CN102600418A - Medicinal composition for treating female climacteric syndrome, and preparation method thereof - Google Patents
Medicinal composition for treating female climacteric syndrome, and preparation method thereof Download PDFInfo
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Abstract
The invention provides a medicinal composition for treating female climacteric syndrome and a preparation method thereof, belonging to the field of medicinal preparation. The preparation method comprises the steps of volatile oil extraction and clathrating, water extraction, preparation making, etc. Compared with preparation prepared by the traditional method, the medicinal composition provided by the invention is prepared by clathrating technology, so that volatile oil stability is improved; ineffective impurities are removed by adopting extraction technology, so that dosage is educed, absorption is accelerated, curative effect is improved, and patient compliance is improved; and modern granulating technology and addition of lubricant are adopted to enhance fluidity, reduce loading error, improve preparation quality and production efficiency.
Description
Technical field
The present invention relates to a kind of preparation of drug combination method, particularly a kind of preparation of drug combination method that is used to treat climacteric syndrome belongs to field of pharmaceutical preparations.
Background technology
Climacteric syndrome is that women's ovarian function fails to the transition period of complete obiteration gradually, a series of symptoms that cause occur changing owing to decrease in estrogen causes psychology and physiology.On Chinese medicine, climacteric syndrome belongs to the category of " all diseases before and after the menopause ".Primary disease be the women before and after menopause, kidney qi is depleted gradually, dash appoint lose empty; Asthenia of essence and blood, menses are gradually exhausted, and menstruation will be broken and the physiological change that menopause occurred that arrives; But some women is because the influence of body constitution or Nervous and Mental Factors and other factors; For the moment can not adapt to these physiological changies, make the negative and positive disequilibrium, internal organs QI and blood functional disorder and the disorderly syndrome of a series of functions that occurs.If feelings will is not smooth, the liver failing to maintain the normal flow of QI is given birth in the stagnation of QI due to depression of the liver, or dysfunction of the spleen in transportation, phlegm-damp, or the fat abundant expectoration of plain body, and feelings will is not smooth, and with the passing of time stagnation of QI due to depression of the liver causes qi stagnation blood stasis, phlegm accumulating with stagnant blood and be disease.If the plain body deficiency of YIN, or exhaustion due to sexual indulgence fecund are empty towards conception vessel because menses is gradually exhausted, asthenia of essence and blood, deficiency of kidney-YIN, the kidney failing to nourish the liver, and cause the hepatic and renal YIN deficiency, excessive rising of liver-YANG; Or deficiency of kidney yin, can not go up the Ji the heart-yin, or hyperactivity of heart-fire, can not meet at kidney down, make heart kidney yin YANG edema fire disequilibrium, form disarmony between the heart and kidney.If innate deficiency of YANG in the body, or the kidney usually involved in chronic disease, or excess of sexual intercourse, the damage kidney yang, insufficiency of kidney-YANG can not warm spleen sun, forms the card of deficiency of spleen-YANG and kidneyYANG.This shows that the traditional Chinese medical science thinks that climacteric syndrome is a deficiency of kidney-QI, menses lacks, so that imbalance of YIN and YANG causes, and therefore when treatment, with the kidney invigorating gas, regulating YIN and YANG is a main method.
Relax more that capsule is that gold is scolded the exclusive product of Tibetan medicine Pharmaceutical limited company, record fascicle, standard numbering: WS-11010 (ZD-1010)-2002 in national standard for traditional Chinese medicines compilation surgery gynecological.Relaxing more, capsule preparations is to be processed by the medical material of following weight proportion: Fructus Amomi Rotundus 188g, Rhizoma Polygonati 32g, Radix Asparagi 32g, Semen Myristicae 32g, Lignum Aquilariae Resinatum 32g, Flos Caryophylli 32g, Rhizoma Gymnadeniae 32g.The back standard of becoming a full member is numbered: WS-11010 (ZD-1010)-2002-2011Z, the easypro more capsule preparations after becoming a full member is to be processed by the medical material of following weight proportion: Fructus Amomi Rotundus 148.5g, Rhizoma Polygonati 25.3g, Radix Asparagi 25.3g, Semen Myristicae 25.3g, Lignum Aquilariae Resinatum 25.3g, Flos Caryophylli 25.3g, Rhizoma Gymnadeniae 25.3g.Method for preparing is: above seven flavors, be ground into fine powder, and mixing incapsulates, and promptly gets.Have the QI and blood regulating, the effect of calming the nerves is used for the dysphoria that climacteric syndrome causes, and is dizzy weak, insomnia.To suffering from menoxenia, gynaecopathia patients such as leucorrhoea grow in quantity treat, and obtain good effect.
Patent tablet for treating climacteric syndrome (CN200610008436.0) provides the method for preparing of tablet for treating climacteric syndrome, and after Fructus Amomi Rotundus, Rhizoma Polygonati, Radix Asparagi, Rhizoma Gymnadeniae decocting were boiled, extracting solution was condensed into thick paste, with Lignum Aquilariae Resinatum, Flos Caryophylli and Semen Myristicae fine powder mixing granulation, tabletting.Patent capsule for treating climacteric syndrome (CN200610008438.X) provides Flos Caryophylli, Lignum Aquilariae Resinatum has been extracted volatile oil, medicinal residues and Fructus Amomi Rotundus, Semen Myristicae, Rhizoma Polygonati, Radix Asparagi, Rhizoma Gymnadeniae mixed extraction, and the water extract concentrates, and extractum and sucrose are granulated, and spray into volatile oil.A kind of easypro more Chinese medicine preparation and preparation method thereof (CN200510105324.2) of patent is full medicated powder end and is used as medicine.Is material base at present not, takes into full account the character of ingredient, adopt new extraction method for preparing with the plant composition.
