CN101461898B - Chinese medicine solid preparation for treating climacteric syndrome and preparation method thereof - Google Patents
Chinese medicine solid preparation for treating climacteric syndrome and preparation method thereof Download PDFInfo
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Abstract
The invention provides traditional Chinese medicine solid preparation for treating climacteric syndrome, which comprises traditional Chinese medicine components and medicine accessories. The traditional Chinese medicine components consist of the following raw materials by weight portion: 3 portions of glossy privet fruit, 2 portions of raspberry, 2 portions of dodder, 2 portions of medlar, 2 portions of fleece-flower root, 1.5 portions of tortoise shell, 3 portions of cortex lycii radicis, 2 portions of ladybell root, 2 portions of dwarf lilyturf turber, 1 portion of seed of wild jujube, 3 portions of rehmannia, 6 portions of white paeony root, 3 portions of red paeony root, 2 portions of angelica, 6 portions of caulis milletiae, 6 portions of nacre, 3 portions of dendrobe, 3 portions of chrysanthemum, 4 portions of yerbadetajo, 2 portions of mulberry leaves, 3 portions of radix cynanchi atrati, 3 portions of rhizome anemarrhenae, and 3 portions of scutellaria, wherein the fleece-flower root and the white paeony root are raw powder, and the other 21 traditional Chinese medicines are extracts obtained by extracting raw material crude drugs. The solid preparation overcomes the defect that the prior preparation has large oral dosage, and has good bioavailability.
Description
Technical field
The present invention is relevant a kind of solid preparation of Chinese medicine of treating climacteric syndrome and preparation method thereof,, the invention relates to a kind of solid preparation of Chinese medicine that contains Semen Ziziphi Spinosae, Radix Salviae Miltiorrhizae and Fructus Schisandrae Chinensis and preparation method thereof that is.
Background technology
Climacteric syndrome is a kind of common clinical disease, and at present the western medical treatment effect is bad, has certain clinical adverse, is everlasting medicine to occur after taking medicine and leave over reaction, influences the mental status, live and work.In the patient crowd of climacteric syndrome, many patients are difficult to accept for the untoward reaction due to the Western medicine.And Chinese medicine is accumulating a large amount of experiences aspect the treatment climacteric syndrome, and, because Chinese medicine is few to nerve, the untoward reaction of spiritual aspect, thereby aspect treatment of climacteric syndrome, have vast potential for future development.
Chinese medicine has a lot of clinical experience sides aspect treatment of climacteric syndrome, female precious ball promptly is the Chinese patent medicine that derives from clinical experience side, records in the 6th of ministry standard.It is nourishing the liver and kidney that function cures mainly, tranquillizing and allaying excitement, blood nourishing acupuncture-stimulating.Be used for climacteric syndrome, the menoxenia that the hepatic and renal YIN deficiency causes, hectic fever hyperhidrosis, insomnia forgetfulness, susceptible to lose temper due to restlessness, dizziness and tinnitus, dry throat and mouth, aching and soreness in limb, diseases such as arthralgia.
Female precious ball is a honeyed pill, is made up of Radix Polygoni Multiflori (black soya bean wine is processed), the Radix Paeoniae Alba, Fructus Ligustri Lucidi (wine is processed), Fructus Rubi, Semen Cuscutae, Fructus Lycii, Carapax Et Plastrum Testudinis, Cortex Lycii, Radix Adenophorae, Radix Ophiopogonis, Semen Ziziphi Spinosae (stir-fry), Radix Rehmanniae, Radix Paeoniae Rubra, Radix Angelicae Sinensis, Caulis Spatholobi, Concha Margaritifera, Herba Dendrobii, Flos Chrysanthemi, Herba Ecliptae, Folium Mori, Radix Cynanchi Atrati, the Rhizoma Anemarrhenae and Radix Scutellariae 23 flavor Chinese medicines.Former pill is that above 23 flavor Chinese crude drugs are ground into fine powder, sieves, and mixing adds the general system of refined honey and water and forms.
The function tonification Liver and kidney of female precious ball, tranquillizing and allaying excitement, blood nourishing acupuncture-stimulating.Be used for climacteric syndrome, the menoxenia that the hepatic and renal YIN deficiency causes, hectic fever hyperhidrosis, insomnia forgetfulness, susceptible to lose temper due to restlessness, dizziness and tinnitus, dry throat and mouth, aching and soreness in limb, diseases such as arthralgia.Not only for climacteric syndrome, and, like hysterectomy sequela etc. good result is arranged also, thereby enormous and latent market is also arranged for the class menopause syndrome that the women causes because of a variety of causes.This kind still is traditional former powder water-honeyed pill dosage form at present, and water-honeyed pill has effect to relax lastingly, can cover characteristics such as adverse drug abnormal smells from the patient and taking convenience, but the method for preparing of Chinese medicine water-honeyed pill is still more backward at present; Production automation level is low, and dosing is big, take inconvenience, and product quality is wayward; Thereby hindered the domestic and overseas foray of this kind, therefore, be badly in need of this medicine is carried out modified form; Work out and can keep it former effective in cure, it is good than pill to be convenient to modern production, dissolution rate and bioavailability again, steady quality; Production mechanization, automaticity are high, output is big, cost is low, and the medicament health is prone to up to standard; Take, carry, more convenient novel form such as storage.But, certainly will cause many difficulties of dosage form improvement because the flavour of a drug of female precious ball composition is various.
Summary of the invention
In view of the female precious ball of conventional dosage forms of present this area and all drawbacks and the defective of preparation technology's existence; The present inventor gropes through experiment in a few years; Tradition prescription preparation to specific has carried out big cholic innovation, has developed the repertoire that has both comprised traditional prescription, has kept the fixed mixing ratio of the raw material components of former prescription again; And curative effect is constant, the novel form of the conventional medicament that is easier to extensively to be used.
The object of the present invention is to provide a kind of solid preparation of Chinese medicine of treating climacteric syndrome; Said preparation had both comprised the repertoire of traditional prescription; Kept the fixed mixing ratio of the raw material components of former prescription again, curative effect is constant, and dissolution rate and bioavailability are better than traditional oral liquid formulation; And take, carry, storage etc. is more convenient, be easier to extensively used.
The present invention also aims to screen and provide a kind of method for preparing of treating the solid preparation of Chinese medicine of climacteric syndrome according to the characteristics of this solid preparation of Chinese medicine; The Chinese medicine preparation of the treatment climacteric syndrome that this method for preparing of process obtains; The fixed mixing ratio of raw material components that has kept the prescription of former honeyed pill; And curative effect is constant, is easier to extensively used.
Intended purposes of the present invention and beneficial effect are realized through following technical scheme.
The invention provides a kind of solid preparation of Chinese medicine of treating climacteric syndrome; It is the Chinese medicine solid orally ingestible; Said preparation comprises Chinese medicinal components and excipient substance, and this Chinese medicinal components is made up of the raw material of following weight portion: 3 parts of 3 parts of Fructus Ligustri Lucidi, 2 parts of Fructus Rubies, 2 parts of Semen Cuscutae, 2 parts of Fructus Lycii, 2 parts of Radix Polygoni Multiflori, 1.5 parts of Carapax Et Plastrum Testudiniss, 3 parts of Cortex Lycii, 2 parts of Radix Adenophoraes, 2 parts of Radix Ophiopogonis, 1 part of Semen Ziziphi Spinosae, 3 parts of Radix Rehmanniae, 6 parts of the Radix Paeoniae Albas, 3 parts of Radix Paeoniae Rubra, 2 parts of Radix Angelicae Sinensis, 6 parts of Caulis Spatholobis, 6 parts of Concha Margaritiferas, 3 parts of Herba Dendrobiis, 3 parts of Flos Chrysanthemis, 4 parts of Herba Ecliptaes, 2 parts on Folium Mori, 3 parts of Radix Cynanchi Atratis, 3 parts of the Rhizoma Anemarrhenaes and Radix Scutellariaes; Wherein, in this solid preparation of Chinese medicine, except that Radix Polygoni Multiflori and the Radix Paeoniae Alba two flavor Chinese medicines are the former powder, all the other 20 simply Chinese medicine be 20 extracts of raw medicinal material through extracting, concentrate, obtaining after the drying of Chinese medicine simply.
