steps A, described use 60% ethanol extraction 3 times, be specially, first use 60% ethanol extraction of 9.5 times of amounts once, the time is 1.5 hours, then with 8 times, measures 60% ethanol extractions twice, each time is 1 hour, during extraction with 60 ℃ of-90 ℃ of heating.
8. the method for the Chinese medicine preparation of sleep disorder is treated in preparation according to claim 7, it is characterized in that: in step B, and described clear paste, the relative density recording in the time of 20 ℃ is 1.2.
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