Relax capsule more because respond well, and taken all factors into consideration patient's physiology, pathological characteristic, through clinical verification, evident in efficacy.Yet; Prior art all adopts raw medicinal material pulverizing, blended simple physical to handle about the more capsular method for preparing of relaxing; The raw material the effective elements of the medicine discharges slowly, badly influences absorbing of effective ingredient, needs badly and introduces modern method for preparing; Quick stripping, onset are provided, absorb the more preparation that better relaxes.
Summary of the invention
The present invention is directed to the deficiency of prior art, a kind of method for preparing that is used for the drug combination preparation of climacteric syndrome is provided.
Technical scheme of the present invention is following:
A kind of method for preparing that is used for the drug combination preparation of climacteric syndrome, the raw material medicines in portions by weight of said pharmaceutical composition consists of: Fructus Amomi Rotundus 100-240 weight portion, Rhizoma Polygonati 15-50 weight portion, Radix Asparagi 15-50 weight portion, Semen Myristicae 15-50 weight portion, Lignum Aquilariae Resinatum 15-50 weight portion, Flos Caryophylli 15-50 weight portion, Rhizoma Gymnadeniae 15-50 weight portion; May further comprise the steps:
(1) form proportioning by crude drug and get Fructus Amomi Rotundus, Semen Myristicae, Lignum Aquilariae Resinatum, Flos Caryophylli totally 4 flavor medical materials, by the 4-12 of 4 flavor medical material gross weights water extraordinarily, adopt steam distillation, extract volatile oil 3-7h, collect volatile oil, medicinal liquid filters, extracting solution A ' and medicinal residues A;
Gained volatile oil is added in the beta-schardinger dextrin-saturated aqueous solution of percent weight in volume 3-7%, the envelope-bulk to weight ratio of volatile oil and beta-schardinger dextrin-is 1ml: 3-10g, under the stirring condition; Keep 40 ℃-60 ℃ of temperature, stir 3-6h, 0-4 ℃ of cold preservation 12-48h; Sucking filtration; Deposition, 40 ℃ of-60 ℃ of vacuum dryings get volatile oil clathrate compound;
(2) form proportioning by crude drug and get Rhizoma Polygonati, Radix Asparagi, Rhizoma Gymnadeniae totally 3 flavor medical materials, mix, add water reflux, extract, 1-4 time with medicinal residues A after step (1) is extracted volatile oil; The amount that at every turn adds water is said 3 flavor medical materials and medicinal residues A gross weight 5-14 a times; Each 1-4h that extracts filters, with the extracting solution A ' merging behind step (1) the extraction volatile oil; Concentrating under reduced pressure is concentrated into that relative density is the fluid extract of 1.20-1.40 under the 50-60 ℃ of condition; Fluid extract is dry, get extract B;
(3) the extract B mixing that the volatile oil clathrate compound that above-mentioned steps (1) is made, step (2) make; Add conventional adjuvant; Be prepared into pharmaceutically acceptable any dosage form according to common process, comprise tablet, capsule, oral liquid, drop pill, granule, concentrated pill etc.
Said adjuvant comprises one or more the combination in solvent, diluent, disintegrating agent, correctives, antiseptic, coloring agent, binding agent, lubricant, the substrate.
Preferred according to the present invention, the raw material medicines in portions by weight of said pharmaceutical composition consists of: Fructus Amomi Rotundus 140-200 weight portion, Rhizoma Polygonati 20-40 weight portion, Radix Asparagi 20-40 weight portion, Semen Myristicae 20-40 weight portion, Lignum Aquilariae Resinatum 20-40 weight portion, Flos Caryophylli 20-40 weight portion, Rhizoma Gymnadeniae 20-40 weight portion;
Further preferred, the raw material medicines in portions by weight of said pharmaceutical composition consists of: Fructus Amomi Rotundus 188 weight portions, Rhizoma Polygonati 32 weight portions, Radix Asparagi 32 weight portions, Semen Myristicae 32 weight portions, Lignum Aquilariae Resinatum 32 weight portions, Flos Caryophylli 32 weight portions, Rhizoma Gymnadeniae 32 weight portions;
Further preferred, the raw material medicines in portions by weight of said pharmaceutical composition consists of: Fructus Amomi Rotundus 148.5 weight portions, Rhizoma Polygonati 25.3 weight portions, Radix Asparagi 25.3 weight portions, Semen Myristicae 25.3 weight portions, Lignum Aquilariae Resinatum 25.3 weight portions, Flos Caryophylli 25.3 weight portions, Rhizoma Gymnadeniae 25.3 weight portions;
Preferred according to the present invention; The present invention is used for the method for preparing of the medicament composition capsule agent of climacteric syndrome, and the raw material medicines in portions by weight of said pharmaceutical composition consists of: Fructus Amomi Rotundus 148.5g, Rhizoma Polygonati 25.3g, Radix Asparagi 25.3g, Semen Myristicae 25.3g, Lignum Aquilariae Resinatum 25.3g, Flos Caryophylli 25.3g, Rhizoma Gymnadeniae 25.3g; May further comprise the steps:
(1) form proportioning by crude drug and get Fructus Amomi Rotundus, Semen Myristicae, Lignum Aquilariae Resinatum, Flos Caryophylli totally 4 flavor medical materials, add water 1795.2g, adopt steam distillation, extract volatile oil 5h, collect volatile oil, medicinal liquid filters, extracting solution A ' and medicinal residues A;
The volatile oil that collection is obtained adds in the beta-schardinger dextrin-saturated aqueous solution of percent weight in volume 6%, and the envelope-bulk to weight ratio of volatile oil and beta-schardinger dextrin-is 1ml: 6g, under the stirring condition; Keep 50 ℃ of temperature; Stir 4h, 4 ℃ of cold preservation 12h, sucking filtration; Precipitate 50 ℃ of vacuum dryings, get volatile oil clathrate compound;
(2) form proportioning by crude drug and get Rhizoma Polygonati, Radix Asparagi, Rhizoma Gymnadeniae totally 3 flavor medical materials, mix, add the water reflux, extract, 2 times with medicinal residues A after step (1) is extracted volatile oil; Add for the first time water 2402.4g, add water 1801.8g for the second time, extract 2h at every turn; Filter; Extract the extracting solution A ' merging behind the volatile oil with step (1), concentrating under reduced pressure is concentrated into relative density under 55 ℃ of conditions and is 1.25 fluid extract; Fluid extract is dry, get extract B;
(3) the extract B mixing that the volatile oil clathrate compound that above-mentioned steps (1) is made, step (2) make; Adding corn starch at 4: 1 according to major ingredient and adjuvant weight ratio, is wetting agent system soft material with volumetric concentration 75% ethanol, crosses 40 eye mesh screens and granulates; Put in 60 ℃ of baking ovens dry; Cross 40 eye mesh screen granulate, encapsulated, promptly get.