Above-mentioned Fructus Ligustri Lucidi is the Fructus Ligustri Lucidi that wine is processed, and is also referred to as Fructus Ligustri Lucidi (wine is processed); Radix Polygoni Multiflori is the Radix Polygoni Multiflori that black soya bean wine is processed, and is also referred to as Radix Polygoni Multiflori (black soya bean wine is processed); Semen Ziziphi Spinosae is the Semen Ziziphi Spinosae of parch, is also referred to as Semen Ziziphi Spinosae (stir-fry).Wine is processed, black soya bean wine is processed and parch is conventional Chinese medicine processing method, and this Fructus Ligustri Lucidi (wine is processed), Radix Polygoni Multiflori (black soya bean wine is processed) and Semen Ziziphi Spinosae (stir-fry) are the Chinese medicine that obtains after the process of preparing Chinese medicine.
Promptly; The invention provides a kind of solid preparation of Chinese medicine of treating climacteric syndrome; It is the Chinese medicine solid orally ingestible; Said preparation comprises Chinese medicinal components and excipient substance, and this Chinese medicinal components is made up of the raw material of following weight portion: 3 parts of 3 parts of Fructus Ligustri Lucidi (wine is processed), 2 parts of Fructus Rubies, 2 parts of Semen Cuscutae, 2 parts of Fructus Lycii, 2 parts of Radix Polygoni Multiflori (black soya bean wine is processed), 1.5 parts of Carapax Et Plastrum Testudiniss, 3 parts of Cortex Lycii, 2 parts of Radix Adenophoraes, 2 parts of Radix Ophiopogonis, 1 part of Semen Ziziphi Spinosae (stir-fry), 3 parts of Radix Rehmanniae, 6 parts of the Radix Paeoniae Albas, 3 parts of Radix Paeoniae Rubra, 2 parts of Radix Angelicae Sinensis, 6 parts of Caulis Spatholobis, 6 parts of Concha Margaritiferas, 3 parts of Herba Dendrobiis, 3 parts of Flos Chrysanthemis, 4 parts of Herba Ecliptaes, 2 parts on Folium Mori, 3 parts of Radix Cynanchi Atratis, 3 parts of the Rhizoma Anemarrhenaes and Radix Scutellariaes; Wherein, In this solid preparation of Chinese medicine; The Radix Polygoni Multiflori (black soya bean wine is processed) and the Radix Paeoniae Alba are former powder, this 20 Chinese medicine raw medicinal material that is those Chinese medicines extract through extracting, concentrate, obtaining after the drying simply of remaining Fructus Ligustri Lucidi (wine is processed), Fructus Rubi, Semen Cuscutae, Fructus Lycii, Carapax Et Plastrum Testudinis, Cortex Lycii, Radix Adenophorae, Radix Ophiopogonis, Semen Ziziphi Spinosae (stir-fry), Radix Rehmanniae, Radix Paeoniae Rubra, Radix Angelicae Sinensis, Caulis Spatholobi, Concha Margaritifera, Herba Dendrobii, Flos Chrysanthemi, Herba Ecliptae, Folium Mori, Radix Cynanchi Atrati, the Rhizoma Anemarrhenae and Radix Scutellariae.
Advantage of the present invention is: the above-mentioned solid preparation of Chinese medicine that the present invention obtains still keeps former powder is used as medicine except that Radix Polygoni Multiflori (black soya bean wine is processed), the Radix Paeoniae Alba two flavors aspect the Chinese medicine composition; All the other flavour of a drug all adopt extraction, concentrate, after the drying; Process preparation again; The crude drug amount of taking that said preparation obtains through converting is identical with the crude drug amount of taking of former honeyed pill, but the real dose of said preparation is merely 1/5th of former dosage form (honeyed pill) dose, has reduced patient's taking dose effectively; And through the test of pesticide effectiveness, toxicological test checking, solid preparation of Chinese medicine of the present invention and the no significant difference of former honeyed pill (pill).
In above-mentioned solid preparation of Chinese medicine of the present invention; Except that the composition that Radix Polygoni Multiflori (black soya bean wine is processed), the former powder of the Radix Paeoniae Alba two flavors are used as medicine; All the other 20 simply the extract of Chinese medicine be: Fructus Ligustri Lucidi, Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi and the Rhizoma Anemarrhenae be its ethanol extract (promptly; The extract that medical material obtains through alcohol extraction); Ten remaining Chinese medicine of the five flavours---Fructus Rubi, Fructus Lycii, Carapax Et Plastrum Testudinis, Radix Adenophorae, Radix Ophiopogonis, Semen Ziziphi Spinosae (stir-fry), Radix Rehmanniae, Radix Paeoniae Rubra, Concha Margaritifera, Herba Dendrobii, Flos Chrysanthemi, Herba Ecliptae, Folium Mori, Radix Cynanchi Atrati, the Rhizoma Anemarrhenae and Radix Scutellariae is its water extract (that is, medical material obtain through water extraction extract).
The ethanol extract of above-mentioned Fructus Ligustri Lucidi, Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi and the Rhizoma Anemarrhenae is that the raw medicinal material of these Chinese medicines extracts the ethanol extract that obtains through alcohol reflux; This alcohol can be methanol, ethanol etc.; In view of formulation products character of the present invention; The pure preferred alcohol that is adopted, this ethanol extract is preferably ethanol extraction.
The water extract of above-mentioned Fructus Rubi, Fructus Lycii, Carapax Et Plastrum Testudinis, Radix Adenophorae, Radix Ophiopogonis, Semen Ziziphi Spinosae (stir-fry), Radix Rehmanniae, Radix Paeoniae Rubra, Concha Margaritifera, Herba Dendrobii, Flos Chrysanthemi, Herba Ecliptae, Folium Mori, Radix Cynanchi Atrati, the Rhizoma Anemarrhenae and Radix Scutellariae is that the raw medicinal material process decocting of these Chinese medicines boils, resulting water extract is filtrated in the mistake leaching.
To the Chinese medicinal components in the solid preparation of Chinese medicine of the present invention; Its concrete technical scheme is: except that the composition that Radix Polygoni Multiflori (black soya bean wine is processed), the former powder of the Radix Paeoniae Alba two flavors are used as medicine; All the other 20 simply the extract of Chinese medicine make through following method: Fructus Ligustri Lucidi, Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi, the Rhizoma Anemarrhenae add the alcohol reflux of 40-95% (mass concentration); Filter, filtrating merges, and reclaims ethanol; Filtrating is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃), and it is the ethanol extract clear paste; All the other Fructus Rubies, Fructus Lycii, Carapax Et Plastrum Testudinis, Radix Adenophorae, Radix Ophiopogonis, Semen Ziziphi Spinosae (stir-fry), Radix Rehmanniae, Radix Paeoniae Rubra, Concha Margaritifera, Herba Dendrobii, Flos Chrysanthemi, Herba Ecliptae, Folium Mori, Radix Cynanchi Atrati, the Rhizoma Anemarrhenae and Radix Scutellariae decocte with water; Filter; Filtrating merges; Filtrating is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃), and it is the water extract clear paste; Above-mentioned ethanol extract and two kinds of clear paste of water extract are merged, be dried to fine powder, be the extract components in the Chinese medicinal components of the present invention; This extract components mixes with Radix Polygoni Multiflori (black soya bean wine is processed) powder and Radix Paeoniae Alba powder, is the Chinese medicinal components in the solid preparation of Chinese medicine of the present invention.
In a preferred embodiment of the invention, the Chinese medicinal components in the solid preparation of Chinese medicine of the present invention obtains through following method:
Radix Polygoni Multiflori, the Radix Paeoniae Alba are ground into fine powder, sieve, and be subsequent use;
Fructus Ligustri Lucidi, Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi, the Rhizoma Anemarrhenae add the alcohol reflux 2 times of 40-95%, and each 1.5 hours, filter, filtrating merges, and reclaims ethanol to there not being the alcohol flavor, is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃); This concentration of ethanol in the 40-95%wt scope all can, preferred 55-85%, more preferably 70%; This concentration of ethanol refers to mass concentration, also can represent by %wt;
Ten five tastes such as all the other Fructus Rubies; Comprise Fructus Rubi, Fructus Lycii, Carapax Et Plastrum Testudinis, Radix Adenophorae, Radix Ophiopogonis, Semen Ziziphi Spinosae (stir-fry), Radix Rehmanniae, Radix Paeoniae Rubra, Concha Margaritifera, Herba Dendrobii, Flos Chrysanthemi, Herba Ecliptae, Folium Mori, Radix Cynanchi Atrati, the Rhizoma Anemarrhenae and Radix Scutellariae; Decocte with water 3 times each 1.5 hours, filters; Filtrating merges, and is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃);
Above-mentioned two kinds of clear paste are merged, be dried to fine powder;
Fine powder and above-mentioned Radix Polygoni Multiflori (black soya bean wine is processed) powder and these two kinds of Chinese medicine fine powder mixings of Radix Paeoniae Alba powder with above-mentioned clear paste obtains promptly get described Chinese medicinal components.
