CN1270736C - Chinese traditional medicine composition for impotence, its preparation method and quality control method - Google Patents

Abstract

The present invention discloses Chinese medicine composition for treating impotence, a preparation method thereof and a quality control method thereof. The composition is prepared from pipe fish, desertliving cistanche, common cnidium fruit, jiuxiang bug, angelica and clove. When prepared, the Chinese medicine composition adopts distillation, decoction and an ethanol extraction method to different components to achieve the sufficient exertion of efficient medicine. Simultaneously, the present invention also provides the quality control method for ingredient identification and content assay to the composition. The composition which is used for treating impotence has the characteristics of high efficiency, stability and no toxic or side effect.

Description

A kind of Chinese medicine composition for the treatment of sexual impotence and preparation method thereof and method of quality control

Invention field

The present invention relates to a kind of Chinese medicine composition, particularly be used for the treatment of the Chinese medicine composition of sexual impotence, relate to the preparation method and the method for quality control of said composition simultaneously.

Background technology

Sexual impotence one disease, all doctor families are many from impairment caused by overstrain, the argument of suffering from a deficiency of the kidney.Recognize that sexual impotence is a kind of pathology reflection of asthenia, arise from impairment of the kidney due to indulgence in sexual activities, the essence in kidney loss is due to the YANG QI deficiency.The product of warming the kidney to invigorate YANGs such as multiselect Semen Cuscutae, Fructus Cnidii, Herba Cistanches, Radix Dipsaci, Ba Ji, benefiting essence and marrow in treatment.It is also more that traditional medicine is set forth the treatment of sexual impotence, as decline of the fire from the gate of life, and vital essence deficiency and coldness and sexual impotence person, suitable Yougui Wan, the kidney-Yang-Reinforcing Bolus is praised and is educated pellet, stone inscription KidneyHarmonizing Pill and so on; If fire does not very decline, and end because of the thin weak person of vim and vigour suitable Bolus as a Kidney-Yin-Tonic, megalosaurus ball, alrodeer pill; Allly ponder over terrified so that the spleen deficiency of the kidney is decreased and positive road flaccidity person, must cultivate heart spleen, suitable seven good fortune drink, GUIPI TANG; It has too person of troubled thoughts fear, and every decrease pressed down yang-energy more, if not beneficial fire, no business eventually should add the attached Fructus Lycii in osmanthus for seven good fortune drink; Damp and hot so that the flaccid foot person of all Liver and kidney is a sexual impotence also, controls and should relieve inflammation or internal heat with hard kidney, must have so that the person of conforming to side is its card inside and outside the fire syndrome fire arteries and veins, suitable YIN nourishing eight flavor balls or red small stream dabuyin pill, Huqian Wan.

Think that after deliberation sexual impotence is how excessive because of indulging in sensual pleasures, serious masturbation, or seminal emission frequently causes deficient, the decline of the fire from the gate of life of vital essence, disturbance of QI-blood.Penis loses profit, so clinical in the majority with decline of the fire from the gate of life person, impotence in male is common clinical, frequently-occurring disease, the current domestic ideal medicine that does not still have the treatment sexual impotence.

Summary of the invention

One object of the present invention is to disclose a kind of Chinese medicine composition of new treatment sexual impotence; Another object of the present invention is the method for a kind of new treatment sexual impotence Chinese medicine composition of open preparation; The object of the invention also is to disclose a kind of method of quality control of new Chinese medicine composition.

The crude drug of pharmaceutical composition of the present invention is formed and proportioning following (by weight):

Solenognathus 100-500 weight portion Herba Cistanches 200-1200 weight portion

Fructus Cnidii 200-1200 weight portion Aspongopus 100-500 weight portion

Radix Angelicae Sinensis 200-1200 weight portion Flos Caryophylli 100-500 weight portion

This preparation of drug combination method:

Get Flos Caryophylli, Fructus Cnidii adds 7-10 times of water gaging, runs through 2-3 hour, extracts volatile oil 9-12 hour with steam distillation, the aqueous solution after distillation device is in addition collected; Medicinal residues and Radix Angelicae Sinensis, Herba Cistanches add 5-7 times of water gaging and decoct 1-3 time, each 1.5-3 hour, merge decoction liquor and above-mentioned aqueous solution, filter, filtrate is concentrated in right amount, and wherein every milliliter of concentrated solution is equivalent to raw medicinal herbs 2g, add ethanol and make the alcohol amount of containing reach 70-80%, fully stir, left standstill 11-13 hour, the leaching supernatant reclaims ethanol, the extractum that to be concentrated into 70-90 ℃ of following relative density be 1.2-1.3, drying under reduced pressure, pulverize, sieve, standby; Solenognathus, Aspongopus add 7-10 and doubly measure the 85-95% alcohol reflux 1-3 time, each 1-3 hour, merge extractive liquid,, reclaim ethanol, concentrate drying under reduced pressure to water content below 4.5-6.5%, add volatile oil and the standby dried cream powder that sieves, even through the colloid mill mill, at last directly or add pharmaceutically acceptable excipient and make clinical acceptable forms, as tablet, oral liquid, capsule, granule etc. through conventional operation.

The method of quality control that this compositions is made medicament comprises discriminating and/or assay.

