CN103251793A - Pharmaceutical composition for improving climacteric symptoms and preparation method of pharmaceutical composition - Google Patents
Pharmaceutical composition for improving climacteric symptoms and preparation method of pharmaceutical composition Download PDFInfo
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Abstract
The invention discloses a pharmaceutical composition for improving climacteric symptoms. The pharmaceutical composition comprises the following materials in parts by weight: 12-20 parts of glossy privet fruits, 12-20 parts of eclipta, 8-15 parts of rhizoma cyperi, 4-10 parts of lilies, 14-25 parts of oysters, 12-20 parts of spina date seeds, 4-14 parts of rhizoma anemarrhenae and 0.1-2.5 parts of oviductus ranae. The preparation method of the pharmaceutical composition comprises the following steps of: extracting and concentrating the glossy privet fruits, the eclipta and the rhizoma cyperi by alcohol to obtain thick extract A; water-extracting and concentrating the lilies, the oysters and the rhizoma anemarrhenae to obtain thick extract B; mixing the thick extract A with the thick extract B, drying, crushing and sieving to dry extract powder; crushing and sieving the oviductus ranae; and mixing the dry extract powder with the oviductus ranae, adding normal auxiliary materials for preparing an oral solid preparation according to a normal process. The pharmaceutical composition disclosed by the invention has the function of improving the climacteric symptoms, and can be used for preparing healthcare food, common food or drugs.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation method thereof, particularly a kind of have pharmaceutical composition of improving menopause syndrome and preparation method thereof.
Background technology
Climacteric is to refer in particular to women's ovarian function to fail gradually to a transition period of complete obiteration from vigorous state for the women, comprises a period of time of menopause and menopause front and back.The traditional Chinese medical science is referred to as " perimenopausal syndrome ".Climacteric, the variation of a series of physiology and psychological aspects can appear in the women, be called climacteric syndrome, concrete manifestation has anxiety, hectic fever, insomnia, osteoporosis etc. a series of by the caused disease phenon of climacteric endocrine disturbance, it is the whole old and feeble result of women and early stage performance and since the women climacteric physiology bigger with mental change, meeting be perplexed by a series of symptoms, thereby influenced physical and mental health, reduced quality of life.
At present owing to do not improve the health care of menopause syndrome in 27 functions that the health food of State Food and Drug Administration's approval can be applied for, i.e. functional evaluation methodology for the climacteric syndrome functional health-care food does not have clear and definite national technical specification, therefore what have much that the health product of this type of effect all apply for is to increase bone density or enhancing immunity function, but again this series products there is demand on the market, therefore be badly in need of carrying out the foundation of related functionality assessment technique method, the present invention is directed to this kind present situation and carried out corresponding exemplary investigation.Therefore say that other prior function of the function ratio of improving menopause syndrome that the present invention declares is more targeted.The raw material of like product is used soybean isoflavone and calcium complement agent more in the market, and soybean isoflavone has some restrictions the suitable crowd who uses, and uses the product of pure Chinese herb compound actually rare according to Chinese medical theory.
Summary of the invention
The object of the invention is to provide a kind of pharmaceutical composition of improving menopause syndrome and preparation method thereof that has.
The present invention seeks to be achieved through the following technical solutions.
The crude drug of pharmaceutical composition of the present invention consists of:
Fructus Ligustri Lucidi 12-20 weight portion, Herba Ecliptae 12-20 weight portion, Rhizoma Cyperi 8-15 weight portion, Bulbus Lilii 4-10 weight portion, Concha Ostreae 14-25 weight portion, Semen Ziziphi Spinosae 12-20 weight portion, Rhizoma Anemarrhenae 4-14 weight portion, Oviductus Ranae 0.1-2.5 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
Fructus Ligustri Lucidi 15-17 weight portion, Herba Ecliptae 15-17 weight portion, Rhizoma Cyperi 10-13 weight portion, Bulbus Lilii 6-8 weight portion, Concha Ostreae 18-20 weight portion, Semen Ziziphi Spinosae 15-17 weight portion, Rhizoma Anemarrhenae 8-10 weight portion, Oviductus Ranae 0.5-2 weight portion.
The crude drug composition of Chinese medicine composition of the present invention is preferably:
Fructus Ligustri Lucidi 15 weight portions, Herba Ecliptae 15 weight portions, Rhizoma Cyperi 11.1 weight portions, Bulbus Lilii 7.2 weight portions, Concha Ostreae 18 weight portions, Semen Ziziphi Spinosae 15 weight portions, the Rhizoma Anemarrhenae 9 weight portions, Oviductus Ranae 1.1 weight portions;
Fructus Ligustri Lucidi 16 weight portions, Herba Ecliptae 16 weight portions, Rhizoma Cyperi 11.5 weight portions, Bulbus Lilii 7 weight portions, Concha Ostreae 19 weight portions, Semen Ziziphi Spinosae 16 weight portions, the Rhizoma Anemarrhenae 9 weight portions, Oviductus Ranae 1.25 weight portions.
The crude drug composition of Chinese medicine composition of the present invention is preferably:
Fructus Ligustri Lucidi 14 weight portions, Herba Ecliptae 14 weight portions, Rhizoma Cyperi 10.3 weight portions, Bulbus Lilii 8 weight portions, Concha Ostreae 17.3 weight portions, Semen Ziziphi Spinosae 15.7 weight portions, the Rhizoma Anemarrhenae 8.3 weight portions, Oviductus Ranae 1.33 weight portions;
Fructus Ligustri Lucidi 13 weight portions, Herba Ecliptae 18 weight portions, Rhizoma Cyperi 9 weight portions, Bulbus Lilii 9 weight portions, Concha Ostreae 15 weight portions, Semen Ziziphi Spinosae 18 weight portions, the Rhizoma Anemarrhenae 5 weight portions, Oviductus Ranae 2.2 weight portions.
The crude drug composition of Chinese medicine composition of the present invention is preferably:
Fructus Ligustri Lucidi 15.7 weight portions, Herba Ecliptae 14 weight portions, Rhizoma Cyperi 12 weight portions, Bulbus Lilii 6.7 weight portions, Concha Ostreae 15.7 weight portions, Semen Ziziphi Spinosae 14.3 weight portions, the Rhizoma Anemarrhenae 9.7 weight portions, Oviductus Ranae 0.97 weight portion;
Fructus Ligustri Lucidi 18 weight portions, Herba Ecliptae 13 weight portions, Rhizoma Cyperi 14 weight portions, Bulbus Lilii 5 weight portions, Concha Ostreae 22 weight portions, Semen Ziziphi Spinosae 14 weight portions, the Rhizoma Anemarrhenae 12 weight portions, Oviductus Ranae 0.2 weight portion.
