CN1589894A - Medicinal composition for treating parafunctional metrorrhagia and its preparation method - Google Patents
Medicinal composition for treating parafunctional metrorrhagia and its preparation method Download PDFInfo
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Abstract
A Chinese medicine for treating the metrorrhagia caused by functional disorder is prepared from 11 Chinese-medicinal materials including motherwort, Chinese angelica root, red peony root, red sage root, etc. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition for the treatment of dysfunctional uterine bleeding and preparation method thereof, this pharmaceutical composition be a kind of be raw material with the Chinese herbal medicine, be equipped with the appropriate amount of drug correctives or/and the compound formulation that drug excipient is prepared from.
Background technology
Dysfunctional uterine bleeding is a common gynecological disease, not only influences patient's orthobiosis, and may cause multiple diseases such as anemia, reproductive tract infection, pelvic inflammatory disease.Therefore, the treatment to this disease is significant.How the medicine that western medical treatment primary disease inefficacy is definite is with hormone or antibiotic symptomatic treatment.Chinese medicine thinks that the generation of primary disease can be by the deficiency of vital energy, the stagnation of QI, heat in blood, blood stasis and cause.Can adopt method of treatment such as nourishing qi to stop, blood-activating and qi-promoting, clearing away heat and cooling blood, blood circulation promoting and blood stasis dispelling at different pattern of syndrome, form corresponding Chinese medicinal formulae and can treat primary disease.
Still it is that Chinese medicine and relevant report are fewer to the medicine of present visible treatment dysfunctional metrorrhagia, as in " Coryza Treated by Syndrome Differentiation dysfunctional uterine bleeding 264 examples " (practical tcm internal medicine magazine was rolled up 173 pages of the 3rd phases in 2003 the 17th) simple typing summary only having been done in the treatment of this disease; Application number is the prescription that 03113819.5 application for a patent for invention discloses a kind of utilization " clearing away heat and cooling blood, blood circulation promoting and blood stasis dispelling " method of treatment; The patent No. is that 98112907.2 patent of invention also discloses a kind of prescription, indication has comprised blood stasis, blood deficiency, three kinds of disease types of heat in blood, and is actual in prescription, though comprised the various medicines at above disease type, but difficult branch primary and secondary between these medicines, discoordination is arranged, it is unclear to cause curing mainly disease.Other has the other drug combination, even can't determine its indication, the reference of also just having no way of.
So market is needed badly a kind of at primary symptom, effective method for treatment or medicine.For addressing this problem, the inventor has studied the traditional Chinese medical science pathogeny and the treatment rule of dysfunctional uterine bleeding, thinks that qi depression to blood stasis is one of this pathogenetic important mechanisms.The traditional Chinese medical science thinks that the woman is this with blood.And liver storing blood.If not smooth because of feelings will, irritability is not dredged, and then easily forms the stagnation of QI.Qi being the governor of blood, the capable then blood of gas is capable, and the stagnation of QI is blood stasis then.Strongly fragrant for a long time and heat-transformation, the absurd row of forcing blood increases so see menstruation, menostaxis.So its method of treatment should be with blood-activating and qi-promoting, blood-arresting catamenia-regulating is this.And this point is treated the weak link place of dysfunctional uterine bleeding medicine, exactly in the market so the exploitation of this type of medicine will bring glad tidings for extensive patients.
Summary of the invention
According to above analysis, the object of the present invention is to provide a kind of pharmaceutical composition for the treatment of dysfunctional uterine bleeding, relate to this preparation of drug combination method simultaneously.