The fineness of fine powder of the present invention referred generally at least to cross 50-200 purpose fine powder, and preferably this fine powder is crossed the surplus slag of 90 mesh sieves≤6%, 70 mesh sieve and all passed through.
Above-mentioned Chinese medicinal components is added right amount of auxiliary materials Mel, starch, calcium sulfate, microcrystalline Cellulose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, micropowder silica gel, Icing Sugar, lactose, magnesium stearate or its combination in any, process needed dosage form and promptly get solid preparation of Chinese medicine of the present invention; This solid preparation of Chinese medicine can be tablet, capsule, granule, pill etc.; This pill is the pill of having got rid of outside the honeyed pill that all flavour of a drug former powder is used as medicine; Can be the pill that pressing obtains, also can be the pill that general method for making obtains, for example the watered pill, water-honeyed pill, micropill etc.
The present invention is added in Mel in the Chinese medicinal components as adjuvant; Promptly; Is that this is a technology as well known to those skilled in the art, repeats no more at this by the difference decision of Chinese medicine preparation (Chinese patent medicine) and Western medicine prepn with Mel as the adjuvant of Chinese medicine preparation (comprising solid preparation of Chinese medicine and liquid preparation of Chinese medicine).
When solid preparation of Chinese medicine of the present invention is tablet; Be conventional right amount of auxiliary materials starch, calcium sulfate, microcrystalline Cellulose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, micropowder silica gel, Icing Sugar, lactose, magnesium stearate or its combination in any that above-mentioned Chinese medicinal components is added tablet; Compacting gets final product in flakes; Also can wrap film-coat in the back in flakes, promptly get coated tablet in compacting.
Solid preparation of Chinese medicine of the present invention is mainly used in the treatment climacteric syndrome, the menoxenia that the hepatic and renal YIN deficiency causes, hectic fever hyperhidrosis, insomnia forgetfulness, susceptible to lose temper due to restlessness, dizziness and tinnitus, dry throat and mouth, aching and soreness in limb, diseases such as arthralgia.
Its former dosage form of Chinese medicine composition in the above-mentioned solid preparation product of the present invention is a honeyed pill, and characteristics are that the crude drug amount is big, so patient's oral dose is also big, certainly will cause patient's psychology and physiological load.
The inventor is through after improveing original traditional oral liquid formulation for this reason; Other solid preparations have been developed; Especially tablet is the solid preparation of representative, and the solid preparation of Chinese medicine of treatment climacteric syndrome of the present invention can comprise preparations such as tablet, granule, powder, the watered pill, honeyed pill, condensed water honeyed pill, capsule; Be preferably tablet, promptly female precious sheet.Female precious sheet is to concentrate a kind of modern Chinese medicine compound preparation of processing by the female precious ball of traditional herbal mixture through extracting.
The different excipient substances that preparation adopted is different, and it is the general knowledge of this area, also is the routine techniques that those skilled in the art are familiar with, and repeats no more at this.
Excipient substance described in the above-mentioned solid preparation of Chinese medicine of the present invention is starch, calcium sulfate, microcrystalline Cellulose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, micropowder silica gel, Icing Sugar, lactose, magnesium stearate or its combination in any, and preferably this excipient substance is microcrystalline Cellulose and/or starch.
The addition of said medicine adjuvant is: the adjuvant gross weight that is added accounts for 0.1～5% of the described product gross weight of processing.
In the solid preparation of the present invention, especially be directed against some dosage form, for example the dispersion pill of pressing preparation; Excipient substance preferably also comprises micropowder silica gel; The micropowder silica gel amount generally is no more than 3% of total formulation weight amount, preferably is no more than 1%, and the effect of micropowder silica gel in preparation is except providing water transport channel; Also can be regarded as satisfying the weight of final product, supply weight with micropowder silica gel for all the components weight sum of said preparation.
Solid preparation of Chinese medicine of the present invention comprises tablet, granule, powder, the watered pill, honeyed pill, condensed water honeyed pill, capsule.
The solid preparation of Chinese medicine of treatment climacteric syndrome of the present invention is the improvement of tradition prescription dosage form (pill); It can keep it former effective in cure; Have advantage such as bioavailability and stabilized quality preferably again, and said preparation production mechanization, automaticity are high, output is big, the medicament health is prone to up to standardly, take simultaneously, carry, storage etc. is more convenient; Being convenient to modern production, is to meet the novel form that the medical sci-tech modernization requires.
Also can understand like this, solid preparation of Chinese medicine of the present invention obtains through following method.That is, the invention provides a kind of method for preparing of treating the solid preparation of Chinese medicine of climacteric syndrome, comprising:
1. Radix Polygoni Multiflori, the Radix Paeoniae Alba are ground into fine powder, sieve, and be subsequent use;
2. Fructus Ligustri Lucidi, Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi, the Rhizoma Anemarrhenae add the alcohol reflux 2 times of 40-95%, and each 1.5 hours, filter, filtrating merges, and reclaims ethanol to there not being the alcohol flavor, is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃); This concentration of ethanol in the 40-95%wt scope all can, preferred 55-85%, more preferably 70%; This concentration of ethanol refers to mass concentration, also can represent by %wt;
3. ten five tastes such as all the other Fructus Rubies; Comprise Fructus Rubi, Fructus Lycii, Carapax Et Plastrum Testudinis, Radix Adenophorae, Radix Ophiopogonis, Semen Ziziphi Spinosae (stir-fry), Radix Rehmanniae, Radix Paeoniae Rubra, Concha Margaritifera, Herba Dendrobii, Flos Chrysanthemi, Herba Ecliptae, Folium Mori, Radix Cynanchi Atrati, the Rhizoma Anemarrhenae and Radix Scutellariae; Decocte with water 3 times each 1.5 hours, filters; Filtrating merges, and is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃);
4. above-mentioned two kinds of clear paste are merged, be dried to fine powder;
5. fine powder and above-mentioned Radix Polygoni Multiflori (black soya bean wine is processed) powder and these two kinds of Chinese medicine fine powder mixings of Radix Paeoniae Alba powder of above-mentioned clear paste being obtained promptly get described Chinese medicinal components; Above-mentioned fine powder is generally 80-120 purpose powder;
6. above-mentioned Chinese medicinal components is added right amount of auxiliary materials, process needed dosage form and promptly get solid preparation of Chinese medicine of the present invention.
Above-mentioned solid preparation of Chinese medicine can be tablet, capsule, granule, pill etc.; This pill is the pill of having got rid of outside the honeyed pill that all flavour of a drug former powder is used as medicine; Can be the pill that pressing obtains, also can be the pill that general method for making obtains, for example the watered pill, water-honeyed pill, micropill etc.
What deserves to be mentioned is; The preferred solid preparation of the present invention is the dosage form that contains the Chinese medicine composition composition of traditional prescription; Tablet for example; For a person skilled in the art; Screening is fit to the extraction and purification process of the improvement dosage form (for example tablet) of the numerous and diverse prescriptions of Chinese medicine of the especially specific component of certain specific prescription, the adjuvant and the proportioning thereof of preparation, and its difficulty is far longer than the screening to the improvement dosage form of chemicals, even difficulty is also greater than to forming the screening of formulation and technology, adjuvant and proportioning thereof of common solid preparation that simple flavour of a drug are no more than the prescriptions of Chinese medicine of 10 flavors.