Discrimination method comprises a kind of and/or several in the following method:

A. get this composite preparation 1-3g, add ethanol 8-15ml, supersound extraction 25-40 minute; Filter, get filtrate as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.1g, makes control medicinal material solution with method; It is an amount of to get the osthole reference substance again, adds ethanol and makes the reference substance solution that every ml contains 90 μ g; According to thin layer chromatography test, draw above-mentioned three kinds of each 10ul of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with normal hexane-ethyl acetate of 8-10: 0.5-1.5, launch, take out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical blue-fluorescence speckle; With the corresponding position of reference substance chromatograph on, show identical bluish violet fluorescence speckle;

B. get this composite preparation 0.3-1g, add acetone 8-12ml, supersound process 12-18 minute, filter, filtrate is as need testing solution; Other gets the eugenol reference substance, adds acetone and makes the solution that every 1ml contains 1.0mg, in contrast product solution; According to the gas chromatography test, injector temperature 150-200 ℃, column temperature is 150-200 ℃, and detector temperature is 200-250 ℃; Get each 2 μ l of above-mentioned two kinds of solution respectively, inject gas chromatograph; In the test sample collection of illustrative plates, eugenol chromatographic peak retention time should be consistent with the reference substance peak.

Assay: chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica, and the methanol-water of 70-80: 20-30 is a mobile phase; The detection wavelength is 320-340nm; Number of theoretical plate calculates by the osthole peak should be not less than 2000; The preparation of reference substance solution: it is an amount of that precision takes by weighing the osthole reference substance, puts in the brown measuring bottle, adds methanol and make the solution that every 1ml contains 30ug, shakes up, and promptly gets reference substance solution; The preparation of need testing solution: get the content under the content uniformity item, mixing, precision takes by weighing about 2g, puts in the brown measuring bottle of 100ml, and it is an amount of to add methanol, and supersound process 30 minutes is put coldly, and methanol is diluted to scale; Shake up, filter, precision is measured subsequent filtrate 1ml, puts in the brown measuring bottle of 10ml, adds methanol and is diluted to scale, shakes up, and promptly gets need testing solution; Algoscopy, accurate respectively reference substance solution and each 10ul of need testing solution of drawing injects chromatograph of liquid, measures, promptly.

This compositions has significant effect in treatment in the impotence, has the effect of obvious QI invigorating tonifying YANG, physiological function that can enhancing body, improves its tolerance of pessimal stimulation to external world, and said composition toxicity is very little, and clinical practice is safe and reliable.

Following experimental example is used to further specify the present invention.Following material and instrument are applicable to each embodiment.

1. laboratory animal

Kunming kind male white mouse, 18-22g, SD rat, 90-110g.Available from Nanjing Medical University's Experimental Animal Center.Soviet Union's kinoplaszm 97003

2. experimental drug

1) extractum (1: 10) made of this compositions, 1g extractum is equivalent to raw medicinal herbs 10g.The clinical consumption per day 3.9g extractum of people/sky 70Kg.Lot number: 990613.Being converted to the mice consumption by body surface area is 0.0102g/20g.High, medium and low dosage group consumption is respectively 2.04g/Kg, 1.02g/Kg, 0.5lg/Kg.

Patent medicine is mixed with: low dose of 0.0254g/mL, middle dosage 0.0508g/mL, high dose 0.1016g/mL.Administration volume 0.2mL/10g

2) Yangzhou, hydrocortisone injection Jiangsu pharmaceutical factory lot number: 990102

3) the multiple Chun Ling Jilin Province of tonifying YANG Longjing City pharmaceutical factory of traditional Chinese medicine lot number: the clinical consumption per day 6g/ of 99070309. people days.Being converted to the mice consumption by body surface area is 0.0156g/20g (being 0.78g/kg).Be mixed with 0.039g/mL, mice administration volume: 0.2mL/10g

4) progesterone injection fairy house Pharmacy stock Co., Ltd (Zhejiang) product batch number: 970331

5) estradiol benzoate Shanghai the 9th pharmaceutical factory's lot number: 990201

3. experimental apparatus

1) YSD-4G pharmacology physiology is used instrument more, Bengbu medical college radio two factories

2) the general software and hardware analytical system of pharmacology physiology (Australian ADInstrument company make)

3) powerlab 8/s Stimulus Isolator (isolated boost converter), (Australian ADInstrument company)

Experimental example 1: the soft capsule that this compositions is made is to the influence experiment of white mice spontaneous activity and mice swimming time

1, the soft capsule made of this compositions is to the influence experiment of white mice spontaneous activity:

Get 60 of male white mouses, be divided into six groups at random, 10 every group.Normal group is not given hydrocortisone, and all the other five groups equal intramuscular injection hydrocortisone (5%, 0.2ml/10g) cause model of yang asthenia.Simultaneously model group is given normal saline (0.2mL/10g) every day, the positive drug group is answered spring spirit (0.78g/kg to tonifying YANG every day, 0.2ml/10g), its excess-three group all irritate stomach give low in a Senior Three dosage be subjected to reagent (0.51g/kg, 1.02g/kg, 2.04g/kg, 0.2ml/10g).Totally four days.After one hour, write down each the weight of animals, autonomic activities number (2min indegree) in administration on the 4th.Experimental result sees Table 1.