Get pharmaceutical composition crude drug of the present invention, add conventional adjuvant, according to common process, make oral solid formulation and include but not limited to capsule, tablet, granule, electuary etc.; Preferred hard capsule.
Preparation of drug combination method of the present invention is as follows:
Fructus Ligustri Lucidi, Herba Ecliptae, Rhizoma Cyperi, the ethanol extraction method is extracted routinely, and being concentrated into 50 ℃ of heat, to survey relative densities be that 1.15～1.25 thick extractum gets thick extractum A; Bulbus Lilii, Concha Ostreae, Semen Ziziphi Spinosae, the Rhizoma Anemarrhenae, water extracting method extracts routinely, and being concentrated into 50 ℃ of heat, to survey relative densities be 1.15～1.25 thick extractum, gets thick extractum B; Thick extractum A and thick extractum B are mixed into thick extractum C, drying, crushing screening gets dry extract; Oviductus Ranae is pulverized, and sieves; Dry extract is mixed with the Oviductus Ranae oil meal, add conventional adjuvant, according to common process, make oral solid formulation and include but not limited to capsule, tablet, granule, electuary etc.
Described ethanol extraction method is: Fructus Ligustri Lucidi, Herba Ecliptae, Rhizoma Cyperi, put in the reflux, extract, jar, and add the 30-70% ethanol extraction, decoct 1-3 time, add water 8-12 at every turn and doubly measure decoction 1-2 hour, filter, merge extractive liquid,, standby.
Described water extracting method is: Bulbus Lilii, Concha Ostreae, Semen Ziziphi Spinosae, the Rhizoma Anemarrhenae, to put in the reflux, extract, jar, and extracting in water decocts 1-3 time, adds water 6-10 at every turn and doubly measures decoction 1-2 hour, filter, merge extractive liquid,, standby.
Described concentrated condition and degree are: 70 ℃ of temperature, pressure 0.08Mpa carry out concentrating under reduced pressure.
The condition of described drying is: adopt boulton process, drying parameter: temperature is 60 ℃, and vacuum is 0.08Mpa, and the time is 50～60 hours.
Described crushing screening selects for use 80 mesh sieves to sieve.
Chinese medicine composition hard capsule of the present invention is preferably as follows preparation method:
Fructus Ligustri Lucidi, Herba Ecliptae, Rhizoma Cyperi decoction pieces are put in the reflux, extract, jar, add 70% ethanol extraction, decoct 2 times, add 12 times of amounts of 70% alcoholic solution at every turn and decoct 1h, filter, and merge extractive liquid,, standby; Bulbus Lilii, Concha Ostreae, Semen Ziziphi Spinosae, the Rhizoma Anemarrhenae are put in the reflux, extract, jar, and extracting in water decocts 3 times, add 6 times of amounts of water at every turn and decoct 1.5h, filter, and merge extractive liquid,, standby; Get alcohol extraction filtrate and put in the vacuum concentration pot, reclaim ethanol, and being concentrated into 50 ℃ of heat, to survey relative densities be 1.15-1.25 that get thick extractum A, the vacuum concentration process parameter: vacuum is 0.08Mpa, temperature: 70 ℃; Water intaking is carried filtrate and is put in the vacuum concentration pot, and being concentrated into 50 ℃ of heat, to survey relative densities be 1.15-1.25, and get thick extractum B, the vacuum concentration process parameter: vacuum is 0.08Mpa, temperature: 70 ℃; Thick extractum A and thick extractum B are mixed into thick extractum C, are heated to 60 ℃ of dryings with the vacuum decompression drying baker, get dry extract C, vacuum decompression drying process parameter: vacuum is 0.08Mpa, temperature: 60 ℃; Dry extract C is ground into 80 order powder, gets dry extract C; Oviductus Ranae is pulverized, and sieves; Dry extract C and Oviductus Ranae oil meal, starch were mixed 30 minutes, cross 80 mesh sieves and get mixed powder D; With mixed powder D, be wetting agent with 90% alcoholic solution, wet granulation adds magnesium stearate, mixes, and filled capsules is namely.
The present composition has the health care that improves menopause syndrome, this function is not listed in 27 kinds of functions of health food of national regulation at present as yet, it is a kind of novel health care, therefore has novelty in function, and prescription of the present invention is the Chinese herb compound that is referred from ancient prescription, have stronger uniqueness, and technology is simple, instant.Therefore the present invention also has stronger novelty on formula for a product and preparation method, can be prepared into multiple product forms such as health food, bread and cheese or medicine clinically, preferentially for the preparation of becoming health food.
The present invention is based on theory of Chinese medical science, select clinical improvements effective Chinese medicine of climacteric combination formula in addition for use, by modern advanced pharmacy means, it is carried out determining of extraction process, removed redundant impurities, preserved Chinese medicine and improved involutional effective ingredient, and the trace element of adding needed by human body and the former powder of valuable Chinese medicine, improve the trace element deficiency that malnutrition causes, and have endocrine regulation, improve involutional health care.In preparation process research, select capsule to cover the bad mouthfeel of Chinese medicine extract, the crowd that is easy to be suited accepts.
Following experimental example and embodiment are used for further specifying but are not limited to the present invention.
Experimental example 1, Fructus Ligustri Lucidi, Herba Ecliptae, cyperol extraction process are investigated
One, optimum extraction process parameter screening test
Fructus Ligustri Lucidi, Herba Ecliptae, Rhizoma Cyperi all are the Chinese medicine of using always, and wherein the Fructus Ligustri Lucidi active component is triterpenoid compound, and the Herba Ecliptae active component is compositions such as wedelolactone, and the active component of Rhizoma Cyperi is saponins, flavonoid.This product is significant composition with wedelolactone, adopts ethanol extraction can obtain better effects.
Equipment is simply universal, with low cost because alcohol extraction has, and production site is less demanding, and operation easily is fit to industrialized great production; Pure extracting method can keep effective ingredient at industrial general employing heat reflow method simultaneously, reaches the purpose of discarding the dross and selecting the essential.Fructus Ligustri Lucidi among the we, Herba Ecliptae, three kinds of medical material main components of Rhizoma Cyperi are all based on liposoluble substance, and this liposoluble substance has the sleep function of improvement, so adopt ethanol to extract as solvent.By selecting L9 (3 for use
4) orthogonal table, design the test of three factors, three horizontal quadratures, and investigation extraction solvent multiple (8 times, 10 times, 12 times), concentration of alcohol (30%, 50%, 70%) and extraction time (1h, 1.5,2h) etc. concrete technological parameter makes to investigate index, the extraction process that screening is best with wedelolactone content in the medical material.