For a large amount of screening operation selected parts that female precious ball improvement dosage form is done following:
(1) technical study
1, the selection of Fructus Ligustri Lucidi seven flavor medicine alcohol extraction conditions such as (wine are processed):
Take by weighing Fructus Ligustri Lucidi 30g, Semen Cuscutae 20g, Cortex Lycii 30g, Radix Angelicae Sinensis 20g, the Rhizoma Anemarrhenae (chinaroot greenbrier sapogenin content is 1.16%) 30g, Caulis Spatholobi 60g 190g altogether in proportion, add 70% ethanol, observe medical material and soak situation.As a result, most of basic softening soaking into after 1 hour, medical material is inhaled the alcohol amount and is about 2 times.
It is generally acknowledged that the factor that influence is extracted has concentration of alcohol, amount of ethanol, extraction time, extraction time etc.Easy in order to test, we are factor A with the concentration of alcohol, and consumption is factor B, and extraction time is factor C, and extraction time is factor D, each factor three level.Table 1 is seen in the gauge outfit design.
Table 1 alcohol extraction factor level table
Because four factors are three levels, so select L
9(3
4) orthogonal table.Each test repeats once.Because of all containing the glycoside composition in Semen Cuscutae, Cortex Lycii and the Rhizoma Anemarrhenae in the flavour of a drug,, extraction process is investigated, and calculated the yield that extracts extractum so be index with the rate of transform of chinaroot greenbrier sapogenin in the Rhizoma Anemarrhenae.
Method step: press L
9(3
4) orthogonal table extracts; Get Fructus Ligustri Lucidi 30g, Semen Cuscutae 20g, Cortex Lycii 30g, Radix Angelicae Sinensis 20g, the Rhizoma Anemarrhenae (chinaroot greenbrier sapogenin content is 1.16%) 30g, Caulis Spatholobi 60g at every turn; Add alcohol before the extraction earlier and soaked 60 minutes, extraction, filtration, cold drying, weigh, calculate paste volume and also measure chinaroot greenbrier sapogenin content; Calculate the rate of transform, add up and select preferred plan with this.
With the content of chinaroot greenbrier sapogenin in the extractum and the chinaroot greenbrier sapogenin cubage rate of transform in the medical material, the result sees table 2,3.
Table 2 chinaroot greenbrier sapogenin rate of transform orthogonal experiments
The variance analysis of the table 3 chinaroot greenbrier sapogenin rate of transform
From the rate of transform of chinaroot greenbrier sapogenin, factor D＞A＞B＞C has significant difference, and optimum condition is A
2B
1C
2D
3, promptly add 8 times of amount 70% alcohol reflux 2 times, each 2 hours.
Get each 190g of raw material respectively, carry out repeated trials by optimum condition, the result sees table 4.
Table 4 extraction process contrast table
2, the research carried of 15 flavor liquid medicine such as Fructus Rubi:
Take by weighing Radix Adenophorae 7.5g, Radix Ophiopogonis 5g, Fructus Rubi 5g, Fructus Lycii 5g, Semen Ziziphi Spinosae (stir-fry) 2.5g, Radix Paeoniae Rubra 7.5g (paeoniflorin content 2.89%), Herba Dendrobii 7.5g, Radix Rehmanniae 7.5g, Flos Chrysanthemi 7.5g, Herba Ecliptae 10g, Folium Mori 5g, Radix Cynanchi Atrati 7.5g, Radix Scutellariae 7.5g, Carapax Et Plastrum Testudinis 3.75g, Concha Margaritifera 15g; Add 10 times of water gagings and soak, constantly observed result.Basically soak into after 1 hour, water absorption is about 3 times.
Set: extracting the water yield is factor A, and extraction time is factor B, and extraction time is factor C, and every factor designs three levels, presses L
9(3
4) orthogonal table makes an experiment, table 5 is seen in design.
Table 5 water extraction factor level design table
Method step: press L
9(3
4) orthogonal table extracts; Get Radix Adenophorae 7.5g, Radix Ophiopogonis 5g, Fructus Rubi 5g, Fructus Lycii 5g, Semen Ziziphi Spinosae (stir-fry) 2.5g, Radix Paeoniae Rubra 7.5g, Herba Dendrobii 7.5g, Radix Rehmanniae 7.5g, Flos Chrysanthemi 7.5g, Herba Ecliptae 10g, Folium Mori 5g, Radix Cynanchi Atrati 7.5g, Radix Scutellariae 7.5g, Carapax Et Plastrum Testudinis 3.75g, Concha Margaritifera 15g at every turn; Soaked earlier before the extraction 60 minutes, and extraction, filtration, cold drying, weighed, calculate paste volume and also measure paeoniflorin content; Calculate the rate of transform, add up and select preferred plan with this.
Calculate the rate of transform with paeoniflorin content in paeoniflorin content in the extractum and the crude drug, the result sees table 6,7.
Table 6 water extraction orthogonal experiments
Table 7 is the analysis of variance table of index with the peoniflorin rate of transform
F
1-0..10(2，2)＝9.00 F
1-0.05(2，2)＝19.00 F
1-0.01(2，2)＝99.00
ANOVA showed significant: with the peoniflorin rate of transform is index, and factor B puies forward the result to the water of this kind has appreciable impact, with B
2For good; Factor A, C put forward the result to the water of this kind and do not make significant difference, and see from intuitive analysis, with A
3, C
1For good.Therefore, with A
3B
2C
1Be optimum condition, that is: add 8 times of decoctings and boil 3 times, each 1.5 hours, consider medical material suction twice water, so confirm that extraction process by water for adding 10 times of water loggings bubbles 60 minutes earlier, decocted 1.5 hours, add 8 times of decoctings again and boil 2 times, each 1.5 hours.
Get each 355g of raw material respectively, carry out repeated trials, the result sees table 8.
Table 8 extraction process contrast table
3, the selection of drying process:
Take by weighing Fructus Ligustri Lucidi (wine is processed, and oleanolic acid content is 0.76%) 30g, Semen Cuscutae 20g, Cortex Lycii 30g, Radix Angelicae Sinensis 20g, Rhizoma Anemarrhenae 30g, Caulis Spatholobi 60g 190g altogether in proportion, add 8 times of amount 70% alcohol reflux 2 times, each 1.5 hours; Get Radix Adenophorae 30g, Radix Ophiopogonis 20g, Fructus Rubi 20g, Fructus Lycii 20g, Semen Ziziphi Spinosae (stir-fry) 10g, Radix Paeoniae Rubra 30g, Herba Dendrobii 30g, Radix Rehmanniae 30g, Flos Chrysanthemi 30g, Herba Ecliptae 40g, Folium Mori 20g, Radix Cynanchi Atrati 30g, Radix Scutellariae 30g, Carapax Et Plastrum Testudinis 15g, Concha Margaritifera 60g; Add 10 times of water logging bubbles 60 minutes earlier; Decocted 1.5 hours; Add 8 times of decoctings again and boil 2 times, each 1.5 hours.
70% alcoholic acid extracting solution reclaims ethanol, merges when being concentrated into relative density and reaching 1.25～1.30 (50 ℃) with the water extract and takes out, and carries out spray drying and attempts.
Instrument and equipment: OPD-8 type spray dryer, the former dry company limited in great river, Shanghai.Centrifugal sprinkler, rotating speed 50Hz; Adopt 160 ℃ of EATs, leaving air temp is actual to be 80 ℃.With this understanding, the fineness of powder that spray is done is suitable, and wall sticking phenomenon does not take place.Paste-forming rate is 19.59%.
4, the selection of granulating process:
After spraying dried cream powder and the former powder of medical material mixing, add appropriate amount of auxiliary materials and use dry granulation.Because of starch is adjuvant commonly used, stable in properties, inoperative with medicine, safe and reliable, cheap and easy to get, and through test, grain forming is also better, so select for use starch as filler.
Instrument and equipment:
TF-MINI type non-slurry pelletizing machine, Japanese friendly Industrial Co., Ltd, pressure: 90kgf/cm
2It is better and stable to make grain shape.
For guaranteeing the stable of end product quality, in the preparation process, need granule is carried out Quality Control, measured angle of repose, bulk density.
(1) mensuration of angle of repose
Adopt the funnel method to measure the granule angle of repose after granulating, repeat 3 times, get its meansigma methods.
The mensuration of table 9 angle of repose
Conclusion: three lot sample article are close angle of repose, and all less than 40 degree, interpret sample has good mobility.
