CN100531721C - Dysmenorrhea treating solid medicine preparation and its preparation process - Google Patents

Abstract

The dysmenorrhea treating solid medicine preparation, named Yikunning, is prepared with angelica, nutagrass flatsedge rhizome, cassia bark, prepared rhizome of rehmannia, white peony root and other five kinds of Chinese medicinal materials; and it features its plasticizer of dextrin and/or lactose oligomer and the spray drying and dry pelletizing capable of maintaining the effective component completely and suitable for continuous GMP production. The medicine contains no ethanol, cane sugar and preservative, is safe, without side effect, and has many other advantages.

Description

A kind of medical solid preparation for the treatment of dysmenorrhea and preparation method thereof

Technical field

The present invention relates to a kind of women's of being used for the treatment of blood deficiency stagnation of QI, menoxenia, through preceding, postmenstrual abdominal pain lumbago, Chinese medicine of women's climacteric syndrome and preparation method thereof.

Background technology:

Along with the quickening of social rhythm and the increase of operating pressure, menoxenia, through preceding, menstrual period stomachache become women's common frdquently encountered disease.Lack in the modern chemistry medicine a kind of treat such disease safe, efficient, can be for the medicine taken for a long time.

This type of Chinese medicine preparation that has had at present is the liquid tincture, and dosage form falls behind, and medicine stability is poor; Contain antiseptic and a large amount of sucrose, the absorption of antiseptic and too much sugar there is no benefit to human body, influences the safe handling of preparation; Also can produce untoward reaction such as hyperglycemia to suffering from some patient who avoids sugared disease; Moreover, also contain preservative benzoic acid and ethanol in the liquid tincture.According to the literature, take the food and the medicine that contain preservative benzoic acid for a long time and can cause liver dysfunction, have potential liver toxicity,, can increase the weight of liver dysfunction particularly for the hepatic disease patient.Ethanol also is that most dysmenorrhea patients are unsuitable.In addition, tincture easily forms caking, influences curative effect of medication; The each dosage of tincture is measured by patient oneself, and dosage is inaccurate, influences the curative effect of preparation.

Summary of the invention:

Technical problem to be solved by this invention is to avoid above-mentioned existing in prior technology weak point, a kind of medical solid preparation for the treatment of dysmenorrhea is provided, to overcome liquid preparation because of containing the harmful effect of ethanol, antiseptic and a large amount of multitudinous sugar to human body, and reach preparation stabilization, effective ingredient is uniformly dispersed, taking convenience, the amount of getting is purpose accurately.

The present invention provides the preparation method of this medical solid preparation simultaneously.

The technical scheme that technical solution problem of the present invention is adopted is:

The female peaceful solid preparation of benefit, make by following bulk drugs:

90 parts of Radix Angelicae Sinensis, 60 parts of Rhizoma Cyperis, 15 parts on Cortex cinnamomi japonici (Ramulus Cinnamomi), 60 parts of Radix Rehmanniae Preparata, 60 parts of the Radix Paeoniae Albas, 60 parts of Rhizoma Chuanxiongs, 60 parts of Herba Leonuris, 30 parts of Rhizoma Corydalis, 15 parts of rhizoma sparganic, 15 parts of Pericarpium Citri junoriss.Be characterized in having in addition adjuvant 40-120 part as forming agent; Described forming agent is at least a in dextrin and the oligomeric lactose.

The preparation method characteristics of solid preparation of the present invention are to carry out as follows:

A. take by weighing raw material Radix Angelicae Sinensis, Rhizoma Cyperi, Cortex cinnamomi japonici (Ramulus Cinnamomi), Radix Rehmanniae Preparata, the Radix Paeoniae Alba, Rhizoma Chuanxiong, Herba Leonuri, Rhizoma Corydalis, rhizoma sparganic and Pericarpium Citri junoris and be ground into coarse powder;

Percolation under b, photograph fluid extract and the extractum item is made solvent with 45% ethanol, floods after 48 hours, with the speed of per minute 1～3ml percolation slowly, collect the liquid of just filtering, continue percolation to filtrate near colourless, merge the liquid of just filtering, the liquid of filtering concentrates, and mixing gets concentrated medicament;

C, adding forming agent stir, and filter spray drying, dry granulation, granulate;

D, granule tabletting, encapsulating capsule or fill are become bag, promptly get product.

Compared with the prior art, beneficial effect of the present invention is embodied in:

1, the present invention adopts solid preparations such as tablet, capsule or granule, and medicine stability is good, easily storage; Taking convenience, dosage are accurate, and preparation does not contain ethanol, antiseptic and sucrose, take safety and have no side effect.2, solid preparation of the present invention is that new technique by spray drying, dry granulation is prepared from.Spray drying technology is by nebulizer medicinal liquid to be sprayed into droplet, is dispersed in the thermal current, makes moisture flash evapn drying, and the loose powdered granule of formation, effective ingredient is not destroyed and reservation fully, has overcome present tincture and be aqueous solution state, effective ingredient is easily degraded and unsettled drawback; Make the effective ingredient mix homogeneously, overcome the easily drawback of caking of tincture; Dry granulation is that mechanical compaction, one-tenth under the medicine dry powder convection drying state are put in order and formed, and makes effective ingredient constant.The said method operating process is simple, is convenient to large-scale production under the seriality GMP condition.