The relation of weight portion of the present invention and parts by volume is g/ml or kg/l.
The present invention has following advantage:
1, characteristics of the present invention are to be material base with the plant composition, take into full account the character of ingredient, adopt new extraction method for preparing; Be prepared from; Compare with the preparation of traditional method preparation, the pharmaceutical composition of method preparation of the present invention has been removed invalid impurity under the prerequisite that keeps former preparation drug effect; And can reduce patient's dosage, improve the compliance of patient's medication.Specifically see the Test Example data declaration.
2, the present invention extracts the volatile oil component of prescription medical material, and adopts beta-cyclodextrin inclusion compound technology, has effectively guaranteed the stable of volatile oil active ingredient.Specifically see the Test Example data declaration.
3, the present invention extracts medical material, is used as medicine with form of extract, and the adding through modern granulation technique and lubricant has strengthened flowability, can reduce the loading amount error, improves the quality of the pharmaceutical preparations and production efficiency.Specifically see the Test Example data declaration.
4, the pharmaceutical composition of the present invention's preparation; Having overcome prior art is crude drug and pulverizes and to be used as medicine; Be not suitable for the shortcoming of modern formulation, adopt the pharmaceutical composition of the present invention's technology gained to can be used for multiple dosage forms such as capsule, granule, oral liquid, pill, drop pill, dispersible tablet.
The specific embodiment
Following embodiment and experimental example are used to further specify but are not limited to the present invention.Use the medicament composition capsule that is used for climacteric syndrome of the method preparation that is the embodiment of the invention 1 in the experimental example.
The raw material medicines in portions by weight proportioning of embodiment 1-5 pharmaceutical composition is following:
Fructus Amomi Rotundus 148.5g, Rhizoma Polygonati 25.3g, Radix Asparagi 25.3g, Semen Myristicae 25.3g, Lignum Aquilariae Resinatum 25.3g, Flos Caryophylli 25.3g, Rhizoma Gymnadeniae 25.3g.
The former commercially available easypro more capsule that uses as a comparison in the experimental example is scolded Tibetan medicine Pharmaceutical limited company product as the Qinghai gold.
Embodiment 1, a kind of preparation that is used for the medicament composition capsule of climacteric syndrome
(1) form proportioning by crude drug and get Fructus Amomi Rotundus, Semen Myristicae, Lignum Aquilariae Resinatum, Flos Caryophylli totally 4 flavor medical materials, add water 1795.2g, use steam distillation, extract volatile oil 5h, collect volatile oil, 6.39ml, medicinal liquid filters, extracting solution A ' and medicinal residues A;
The volatile oil that collection is obtained adds in the beta-schardinger dextrin-saturated aqueous solution of percent weight in volume 6%, and the envelope-bulk to weight ratio of volatile oil and beta-schardinger dextrin-is 1ml: 6g, under the stirring condition; Keep 50 ℃ of temperature; Stir 4h, 4 ℃ of cold preservation 12h, sucking filtration; Precipitate 50 ℃ of vacuum dryings, get volatile oil clathrate compound 43g;
(2) form proportioning by crude drug and get Rhizoma Polygonati, Radix Asparagi, Rhizoma Gymnadeniae totally 3 flavor medical materials, mix, add the water reflux, extract, 2 times with medicinal residues A after step (1) is extracted volatile oil; Add for the first time water 2402.4g, add water 1801.8g for the second time, extract 2h at every turn; Filter; Extract the extracting solution A ' merging behind the volatile oil with step (1), concentrating under reduced pressure is concentrated into relative density under 55 ℃ of conditions and is 1.25 fluid extract; Fluid extract is dry, get extract B 64.5g;
(3) the extract B mixing that the volatile oil clathrate compound that above-mentioned steps (1) is made, step (2) make; Adding corn starch at 4: 1 according to major ingredient and adjuvant weight ratio, is wetting agent system soft material with volumetric concentration 75% ethanol, crosses 40 eye mesh screens and granulates; Put in 60 ℃ of baking ovens dry; Cross 40 eye mesh screen granulate, process capsule, every dress 0.3g.