The soft capsule that this compositions of table 1. is made is to the influence experiment (n=10) of white mice spontaneous activity

Group	Dosage (g/kg.d)	Number of animals (only)	Movable number
				Dosage high dose in the normal control group model matched group positive controls low dosage	- - 0.78 0.51 1.02 2.04	10 10 10 10 10 10	68±20 43±17 57±9* 60±11** 62±15** 65±19**

Model group and normal group be Δ Δ p＜0.01 relatively, and administration group and model group be * * p＜0.01 relatively

2, the soft capsule made of this compositions is to the influence of mice swimming time

Get 60 of white mice, be divided into six groups at random, 10 every group.(1) normal group, and (2) YANG asthenia disease model group (hydrocortisone 5ml/Kg, im), (3) positive drug group (hydrocortisone+tonifying YANG multiple spring spirit), (4)-(6) hydrocortisone+the be subjected to large, medium and small dosage of reagent.Each organizes equal gastric infusion once, and medication and dosage are with 1.(model group is given normal saline 20mL/Kg), totally three days.1 hour begins to test after administration on the 3rd.Swimming groove (depth of water 30cm, 28 ℃ of water temperatures).The white mice abdominal part bears a heavy burden (body weight 10%), and opening entry is put into the time that swimming groove to mice sinks to bottom land, and record data are also handled.The results are shown in Table 2,3

The soft capsule that this compositions of table 2. is made is to the mice influence of swimming time-to-live

Group	Dosage (g/kg.d)	Number of animals (only)	Swimming time (s)
				Dosage high dose in the normal control group model matched group positive controls low dosage	- - 0.78 0.51 1.02 2.04	10 10 10 10 10 10	570.2±361.2 68.3±40.9 ΔΔ 100.5±22.3 ** 65.3±11.8 178.9±109.7 ** 192.4±103.7 **

The soft capsule that this compositions of table 3. is made is to the influence of mice body weight

Group	Dosage (g/kg.d)	Number of animals (only)	Movable number
					Before the administration	After the administration
			Dosage high dose in the normal control group model matched group positive controls low dosage	- - 0.78 0.51 1.02 2.04			10 10 10 10 10 10	18.7±1.3 19.4±2.7 19.0±1.4 19.2±2.7 19.0±2.6 19.8±3.3	23.1±1.8 18.9±2.2 ΔΔ 19.5±1.6 19.5±2.3 21.5±2.6 ** 22.8±3.0 **

Model group and normal group be p＜0.01 relatively, and administration group and model group be * * p＜0.01 relatively

By last table 1,2,3 as can be known, the animal activity of model of yang asthenia reduces, and loses weight.Bradykinesia, the glue tail is cold, the hogback that curls, yang deficiency performance such as cold physique glue such as Mao Song are cold.And positive group and Solenognathus kidney tonifying soft capsule are respectively organized weight of mice, and activity increases, and reaction is quick.The performance of yang deficiency such as curling cold physique improves.The muscle power of mice strengthens.Swimming time prolongs.Illustrate that Solenognathus kidney tonifying soft capsule has the effect of QI invigorating tonifying YANG, physiological function that can enhancing body, improve its tolerance of pessimal stimulation to external world.

Experimental example 2: the soft capsule that this compositions is made is to the preclinical influence of white mice erection

The preclinical influence of the mice erection that 1, yang deficiency caused: get 48 of male white mouses, be divided into six groups at random, 8 every group.Not administration of normal group, give model group every day normal saline (0.2mL/10g), the positive drug group is answered spring spirit 0.78g/kg to tonifying YANG every day, the Solenognathus kidney tonifying soft capsule of a Senior Three dosage group during the equal oral administration gavage of its excess-three group is given and hanged down (0.51g/Kg, 1.02g/Kg, 2.04g/Kg), the administration volume is that 0.2ml/10g is except that normal group, five groups of intramuscular injection hydrocortisone (5%, 5ml/g, continuous three days) are made the YANG asthenia disease model simultaneously.Each is organized gastric infusion and gives electricity irritation after ten days.Use YSD-4G pharmacology physiology to use instrument, 0.5 second electricity irritation B time, frequency 8Hz, voltage 10v more.Stimulate mice penis head and skin of penis place.Measure the erection time (timing when stimulating beginning certainly), data are carried out statistical.The results are shown in Table 4

The soft capsule tonifying YANG experiment erection incubation period that table 4, this compositions are made

Group	Dosage (g/kg.d)	Number of animals (only)	Swimming time (s)
				Dosage high dose in the normal control group model matched group positive controls low dosage	- - 0.78 0.51 1.02 2.04	8 8 8 8 8 8	18±7 49±14 ΔΔ 30±20 * 27±15 ** 31±21 18±10 **

Model group and normal group be Δ Δ p＜0.01 relatively, and administration group and model group be * * p＜0.01 relatively