In the medical material ratio in the prescription, the clean medical material that takes by weighing 1/10 recipe quantity is tested, measure the content of extract wedelolactone, calculate the medical material paste-forming rate, finally convert out wedelolactone content in the medical material, the wedelolactone assay method is seen one one of the Pharmacopoeia of the People's Republic of China (version in 2010), concrete test arrangement and the results are shown in Table 1, table 2, table 3.
Table 1 extraction process parameter is investigated the factor level table
| Level | A quantity of solvent (doubly) | B alcohol concentration (%) | C extraction time (h) |
| 1 | 8 | 30 | 1 |
| 2 | 10 | 50 | 1.5 |
| 3 | 12 | 70 | 2 |
Table 2 extraction process orthogonal test is arranged and experimental result
Table 3 analysis of variance table
According to table 1,2,3, use intuitive analysis method A as can be seen
3B
3C
1Be optimum extraction process, namely the solvent consumption is 12 times, 70% alcohol solvent, and extraction time is 1 hour.In addition, orthogonal experiments is carried out variance analysis, and analysis result sees Table 3, therefrom as can be seen: have only B factor (concentration of alcohol) that significant difference is arranged in three factors, be that concentration of alcohol is to influence that wedelolactone content is principal element in this medical material, this and intuitive analysis method conclusion match.So determine the optimum extraction process parameter of Fructus Ligustri Lucidi, Herba Ecliptae, Rhizoma Cyperi be: each 12 times of amounts of amount of water, extract solvent 70% ethanol, extraction time is each 1 hour.
Two, extraction time list factor is relatively:
On the basis of above technical study, extraction time is carried out single factor comparative test, do not do single factor for 1 time relatively to extracting, investigate and extract 2 times and 3 times to the influence of the content of the paste-forming rate of extract and 1,8,9-trihydroxy-3-methoxy-benzo[4,5.Select 12 times of amounts of the each solubilization dosage of technology for use, extracting solvent is 70% ethanol, and extraction time is each 1 hour, extraction time is respectively 2 times and 3 times compares, and the result is as follows, sees Table 4.
The contrast of table 4 extraction time
| Extraction time | Paste-forming rate (%) | Wedelolactone content (mg/g) |
| 2 | 17.14 | 0.092 |
| 2 | 16.94 | 0.090 |
| 3 | 17.65 | 0.102 |
| 3 | 17.54 | 0.097 |
Analyzed as seen by table 4, in the extraction time of 2 times and 3 times contrasted, wherein contrasting with 3 times paste-forming rate and 1,8,9-trihydroxy-3-methoxy-benzo[4,5 content for 2 times did not have significant difference, does not reach best paste-forming rate and content and extract 1 time.For considering the various factors that can run in the production, such as the extraction efficiency height, loss in the production etc. factor, be lower than the consideration of the test data of laboratory with extraction efficiency in the actual production, adopt final technology: each 12 times of amounts of solubilization dosage, extracting solvent is 70% ethanol, extraction time is each 1 hour, extract 2 times, get final product extraction effect preferably.
Experimental example 2, Bulbus Lilii, Concha Ostreae, Semen Ziziphi Spinosae, the research of Rhizoma Anemarrhenae extraction process by water
Bulbus Lilii, Concha Ostreae, Semen Ziziphi Spinosae, the Rhizoma Anemarrhenae all are the Chinese medicine of using always, based on saponins, polysaccharide composition, adopt water extraction can obtain better effects.
To have equipment simply universal, with low cost because water is carried, and production site is less demanding, and operation easily is fit to industrialized great production; The water extracting method can keep effective ingredient at industrial general employing heat reflow method simultaneously, reaches the purpose of discarding the dross and selecting the essential.Bulbus Lilii among the we, Concha Ostreae, Semen Ziziphi Spinosae, four kinds of medical material main components of the Rhizoma Anemarrhenae are all based on water-soluble substances, and this water-soluble substances has the sleep function of improvement, so adopt water to extract as solvent.By selecting L9 (3 for use
4) orthogonal table, design the test of three factors, three horizontal quadratures, and investigation extraction solvent multiple (6 times, 8 times, 10 times), extraction time and extraction time (1h, 1.5h, 2h) etc. concrete technological parameter makes to investigate index, the extraction process that screening is best with total saponin content in the medical material.
In the medical material ratio in the prescription, the clean medical material that takes by weighing 1/10 recipe quantity is tested, measure the content of extract total saponins, calculate the medical material paste-forming rate, finally convert out total saponin content in the medical material, the total saponins assay method is seen one one of " health food technology standard " (version in 2003), concrete test arrangement and the results are shown in Table 5, table 6, table 7.
Table 5 extraction process parameter is investigated the factor level table
| Level | Quantity of solvent (doubly) | Extraction time | Extraction time (h) |
| 1 | 6 | 1 | 1 |
| 2 | 8 | 2 | 1.5 |
| 3 | 10 | 3 | 2 |
Table 6 extraction process orthogonal test is arranged and experimental result
Table 7 analysis of variance table
According to table 5,6,7, use intuitive analysis method A as can be seen
1B
3C
2Be optimum extraction process, namely the solvent consumption is 6 times, extraction time 3 times, and extraction time is 1.5 hours.In addition, orthogonal experiments is carried out variance analysis, analysis result sees Table 7, therefrom as can be seen: A, B factor (solvent multiple, extraction time) have significant difference in three factors, be that solvent multiple and extraction time are to influence that total saponin content is principal element in this medical material, this and intuitive analysis method conclusion match.So determine the optimum extraction process parameter of Bulbus Lilii, Concha Ostreae, Semen Ziziphi Spinosae, the Rhizoma Anemarrhenae be: each 6 times of amounts of amount of water, to extract 3 times, extraction time is each 1.5 hours.
Concentrated, dry, the disintegrating process of experimental example 3, alcohol-extracted extract and the water extracted immersing paste are investigated
Through laboratory lab scale research, we formulate the degree that technology concentrates condition and concentrates, and 70 ℃ of temperature, pressure 0.08Mpa carry out concentrating under reduced pressure, and being concentrated into relative density is that 1.15～1.25(50 ℃ of heat is surveyed) thick extractum; The dry boulton process that adopts carries out drying parameter: temperature is 60 ℃, and vacuum is 0.08Mpa, and the time is 50～60 hours; Crushing screening selects for use 80 mesh sieves to sieve.This technology is amplified the production correcting action through pilot scale, determines scientific and reasonable technical data.