(2) mensuration of bulk density
Sample particle is evenly flowed in the graduated cylinder of 100ml, whenever hang down graduated cylinder from 2.5 centimetres of eminences and hit on the hardwood surface, hit altogether 3 times, weigh, example weight is promptly got divided by sample volume at a distance from 2 seconds.Repeat 3 times, get its meansigma methods.
The mensuration of table 10 bulk density
(3) hygroscopicity is investigated
Get small-sized glass exsiccator, be mixed with a series of different relative humidity, 26 ℃ of constant temperature, balance 24 hours with the sulphuric acid and the water of different proportion.
The about 1g of sample thief accurate claims surely, puts in the weighing botle of constant weight, puts in the above-mentioned exsiccator in each exsiccator parallel three parts respectively; Place after 12 hours, take out, the accurate title, decide, and calculates hydroscopicity; With the relative humidity is abscissa, and hydroscopicity is a vertical coordinate, draws sucting wet curve, and the result sees the following form.
Table 11 sulphuric acid-water is to sample average hydroscopicity under the humidity
Conclusion: the critical relative humidity of these article is 58%, and the relative humidity of should in technical process, noting controling environment in view of the above is below 58%.
5, tabletting (preparation of the present invention is following to be example with the tablet)
Instrument and equipment: GZPL-8 high speed tablet press (Beijing Gylongli Sci.&Tech. Co., Ltd.)
More than three batches of granules tablettings respectively.Add a small amount of magnesium stearate, mixing; Pressure 50kn regulates loading 0.5g, tabletting, and the result sees table 12.
Three crowdes of tabletting results of table 12
From three crowdes of tabletting results, more than the plain sheet that extrudes of particulate character meet the requirement of coating with sheet.
6, coating
Draw through overtesting: during coating total augment weight 3%, smooth in appearance, color and luster is even.Therefore the tablet total augment weight is less than 5% after can considering coating.
By above experiment, the present invention confirms that preparation technology is:
23 flavors in the prescription, Radix Polygoni Multiflori (black soya bean wine is processed), the Radix Paeoniae Alba are ground into fine powder, sieve, and be subsequent use;
Fructus Ligustri Lucidi (wine is processed), Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi, the Rhizoma Anemarrhenae add 8 times of amount 70% alcohol reflux 2 times; Each 1.5 hours, filter, filtrating merges; Reclaim ethanol to there not being the alcohol flavor, be evaporated to relative density 1.25～1.30 (50 ℃) below 60 ℃;
Ten five tastes such as all the other Fructus Rubies add 10,8,8 times of decoctings to boil 3 times, and each 1.5 hours, filter, filtrating merges, and is evaporated to the clear paste of relative density 1.25～1.30 (50 ℃) below 60 ℃; Above-mentioned two kinds of clear paste are merged, be dried to fine powder;
Above-mentioned two kinds of fine powder mixings; Add right amount of auxiliary materials starch, calcium sulfate, microcrystalline Cellulose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, micropowder silica gel, Icing Sugar, lactose, magnesium stearate or its combination in any; This adjuvant be described Chinese patent medicine process the finished product gross weight 0.1～5%, process granule, be pressed into 1000; The bag film-coat promptly gets.
Conclusion: qualified through check three lot sample article.This process stabilizing is rationally feasible, is suitable for big production.
Pilot scale three quality of lot testing results show that this process stabilizing is rationally feasible, are suitable for the big production of industry.
Solid preparation of Chinese medicine of the present invention is example with the tablet, and it is the taupe tablet, sweet in the mouth, little hardship; Many batches of female precious sheets are checked that heavy metal is all less than 10ppm in the sample, and arsenic salt is less than 2ppm; Weight differential, disintegration, microbial limit all meet " pertinent regulations under tablet item of Chinese pharmacopoeia version in 2005.
Specification requirement according to new drug (Chinese medicine) steady quality Journal of Sex Research; Adopt the female precious sheet three lot sample article (lot number 050201,050202,050203) of simulation commercially available back; Put under normal temperature condition and 37～40 ℃ and relative humidity 75% preservation condition and carry out study on the stability; Time is six months, and the examination project is to declare clinical trial according to these article to use quality standard, works out the examination project in conjunction with " requirement of new Chinese medicine stability test ": character, discriminating, moisture, disintegration, assay, limit test of microbe etc.; And examine with quality standard detecting method; The above-mentioned each item testing result of the result of appraisal relatively had no significant change with " 0 " moon, explained that solid preparation of Chinese medicine of the present invention is that example has preferable quality stability with the tablet.
If no specified otherwise is times of weight, the percent concentration of alcohol is a mass concentration to " doubly amount " among this paper.
Solid preparation of Chinese medicine of the present invention is an example with the tablet, is designated hereinafter simply as tablet or female precious sheet.
The pharmacological toxicology result of study
1. female precious sheet is to the influence of the female climacteric syndrome animal model of naturally-aged neural activity, memory function, sex hormone level.
Select 12-14 month female SD rat.Be divided into 7 groups at random by body weight: model group; Female precious sheet big (1.62g crude drug/kg), in (0.81g crude drug/kg), little (dose groups of 0.41g crude drug/kg) is equivalent to 2.0,1.0,0.5 times of clinical plan dose,equivalent; Female precious ball divides into groups with female precious sheet, and other gets healthy 4 months old rats as blank.Blank group and model control group are irritated stomach with the volume deionized water, and other group is given relative medicine, irritates stomach every day once, and each is organized the administration volume and is the 1.0ml/100g body weight, and successive administration 23d-28d measures each item index.
The result shows: every day with 1.62g/kg, 0.81g/kg, the 0.41g/kg. dosage filling female precious sheet of stomach and female precious ball once; The naturally-aged rat had under strange environment obviously alleviate the emotional response effect; Reduce the modification number of times of standing; With model group significant difference is arranged more all, female precious sheet and female precious ball comparing difference do not have significance, have reflected that the female precious sheet of naturally-aged rat is had and the close sedation of female precious ball.Irritate the female precious sheet of stomach with 0.81g/kg, 0.41g/kg dosage and once reach every day with 1.62g/kg, 0.81g/kg, the female precious ball of 0.41g/kg dosage filling stomach every day; Continuous 26 days; Can prolong the incubation period that old and feeble rat gets into the darkroom, reduce getting into the errors number that camera bellows is shocked by electricity in 3 minutes, the significance meaning all arranged with the model group comparing difference; Female precious sheet and female precious ball comparing difference do not have significance, have reflected that the female precious sheet of naturally-aged rat is had the effect that improve memory function close with female precious ball.Every day with 1.62g/kg, 0.81g/kg, the 0.41g/kg dosage filling female precious sheet of stomach and female precious ball once; Continuous 28 days; The content of estradiol in the naturally-aged rat blood serum is obviously raise; 0.81g/kg dosage can make, and progesterone levels obviously raises in the naturally-aged rat blood serum, female precious sheet of three dose groups and female precious ball can increase the adrenal weight of naturally-aged rat; 0.81g/kg, two dose groups of 0.41g/kg can increase uterus weight; 0.81g/kg the female precious sheet of dosage can increase the ovary organ coefficient; Female precious sheet and female precious ball have obvious rising effect to the norepinephrine in the naturally-aged rat cerebral tissue (NE); Female precious sheet small dose group can increase follicle number, uterus acinus number and the endometrium thickness in the old and feeble rat ovary; Middle dose groups can increase corpus luteum number and endometrium thickness in the ovary; The heavy dose of group of female precious ball can increase follicle number, uterus acinus number and endometrium thickness in the old and feeble rat ovary; Middle dose groups can increase uterus acinus number, and small dose group can increase endometrium thickness, with the model group comparing difference significance meaning is arranged all; Female precious sheet and female precious ball comparing difference do not have significance, have reflected the effect that the female precious sheet of naturally-aged rat is had the close rising estrogen level of female precious ball.
2. female precious sheet adds castration stress the mouse model neural activity, the influence of the length of one's sleep, sex hormone level.