2, to the preclinical influence of castrated rats rat erection

Get 72 of male rats, be divided into six groups at random.Normal control group (distilled water 10ml/kg.d), model control group (distilled water 10ml/kg.d), positive drug group (the multiple spring spirit of tonifying YANG 0.54g/kg.d), the basic, normal, high dosage group of the soft capsule that this compositions is made (0.35g/kg.d, 0.70g/kg.d, 1.40g/kg.d).Except that the normal control group, more than each group, all carry out castration operation, make the YANG asthenia disease model.The castration operation: get male rat, pentobarbital sodium (0.6%, 0.9ml/100g) anesthesia, back of the body position is fixing, and testis is clamp-oned scrotum from the abdominal cavity, and the 1cm osculum is cut at the place at the scrotum testis, extrudes testis, and skin suture is extractd in ligation.Note sterilization in the operation process.Postoperative intramuscular injection penicillin 20,000 u/kg.d, continuous five days.Administration: above each group, operation back beginning in the 5th day certainly, be administered once every day (ig) continuous 20 days, experimentized on the 21st day.Electricity irritation experiment: after the administration the 21st day, the stimulating electrode of powerlab StimulusIsolator (ADInsrument) is placed rat penis position, thorn evokes Glans penis portion and surrounding skin, current intensity 4mA, 50Hz.Record begins to the time (erecing incubation period) that penis erects from stimulation, and the result carries out the t check.(incubation period＞60 second press 60s calculate), vertebra is put to death rat, takes out rat preputial glands, seminal fluid capsule and prostate, levator ani, penis, takes by weighing weight in wet base rapidly, calculates organ coefficient and also carries out t with model group and check.Experimental result sees Table 5,6

The soft capsule that this compositions of table 5. is made is to the preclinical influence of rat erection

Group	Dosage (g/kg.d)	Number of animals (only)	Erection incubation period (s)
				Dosage high dose in the normal control group model matched group positive controls low dosage	- - 0.54 0.35 1.70 1.40	12 12 12 12 12 12	16.99±7.01 56.14±4.61 ΔΔ 45.28±11.43 ** 45.05±11.43 ** 41.9±13.09 ** 39.72±11.69 **

Model group and normal group be Δ Δ p＜0.01 relatively, and administration group and model group be * * p＜0.01 relatively

Table 6. Solenognathus kidney tonifying soft capsule to the influence of castrated rats organ coefficient (X ± SD, n=12)

Group	Dosage g/kg d	Body weight (g)	The preputial glands coefficient	Prostate+seminal fluid capsule coefficient	The levator ani coefficient	The penis coefficient
							Dosage high dose in the normal control group model matched group positive controls low dosage	- - 0.54 0.35 0.70 1.40	274±24 224±19 ΔΔ 235±14 226±20 236±19 244±23	0.0389±0.0099 0.0229±0.0063 ΔΔ 0.0256±0.0048 0.0288±0.0100* 0.0299±0.0070** 0.0253±0.0074	0.4746±0.0849 0.0341±0.0068 ΔΔ 0.0414±0.0165 0.0360±0.0066 0.0456±0.01677* 0.0522±0.0312*	0.0745±0.0128 0.0167±0.0041 ΔΔ 0.0203±0.0072 0.0258±0.0144* 0.0269±0.0149* 0.0268±0.0127*	0.1122±0.0281 0.0356±0.0003 ΔΔ 0.0366±0.0053 0.0365±0.0087 0.0349±0.0100 0.0375±0.0060

Annotate: Δ Δ and normal group be P＜0.01 relatively, compares with model group: * P＜0.05, * * P＜0.01

By table 4,5,6 results as can be known, the model of yang asthenia that hydrocortisone causes can make the prolongation of latency of mice erection.And the soft capsule that this compositions is made can shorten the incubation period of the mice erection that causes because of yang deficiency.With model group the difference (p＜0.01) of significance is arranged relatively.And certain dose-effect relationship is arranged.The operation castration can make rat erection prolong greatly incubation period.And each genitals's of animal weight and preputial glands coefficient, prostate+seminal fluid capsule coefficient, levator ani coefficient, and the penis coefficient significantly reduces, and relatively there were significant differences (P＜0.010) with model group.And positive drug and Solenognathus kidney tonifying soft capsule can resist the sexual impotence that castration causes.Shortened the incubation period of erection.And preputial glands coefficient, prostate+seminal fluid capsule coefficient, the levator ani coefficient of castrated rats are improved.

Experimental example 3: rat mating test

Get 50 of male Mus, be divided into five groups at random: normal control group (distilled water 10ml/Kg.d), the multiple spring spirit group of tonifying YANG (0.54g/Kg.d), the basic, normal, high dosage group of the soft capsule that this compositions is made (0.35g/Kg.d, 0.70g/Kg.d, 1.40g/Kg.d).Below respectively organize every day IG and be administered once continuous 20 days.Female Mus is prepared: get 50 of female Mus, pentobarbital sodium (0.6%, 0.9ml/100g) intraperitoneal injection of anesthesia, the abdomen position is fixed, and implements the bilateral ovaries enucleation.Method is: get under the last rib midaxillary line and, wipe out and become mildewed apart from about 2cm place, the spinal column outside, incision skin and the about 1.5-2.0cm of dorsal muscles, the shinny liparitosis of a visible milky in the otch visual field, ovary be embedding wherein.Clamp liparitosis gently with pincet and pull out outside the otch, the visible pink yellow ovary of fractionation of fatty, its following fallopian tube of ligation is extractd ovary.Postoperative is taken advantage of a situation cornua uteri is sent in the abdominal cavity.Extract other side ovary, suture muscles and skin with method.Postoperative intramuscular injection penicillin 20,000 μ/Kg.d, continuous five days.Two weeks of operation back are carried out mating test with male Mus.Preceding 48hr intramuscular injection estradiol benzoate 20ug/ of experiment, 24hr intramuscular injection Progesterone 50 μ g/ only before the copulation.