Experimental example 4, hybrid technique are investigated
Water is carried, alcohol-extracted extract powder and starch mix the back in different time, different location sampling sample appearance observed result, sees Table 8:
Table 8
By last table, we can see: mixed inhomogeneous in the time of 10 minutes, mixed inhomogeneous in 20 minutes, mix even substantially in the time of 30 minutes, mix the homogeneous non-variegation after 40 minutes, mix homogeneously is described, thus we think incorporation time with the mixed powder of medicinal substances extract dried cream powder and starch be decided to be 30 minutes more suitable.
The selection of experimental example 5, dosage form
This product is to be used as medicine with Chinese medicine medical material extract powder mixed powder, is fit to make hard capsule.Capsule preparations has stable in properties, and production technology is simple, the characteristics that supplementary product consumption is few, can save production cost greatly, compare than other liquid preparations, be accepted by the patient easilier, many based on decoction such as the traditional liquid dosage form, taking dose is bigger, carries inconvenience, and taste also is difficult for being accepted by the people, and make hard capsule, can cover the smells such as bitterness, fishy smell of content, and profile is bright and clean attractive in appearance, edible and carry all very convenient; Compare with pill with tablet in addition, hard capsule disintegrate in gastrointestinal tract is very fast, and produce effects Kuai ﹑ has absorbed ﹑ drug bioavailability height, but and Fang Chao ﹑ lucifuge, stable in properties is convenient to preserve, and prolongs to discharge the health care material.Therefore this product selects for use hard capsule preparation as the dosage form of product.
Experimental example 6, processing technology routine design considerations
Fructus Ligustri Lucidi, Herba Ecliptae, Rhizoma Cyperi all are the Chinese medicine of using always, and wherein the Fructus Ligustri Lucidi active component is triterpenoid compound, and the Herba Ecliptae active component is compositions such as wedelolactone, and the active component of Rhizoma Cyperi is saponins, flavonoid.This product is significant composition with wedelolactone, adopts ethanol extraction can obtain better effects.Bulbus Lilii, Concha Ostreae, Semen Ziziphi Spinosae, the Rhizoma Anemarrhenae all are the Chinese medicine of using always, based on saponins, polysaccharide composition, adopt water extraction can obtain better effects.Adopt the concentrating under reduced pressure method to concentrate to said extracted liquid, can to reduce in the product effective ingredient destroyed because the concentrating under reduced pressure method concentrates, and strengthened concentrating efficiency.
The selection foundation of experimental example 7, capsule adjuvant
Adjuvant commonly used has dextrin, starch and microcrystalline Cellulose.Wherein the microcrystalline Cellulose price is higher relatively, and dextrin and starch are relatively cheap, but the moisture resistance of dextrin is poor; Because the content of this product mainly is the Chinese crude drug extract, Chinese medicine extract very easily is subjected to the influence of humiture in storage, the moisture absorption, caking phenomenon taking place, for avoiding extract the moisture absorption, deliquescing, caking phenomenon take place in storage, needs to add an amount of filler in preparation process, characteristics according to above several adjuvants, we select starch as the capsule filler, because starch is white powder, and odorless, tasteless, be the capsule excipient of using always; Therefore its moisture resistance is strong than dextrin, adds a certain amount of starch improving the product resistance to water soak, and starch characteristics such as to have character highly stable, and appearance luster is good, and cost is low, is fit to this product.
In addition, the flowability of powder adds an amount of magnesium stearate, to guarantee the accuracy of capsule loading amount during for the enhancing filled capsules.Magnesium stearate does not easily have the fine powder of grittiness for white, is commonly used for fluidizer in food, medicine.
The formulation of experimental example 8, capsule specification
This product is through the lab scale technical study, dried cream yield after Fructus Ligustri Lucidi, Herba Ecliptae, Rhizoma Cyperi are extracted is about about 16%～19%, dried cream yield after Bulbus Lilii, Concha Ostreae, Semen Ziziphi Spinosae, the Rhizoma Anemarrhenae extract is about about 14%～31%, according to the day amount, add the supplementary product starch and the magnesium stearate that meet the preparation process requirement, determine that the capsule loading amount is the 0.5g/ grain, edible 3 times of every day, each edible 3, it is suitable to take a number, meets to take custom.
Experimental example 9, climacteric syndrome functional evaluation experimental study
1. experiment purpose
Select for use castration female rats (ovary is dispeled) model to experimentize, after giving capsule of the present invention (pressing the condensed cream of embodiment 1 preparation) some cycles, observe given the test agent to " nerve-endocrine network " index of correlation, uterus coefficient, and the influence of behavioristics's index.
2. experiment material
2.1 given the test agent
Capsule of the present invention (pressing the condensed cream of embodiment 1 preparation), Beijing Zhongyan Tongrentang Medical Development Co., Ltd. provides.
2.2 laboratory animal and raising situation
(1) laboratory animal
The Wistar rat, the SPF level, female, body weight 180g-220g is available from Test Animal Centre, Academy of Military Medical Sciences, P.L.A.Licence numbering: 2007-004 SCXK-(army).
(2) feedstuff
Common Mus full-valence pellet feed II number is available from Beijing section Australia feed corporation,Ltd that pulls together.Credit number: the SCXK(capital) 2009-0012.
(3) raising condition
Experimental animal feeding in SPF level animal housing, fluorescent lamp lighting, the 12h light and shade cycle, freely drink water, diet, 22 ℃ ± 2 ℃ of temperature ,-10 times/h blows 6 times.
2.3 experiment reagent (replenishing)
Estradiol (E2), follicule-stimulating hormone (FSH) (FSH), lutropin (LH) ria-determination test kit, 5-hydroxy tryptamine (5-HT), dopamine (DA), norepinephrine (NE) ria-determination test kit, BCA protein content determination test kit, pentobarbital sodium
2.4 experimental apparatus
The BCD-257SL of Haier refrigerating refrigerator: Qingdao HaiEr Co., Ltd.
Sartorious BT124S precise electronic balance: Sai Duolisi scientific instrument (Beijing) company limited.
Prologue behavioral experiment video analytic system, cross maze experiment video analytic system, SLY-ETS toy behavioral activity record analysis system, the large hunting park in Beijing Science and Technology Ltd. produces.Its software kit can the every behavioral indicator of real time record toy, and path of animal movement figure and monitoring video in real time, preserves with Excel data base form.
Olympus medical optical microscope.
Put and exempt from instrument.