The specific embodiment:

Embodiment 1:

The preparation of the female peaceful tablet of benefit

Take by weighing raw material Radix Angelicae Sinensis 90g, Rhizoma Cyperi 60g, Cortex cinnamomi japonici (Ramulus Cinnamomi) 15g, Radix Rehmanniae Preparata 60g, Radix Paeoniae Alba 60g, Rhizoma Chuanxiong 60g, Herba Leonuri 60g, Rhizoma Corydalis 30g, rhizoma sparganic 15g, Pericarpium Citri junoris 15g.

More than ten the flavor, be ground into coarse powder, according to the percolation under fluid extract and the extractum item, use 45% alcohol solvent, flood after 48 hours, with the speed of per minute 1～3ml percolation slowly, collect the about 750ml of liquid that just filters, continue percolation to filtrate near colourless, merge the liquid of just filtering, the liquid of filtering be concentrated into relative density be 1.06～1.12 (50 ℃ time) concentrated solution.

Add dextrin 80g, filter spray drying, the inlet temperature 170-180 during spray drying ℃ (being preferably 180 ℃), leaving air temp is 70-80 ℃ (being preferably 80 ℃), getting moisture is the dry fine powder of 4%-6%, dry granulation, and the temperature of charge during granulation is below 60 ℃, granulate, get brown yellow granule 160g, feeble QI, it is sweet to distinguish the flavor of.400 of tablettings.

Embodiment 2:

The preparation of the female Yiganning capsule of benefit

Preparation process is with embodiment 1, and different is with the granule filling capsule, gets 400 of capsules.

Embodiment 3:

The preparation of the female peaceful granule of benefit

Preparation process is with embodiment 1, and different is that the forming agent that is added is oligomeric lactose 120g, dry granulation (temperature of charge is below 60 ℃), and granulate gets brown yellow granule 200g, feeble QI, it is sweet to distinguish the flavor of, and granule filling is become bag, and every bag of 1g gets 200 bags of granules.

In the concrete preparation process:

About of the influence of concentrated solution relative density to drying process with atomizing

The spray drying efficient of medicinal liquid is relevant with the concentration of medicinal liquid, according to table 1, with the relative density 1.06～1.12 (50 ℃) of concentrated solution as striking point.

Table 1 concentrated solution relative density is to the influence of drying process with atomizing

About the influence of spray drying powder to effective ingredient

Carry out spray drying under suitable condition, effective ingredient is kept fully and be not destroyed, spray drying is also very important to grain forming, before and after the spray drying and the spray drying under the different condition influence of active constituent content and moisture be the results are shown in Table 2.

The variation of effective ingredient (ferulic acid, peoniflorin) retention rate before and after table 2 spray drying

Result of the test shows, selects 170-180 ℃ of air intake, and spray drying is carried out in 70-80 ℃ of air-out, and to the almost not influence of effective ingredient ferulic acid, content of paeoniflorin, and water content is 4.0～6.0%, can directly make granularity, granule that hardness is suitable.

About stability study to the female peaceful tincture of benefit, the female peaceful sheet of benefit, beneficial female Yiganning capsule

The female peaceful tincture of benefit, benefit female peaceful sheet, beneficial female Yiganning capsule being carried out stable contrast test, adopt the room temperature test that keeps sample, is index with ferulic acid, paeoniflorin content, experimental result such as table 3.

The stable contrast test of the female peaceful tincture of table 3 benefit, the female peaceful sheet of benefit, beneficial female Yiganning capsule

By technology such as spray dryinges the female peaceful tincture of benefit is made solid preparation, effective ingredient did not have significant change in 12 months, and the effective ingredient of the female peaceful tincture of benefit obviously descends.

Content of ferulic acid is measured

Measure according to high performance liquid chromatography (2000 editions one appendix VI D of Chinese Pharmacopoeia).

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler, and methanol-0.1% trifluoroacetic acid aqueous solution (35:65) is a mobile phase (v/v); The detection wavelength is 313nm.Number of theoretical plate calculates by the ferulic acid peak should be not less than 3000.

The preparation of reference substance solution: be taken at the ferulic acid reference substance 1.0mg that is dried to constant weight in the exsiccator, the accurate title, decide, and puts in the 10ml measuring bottle, adds mobile phase and be diluted to scale, shakes up, and makes the solution that every 1ml contains 0.1mg approximately, promptly.

The preparation of need testing solution: get this product powder 0.5g, the accurate title, decide, and puts in the 25ml measuring bottle, adds 50% methanol 20ml supersound extraction 30 minutes, adds 50% methanol again and be diluted to scale, shakes up, and centrifugal, supernatant is crossed 0.45 μ m microporous filter membrane, promptly.

Algoscopy: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject hplc determination, calculate, promptly.