Mating test: a male Mus is put into the mouse cage that cleaning is placed with bedding and padding adapt to 5min separately, drop into 1 of the female Mus got ready then, pick up counting in dropping into certainly, observation index is:

(1) catches incubation period: be fed into the time that male Mus catches female Mus for the first time from female Mus

(2) ejaculation latency: be fed into the time that male Mus catches female Mus copulation ejaculation for the first time from female Mus, it is standard that the ejaculation time is licked external genitalia with male Mus post-coitum.

(3) male Mus catches female Mus number of times and ejaculation frequency in the 20min

(4) animal that each group is caught, ejaculated in the 20min accounts for the percentage rate of animal in the group, i.e. catch rate and ejaculation rate.

Laboratory observation personnel give training in advance.Strictly controlled environment temperature, humidity in the experimentation, faint light, peace and quiet are carried out in experiment in night.Laboratory observation divides to be finished in two days, 25 of every days, extracted 5 at random out, parallel laboratory test for every group.Experiment finishes back one week of administration, gets the rat testicle epididymis and weighs, and calculates organ coefficient and carries out the t check.The results are shown in Table 7

The soft capsule that this compositions of table 7 is made is to the influence of male rat mating ability

Group	Dosage (g/kg)	Number of animals	Catch incubation period (min)	Catch number of times	Ejaculation latency (min)	Ejaculation frequency	Ejaculation rate %	Catch rate %
									Dosage group high dose group in the positive group of the normal control group low dose group	0.54 0.35 0.70 1.40	10 10 10 10 10	0.76±0.56 0.29±0.19* 0.46±0.60 0.37±0.17* 0.27±0.21*	15±7 25±14* 25±14* 27±8** 28±9**	2.24±2.92 0.76±1.10** 0.62±0.62** 0.47±0.27** 0.52±0.52**	13±7 20±10* 21±12* 23±8** 24±5**	90 90 100 100 100	90 90 100 100 100

Annotate: * compares p＜0.05 with normal group, and * * and normal group be p＜0.01 relatively

The soft capsule that this compositions of table 8 is made is to the influence of normal rat testicle epididymis

Group	Dosage (g/kg)	Number of animals (only)	Body weight (g)	Weight coefficient of testis	The epididymis coefficient
						Dosage group high dose group in the multiple spring spirit of the NS matched group tonifying YANG group low dose group	- 0.54 0.35 0.70 1.40	10 10 10 10 10	368.1±0.068 374.9±32.4 379.2±20.8 360.2±30.9 347.2±24.2	0.883±0.068 0.895±0.098 0.871±0.089 0.902±0.074 0.934±0.096	0.276±0.043 0.273±0.034 0.300±0.036 0.304±0.050 0.281±0.034

Annotate: each group compares p＞0.05 with normal group

The result: compare with the normal control group, this product can significantly strengthen the mating ability of rat.

The following example all can be realized the effect of above-mentioned experimental example.

Embodiment 1:

Solenognathus 333.3g Herba Cistanches 1111g Fructus Cnidii 1111g

Aspongopus 333.3g Radix Angelicae Sinensis 1111g Flos Caryophylli 333.3g

Flos Caryophylli, Fructus Cnidii add 8 times of water gagings, run through 2.2 hours, extract volatile oil 10 hours with steam distillation, and the aqueous solution after distillation device is in addition collected; Medicinal residues and Radix Angelicae Sinensis, Herba Cistanches add 6 times of water gagings and decoct 2 times, each 2 hours, merge decoction liquor and above-mentioned aqueous solution, filter, filtrate is concentrated in right amount, and wherein every milliliter of concentrated solution is equivalent to raw medicinal herbs 2g, add ethanol and make and contain alcohol amount and reach 75%, fully stir, left standstill 12 hours, the leaching supernatant reclaims ethanol, is concentrated into 80 ℃ of following relative densities and is 1.25 extractum, drying under reduced pressure, pulverize, sieve, standby; Solenognathus, Aspongopus add 8 times of amount 90% alcohol reflux 2 times, each 1.5 hours, merge extractive liquid, reclaimed ethanol, concentrate drying under reduced pressure to water content below 5.0%, mix with an amount of refined edible vegetable oil, add volatile oil and the standby dried cream powder that sieves, even through the colloid mill mill, be pressed into 1000 of soft capsules, promptly get the soft capsule of compositions, every dress 0.55g is equivalent to crude drug 4.33g.

Embodiment 2:

Solenognathus 361g Herba Cistanches 1083g Fructus Cnidii 1083g

Aspongopus 361g Radix Angelicae Sinensis 1083g Flos Caryophylli 361g

Flos Caryophylli, Fructus Cnidii add 8 times of water gagings, run through 2.2 hours, extract volatile oil 10 hours with steam distillation, and the aqueous solution after distillation device is in addition collected; Medicinal residues and Radix Angelicae Sinensis, Herba Cistanches add 6 times of water gagings and decoct 2 times, each 2 hours, merge decoction liquor and above-mentioned aqueous solution, filter, filtrate is concentrated in right amount, and wherein every milliliter of concentrated solution is equivalent to raw medicinal herbs 2g, adds ethanol and makes and contain alcohol amount and reach 75%, fully stir, left standstill 12 hours, the leaching supernatant reclaims ethanol, be concentrated into 80 ℃ of following relative densities and be 1.25 extractum, standby; Solenognathus, Aspongopus add 8 times of amount 90% alcohol reflux 2 times, and each 1.5 hours, merge extractive liquid, reclaimed ethanol, concentrates, and adds above-mentioned extractum, add 1 times of amount dextrin, and drying under reduced pressure is pulverized, and makes dried cream powder; Volatile oil with the dried cream powder mixing granulation, is made 1000 of capsules after wrapping up with beta-schardinger dextrin-, promptly gets the hard capsule of compositions, and every dress 0.35g is equivalent to crude drug 4.33g.