3. experimental technique
3.1 given the test agent dosage arranges
Capsule of the present invention (by the condensed cream of embodiment 1 preparation) human body recommended dose is 9.6g/ day, 6 times of behaving of rat bioequivalence dosage, people's standard body weight is set at 60kg, therefore the dose,equivalent that is tried the thing rat is 9.6g * 6 ÷ 60kg=0.96g(condensed creams)/kg, this is middle dosage, upper and lowerly respectively establish two dosage, be 3 dosage altogether: the 0.48g(condensed cream)/kg, 0.96g(condensed cream)/kg, 1.92(g/kg condensed cream) is equivalent to 3 times, 6 times and 12 times of people's recommended dose respectively.
3.2 zoopery grouping
The laboratory animal adaptability was raised after 5 days, and rat is divided into 5 groups at random by body weight, 15 every group.Be respectively: the blank group of sham-operation, model group, capsule in high dose group of the present invention, dosage group and capsule low dose group of the present invention in the capsule of the present invention.
3.3 given the test agent gives method
The high, medium and low dosage group of capsule of the present invention gives capsule of the present invention (pressing the condensed cream of embodiment 1 preparation) 1.92g/kg respectively, and 0.96g/kg and 0.48g/kg, route of administration are per os filling stomach and give, and the filling body of stomach amasss and is 0.5ml/100g body weight rat.The blank group of sham-operation and model group all give the equal-volume distilled water solution.
3.4 experimental technique
Three dosage groups of model group and given the test agent prepare female castrated rats (bilateral oophorectomy) model: rat 0.1% pentobarbital sodium 0.5ml/100g body weight (50mg/kg) intraperitoneal injection of anesthesia.Anesthetized rat is got the ventricumbent position, the cropping of 1/3 place, preserved skin in the back, povidone iodine routine disinfection.Be the about 2～3cm of stringer otch from lumbar vertebra downwards along the back median line, cut skin, along scapular line respectively at cutting off psoas muscle under the both sides of the chest of the left and right sides, two ligation are done at cornua uteri in the uterus that exposes ovary and closely link to each other, and cut off after the ligation, with ovariectomy, skin suture.The continuous lumbar injection of postoperative 720,000 units/kg penicillin, in case infect, 1 time/d, continuous 5 days, the operation back began to observe to the rat vagina smear on the 3rd day, continuous 5d, every day 1 time is to determine that ovary excises fully.Laboratory animal all enters diestrus from the 5th day of postoperative, but proestrus no longer appears in animal, and estrous estrogen changes, and animal meets " climacteric " performance basically.
Sham-operation is blank organizes rat except not all right ovariectomy, the same model group of all the other steps.
After the modeling 9 days, except the blank group of sham-operation and model group give the equal-volume distilled water, all the other each organize and begin to irritate stomach and give given the test agent, every day 1 time, continuous 45 days, carry out body weight determination weekly.
3.4.1 behavioristics is detected
3.4.1.1 elevated plus-maze test
Rat continuous irrigation stomach after last gives given the test agent 30min, carries out the test and appraisal in overhead cross labyrinth.During the experiment beginning, rat is put into overhead cross labyrinth central authorities, head is observed the active situation of rat in the 5min towards opening arm.Observe and record the following index: enter out the arm number of times, enter and close arm number of times and the time between two arms.Calculating the time that rat enters out arm respectively accounts for total time the percentage ratio (OT%) of (open arm and close the time sum that arm is detained), and the number of times that rat enters out arm accounts for the percentage ratio (OE%) of total degree (open arm and close the arm sum).All enter out arm or close arm with the rat four paws during observation and be as the criterion.
3.4.1.2 light and shade case experiment
Rat continuous irrigation stomach after last gives given the test agent 30min, places camera-lucida central authorities with rat, and the back of the body is towards passage, and the active situation of the interior rat of observation 5min also records the light and shade case time of staying and wears the case number of times.
More than during two kinds of behavioristics test experience operations, should keep the external environment peace and quiet, put into the Excreta of cleaning out case before the rat at every turn, guarantee the objectivity of every batch of detection as far as possible.
3.4.2 rat reproductive organs (uterus) organ coefficient is measured
Rat continuous irrigation stomach 45 days, last takes by weighing rat body weight after giving given the test agent 30min,, dissects and gets the uterus with after the 0.5ml/100g intraperitoneal injection of anesthesia success with 0.1% pentobarbital sodium, takes by weighing uterus weight.Calculate the uterus organ coefficient.
Uterus organ coefficient=uterus weight/body weight * 100
3.4.3 rat " nerve-endocrine " network index of correlation detects
3.4.3.1 the rat blood serum hormonal readiness is measured
Behind the rat extracting blood, centrifugal with 2000r/min after room temperature leaves standstill 2h naturally, get serum, measure serum estradiol (E2), follicule-stimulating hormone (FSH) (FSH), lutropin (LH) level with radio immunoassay.
3.4.3.2 rat hypothalamus is organized NE, DA, the detection of 5-HT
After animal is got blood, on ice pan, open cranium rapidly, cut hypothalamus, scope is: the kiss side is to preceding associating, and the tail side is to the mammillary body rear portion, and the outside is the hypothalamus lateral sulcus, dorsal part is to preceding combined level height, and the tissue of getting comprises hypothalamus bottom side district, anterior hypothalamic region with look the proparea.The hypothalamus that takes out is put-80 ℃ of preservations.Inferior colliculus cerebral tissue homogenate is put the method for exempting from and is measured norepinephrine in the homogenate (NE), dopamine (DA), 5-hydroxy tryptamine (5-HT) content respectively, and the BCA method is measured the tissue homogenate protein content.
4. statistical method
Experimental data is with " mean+SD
Expression.Data are carried out homogeneity test of variance earlier.Variance selects for use One-Way ANOVA method to carry out comparing between each group together; Heterogeneity of variance select for use t ' check organize between relatively.
5. experimental result
5.1 given the test agent is to the influence of castration female rats uterus organ coefficient
Table 9 capsule of the present invention is to the influence of castration female rats uterus organ coefficient
Annotate: compare with the blank group of sham-operation,
△ △ △P＜0.001; Compare with model group,
*P＜0.05.
The result shows that model group and given the test agent are respectively organized castration female rats uterus organ coefficient and significantly reduced, and with the blank group of sham-operation significant difference (all P＜0.001) is arranged relatively, shows model modeling success.Compare with model group, capsule in high dose group of the present invention is elevation model rat uterus organ coefficient (P＜0.05) significantly.The result shows the effect that capsule of the present invention has increases castration rat model uterus organ coefficient preferably.The results are shown in Table 9.