Embodiment 2, a kind of preparation that is used for the pharmaceutical composition tablet of climacteric syndrome
(1) form proportioning by crude drug and get Fructus Amomi Rotundus, Semen Myristicae, Lignum Aquilariae Resinatum, Flos Caryophylli totally 4 flavor medical materials, add water 2244g, use steam distillation, extract volatile oil 5h, collect volatile oil, 6.24ml, medicinal liquid filters, extracting solution A ' and medicinal residues A;
The volatile oil that collection is obtained adds in the beta-schardinger dextrin-saturated aqueous solution of percent weight in volume 4%, and the envelope-bulk to weight ratio of volatile oil and beta-schardinger dextrin-is 1ml: 4g, under the stirring condition; Keep 40 ℃ of temperature; Stir 5h, 4 ℃ of cold preservation 24h, sucking filtration; Precipitate 40 ℃ of vacuum dryings, get volatile oil clathrate compound 30g;
(2) form proportioning by crude drug and get Rhizoma Polygonati, Radix Asparagi, Rhizoma Gymnadeniae totally 3 flavor medical materials, mix, add the water reflux, extract, 2 times with medicinal residues A after step (1) is extracted volatile oil; Add water 2402.4g at every turn; Each 2h that extracts filters, with the extracting solution A ' merging behind step (1) the extraction volatile oil; Concentrating under reduced pressure is concentrated into relative density under 50 ℃ of conditions and is 1.27 fluid extract; Fluid extract is dry, get extract B 64.9g;
(3) the extract B mixing that the volatile oil clathrate compound that above-mentioned steps (1) is made, step (2) make according to common process, adds conventional adjuvant, processes tablet, and the bag film-coat promptly gets.
Embodiment 3, a kind of preparation that is used for the medicament composition granule agent of climacteric syndrome
(1) form proportioning by crude drug and get Fructus Amomi Rotundus, Semen Myristicae, Lignum Aquilariae Resinatum, Flos Caryophylli totally 4 flavor medical materials, add water 1346.4g, use steam distillation, extract volatile oil 6h, collect volatile oil, 6.34ml, medicinal liquid filters, extracting solution A ' and medicinal residues A;
The volatile oil that collection is obtained adds in the beta-schardinger dextrin-saturated aqueous solution of percent weight in volume 5%, and the envelope-bulk to weight ratio of volatile oil and beta-schardinger dextrin-is 1ml: 5g, under the stirring condition; Keep 60 ℃ of temperature; Stir 6h, 4 ℃ of cold preservation 12h, sucking filtration; Precipitate 60 ℃ of vacuum dryings, get volatile oil clathrate compound 37g;
(2) form proportioning by crude drug and get Rhizoma Polygonati, Radix Asparagi, Rhizoma Gymnadeniae totally 3 flavor medical materials, mix, add the water reflux, extract, 2 times with medicinal residues A after step (1) is extracted volatile oil; Add for the first time water 3003g, extract 2h, add water 2402.4g for the second time; Extract 1h, filter, with the extracting solution A ' merging behind step (1) the extraction volatile oil; Concentrating under reduced pressure is concentrated into relative density under 60 ℃ of conditions and is 1.20 fluid extract; Fluid extract is dry, get extract B 66.1g;
(3) the extract B mixing that the volatile oil clathrate compound that above-mentioned steps (1) is made, step (2) make according to common process, adds conventional adjuvant, processes granule, promptly gets.
Embodiment 4, a kind of preparation that is used for the pharmaceutical composition concentrated pill of climacteric syndrome
(1) form proportioning by crude drug and get Fructus Amomi Rotundus, Semen Myristicae, Lignum Aquilariae Resinatum, Flos Caryophylli totally 4 flavor medical materials, add water 1346.4g, use steam distillation, extract volatile oil 5h, collect volatile oil, 6.43ml, medicinal liquid filters, extracting solution A ' and medicinal residues A;
The volatile oil that collection is obtained adds in the beta-schardinger dextrin-saturated aqueous solution of percent weight in volume 6%, and the envelope-bulk to weight ratio of volatile oil and beta-schardinger dextrin-is 1ml: 6g, under the stirring condition; Keep 50 ℃ of temperature; Stir 5h, 3 ℃ of cold preservation 48h, sucking filtration; Precipitate 50 ℃ of vacuum dryings, get volatile oil clathrate compound 42g;
(2) form proportioning by crude drug and get Rhizoma Polygonati, Radix Asparagi, Rhizoma Gymnadeniae totally 3 flavor medical materials, mixes, add the water reflux, extract, 3 times, add water 2402.4g the first time with medicinal residues A after step (1) is extracted volatile oil; Extract 2h, add water 1801.8g for the second time, extract 1h; The amount that adds water for the third time is said 3 flavor medical materials and medicinal residues A gross weight 6 times, extracts 1h, filters; Extract the extracting solution A ' merging behind the volatile oil with step (1), concentrating under reduced pressure is concentrated into relative density under 55 ℃ of conditions and is 1.22 fluid extract; Fluid extract is dry, get extract B 65.5g;
(3) the extract B mixing that the volatile oil clathrate compound that above-mentioned steps (1) is made, step (2) make according to common process, adds conventional adjuvant, processes concentrated pill, promptly gets.
Embodiment 5, a kind of preparation that is used for the medicament composition dropping pills of climacteric syndrome
(1) form proportioning by crude drug and get Fructus Amomi Rotundus, Semen Myristicae, Lignum Aquilariae Resinatum, Flos Caryophylli totally 4 flavor medical materials, add water 1795.2g, use steam distillation, extract volatile oil 6h, collect volatile oil, 6.29ml, medicinal liquid filters, extracting solution A ' and medicinal residues A;
The volatile oil that collection is obtained adds in the beta-schardinger dextrin-saturated aqueous solution of percent weight in volume 4%, and the envelope-bulk to weight ratio of volatile oil and beta-schardinger dextrin-is 1ml: 4g, under the stirring condition; Keep 50 ℃ of temperature; Stir 4h, 4 ℃ of cold preservation 12h, sucking filtration; Precipitate 50 ℃ of vacuum dryings, get volatile oil clathrate compound 29.6g;
(2) form proportioning by crude drug and get Rhizoma Polygonati, Radix Asparagi, Rhizoma Gymnadeniae totally 3 flavor medical materials, mix, add the water reflux, extract, 2 times with medicinal residues A after step (1) is extracted volatile oil; Add water 1801.8g at every turn; Each 2h that extracts filters, with the extracting solution A ' merging behind step (1) the extraction volatile oil; Concentrating under reduced pressure is concentrated into relative density under 50 ℃ of conditions and is 1.27 fluid extract; Fluid extract is dry, get extract B 63.8g;
(3) the extract B mixing that the volatile oil clathrate compound that above-mentioned steps (1) is made, step (2) make according to common process, adds conventional adjuvant, processes drop pill, promptly gets.