Embodiment 3: the method for quality control of this composite preparation:

Differentiate: get this composite preparation 2g, add ethanol 10ml, supersound extraction 30 minutes; Filter, get filtrate as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.1g, makes control medicinal material solution with method; It is an amount of to get the osthole reference substance again, adds ethanol and makes the reference substance solution that every ml contains 90ug; According to the thin layer chromatography test, draw above-mentioned three kinds of each 10ul of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with normal hexane-ethyl acetates of 9: 1, launch, take out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical blue-fluorescence speckle; With the corresponding position of reference substance chromatograph on, show identical bluish violet fluorescence speckle;

Get this composite preparation 0.5g, add acetone 10ml, supersound process 15 minutes filters, and filtrate is as need testing solution; Other gets the eugenol reference substance, adds acetone and makes the solution that every 1ml contains 1.0mg, in contrast product solution; According to the gas chromatography test, 200 ℃ of injector temperatures, column temperature are 180 ℃, and detector temperature is 220 ℃; Get each 2 μ l of above-mentioned two kinds of solution respectively, inject gas chromatograph; In the test sample collection of illustrative plates, Flos Caryophylli peak retention time should be consistent with the reference substance peak.

Assay: chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler, and 75: 25 methanol-water is a mobile phase; The detection wavelength is 322nm; Number of theoretical plate calculates by the osthole peak should be not less than 2000; It is an amount of that the preparation of reference substance solution, precision take by weighing the osthole reference substance, puts in the brown measuring bottle, adds methanol and make the solution that every 1ml contains 30ug, shakes up, and promptly gets reference substance solution; The content under the content uniformity item is got in the preparation of need testing solution, mixing, and precision takes by weighing about 2g, puts in the brown measuring bottle of 100ml, and it is an amount of to add methanol, and supersound process 30 minutes is put coldly, and methanol is diluted to scale; Shake up, filter, precision is measured subsequent filtrate 1ml, puts in the brown measuring bottle of 10ml, adds methanol and is diluted to scale, shakes up, and promptly gets need testing solution; Algoscopy, accurate respectively reference substance solution and each 10ul of need testing solution of drawing injects chromatograph of liquid, measures, and calculates, and every of this product contains Fructus Cnidii with osthole (C ₆H ₁₂O) calculate, should be less than 4.0mg.

Claims (13)

1, a kind of pharmaceutical composition for the treatment of sexual impotence is characterized in that this pharmaceutical composition made by following raw material medicaments:

Solenognathus 100 weight portion Herba Cistanches 200 weight portions

Fructus Cnidii 200 weight portion Aspongopuss 100 weight portions

Radix Angelicae Sinensis 200 weight portion Flos Caryophyllis 100 weight portions.

2, a kind of pharmaceutical composition for the treatment of sexual impotence is characterized in that this pharmaceutical composition made by following raw material medicaments:

Solenognathus 500 weight portion Herba Cistanches 1200 weight portions

Fructus Cnidii 1200 weight portion Aspongopuss 500 weight portions

Radix Angelicae Sinensis 1200 weight portion Flos Caryophyllis 500 weight portions.

3, a kind of pharmaceutical composition for the treatment of sexual impotence is characterized in that this pharmaceutical composition made by following raw material medicaments:

Solenognathus 361 weight portion Herba Cistanches 1083 weight portion Fructus Cnidiis 1083 weight portions

Aspongopus 361 weight portion Radix Angelicae Sinensis 1083 weight portion Flos Caryophyllis 361 weight portions.

4, a kind of pharmaceutical composition for the treatment of sexual impotence is characterized in that this pharmaceutical composition made by following raw material medicaments:

Solenognathus 333.3 weight portion Herba Cistanches 1111 weight portion Fructus Cnidiis 1111 weight portions

Aspongopus 333.3 weight portion Radix Angelicae Sinensis 1111 weight portion Flos Caryophyllis 333.3 weight portions.

5,, it is characterized in that this pharmaceutical composition adds excipient as claim 1,2,3 or 4 described pharmaceutical compositions.