5.2 given the test agent is to the shuttle back and forth influence of behavior of castration female rats light and shade
Table 10 capsule of the present invention is to the shuttle back and forth influence of behavior of female castrated rats light and shade
Annotate: compare with the blank group of sham-operation,
△P＜0.05,
△ △P＜0.01,
△ △ △P＜0.001; Compare with model group,
*P＜0.05,
*P＜0.01,
* *P＜0.001.
Result of study shows, model group rat camera-lucida time of staying and wear case time number average and significantly reduce, with the blank group of sham-operation significant difference (P＜0.001,0.05 respectively) is arranged relatively, show the rat model castration after, produced tangible anxiety behavior.With model group relatively, capsule in high dose group of the present invention can significantly raise rat camera-lucida time of staying and wear case number of times (P＜0.001,0.01 respectively), middle dosage group can significantly raise rat camera-lucida time of staying and wear case number of times (all P＜0.05).
The result shows that the behavior of shuttling back and forth has potentiation preferably to capsule of the present invention to castration female rats light and shade, embodies angst resistance effect preferably.The results are shown in Table 10.
5.3 given the test agent is to the influence of female castrated rats cross labyrinth behavioral activity
Table 11 capsule of the present invention is to the influence of female castrated rats OE% and OT%
Annotate: compare with the blank group of sham-operation,
△P＜0.05,
△ △P＜0.01,
△ △ △ P＜0.001; Compare with model group,
*P＜0.05,
*P＜0.01,
* *P＜0.001.
Experimental result shows that the blank group of model group and sham-operation compares, and female castrated rats OE% and OT% significantly reduce (all P＜0.01), show tangible anxiety symptom.Capsule in high dose group of the present invention can significantly lower rat model OT%, with model group significant difference (P＜0.05) is arranged relatively.Show that given the test agent has the effect that improves the overhead cross of the female rat model of castration labyrinth anxiety symptom preferably.The results are shown in Table 11.
5.4 given the test agent is to the influence of female castrated rats hormone serum level
Table 12 capsule of the present invention is to the influence of female castrated rats serum E2, FSH, LH level
Annotate: compare with the blank group of sham-operation,
△ △P＜0.01,
△ △ △P＜0.001; Compare with model group,
*P＜0.05,
*P＜0.01,
* *P＜0.001.
The experimental result demonstration, model group rat blood serum E2 level descends, and FSH, LH level rise, and with the blank group of sham-operation significant difference (difference P＜0.01,0.001,0.001) are arranged more all, illustrate that this experiment modeling meets the climacteric feature.Compare with model group, three dosage groups of capsule of the present invention serum E2 level (P＜0.01 respectively that all can raise in various degree, 0.05,0.05), capsule height of the present invention, in two dosage groups can reduce serum FSH level (P＜0.001,0.01 respectively), capsule three each dosage groups of the present invention all can significantly reduce LH level (P＜0.001 respectively, 0.01,0.01).Show that given the test agent has the better effect that castration rat model hormone serum level changes that improves.The results are shown in Table 12.
5.5 given the test agent is to the influence of castrated rats hypothalamus neurotransmitter
Table 13 capsule of the present invention is to the influence of female castrated rats hypothalamus NE, DA and 5-HT content
Annotate: compare with the blank group of sham-operation,
△P＜0.05,
△ △P＜0.01; Compare with model group,
*P＜0.05,
*P＜0.01.
Experimental result shows that NE, DA, 5-HT content all significantly raise in the model group rat hypothalamus tissue, with the blank group of sham-operation significant difference (difference P＜0.05,0.01,0.05) is arranged more all.Compare with model group, capsule in high dose group of the present invention all can reduce NE in the inferior colliculus cerebral tissue, DA and 5-HT content (difference P＜0.01,0.01,0.05) in various degree.Show that given the test agent has the effect of neurotransmitter content in the better adjusting trend model rat hypothalamus.The results are shown in Table 13.
6. conclusion
Capsule of the present invention can obviously improve the function of castration female rats hypothalamus peptide class neurotransmitter, corrects the disorder of hypothalamus monoamine neurotransmitter; Disorder has better regulating action to the rat model reproductive endocrine; And the anxiety behavioristics that can significantly improve rat model changes.Above-mentioned result of study can be capsule of the present invention and improves the climacteric syndrome function certain experimental basis is provided.
Following embodiment all can realize the described effect of above-mentioned experimental example.
Embodiment 1 hard capsule of the present invention
Prescription: Fructus Ligustri Lucidi 450g, Herba Ecliptae 450g, Rhizoma Cyperi 333g, Bulbus Lilii 216g, Concha Ostreae 540g,
Semen Ziziphi Spinosae 450g, Rhizoma Anemarrhenae 270g, Oviductus Ranae 33g, magnesium stearate 2.4g, starch, an amount of, make 1000 capsules, the 0.5g/ grain;
Technology:
(1) extraction, filtration, concentrated, dry
1. the extraction of medical material
Fructus Ligustri Lucidi, Herba Ecliptae, Rhizoma Cyperi decoction pieces are put in the reflux, extract, jar, add 70% ethanol extraction, decoct 2 times, and 12 times of amounts of each solubilizer decoct 1h, filter (filter material is 80 order nylon cloths), and merge extractive liquid,, standby.Bulbus Lilii, Concha Ostreae, Semen Ziziphi Spinosae, the Rhizoma Anemarrhenae are put in the reflux, extract, jar, and extracting in water decocts 3 times, add 6 times of amounts of water at every turn and decoct 1.5h, filter (filter material is 80 order nylon cloths), and merge extractive liquid,, standby.
2. vacuum concentration
Get alcohol extraction filtrate and put in the vacuum concentration pot, reclaim ethanol, and to be concentrated into relative density be that 1.15-1.25(50 ℃ of heat is surveyed), get thick extractum A.
Water intaking is carried filtrate and is put in the vacuum concentration pot, and to be concentrated into relative density be that 1.15-1.25(50 ℃ of heat is surveyed), get thick extractum B.
The vacuum concentration process parameter: vacuum is 0.08Mpa, temperature: 70 ℃.
3. dry
Thick extractum A and thick extractum B are mixed, put vacuum drying oven and be heated to 60 ℃ of dryings, vacuum is 0.08Mpa, gets dry extract.Dry extract is pulverized with universal mill, crosses 80 mesh sieves, gets dry extract.
(2) hybrid technique of fine powder raw material
Starch is crossed 80 mesh sieves, and is stand-by.Oviductus Ranae is pulverized, and crosses 80 mesh sieves, and is stand-by.
With dry extract with crossed 80 purpose starch and put abundant mixing in the three-dimensional mixer with Oviductus Ranae, mixed 30 minutes, get mixed powder.