Content of paeoniflorin is measured

This preparation is measured according to high performance liquid chromatography (" 2000 editions one appendix VI D of Chinese pharmacopoeia).Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler, methanol: sour water (20-40:80-60) is a mobile phase, and the detection wavelength is 230nm, and number of theoretical plate calculates by the peoniflorin peak should be not less than 3000;

The preparation of reference substance solution: it is an amount of to be taken at 60 ℃ of peoniflorin reference substances that are dried to constant weight, makes the solution that every 1ml contains 0.2mg with mobile phase, promptly;

The preparation of need testing solution: get in female peaceful sheet of benefit or beneficial female Yiganning capsule 1g to the 100ml measuring bottle, add mobile phase and be diluted to scale, shake up, membrane filtration, promptly;

Measure: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, calculate with external standard method, promptly.

The various solid preparations of the present invention comprise that tablet, capsule and granule adopt mensuration ferulic acid and content of paeoniflorin to carry out quality control, compare with the national standard of the existing quality control of tincture, quality standard of the present invention has had significant raising, control the quality of product effectively, guaranteed stability of drug and curative effect.

Claims (2)

1, a kind of medical solid preparation for the treatment of dysmenorrhea is made by following bulk drugs: 90 parts of Radix Angelicae Sinensis, 60 parts of Rhizoma Cyperis, 15 parts on Cortex cinnamomi japonici (Ramulus Cinnamomi), 60 parts of Radix Rehmanniae Preparata, 60 parts of the Radix Paeoniae Albas, 60 parts of Rhizoma Chuanxiongs, 60 parts of Herba Leonuris, 30 parts of Rhizoma Corydalis, 15 parts of rhizoma sparganic, 15 parts of Pericarpium Citri junoriss; It is characterized in that having in addition adjuvant 40-120 part as forming agent; Described solid preparation is tablet or capsule, and used forming agent is dextrin 80g; Preparation process is carried out as follows:

A, get Radix Angelicae Sinensis, Rhizoma Cyperi, Cortex cinnamomi japonici (Ramulus Cinnamomi), Radix Rehmanniae Preparata, the Radix Paeoniae Alba, Rhizoma Chuanxiong, Herba Leonuri, Rhizoma Corydalis, rhizoma sparganic and Pericarpium Citri junoris, be ground into coarse powder jointly;

Percolation under b, photograph fluid extract and the extractum item is used 45% alcohol solvent, floods after 48 hours, with the speed of per minute 1～3ml percolation slowly, collect the about 750ml of liquid that just filters, it is approaching colourless to filtrate to continue percolation, merge the liquid of just filtering, mixing, concentrate concentrated solution;

C, adding dextrin stir, filter spray drying, dry granulation, granulate;

D, brown yellow granule 160g, granule is pressed into 400 in tablet, or 400 of fill capsules;

Relative density when it is characterized in that 50 ℃ of gained concentrated solutions among the described step b is 1.06～1.12; Spray-dired inlet temperature is that 170-180 ℃, leaving air temp are 70-80 ℃ among the described step c, and making powder moisture is 4%～6%, and the temperature of charge during described dry granulation is below 60 ℃.

2, a kind of medical solid preparation for the treatment of dysmenorrhea is made by following bulk drugs: 90 parts of Radix Angelicae Sinensis, 60 parts of Rhizoma Cyperis, 15 parts on Cortex cinnamomi japonici (Ramulus Cinnamomi), 60 parts of Radix Rehmanniae Preparata, 60 parts of the Radix Paeoniae Albas, 60 parts of Rhizoma Chuanxiongs, 60 parts of Herba Leonuris, 30 parts of Rhizoma Corydalis, 15 parts of rhizoma sparganic, 15 parts of Pericarpium Citri junoriss; It is characterized in that having in addition adjuvant 40-120 part as forming agent; Described solid preparation is a granule, and used forming agent is oligomeric lactose 120g; Preparation process is carried out as follows:

A, get Radix Angelicae Sinensis, Rhizoma Cyperi, Cortex cinnamomi japonici (Ramulus Cinnamomi), Radix Rehmanniae Preparata, the Radix Paeoniae Alba, Rhizoma Chuanxiong, Herba Leonuri, Rhizoma Corydalis, rhizoma sparganic and Pericarpium Citri junoris, be ground into coarse powder jointly;

Percolation under b, photograph fluid extract and the extractum item is used 45% alcohol solvent, floods after 48 hours, with the speed of per minute 1～3ml percolation slowly, collect the about 750ml of liquid that just filters, it is approaching colourless to filtrate to continue percolation, merge the liquid of just filtering, mixing, concentrate concentrated solution;

C, adding oligomeric lactose stir, filter spray drying, dry granulation, granulate;

D, brown yellow granule 200g, with every bag of 1g, 200 bags of granules of dress;

Relative density when it is characterized in that 50 ℃ of gained concentrated solutions among the described step b is 1.06～1.12; Spray-dired inlet temperature is that 170-180 ℃, leaving air temp are 70-80 ℃ among the described step c, and making powder moisture is 4%～6%, and the temperature of charge during described dry granulation is below 60 ℃.