Select healthy ICR strain female mice, animal is excised bilateral ovaries with the intraperitoneal anesthesia of 200mg/kg chloral hydrate; Postoperative 24 hours with the mouse tail tip with immobilization with adhesive tape in the stand edge; The nose drop suspention, once a day, each about 30 minutes; And blow whistle as sonic stimulation so continuous 10 days.Above model mice is divided into 7 groups at random by body weight: model group, female precious sheet big (2.32g crude drug/kg), in (1.16g crude drug/kg), little (0.58g crude drug/kg), be equivalent to 2.0,1.0,0.5 times of clinical plan dose,equivalent; Female precious ball divides into groups with female precious sheet.Other gets 12 capable sham-operations of healthy mice as the blank group, and blank group and model control group are irritated stomach with the volume deionized water, and other group is given relative medicine; Irritate stomach every day once; Each is organized the administration volume and is the 0.5ml/20g body weight, and successive administration 11d-17d measures index of correlation.
The result shows: female precious sheet and female precious ball obviously increase animal sleep number of elements due to the pentobarbital sodium sub-threshold dose at 2.32g/kg, 1.16g/kg, 0.58g/kg dosage successive administration 13d-16d; Pentobarbital sodium is obviously shortened the incubation period length of one's sleep; Prolong the length of one's sleep; With the model group comparing difference significance meaning is arranged all, female precious sheet and female precious ball comparing difference do not have significance, show castration is added the sedation that stress the female precious sheet of mice has the close collaborative pentobarbital sodium of female precious ball; Female precious sheet and female precious ball successive administration 17d have certain rising effect to estradiol in the mice serum and progesterone content, but not statistically significant.
3. the influence of the act end reaction that female precious sheet causes the disappointed motionless behavior of mice and morphine.
Select healthy ICR strain female mice body weight 18-20g; Be divided into 7 groups at random by body weight; Be respectively: blank group, female precious sheet big (2.32g crude drug/kg), in (1.16g crude drug/kg), little (0.58g crude drug/kg), be equivalent to 2.0,1.0,0.5 times of clinical plan dose,equivalent; Female precious ball divides into groups with female precious sheet, and the blank group gives with the volume deionized water, and other group is given relative medicine, irritates stomach every day once, and the administration volume is the 0.5ml/20g body weight, successive administration 7-8 days, measures index of correlation.
The result shows: female precious sheet and the female female precious sheet of precious ball successive administration 11d and female precious ball 2.32g/kg, 1.16g/kg, 0.58g/kg dosage, all can prolong the mice straub tail reaction incubation period that morphine causes, and alleviate the straub tail reaction that mice is caused by excited, anxiety; Obviously prolong because of the motionless time of suspension; With blank group comparing difference the significance meaning is arranged all; Female precious sheet and female precious ball comparing difference do not have significance; Show that female precious sheet has the close tranquilizing effect of female precious ball, can alleviate climacteric women anxiety and intense strain, alleviate menopause syndrome.
4. female precious sheet is to the influence of scopolamine, Anisodine induced mice learning and memory acquired disturbance.
Select healthy ICR strain female mice body weight 18-20g; Be divided into 8 groups at random by body weight; Be respectively: blank group, model control group, female precious sheet big (2.32g crude drug/kg), in (1.16g crude drug/kg), little (0.58g crude drug/kg), be equivalent to 2.0,1.0,0.5 times of clinical plan dose,equivalent; Female precious ball divides into groups with female precious sheet, and blank group and model control group give with the volume deionized water, and other group is given relative medicine, irritates stomach every day once, and the administration volume is the 0.5ml/20g body weight, successive administration 7-10 days.All the other respectively organize lumbar injection scopolamine 5mg/kg and Anisodine 10mg/kg causes learning and memory acquired disturbance model to remove the blank group, measure index of correlation.
The result shows: female precious sheet and the female female precious sheet of precious ball successive administration 7-11d and female precious ball 2.32g/kg, 1.16g/kg, 0.58g/kg dosage; To the effect of having clear improvement of scopolamine induced mice dysmnesia; Reduce mice errors number in water maze, the 2.32g/kg dose groups can obviously shorten the mice disembarkation time; Female precious sheet at 2.32g/kg, 1.16g/kg, 0.58g/kg dosage and female precious ball 2.32g/kg, 1.16g/kg dosage to the effect of having clear improvement of Anisodine induced mice dysmnesia; Can prolong mice and get into darkroom incubation period; Reduce errors number in the 3min, with the model control group comparing difference significance meaning is arranged all, female precious sheet and female precious ball comparing difference do not have significance; Showing that female precious sheet and female precious ball all have improves the animal dysmnesia that chemical substance causes, function in delaying senility.
5. female precious sheet is to the influence of rat sweat secretion.
Select healthy SD strain female rats body weight 190-210g; Be divided into 7 groups at random by body weight; Be respectively: blank group, female precious sheet big (1.62g crude drug/kg), in (0.81g crude drug/kg), little (0.41g crude drug/kg), be equivalent to 2.0,1.0,0.5 times of clinical plan dose,equivalent; Female precious ball divides into groups with female precious sheet; The blank group gives with the volume deionized water, and other group is given relative medicine, irritates stomach every day once; The administration volume is the 1.0ml/100g body weight; Successive administration 12 days is respectively organized rat skin lower injection pilocarpine 3.5mg/100g and is faced upward fixedly rat of position after the last administration, measure sufficient sole of the foot antiperspirant and count.
The result shows: female precious sheet and female precious ball are at 1.62g/kg, 0.81g/kg, 0.41g/kg dosage; All can obviously suppress the sufficient sole of the foot portion sweat gland secretion that causes because of the subcutaneous injection pilocarpine; With blank group comparing difference the significance meaning is arranged all; Female precious sheet and female precious ball comparing difference do not have significance, show that female precious sheet has the symptom of the close alleviation Woman climacteric hectic fever hyperhidrosis of female precious ball.
Comprehensive above Pharmacodynamic test of active extract result; Show that female precious sheet has endocrine regulation raising estrogen, improves functions such as memory, tranquillizing and allaying excitement, anxiety under this test dose and experimental condition, have obviously to alleviate the related indication effect of climacteric syndrome.
Acute toxicity test:
For the female precious sheet of reflection is to mice toxic reaction in a short time comprehensively, employing mice maximum dosage-feeding test carrying out acute toxicity test is studied.Under this experiment condition; Select ICR strain cleaning level mice for use, irritate stomach and give the female precious sheet medicinal liquid of 2.68g crude drug/ml (maximum administration concentration) 40ml/kg. time, observe 7d continuously; Do not see dead mouse and obvious toxic-side effects; Put to death spoil behind the 7d and dissect, naked eyes are not seen obvious pathological change, and main organs is not made significant difference.Experimental result shows that the maximum dosage of female precious sheet mice is 107.2g crude drug/kg, is equivalent to 916 times of clinical plan consumption, and mice is safe under this dosage.
The anxious poison of female precious ball is tested in 2002 and is accomplished, and its maximum dosage-feeding is 8.333g crude drug/kg, is equivalent to 100 times of clinical consumption.
Above result shows female precious sheet maximum dosage-feeding 107.2 crude drugs/kg apparently higher than female precious ball 8.333g crude drug/kg, and safety is more guaranteed.
Long term toxicity test:
The result shows to the female precious sheet of rat continuous irrigation stomach 11.7,5.8,2.9g crude drug/kg26 week, does not see and the relevant obvious toxicity of female precious sheet that female precious sheet no-effect level is 11.7g crude drug/kg/ days, is equivalent to draft 100 times of the daily dosage of people (60kg) approximately.
6 months long term toxications of female precious sheet were accomplished in 2002; Dosage dosage is 4.20,2.10,1.05g crude drug/kg, is equivalent to 50,25,12.6 times of clinical consumption, and the result shows that 4.20g crude drug/kg dose groups is in administration 17-21 week the weight of animals; RBC, HGB in the hemogram; The ovary coefficient significantly is lower than the blank group, and other index and blank group comparing difference do not have the significance meaning, and the prompting non-toxic is 2.10g crude drug/kg.
Above result shows that female precious sheet no-effect level is 11.7g crude drug/kg/ days, is equivalent to draft the day for human beings 100 times with dosage approximately.Female precious ball non-toxic is 2.10g crude drug/kg/ days, is equivalent to the day for human beings with more than 25 times of dosage.Female precious sheet non-toxic is apparently higher than female precious ball, and safety is more guaranteed.