Experimental example 1, stability test
With volatile oil is index, investigates the stability of the pharmaceutical composition that is used for climacteric syndrome.
Press the method for embodiment 1 and extract volatile oil, and enclose, preparation simultaneously is used for the medicament composition capsule of climacteric syndrome; By the former easypro more capsule of more capsular method for preparing preparation that relaxes of background technology part; Identical conditions (40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5%) held 0,1,2,3,6 month detects volatile oil content, and the result sees table 1.
Table 1 beta-cyclodextrin inclusion compound is to the investigation result of volatile oil stability
The result shows, volatile oil of the present invention with beta-cyclodextrin inclusion compound after, can improve the stability of volatile oil in preparation.
Experimental example 2, craft screening experiment
1, extraction process optimization test
(1) The effects of different extraction times
Get Fructus Amomi Rotundus 148.5g by the crude drug proportioning, Semen Myristicae 25.3g, Lignum Aquilariae Resinatum 25.3g, Flos Caryophylli 25.3g; Totally 4 flavors amount to 224.4g, add 8 times of weight water extraction volatile oil 5 hours, extract behind the volatile oil extracting solution in addition device preserve, extract medicinal residues and Rhizoma Polygonati 25.3g behind the volatile oil; Radix Asparagi 25.3g, Rhizoma Gymnadeniae 25.3g merges, and amounts to 300.3g, adds the water reflux, extract, 3 times; The amount that at every turn adds water is 8 times of weight, and volatile oil extracting solution and aqueous extract merging for the first time concentrate; Measure dried cream yield and polyoses content, second and third time aqueous extract concentrates separately respectively, measures dried cream yield, polyoses content.Result of the test is seen table 2
The The effects of the different extraction times of table 2
Can know according to measuring the result; With medicinal residues and Rhizoma Polygonati, Radix Asparagi, the Rhizoma Gymnadeniae united extraction 2 times that extract behind the volatile oil, each 2 hours, its polysaccharide extract rate was respectively (is 100% by 3 extraction polysaccharide summations) more than 90%; So extract 2 times, extract and just can satisfy extraction effect in 2 hours at every turn.
(2) different extraction times
Get Fructus Amomi Rotundus 148.5g by the crude drug proportioning, Semen Myristicae 25.3g, Lignum Aquilariae Resinatum 25.3g, Flos Caryophylli 25.3g; Totally 4 flavors amount to 224.4g, add 8 times of weight water extraction volatile oil 5 hours, extract behind the volatile oil extracting solution in addition device preserve, extract medicinal residues and Rhizoma Polygonati 25.3g behind the volatile oil; Radix Asparagi 25.3g, Rhizoma Gymnadeniae 25.3g merges, and amounts to 300.3g; Add the water reflux, extract, 2 times, the amount that at every turn adds water is 8 times of weight, and extraction time extracted according to the extraction time that relates in the table 3; Merge extractive liquid, concentrates respectively, measures dried cream yield and polyoses content.Measure the result and see table 3.
The The effects of table 3 different extraction times
Can know that according to measuring the result paste-forming rate and polysaccharide all can increase along with the prolongation of extraction time, extraction time is when being 2+1 hour; Polyoses content is 3.84g, and is slightly little, in the time of extraction time 2+2 and 2+3 hour; Paste-forming rate and polyoses content all differ not quite, and therefore preferred extraction time is each 2 hours.
(3) different extraction solvent consumptions
Get Fructus Amomi Rotundus 148.5g by the crude drug proportioning, Semen Myristicae 25.3g, Lignum Aquilariae Resinatum 25.3g, Flos Caryophylli 25.3g; Totally 4 flavors amount to 224.4g, add 8 times of weight water extraction volatile oil 5 hours, extract behind the volatile oil extracting solution in addition device preserve, extract medicinal residues and Rhizoma Polygonati 25.3g behind the volatile oil; Radix Asparagi 25.3g, Rhizoma Gymnadeniae 25.3g merges, and amounts to 300.3g; Add the water reflux, extract, 2 times, extracted 2 hours at every turn, the amount that at every turn adds water is extracted according to the consumption that designs in the table 4; Merge extractive liquid, concentrates, and measures dried cream yield and polyoses content.Measure the result and see table 4.
The The effects of the different solvent consumptions of table 4
Can know according to measuring the result; Paste-forming rate and polyoses content all can increase along with increasing of extraction solvent; The solvent amount is that 6+6 is when doubly measuring; Paste-forming rate and polyoses content are all slightly little, and the extracted amount difference of paste-forming rate and polyoses content is not very big when extracted amount is 8+6 and 8+8, and therefore preferred extraction solvent amount is 8+6 times.
In sum, extraction process is preferably and adds the water reflux, extract, 2 times, extracts 2 hours at every turn, adds 8 times of amounts for the first time, adds 6 times of amounts for the second time.
Experimental example 3, hydroscopicity and mobile the investigation
(1) calculating of extract and adjuvant amount ratio in the prescription: the more every capsules dress of the former technology of the capsule 0.3g that relaxes, take the 3-4 grain at every turn, be equivalent to crude drug 0.9-1.2g.After will being equivalent to the medicinal material extract of 1000 of former capsules, can relax more about 80g of pharmaceutical capsules compositions and volatile oil clathrate compound mixing amount to 120g, are equivalent to the about 300g of crude drug.Former capsule is taken crude drug by 1.2g at every turn, is equivalent to take extract 0.48g.The used capsule shells loading of thing combined according to the invention, every capsules dress 0.3g is by take 2 calculations at every turn; 0.12g adjuvant space can be arranged; Be that adjuvant and principal agent proportioning are 1: 4, the present composition is processed and is taken 2 behind the capsule at every turn and get final product, and has reduced patient's dosage.