6, as claim 1,2,3 or 4 described preparation of drug combination methods, it is characterized in that this method is: get Flos Caryophylli, Fructus Cnidii adds 7-10 times of water gaging, ran through 2-3 hour, and extracted volatile oil 9-12 hour with steam distillation, the aqueous solution after distillation device is in addition collected; Medicinal residues and Radix Angelicae Sinensis, Herba Cistanches add 5-7 times of water gaging and decoct 1-3 time, each 1.5-3 hour, merge decoction liquor and above-mentioned aqueous solution, filter, filtrate is concentrated in right amount, and wherein every milliliter of concentrated solution is equivalent to raw medicinal herbs 2g, add ethanol and make the alcohol amount of containing reach 70-80%, fully stir, left standstill 11-13 hour, the leaching supernatant reclaims ethanol, the extractum that to be concentrated into 70-90 ℃ of following relative density be 1.2-1.3, drying under reduced pressure, pulverize, sieve, standby; Solenognathus, Aspongopus add 7-10 and doubly measure the 85-95% alcohol reflux 1-3 time, each 1-3 hour, merge extractive liquid,, reclaim ethanol, concentrate drying, add volatile oil and the standby dried cream powder that sieves, excipient direct through common process at last or that adding is pharmaceutically accepted is made the dosage form of clinical acceptance.

7, preparation of drug combination method as claimed in claim 6, it is characterized in that this method for get Flos Caryophylli, Fructus Cnidii adds 8 times of water gagings, runs through 2 hours, extracts volatile oil 10 hours with steam distillation, the aqueous solution after distillation device is in addition collected; Medicinal residues and Radix Angelicae Sinensis, Herba Cistanches add 6 times of water gagings and decoct 2 times, each 2 hours, merge decoction liquor and above-mentioned aqueous solution, filter, filtrate is concentrated in right amount, and wherein every milliliter of concentrated solution is equivalent to raw medicinal herbs 2g, add ethanol and make and contain liquor-saturated amount and reach 75%, fully stir, left standstill 12 hours, the leaching supernatant reclaims ethanol, is concentrated into 80 ℃ of following relative densities and is 1.25 extractum, drying under reduced pressure, pulverize, sieve, standby; Solenognathus, Aspongopus add 8 times of amount 90% alcohol reflux 2 times, each 1.5 hours, merge extractive liquid,, reclaim ethanol, concentrate drying under reduced pressure to water content below 5.0%, mixes adding volatile oil and the standby dried cream powder that sieves with an amount of refined edible vegetable oil, even through the colloid mill mill, be pressed into soft capsule.

8,, it is characterized in that discrimination method in this method comprises one or more in the following discriminating as the method for quality control of claim 1,2,3 or 4 described pharmaceutical compositions:

A. get this composite preparation 2g, add ethanol 8-15ml supersound extraction 25-40 minute; Filter,

Get filtrate as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.1g, makes control medicinal material solution with method; It is an amount of to get the osthole reference substance again, adds ethanol and makes the reference substance solution that every ml contains 90ug; According to thin layer chromatography test, draw above-mentioned three kinds of each 10ul of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with n-hexane-ethyl acetate of 8-10: 0.5-1.5, launch, take out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical blue-fluorescence speckle; With the corresponding position of reference substance chromatograph on, show identical bluish violet fluorescence speckle;

B. get this compositions 0.5g, add acetone 8-12ml, supersound process 12-18 minute, filter, filtrate is as need testing solution; Other gets the eugenol reference substance, adds acetone and makes the solution that every 1ml contains 1.0mg, in contrast product solution; According to the gas chromatography test, injector temperature 150-200 ℃, column temperature is 150-200 ℃, and detector temperature is 200-250 ℃; Get each 2 μ l of above-mentioned two kinds of solution respectively, inject gas chromatograph; In the test sample collection of illustrative plates, Flos Caryophylli peak retention time should be consistent with the reference substance peak.

9, the method for quality control of pharmaceutical composition as claimed in claim 8 is characterized in that discrimination method in this method comprises one or more in the following discriminating:

A. get this composite preparation 2g, add ethanol 10ml supersound extraction 30 minutes; Filter, get filtrate as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.1g, makes control medicinal material solution with method; It is an amount of to get the osthole reference substance again, adds ethanol and makes the reference substance solution that every ml contains 90ug; According to thin layer chromatography test, draw above-mentioned three kinds of each 10ul of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with normal hexane-ethyl acetate of 9:1, launch, take out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical blue-fluorescence speckle; With the corresponding position of reference substance chromatograph on, show identical bluish violet fluorescence speckle;

B. get this compositions 0.5g, add acetone 10ml, supersound process 15 minutes filters, and filtrate is as need testing solution; Other gets the eugenol reference substance, adds acetone and makes the solution that every 1ml contains 1.0mg, in contrast product solution; According to the gas chromatography test, 200 ℃ of injector temperatures, column temperature are 180 ℃, and detector temperature is 220 ℃; Get each 2 μ l of above-mentioned two kinds of solution respectively, inject gas chromatograph; In the test sample collection of illustrative plates, eugenol chromatographic peak retention time should be consistent with the reference substance peak.

10,, it is characterized in that the assay in this method is as the method for quality control of claim 1,2,3 or 4 described pharmaceutical compositions:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler, and the methanol of 70-80: 20-30--water is mobile phase; The detection wavelength is 320-340nm; Number of theoretical plate calculates by the osthole peak should be not less than 2000; The preparation of reference substance solution: it is an amount of that precision takes by weighing the osthole reference substance, puts in the brown measuring bottle, adds methanol and make the solution that every 1ml contains 30ug, shakes up, and promptly gets reference substance solution; The preparation of need testing solution: get the content under the content uniformity item, mixing, precision takes by weighing about 2g, puts in the brown measuring bottle of 100ml, and it is an amount of to add methanol, and supersound process 30 minutes is put coldly, and methanol is diluted to scale; Shake up, filter, precision is measured subsequent filtrate 1ml, puts in the brown measuring bottle of 10ml, adds methanol and is diluted to scale, shakes up, and promptly gets need testing solution; Algoscopy: accurate respectively reference substance solution and each 10ul of need testing solution of drawing, inject chromatograph of liquid, measure, calculate, this composition material medicine 4.33g contains Fructus Cnidii and calculates with osthole, should be less than 4.0mg.