Study of pharmacy shows; The solid preparation of Chinese medicine preparation technology of improvement of the present invention is comparatively reasonable; Quality controllable, and have preferable quality stability, pharmacodynamic study is the result show; Female precious extract of bolus has endocrine regulation, improves memory, tranquillizing and allaying excitement, anxiety under test dose, alleviate the effect of climacteric syndrome symptom.Toxicologic study result shows that female precious sheet has safety preferably, 107.2g crude drug/kg body weight; Be equivalent to 916 times of clinical application amount, observed continuously seven days, untoward reaction and animal dead do not occur; Compare with female precious ball; Female precious sheet maximum dosage-feeding 107.2 crude drugs/kg, apparently higher than female precious ball 8.333g crude drug/kg, safety is more guaranteed; Long term toxicity test (six months) is the result represent, during the whole administration, animal behavior, motion, the no abnormal performance of the mental status are ingested, two just normal, do not have significant difference between each group of body weight gain rate, do not have dead; Urinate eight, routine blood test and 10 biochemical indicators of serum equal not statistically significant between each group; It is all normal that each organizes heart rate, electrocardiogram, and each internal organs outward appearance of each treated animal is not all found macroscopic pathological change, there was no significant difference between each group of main organs coefficient; Histopathologic examination, 17 kinds of internal organs such as each treated animal heart, liver, spleen, lung, kidney do not see that all drug-induced toxic pathology changes as a result.Compare with female precious ball, female precious sheet no-effect level is 11.7g crude drug/kg/ days, is 2.10g crude drug/kg/ days apparently higher than female precious ball non-toxic.
Female precious sheet non-toxic is apparently higher than female precious ball, and safety is more guaranteed, and the problem that this desire of the present invention just solves also is the object of the invention, fact proved that the present invention has reached Expected Results.
Can find out that from above-mentioned result of study female precious sheet preparation technology is reasonable, stable and controllable for quality, pharmacological action is clear and definite, and safety is better, for its clinical treatment climacteric syndrome provides experimental basis.
Solid preparation of Chinese medicine of the present invention comprises tablet, and except that Radix Polygoni Multiflori (black soya bean wine is processed), the Radix Paeoniae Alba two flavors still keep former powder is used as medicine, all the other flavour of a drug are processed preparation after all adopting extractions, concentrated, drying.It is identical with pill to take the crude drug amount, and through the test of pesticide effectiveness, toxicological test checking, tablet and pill do not have significant difference.But two of the every clothes of tablet, totally one grammes per square metre is merely 1/5th of former dosage form dose, has reduced taking dose effectively.
The specific embodiment
Specify the present invention below in conjunction with embodiment, but do not limit practical range of the present invention.
Right amount of auxiliary materials in following examples refers to the gross weight that the adjuvant amount that adds and recipe quantity sum be equal to final products in theory and gets final product; Consider inevitable waste in the practical operation; Those skilled in the art can do with adjustment according to the quantity size of concrete kind, dosage form and the production of producing, and it is a routine techniques.
Embodiment 1: female precious sheet
Prescription (kg): Fructus Ligustri Lucidi (wine is processed) 3 Fructus Rubies 2 Semen Cuscutae 2
Fructus Lycii 2 Radix Polygoni Multiflori (black soya bean wine is processed) 2
Carapax Et Plastrum Testudinis 1.5 Cortex Lycii 3 Radix Adenophoraes 2
Semen Ziziphi Spinosaes Radix Ophiopogonis 2 (stir-fry) 1
Radix Rehmanniae 3 Radix Paeoniae Albas 6 Radix Paeoniae Rubra 3
Radix Angelicae Sinensis 2 Caulis Spatholobis 6 Concha Margaritiferas 6
Herba Dendrobii 3 Flos Chrysanthemis 3 Herba Ecliptaes 4
Folium Mori 2 Radix Cynanchi Atratis 3 Rhizoma Anemarrhenaes 3
Radix Scutellariae 3 (above mass unit is a kilogram)
Adjuvant: microcrystalline Cellulose, starch are an amount of.
Preparation technology:
More than 23 the flavor, Radix Polygoni Multiflori, the Radix Paeoniae Alba are ground into fine powder, sieve; Fructus Ligustri Lucidi, Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi, the Rhizoma Anemarrhenae add 70% alcohol reflux 2 times, and each 1.5 hours, filter, filtrating merges, and reclaims ethanol to there not being the alcohol flavor, is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃); Ten five tastes such as all the other Fructus Rubies, decocte with water 3 times, each 1.5 hours, filter, filtrating merges, and is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃), and two kinds of clear paste merge, and are dried to fine powder; With above-mentioned two kinds of fine powder mixings, add microcrystalline Cellulose, starch is an amount of, processes granule, is pressed into 1000, the bag film-coat promptly gets.
Embodiment 2: the watered pill (compacting)
Prescription: with embodiment 1.
Preparation technology:
More than 23 the flavor, Radix Polygoni Multiflori, the Radix Paeoniae Alba are ground into fine powder, sieve, and be subsequent use; Fructus Ligustri Lucidi, Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi, the Rhizoma Anemarrhenae add 75% alcohol reflux 2 times, and each 1 hour, filter, filtrating merges, and reclaims ethanol to there not being the alcohol flavor, is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃); Ten five tastes such as all the other Fructus Rubies, decocte with water 3 times was respectively 2,1.5,1.5 hours, filtered, and filtrating merges, and is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃), and above-mentioned two kinds of clear paste are merged, and is dried to fine powder; With above-mentioned two kinds of fine powder mixings, add right amount of auxiliary materials water, process the watered pill 1000 grams, the bag film-coat promptly gets.
Embodiment 3: capsule
Prescription: with embodiment 1.Adjuvant is low-substituted hydroxypropyl cellulose and starch.
Preparation technology:
More than 23 the flavor, Radix Polygoni Multiflori, the Radix Paeoniae Alba are ground into fine powder, sieve, and be subsequent use; Fructus Ligustri Lucidi, Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi, the Rhizoma Anemarrhenae add 70% alcohol reflux 2 times, and each 1.5 hours, filter, filtrating merges, and reclaims ethanol to there not being the alcohol flavor, is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃); Ten five tastes such as all the other Fructus Rubies, decocte with water 3 times, each 1.5 hours, filter, filtrating merges, and is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃), and above-mentioned two kinds of clear paste are merged, and adds low-substituted hydroxypropyl cellulose and starch, spray drying system granule; Incapsulate, process 1000, promptly get.
Embodiment 4: granule
Prescription: with embodiment 1.Adjuvant is a starch.
Preparation technology:
More than 23 the flavor, Radix Polygoni Multiflori, the Radix Paeoniae Alba are ground into fine powder, sieve, and be subsequent use; Fructus Ligustri Lucidi, Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi, the Rhizoma Anemarrhenae add 65% alcohol reflux 2 times, and each 2 hours, filter, filtrating merges, and reclaims ethanol to there not being the alcohol flavor, is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃); Ten five tastes such as all the other Fructus Rubies, decocte with water 3 times was respectively 2,1,1 hours, filtered; Filtrating merges, and is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃), and above-mentioned two kinds of clear paste are merged spray drying; Add starch, system granule 1000 grams, packing promptly gets.
Embodiment 5: tablet
Prescription: with embodiment 1.
Adjuvant: microcrystalline Cellulose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose and magnesium stearate.
Preparation technology:
More than 23 the flavor, Radix Polygoni Multiflori, the Radix Paeoniae Alba are ground into fine powder, sieve; Fructus Ligustri Lucidi, Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi, the Rhizoma Anemarrhenae add 70% alcohol reflux 2 times, and each 1.5 hours, filter, filtrating merges, and reclaims ethanol to there not being the alcohol flavor, is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃); Ten five tastes such as all the other Fructus Rubies, decocte with water filters, and filtrating merging is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃), and above-mentioned two kinds of clear paste are merged, and adds equivalent crospolyvinylpyrrolidone and low-substituted hydroxypropyl cellulose, processes granule; Adding starch, magnesium stearate are pressed into 1000 in right amount, and the bag film-coat promptly gets.
Embodiment 6 water-honeyed pill
Prescription: with embodiment 1.Adjuvant: Mel, water.