(2) selection of adjuvant prescription: selecting microcrystalline Cellulose, lactose, dextrin, corn starch is adjuvant; Take by weighing pharmaceutical composition and the adjuvant that a certain amount of the present invention is used for climacteric syndrome by table 5; Cross 80 mesh sieve mixings; Put constant weight in the exsiccator, investigate the hydroscopicity and the angle of repose of the pharmaceutical composition fine powder that is used for climacteric syndrome of embodiment 1 preparation.
Compatibility prescription (the unit: g) of table 5 adjuvant and pharmaceutical composition
(3) mensuration of hydroscopicity: the glass exsiccator that the bottom is filled the sodium chloride supersaturated solution is put into 25 ℃ constant incubator constant temperature 24h, and the interior humidity relatively of exsiccator this moment is 75%.Put into the pharmaceutical composition medicated powder that is used for climacteric syndrome of thick about 2mm in the weighing botle bottom of constant weight; The glass exsiccator interior (the weighing bottle cap is opened) of accurately weighing and being placed on the sodium chloride supersaturated solution; In 25 ℃ constant incubator, keep; Regularly weighing is calculated as follows hydroscopicity:
Hydroscopicity (%)=(medicated powder weight after the moisture absorption-moisture absorption prodrug grain weight amount)/moisture absorption prodrug grain weight amount * 100% divides into groups according to above-mentioned tested number, and each operates parallel 2 parts, and the result sees table 6.
Table 6 hydroscopicity is measured the result
Can be known by the result, be index with the hydroscopicity, is good with corn starch and microcrystalline Cellulose in the various adjuvants.
(4) measure angle of repose: adopt the fixed funnel method; With the series connection of 3 funnels and be fixed in the height place of 1cm on the graph paper of horizontal positioned; The pharmaceutical composition medicated powder of carefully different auxiliary material being processed that is used for climacteric syndrome is poured uppermost funnel into till the medicated powder cone tip that bottom funnel forms touches bell mouth along hopper walls respectively; Measure the diameter (surveying repeatedly 6 times) of conical base by graph paper, calculate angle of repose, the result sees table 7.
Measure the result angle of repose of table 7 prescription medicated powder
Can be known by the result, be index with the angle of repose, is good with microcrystalline Cellulose and corn starch.
Comprehensive above-mentioned result of the test will make the medicated powder good fluidity, and hydroscopicity is low, can reduce production costs again, and be suitable then with corn starch.So selecting corn starch is adjuvant.
(5) with the corn starch be the granule and the powder properties comparison of adjuvant
1. getting the pharmaceutical composition 40g that is used for climacteric syndrome of embodiment 1 method preparation, add corn starch 10g, is wetting agent system soft material with 75% ethanol; Crossing 40 eye mesh screens granulates; Put drying in 60 ℃ of baking ovens, cross 40 eye mesh screen granulate, promptly get composition grain.
2. get the pharmaceutical composition 40g that is used for climacteric syndrome of embodiment 1 method preparation, add corn starch 10g, mix homogeneously is crossed 80 eye mesh screens, promptly gets composition powder.
3. measure hydroscopicity according to above-mentioned (3), measure angle of repose according to above-mentioned (4), the result sees table 8.
Table 8 corn starch granules and medicated powder angle of repose and hydroscopicity are measured the result
Can be known by above-mentioned result of the test, be adjuvant with the corn starch and process granule, can improve stability of formulation and flowability, the content uniformity in helping reducing to produce improves the quality of the pharmaceutical preparations.
Experimental example 4, the clinical trial of treatment climacteric syndrome
1. case diagnosis standard
Formulate diagnostic criteria with reference to " Chinese medicine, natural drug treatment climacteric syndrome clinical trial technological guidance principle " and data of literatures:
1. 40～60 years old age
2. menstruation menolipsis is more than 3 months, and the hectic fever sweating is a cardinal symptom;
3. can be with irritated irritability, palpitation and insomnia, headache uncomfortable in chest, abnormal emotion-thought, hypomnesis, fluctuation of blood pressure, waist and leg ache etc.
4. blood estradiol (estrodiol, E2)＜30pg/ml, follicle stimulating hormone (Follicle Stimulating Hormone, FSH)＞10IU/L;
2. case is included standard in
(1) meets the climacteric syndrome diagnostic criteria
(2) age 40-60 year
(3) Kupperman Index scoring was greater than 15 fens persons
(4) patient participates in research voluntarily
3. case exclusion standard
(1) do not meet the Western medicine diagnose standard
(2) age＜40 or＞60 years old person
(3) hypertension or pheochromocytoma patient
(4) hyperthyroidism patient
(5) mammary X-ray inspection or breast ultrasound inspection, the patient of discovery malignant breast tumor evidence
(6) uterine malignant tumour patient, endometrial hyperplasia patient are found in uterus ultrasound diagnosis
(7) mycete or bacillary vaginal infection, urinary system infection patient
(8) bilateral ovaries excision, ovarian tumor and premature ovarian failure person
(9) allergic constitution or to this medicine allergy sufferers
(10) merge serious primary disease such as cardiovascular and cerebrovascular, liver, kidney and hemopoietic system etc. and psychotic
(11) using estrogen and progestogen class medicine or similar Chinese medicine person
4. the scheme of taking medicine
Test group patient takes embodiment 1 capsule, one time 2,3 times on the one; The matched group patient takes the former preparation more capsule that relaxes, one time 4,3 times on the one; Eliminating cold for resuscitation mouth of a river clothes.Taking 28 days continuously is a course of treatment.