(3) granulate
Getting mixed powder, is wetting agent with 90% alcoholic solution, granulates with wet granulator.Dried granule can be broken and have harsh feeling to be advisable to twist with the fingers through light finger.
Granulation parameter: 70 ℃ of inlet temperature.
(4) always mix technology
Get qualified dried granule, add magnesium stearate, put in the three-dimensional mixer, mixed 20 minutes.
(5) capsule is filled, is polished
Adopt automatic capsule filling machine that above-mentioned qualified granule is filled in No. 0 capsule by operating process, adjust loading amount to every heavy 0.5g, in machine for automatically polishing, polish.
Embodiment 2 tablets of the present invention
Prescription: Fructus Ligustri Lucidi 420g, Herba Ecliptae 470g, Rhizoma Cyperi 310g, Bulbus Lilii 240g, Concha Ostreae 520g, Semen Ziziphi Spinosae 470g, Rhizoma Anemarrhenae 250g, Oviductus Ranae 40g, magnesium stearate 2.4g, starch, an amount of.,
Add conventional adjuvant, according to common process, make tablet.
Embodiment 3 granules of the present invention
Fructus Ligustri Lucidi 470g, Herba Ecliptae 420g, Rhizoma Cyperi 360g, Bulbus Lilii 200g, Concha Ostreae 560g, Semen Ziziphi Spinosae 430g, Rhizoma Anemarrhenae 290g, Oviductus Ranae 29g, magnesium stearate 2.4g, starch, an amount of.
Add conventional adjuvant, according to common process, make granule.
Embodiment 4:
Fructus Ligustri Lucidi 13Kg, Herba Ecliptae 18Kg, Rhizoma Cyperi 9Kg, Bulbus Lilii 9Kg, Concha Ostreae 15Kg, Semen Ziziphi Spinosae 18Kg, Rhizoma Anemarrhenae 5Kg, Oviductus Ranae 2.2Kg.Add conventional adjuvant, according to common process, make tablet.
Embodiment 5:
Prescription: Fructus Ligustri Lucidi 18Kg, Herba Ecliptae 13Kg, Rhizoma Cyperi 14Kg, Bulbus Lilii 5Kg, Concha Ostreae 22Kg, Semen Ziziphi Spinosae 14Kg, Rhizoma Anemarrhenae 12Kg, Oviductus Ranae 0.2Kg.Add conventional adjuvant, according to common process, make granule.
Embodiment 6:
Fructus Ligustri Lucidi 16Kg, Herba Ecliptae 16Kg, Rhizoma Cyperi 11.5Kg, Bulbus Lilii 7Kg, Concha Ostreae 19Kg, Semen Ziziphi Spinosae 16Kg, Rhizoma Anemarrhenae 9Kg, Oviductus Ranae 1.25Kg.
Technology:
(1) extraction, filtration, concentrated, dry
1. the extraction of medical material
Fructus Ligustri Lucidi, Herba Ecliptae, Rhizoma Cyperi decoction pieces are put in the reflux, extract, jar, add 70% ethanol extraction, decoct 2 times, and 12 times of amounts of each solubilizer decoct 1h, filter (filter material is 80 order nylon cloths), and merge extractive liquid,, standby.Bulbus Lilii, Concha Ostreae, Semen Ziziphi Spinosae, the Rhizoma Anemarrhenae are put in the reflux, extract, jar, and extracting in water decocts 3 times, add 6 times of amounts of water at every turn and decoct 1.5h, filter (filter material is 80 order nylon cloths), and merge extractive liquid,, standby.
2. vacuum concentration
Get alcohol extraction filtrate and put in the vacuum concentration pot, reclaim ethanol, and to be concentrated into relative density be that 1.15-1.25(50 ℃ of heat is surveyed), get thick extractum A.
Water intaking is carried filtrate and is put in the vacuum concentration pot, and to be concentrated into relative density be that 1.15-1.25(50 ℃ of heat is surveyed), get thick extractum B.
The vacuum concentration process parameter: vacuum is 0.08Mpa, temperature: 70 ℃.
3. dry
Thick extractum A and thick extractum B are mixed, put vacuum drying oven and be heated to 60 ℃ of dryings, vacuum is 0.08Mpa, gets dry extract.Dry extract is pulverized with universal mill, crosses 80 mesh sieves, gets dry extract.
(2) hybrid technique of fine powder raw material
Starch is crossed 80 mesh sieves, and is stand-by.Oviductus Ranae is pulverized, and crosses 80 mesh sieves, and is stand-by.
With dry extract with crossed 80 purpose starch and put abundant mixing in the three-dimensional mixer with Oviductus Ranae, mixed 30 minutes, get mixed powder.
(3) granulate
Getting mixed powder, is wetting agent with 90% alcoholic solution, granulates with wet granulator.Dried granule can be broken and have harsh feeling to be advisable to twist with the fingers through light finger.
Granulation parameter: 70 ℃ of inlet temperature.
(4) always mix technology
Get qualified dried granule, add magnesium stearate, put in the three-dimensional mixer, mixed 20 minutes.
(5) capsule is filled, is polished
Adopt automatic capsule filling machine that above-mentioned qualified granule is filled in No. 0 capsule by operating process, adjust loading amount to every heavy 0.5g, in machine for automatically polishing, polish.
Claims (10)
1. one kind has the pharmaceutical composition that improves menopause syndrome, it is characterized in that the crude drug of said composition consists of:
Fructus Ligustri Lucidi 12-20 weight portion, Herba Ecliptae 12-20 weight portion, Rhizoma Cyperi 8-15 weight portion, Bulbus Lilii 4-10 weight portion, Concha Ostreae 14-25 weight portion, Semen Ziziphi Spinosae 12-20 weight portion, Rhizoma Anemarrhenae 4-14 weight portion, Oviductus Ranae 0.1-2.5 weight portion.
2. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of said composition consists of:
Fructus Ligustri Lucidi 15-17 weight portion, Herba Ecliptae 15-17 weight portion, Rhizoma Cyperi 10-13 weight portion, Bulbus Lilii 6-8 weight portion, Concha Ostreae 18-20 weight portion, Semen Ziziphi Spinosae 15-17 weight portion, Rhizoma Anemarrhenae 8-10 weight portion, Oviductus Ranae 0.5-2 weight portion.
3. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of said composition consists of:
Fructus Ligustri Lucidi 15 weight portions, Herba Ecliptae 15 weight portions, Rhizoma Cyperi 11.1 weight portions, Bulbus Lilii 7.2 weight portions, Concha Ostreae 18 weight portions, Semen Ziziphi Spinosae 15 weight portions, the Rhizoma Anemarrhenae 9 weight portions, Oviductus Ranae 1.1 weight portions;
Or Fructus Ligustri Lucidi 16 weight portions, Herba Ecliptae 16 weight portions, Rhizoma Cyperi 11.5 weight portions, Bulbus Lilii 7 weight portions, Concha Ostreae 19 weight portions, Semen Ziziphi Spinosae 16 weight portions, the Rhizoma Anemarrhenae 9 weight portions, Oviductus Ranae 1.25 weight portions;
Or Fructus Ligustri Lucidi 14 weight portions, Herba Ecliptae 14 weight portions, Rhizoma Cyperi 10.3 weight portions, Bulbus Lilii 8 weight portions, Concha Ostreae 17.3 weight portions, Semen Ziziphi Spinosae 15.7 weight portions, the Rhizoma Anemarrhenae 8.3 weight portions, Oviductus Ranae 1.33 weight portions;
Or Fructus Ligustri Lucidi 13 weight portions, Herba Ecliptae 18 weight portions, Rhizoma Cyperi 9 weight portions, Bulbus Lilii 9 weight portions, Concha Ostreae 15 weight portions, Semen Ziziphi Spinosae 18 weight portions, the Rhizoma Anemarrhenae 5 weight portions, Oviductus Ranae 2.2 weight portions;
Or Fructus Ligustri Lucidi 15.7 weight portions, Herba Ecliptae 14 weight portions, Rhizoma Cyperi 12 weight portions, Bulbus Lilii 6.7 weight portions, Concha Ostreae 15.7 weight portions, Semen Ziziphi Spinosae 14.3 weight portions, the Rhizoma Anemarrhenae 9.7 weight portions, Oviductus Ranae 0.97 weight portion;
Or Fructus Ligustri Lucidi 18 weight portions, Herba Ecliptae 13 weight portions, Rhizoma Cyperi 14 weight portions, Bulbus Lilii 5 weight portions, Concha Ostreae 22 weight portions, Semen Ziziphi Spinosae 14 weight portions, the Rhizoma Anemarrhenae 12 weight portions, Oviductus Ranae 0.2 weight portion.
4. as described any one pharmaceutical composition of claim 1-3, it is characterized in that getting crude drug, add conventional adjuvant, according to common process, make oral solid formulation: capsule, tablet, granule or electuary.
5. any one pharmaceutical composition as claimed in claim 4 is characterized in that described dosage form is hard capsule.
6. the preparation method of oral solid formulation as claimed in claim 4 is characterized in that this method is:
Fructus Ligustri Lucidi, Herba Ecliptae, Rhizoma Cyperi, the ethanol extraction method is extracted routinely, and being concentrated into 50 ℃ of heat, to survey relative densities be that 1.15～1.25 thick extractum gets thick extractum A; Bulbus Lilii, Concha Ostreae, Semen Ziziphi Spinosae, the Rhizoma Anemarrhenae, water extracting method extracts routinely, and being concentrated into 50 ℃ of heat, to survey relative densities be 1.15～1.25 thick extractum, gets thick extractum B; Thick extractum A and thick extractum B are mixed into thick extractum C, drying, crushing screening gets dry extract; Oviductus Ranae is pulverized, and sieves; Dry extract is mixed with the Oviductus Ranae oil meal, add conventional adjuvant, according to common process, make oral solid formulation and include but not limited to capsule, tablet, granule, electuary etc.
7. preparation method as claimed in claim 6 is characterized in that in this method:
Described ethanol extraction method is: Fructus Ligustri Lucidi, Herba Ecliptae, Rhizoma Cyperi, put in the reflux, extract, jar, and add the 30-70% ethanol extraction, decoct 1-3 time, add water 8-12 at every turn and doubly measure decoction 1-2 hour, filter, merge extractive liquid,, standby;
Described water extracting method is: Bulbus Lilii, Concha Ostreae, Semen Ziziphi Spinosae, the Rhizoma Anemarrhenae, to put in the reflux, extract, jar, and extracting in water decocts 1-3 time, adds water 6-10 at every turn and doubly measures decoction 1-2 hour, filter, merge extractive liquid,, standby;
Described concentrated condition and degree are: 70 ℃ of temperature, pressure 0.08Mpa carry out concentrating under reduced pressure;
The condition of described drying is: adopt boulton process, drying parameter: temperature is 60 ℃, and vacuum is 0.08Mpa, and the time is 50～60 hours;
Described crushing screening selects for use 80 mesh sieves to sieve.
8. the preparation method of hard capsule as claimed in claim 5 is characterized in that this method is:
Fructus Ligustri Lucidi, Herba Ecliptae, Rhizoma Cyperi decoction pieces are put in the reflux, extract, jar, add 70% ethanol extraction, decoct 2 times, add 12 times of amounts of water at every turn and decoct 1h, filter, and merge extractive liquid,, standby; Bulbus Lilii, Concha Ostreae, Semen Ziziphi Spinosae, the Rhizoma Anemarrhenae are put in the reflux, extract, jar, and extracting in water decocts 3 times, add 6 times of amounts of water at every turn and decoct 1.5h, filter, and merge extractive liquid,, standby; Get alcohol extraction filtrate and put in the vacuum concentration pot, reclaim ethanol, and being concentrated into 50 ℃ of heat, to survey relative densities be 1.15-1.25 that get thick extractum A, the vacuum concentration process parameter: vacuum is 0.08Mpa, temperature: 70 ℃; Water intaking is carried filtrate and is put in the vacuum concentration pot, and being concentrated into 50 ℃ of heat, to survey relative densities be 1.15-1.25, and get thick extractum B, the vacuum concentration process parameter: vacuum is 0.08Mpa, temperature: 70 ℃; Thick extractum A and thick extractum B are mixed into thick extractum C, are heated to 60 ℃ of dryings with the vacuum decompression drying baker, get dry extract C, vacuum decompression drying process parameter: vacuum is 0.08Mpa, temperature: 60 ℃; Dry extract C is ground into 80 order powder, gets dry extract C; Oviductus Ranae is pulverized, and sieves; Dry extract C and Oviductus Ranae oil meal, starch were mixed 30 minutes, cross 80 mesh sieves and get mixed powder D; With mixed powder D, be wetting agent with 90% alcoholic solution, wet granulation adds magnesium stearate, mixes, and filled capsules is namely.
9. has application in the product that improves menopause syndrome as described any one pharmaceutical composition of claim 1-3 in preparation.
10. application as claimed in claim 9 is characterized in that described product form is health food, bread and cheese or medicine.
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