Preparation technology:
More than 23 the flavor, Radix Polygoni Multiflori, the Radix Paeoniae Alba are ground into fine powder, sieve, and be subsequent use; Fructus Ligustri Lucidi, Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi, the Rhizoma Anemarrhenae add 70% alcohol reflux 2 times, and each 1.5 hours, filter, filtrating merges, and reclaims ethanol to there not being the alcohol flavor, is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃); Ten five tastes such as all the other Fructus Rubies, decocte with water 3 times each 1.5 hours, filters; Filtrating merges, and is concentrated into the clear paste of relative density 1.25～1.30 (50 ℃), and above-mentioned two kinds of clear paste are merged spray drying; Add 35% refined honey and suitable quantity of water, process 1000 gram water-honeyed pills, promptly get.
Claims (9)
1. solid preparation of Chinese medicine of treating climacteric syndrome; Comprise Chinese medicinal components and excipient substance, this Chinese medicinal components is made up of the raw material of following weight portion: 3 parts of 3 parts of Fructus Ligustri Lucidi, 2 parts of Fructus Rubies, 2 parts of Semen Cuscutae, 2 parts of Fructus Lycii, 2 parts of Radix Polygoni Multiflori, 1.5 parts of Carapax Et Plastrum Testudiniss, 3 parts of Cortex Lycii, 2 parts of Radix Adenophoraes, 2 parts of Radix Ophiopogonis, 1 part of Semen Ziziphi Spinosae, 3 parts of Radix Rehmanniae, 6 parts of the Radix Paeoniae Albas, 3 parts of Radix Paeoniae Rubra, 2 parts of Radix Angelicae Sinensis, 6 parts of Caulis Spatholobis, 6 parts of Concha Margaritiferas, 3 parts of Herba Dendrobiis, 3 parts of Flos Chrysanthemis, 4 parts of Herba Ecliptaes, 2 parts on Folium Mori, 3 parts of Radix Cynanchi Atratis, 3 parts of the Rhizoma Anemarrhenaes and Radix Scutellariaes; Wherein, The Radix Polygoni Multiflori and the Radix Paeoniae Alba are the former powder of raw medicinal material, and Fructus Ligustri Lucidi, Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi and the Rhizoma Anemarrhenae are its ethanol extract, and Fructus Rubi, Fructus Lycii, Carapax Et Plastrum Testudinis, Radix Adenophorae, Radix Ophiopogonis, Semen Ziziphi Spinosae, Radix Rehmanniae, Radix Paeoniae Rubra, Concha Margaritifera, Herba Dendrobii, Flos Chrysanthemi, Herba Ecliptae, Folium Mori, Radix Cynanchi Atrati and Radix Scutellariae are its water extract; And; Said Fructus Ligustri Lucidi is the Fructus Ligustri Lucidi that wine is processed, and said Radix Polygoni Multiflori is the Radix Polygoni Multiflori that black soya bean wine is processed, and said Semen Ziziphi Spinosae is the Semen Ziziphi Spinosae of parch.
2. solid preparation of Chinese medicine as claimed in claim 1, wherein, described solid preparation of Chinese medicine comprises tablet, granule, powder, the watered pill, honeyed pill, condensed water honeyed pill, capsule.
3. solid preparation of Chinese medicine as claimed in claim 1; Wherein, Described excipient substance comprises Mel, starch, calcium sulfate, microcrystalline Cellulose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, micropowder silica gel, Icing Sugar, lactose, magnesium stearate or its combination in any, and this adjuvant is 0.1～5% of a described solid preparation of Chinese medicine gross weight.
4. solid preparation of Chinese medicine as claimed in claim 1, wherein, described solid preparation of Chinese medicine is a tablet.
5. solid preparation of Chinese medicine as claimed in claim 4; Wherein, described excipient substance comprises Mel, starch, calcium sulfate, microcrystalline Cellulose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, micropowder silica gel, Icing Sugar, lactose, magnesium stearate or its combination in any.
6. solid preparation of Chinese medicine as claimed in claim 1, wherein, described Chinese medicinal components obtains through following method:
(1) Radix Polygoni Multiflori, the Radix Paeoniae Alba are ground into fine powder;
(2) Fructus Ligustri Lucidi, Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi, the Rhizoma Anemarrhenae add the alcohol reflux of 40-95%wt, filter, and filtrate recycling ethanol is concentrated into the clear paste of 50 ℃ of following relative densities 1.25～1.30;
(3) Fructus Rubi, Fructus Lycii, Carapax Et Plastrum Testudinis, Radix Adenophorae, Radix Ophiopogonis, Semen Ziziphi Spinosae, Radix Rehmanniae, Radix Paeoniae Rubra, Concha Margaritifera, Herba Dendrobii, Flos Chrysanthemi, Herba Ecliptae, Folium Mori, Radix Cynanchi Atrati and Radix Scutellariae; Decocte with water; Filter, filtrating is concentrated into the clear paste of 50 ℃ of following relative densities 1.25～1.30;
(4) clear paste with above-mentioned steps (2) and (3) merges, and is dried to fine powder;
(5) fine powder that above-mentioned clear paste is obtained mixes with above-mentioned Radix Polygoni Multiflori fine powder and Radix Paeoniae Alba fine powder, gained be described Chinese medicinal components.
7. the method for preparing of the solid preparation of Chinese medicine of the described treatment climacteric syndrome of claim 1, this method comprises:
(1) Radix Polygoni Multiflori, the Radix Paeoniae Alba are ground into fine powder;
(2) Fructus Ligustri Lucidi, Semen Cuscutae, Cortex Lycii, Radix Angelicae Sinensis, Caulis Spatholobi, the Rhizoma Anemarrhenae add the alcohol reflux of 40-95%wt, filter, and filtrate recycling ethanol is concentrated into the clear paste of 50 ℃ of following relative densities 1.25～1.30;
(3) Fructus Rubi, Fructus Lycii, Carapax Et Plastrum Testudinis, Radix Adenophorae, Radix Ophiopogonis, Semen Ziziphi Spinosae, Radix Rehmanniae, Radix Paeoniae Rubra, Concha Margaritifera, Herba Dendrobii, Flos Chrysanthemi, Herba Ecliptae, Folium Mori, Radix Cynanchi Atrati and Radix Scutellariae; Decocte with water; Filter, filtrating is concentrated into the clear paste of 50 ℃ of following relative densities 1.25～1.30;
(4) clear paste with above-mentioned steps (2) and (3) merges, and is dried to fine powder;
(5) fine powder that above-mentioned clear paste is obtained mixes with above-mentioned Radix Polygoni Multiflori fine powder and Radix Paeoniae Alba fine powder, promptly gets described Chinese medicinal components;
(6) Chinese medicinal components that above-mentioned steps (5) is obtained adds supplementary product starch, calcium sulfate, microcrystalline Cellulose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, micropowder silica gel, Icing Sugar, lactose, magnesium stearate or its combination in any, processes needed solid preparation of Chinese medicine.
8. the method for preparing of solid preparation of Chinese medicine as claimed in claim 7, wherein, described adjuvant is starch and/or microcrystalline Cellulose.
9. the method for preparing of solid preparation of Chinese medicine as claimed in claim 8, wherein, processing needed solid preparation of Chinese medicine is tablet.
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| CN106408129B (en) * | 2016-09-28 | 2021-05-07 | 河南中医药大学 | Method for detecting quality of traditional Chinese medicine decoction by relative density |
| CN110575495A (en) * | 2019-09-29 | 2019-12-17 | 甘肃中医药大学 | traditional Chinese medicine compound preparation for preventing and treating perimenopausal syndrome and preparation method thereof |
| CN115671217B (en) * | 2022-11-25 | 2023-08-01 | 长春中医药大学 | Traditional Chinese medicine formula for treating various symptoms before and after menopause |
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| CN1613457A (en) * | 2003-09-28 | 2005-05-11 | 赵如松 | Yinping yangmi pills |
| CN101293063A (en) * | 2007-04-26 | 2008-10-29 | 北京亚东生物制药有限公司 | Composition for treating climacteric syndrome, preparation and quality control method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1613457A (en) * | 2003-09-28 | 2005-05-11 | 赵如松 | Yinping yangmi pills |
| CN101293063A (en) * | 2007-04-26 | 2008-10-29 | 北京亚东生物制药有限公司 | Composition for treating climacteric syndrome, preparation and quality control method thereof |
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| Title |
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| 药典委员会.昆宝丸.《***颁药品标准》.1992,第76页. * |
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