Patient's period in a medicine is taken similar or related drugs without must not agree, must not use estrogen and progestational hormone medicine, does not drink, and does not smoke, and diet is suitable light.
5. testing program
To meet case and go into to organize climacteric syndrome patient's 120 examples of standard, be divided into 2 groups at random, be respectively test group and matched group, every group 60 example.The scheme regulation is taken the relative medicine treatment according to taking medicine.Adopt the Kupperman table to mark before and after taking medicine
6. observation index
The Kupperman point system that adopts domestic improvement is marked before and after the patient is taken medicine, and observes patient's relevant symptoms, sign changes.Measure the patients with hepatic renal function before and after taking medicine.
7. therapeutic evaluation standard
(1) recovery from illness treatment back Kupperman scoring subtracting branch rate >=75%, transference cure; Drug withdrawal is not recurred in January;
(2) produce effects treatment back Kupperman scoring subtracting branch rate >=50%, symptom is most of to disappear, and does not influence patient's live and work;
(3) effectively treat back Kupperman scoring subtracting branch rate >=25%, symptom part less disappears, and slightly influences patient's live and work;
(4) Kupperman scoring subtracting branch rate＜25% after the futile treatment, symptom does not have to improve basically, influences patient's live and work;
Annotate: computing formula (nimodipine method) is: integration * 100% before (integration before the treatment-treatment back integration) ÷ treatment
8. result of the test
Result's { example (%) } of table 9 embodiment 1 composition capsule treatment climacteric syndrome
χ
2Check is compared * P＜0.05 with matched group
The above results shows: embodiment 1 composition capsule and former preparation are all effective in cure to climacteric syndrome.Matched group 60 routine patients cure 11 examples, and cure rate is 18.3%; Produce effects 24 examples, obvious effective rate are 40%; Effective 9 examples, effective percentage are 15%; Invalid 16 examples, inefficiency are 26.7%; Total effective rate is 73.3%.Test group 60 routine patients cure 13 examples, and cure rate is 21.7%; Produce effects 28 examples, obvious effective rate are 46.7%; Effective 11 examples, effective percentage are 18.3%; Invalid 8 examples, inefficiency are 13.3%; Total effective rate is 86.7%.Through χ
2Check is compared with matched group, and the test group total effective rate significantly is superior to matched group (P＜0.05).Prompting embodiment 1 composition capsule treatment climacteric syndrome effect is superior to former preparation.
In addition, two groups of patients do not see tangible untoward reaction in drug administration process, and the patients with hepatic renal function detects index all in normal range before and after taking medicine.
Claims (6)
1. method for preparing that is used for the drug combination preparation of climacteric syndrome, the raw material medicines in portions by weight of said pharmaceutical composition consists of: Fructus Amomi Rotundus 100-240 weight portion, Rhizoma Polygonati 15-50 weight portion, Radix Asparagi 15-50 weight portion, Semen Myristicae 15-50 weight portion, Lignum Aquilariae Resinatum 15-50 weight portion, Flos Caryophylli 15-50 weight portion, Rhizoma Gymnadeniae 15-50 weight portion; It is characterized in that, may further comprise the steps:
(1) form proportioning by crude drug and get Fructus Amomi Rotundus, Semen Myristicae, Lignum Aquilariae Resinatum, Flos Caryophylli totally 4 flavor medical materials, by the 4-12 of 4 flavor medical material gross weights water extraordinarily, adopt steam distillation, extract volatile oil 3-7h, collect volatile oil, medicinal liquid filters, extracting solution A ' and medicinal residues A;
Gained volatile oil is added in the beta-schardinger dextrin-saturated aqueous solution of percent weight in volume 3-7%, the envelope-bulk to weight ratio of volatile oil and beta-schardinger dextrin-is 1ml: 3-10g, under the stirring condition; Keep 40 ℃-60 ℃ of temperature, stir 3-6h, 0-4 ℃ of cold preservation 12-48h; Sucking filtration; Deposition, 40 ℃ of-60 ℃ of vacuum dryings get volatile oil clathrate compound;
(2) form proportioning by crude drug and get Rhizoma Polygonati, Radix Asparagi, Rhizoma Gymnadeniae totally 3 flavor medical materials, mix, add water reflux, extract, 1-4 time with medicinal residues A after step (1) is extracted volatile oil; The amount that at every turn adds water is said 3 flavor medical materials and medicinal residues A gross weight 5-14 a times; Each 1-4h that extracts filters, with the extracting solution A ' merging behind step (1) the extraction volatile oil; Concentrating under reduced pressure is concentrated into that relative density is the fluid extract of 1.20-1.40 under the 50-60 ℃ of condition; Fluid extract is dry, get extract B;
(3) the extract B mixing that the volatile oil clathrate compound that above-mentioned steps (1) is made, step (2) make; Add conventional adjuvant; Be prepared into pharmaceutically acceptable any dosage form according to common process, comprise tablet, capsule, oral liquid, pill, drop pill, granule, concentrated pill.
2. a kind of method for preparing that is used for the drug combination preparation of climacteric syndrome as claimed in claim 1; It is characterized in that said adjuvant comprises one or more the combination in solvent, diluent, disintegrating agent, correctives, antiseptic, coloring agent, binding agent, lubricant or the substrate.
3. a kind of method for preparing that is used for the drug combination preparation of climacteric syndrome as claimed in claim 1; It is characterized in that the raw material medicines in portions by weight of said pharmaceutical composition consists of: Fructus Amomi Rotundus 140-200 weight portion, Rhizoma Polygonati 20-40 weight portion, Radix Asparagi 20-40 weight portion, Semen Myristicae 20-40 weight portion, Lignum Aquilariae Resinatum 20-40 weight portion, Flos Caryophylli 20-40 weight portion, Rhizoma Gymnadeniae 20-40 weight portion.