11, as the method for quality control of claim 1,2,3 or 4 described pharmaceutical compositions, comprise the steps:

Get this composite preparation 2g, add ethanol 8-15ml supersound extraction 25-40 minute; Filter, get filtrate as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.1g, makes control medicinal material solution with method; It is an amount of to get the osthole reference substance again, adds ethanol and makes the reference substance solution that every ml contains 90ug; According to thin layer chromatography test, draw above-mentioned three kinds of each 10ul of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with normal hexane-ethyl acetate of 8-10: 0.5-1.5, launch, take out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical blue-fluorescence speckle; With the corresponding position of reference substance chromatograph on, show identical bluish violet fluorescence speckle; Get this composite preparation 0.5g, add acetone 8-12ml, supersound process 12-18 minute, filter, filtrate is as need testing solution; Other gets the eugenol reference substance, adds acetone and makes the solution that every 1ml contains 1.0mg, in contrast product solution; According to the gas chromatography test, injector temperature 150-200 ℃, column temperature is 170-190 ℃, and detector temperature is 200-240 ℃; Get each 2 μ l of above-mentioned two kinds of solution respectively, inject gas chromatograph; In the test sample collection of illustrative plates, Flos Caryophylli peak retention time should be consistent with the reference substance peak;

Assay: chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica, and the methanol of 70-80: 20-30--water is mobile phase; The detection wavelength is 320-340nm; Number of theoretical plate calculates by the osthole peak should be not less than 2000; The preparation of reference substance solution: it is an amount of that precision takes by weighing the osthole reference substance, puts in the brown measuring bottle, adds methanol and make the solution that every 1ml contains 30ug, shakes up, and promptly gets reference substance solution; The preparation of need testing solution: get the content under the content uniformity item, mixing, precision takes by weighing about 2g, puts in the brown measuring bottle of 100ml, and it is an amount of to add methanol, and supersound process 30 minutes is put coldly, and methanol is diluted to scale; Shake up, filter, precision is measured subsequent filtrate 1ml, puts in the brown measuring bottle of 10ml, adds methanol and is diluted to scale, shakes up, and promptly gets need testing solution; Algoscopy, accurate respectively reference substance solution and each 10ul of need testing solution of drawing injects chromatograph of liquid, measures, and calculates, and this composite preparation 4.33g contains Fructus Cnidii with osthole C ₆H ₁₂O calculates, and should be less than 4.0mg.

12, the method for quality control of pharmaceutical composition as claimed in claim 11 comprises the steps:

Differentiate: get this composite preparation 2g, add ethanol 10ml supersound extraction 30 minutes; Filter, get filtrate as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.1g, makes control medicinal material solution with method; It is an amount of to get the osthole reference substance again, adds ethanol and makes the reference substance solution that every ml contains 90ug; According to the thin layer chromatography test, draw above-mentioned three kinds of each 10ul of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with n-hexane-ethyl acetates of 9: 1, launch, take out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical blue-fluorescence speckle; With the corresponding position of reference substance chromatograph on, show identical bluish violet fluorescence speckle; Get this compositions 0.5g, add acetone 10ml, supersound process 15 minutes filters, and filtrate is as need testing solution; Other gets the eugenol reference substance, adds acetone and makes the solution that every 1ml contains 1.0mg, in contrast product solution; According to the gas chromatography test, 200 ℃ of injector temperatures, column temperature are 180 ℃, and detector temperature is 220 ℃; Get each 2 μ l of above-mentioned two kinds of solution respectively, inject gas chromatograph; In the test sample collection of illustrative plates, Flos Caryophylli peak retention time should be consistent with the reference substance peak;

Assay: chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler, and 75: 25 methanol--water is mobile phase; The detection wavelength is 322nm; Number of theoretical plate calculates by the osthole peak should be not less than 2000; The preparation of reference substance solution: it is an amount of that precision takes by weighing the osthole reference substance, puts in the brown measuring bottle, adds methanol and make the solution that every 1ml contains 30ug, shakes up, and promptly gets reference substance solution; The preparation of need testing solution: get the content under the content uniformity item, mixing, precision takes by weighing about 2g, puts in the brown measuring bottle of 100ml, and it is an amount of to add methanol, and supersound process 30 minutes is put coldly, and methanol is diluted to scale; Shake up, filter, precision is measured subsequent filtrate 1ml, puts in the brown measuring bottle of 10ml, adds methanol and is diluted to scale, shakes up, and promptly gets need testing solution; Algoscopy: accurate respectively reference substance solution and each 10ul of need testing solution of drawing, inject chromatograph of liquid, measure, to calculate, every of this product contains Fructus Cnidii with osthole C ₆H ₁₂O calculates, and should be less than 4.0mg.

13, as claim 1,2, the application of 3 or 4 described pharmaceutical compositions in the medicine of preparation treatment sexual impotence.