4. like the arbitrary described a kind of method for preparing that is used for the drug combination preparation of climacteric syndrome of claim 1-3; It is characterized in that the raw material medicines in portions by weight of said pharmaceutical composition consists of: Fructus Amomi Rotundus 188 weight portions, Rhizoma Polygonati 32 weight portions, Radix Asparagi 32 weight portions, Semen Myristicae 32 weight portions, Lignum Aquilariae Resinatum 32 weight portions, Flos Caryophylli 32 weight portions, Rhizoma Gymnadeniae 32 weight portions.
5. like the arbitrary described a kind of method for preparing that is used for the drug combination preparation of climacteric syndrome of claim 1-3; It is characterized in that the raw material medicines in portions by weight of said pharmaceutical composition consists of: Fructus Amomi Rotundus 148.5 weight portions, Rhizoma Polygonati 25.3 weight portions, Radix Asparagi 25.3 weight portions, Semen Myristicae 25.3 weight portions, Lignum Aquilariae Resinatum 25.3 weight portions, Flos Caryophylli 25.3 weight portions, Rhizoma Gymnadeniae 25.3 weight portions.
6. like the arbitrary described a kind of method for preparing that is used for the drug combination preparation of climacteric syndrome of claim 1-3, the raw material medicines in portions by weight of said pharmaceutical composition consists of: Fructus Amomi Rotundus 148.5g, Rhizoma Polygonati 25.3g, Radix Asparagi 25.3g, Semen Myristicae 25.3g, Lignum Aquilariae Resinatum 25.3g, Flos Caryophylli 25.3g, Rhizoma Gymnadeniae 25.3g; It is characterized in that, may further comprise the steps:
(1) form proportioning by crude drug and get Fructus Amomi Rotundus, Semen Myristicae, Lignum Aquilariae Resinatum, Flos Caryophylli totally 4 flavor medical materials, add water 1795.2g, adopt steam distillation, extract volatile oil 5h, collect volatile oil, medicinal liquid filters, extracting solution A ' and medicinal residues A;
The volatile oil that collection is obtained adds in the beta-schardinger dextrin-saturated aqueous solution of percent weight in volume 6%, and the envelope-bulk to weight ratio of volatile oil and beta-schardinger dextrin-is 1ml: 6g, under the stirring condition; Keep 50 ℃ of temperature; Stir 4h, 4 ℃ of cold preservation 12h, sucking filtration; Precipitate 50 ℃ of vacuum dryings, get volatile oil clathrate compound;
(2) form proportioning by crude drug and get Rhizoma Polygonati, Radix Asparagi, Rhizoma Gymnadeniae totally 3 flavor medical materials, mix, add the water reflux, extract, 2 times with medicinal residues A after step (1) is extracted volatile oil; Add for the first time water 2402.4g, add water 1801.8g for the second time, extract 2h at every turn; Filter; Extract the extracting solution A ' merging behind the volatile oil with step (1), concentrating under reduced pressure is concentrated into relative density under 55 ℃ of conditions and is 1.25 fluid extract; Fluid extract is dry, get extract B;
(3) the extract B mixing that the volatile oil clathrate compound that above-mentioned steps (1) is made, step (2) make; Adding corn starch at 4: 1 according to major ingredient and adjuvant weight ratio, is wetting agent system soft material with volumetric concentration 75% ethanol, crosses 40 eye mesh screens and granulates; Put in 60 ℃ of baking ovens dry; Cross 40 eye mesh screen granulate, encapsulated, promptly get.
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| CN2012100891420A CN102600418A (en) | 2012-03-29 | 2012-03-29 | Medicinal composition for treating female climacteric syndrome, and preparation method thereof |
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| CN2012100891420A CN102600418A (en) | 2012-03-29 | 2012-03-29 | Medicinal composition for treating female climacteric syndrome, and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105194504A (en) * | 2014-05-27 | 2015-12-30 | 山东阿如拉药物研究开发有限公司 | Use of Shugeng capsule in preparation of nerve protection drugs |
| CN107007758A (en) * | 2017-05-25 | 2017-08-04 | 山东省疾病预防控制中心 | It is a kind of for pharmaceutical composition of women's climacteric syndrome and its preparation method and application |
| CN111068019A (en) * | 2019-11-22 | 2020-04-28 | 内蒙古民族大学 | Mongolian medicine composition and its action and application |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1840134A (en) * | 2006-01-21 | 2006-10-04 | 端智 | Capsule for treating climacteric syndrome |
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2012
- 2012-03-29 CN CN2012100891420A patent/CN102600418A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1840134A (en) * | 2006-01-21 | 2006-10-04 | 端智 | Capsule for treating climacteric syndrome |
Non-Patent Citations (1)
| Title |
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| 国家药品监督管理局: "《国家药品监督管理局，国家中成药标准汇编，中成药地方标准上升国家标准部分，外科 妇科分册》", 31 December 2002 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105194504A (en) * | 2014-05-27 | 2015-12-30 | 山东阿如拉药物研究开发有限公司 | Use of Shugeng capsule in preparation of nerve protection drugs |
| CN105194504B (en) * | 2014-05-27 | 2018-11-16 | 山东金诃药物研究开发有限公司 | The more capsule that relaxes is preparing the application having in neuroprotective medicine |
| CN107007758A (en) * | 2017-05-25 | 2017-08-04 | 山东省疾病预防控制中心 | It is a kind of for pharmaceutical composition of women's climacteric syndrome and its preparation method and application |
| CN111068019A (en) * | 2019-11-22 | 2020-04-28 | 内蒙古民族大学 | Mongolian medicine composition and its action and application |
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