The pharmaceutical composition of the treatment dysfunctional uterine bleeding that the present invention developed is made by following materials of weight proportions
Herba Leonuri 25-35 weight portion Radix Angelicae Sinensis 25-35 weight portion Radix Paeoniae Rubra 25-35 weight portion
Radix Salviae Miltiorrhizae 25-35 weight portion Radix Curcumae 15-25 weight portion Radix Achyranthis Bidentatae 25-35 weight portion
Fructus Aurantii 15-25 weight portion Radix Aucklandiae 5-15 weight portion Herba Schizonepetae 15-25 weight portion
Rhizoma Zingiberis 5-15 weight portion Radix Rubiae 15-25 weight portion
The optimum weight proportioning that constitutes the raw material of above-mentioned medicament is:
Herba Leonuri 30 weight portion Radix Angelicae Sinensis 30 weight portion Radix Paeoniae Rubra 30 weight portions
Radix Salviae Miltiorrhizae 30 weight portion Radix Curcumaes 20 weight portion Radix Achyranthis Bidentataes 30 weight portions
The Fructus Aurantii 20 weight portion Radix Aucklandiae 10 weight portion Herba Schizonepetae 20 weight portions
Rhizoma Zingiberis 10 weight portion Radix Rubiaes 20 weight portions
Herba Schizonepetae in the above-mentioned raw materials should be fried into charcoal, and Rhizoma Zingiberis should be fried into charcoal, and Radix Achyranthis Bidentatae is a Radix Cyathulae.More than 11 flavor Chinese medicines, except that Rhizoma Zingiberis, Herba Schizonepetae, all handle according to the Chinese medicine processing standard, its role is to make the easier extraction of active ingredient in each raw material, to strengthen the property of medicine, make better drug curative effect of the present invention.
The medicine of above-mentioned treatment dysfunctional uterine bleeding also can add the medicine correctives or/and drug excipient.Said medicine correctives is one or more the combination in sucrose, simple syrup, sodium benzoate, stevioside, the protein sugar, so that the medicament of prepared one-tenth has good mouthfeel, overcome and produce abnormal flavour behind the above Chinese herbal medicine compatibility and be difficult to the drawback that enters the mouth or swallow.Said drug excipient is one or more the combination in dextrin, magnesium stearate, microcrystalline Cellulose, carboxymethyl starch sodium, starch, Pulvis Talci, sodium bicarbonate, the citric acid, with the oral formulations that medication preparation of the present invention is become to be convenient to take.
Aforementioned pharmaceutical compositions of the present invention can be prepared into any pharmaceutical preparation that is suitable for using clinically according to the Chinese medicine preparation technology of routine, as: oral liquid, granule, tablet, capsule.The preferred dosage form of the present invention is oral liquid, granule
The preparation method of the medicine of the treatment dysfunctional uterine bleeding that the present invention proposes comprises the steps:
Radix Angelicae Sinensis, Radix Curcumae, Fructus Aurantii, the Radix Aucklandiae add the water distillation, collect Aromatic water, and cold preservation is standby.Or divide and get volatile oil, make the betacyclodextrin clathrate.Medicinal residues after the distillation and Herba Leonuri, Radix Paeoniae Rubra, Radix Salviae Miltiorrhizae, Radix Achyranthis Bidentatae, Herba Schizonepetae charcoal, carbonized Rhizoma Zingiberis, after medicines such as Radix Rubiae are soaked 2-4 hour, adding 6-10 times of water gaging decocts 2-3 time, each 1-2 hour, medicinal liquid after decocting liquid and the distillation merges, filter, be concentrated into relative density 1.10～1.20 (80 ℃), put cold, adding ethanol makes the alcohol amount of containing reach 60-70%, airtight, left standstill 24-48 hour, filter, filtrate recycling ethanol, and be concentrated into relative density 1.15～1.22 (60 ℃), according to the dosage form needs, add Aromatic water or inclusion, add an amount of medicine correctives again or/and drug excipient, make oral liquid, or granule, or tablet, or oral formulations such as capsule, promptly get described medicine.
Preparation method after preferred comprises the steps:
Radix Angelicae Sinensis, Radix Curcumae, Fructus Aurantii, the Radix Aucklandiae add the water distillation, collect Aromatic water 400ml, and cold preservation is standby.Medicinal water logging bubble such as medicinal residues and Herba Leonuri, Radix Paeoniae Rubra, Radix Salviae Miltiorrhizae, Radix Achyranthis Bidentatae, Herba Schizonepetae charcoal, carbonized Rhizoma Zingiberis, Radix Rubiae is after 2.5 hours, adding 8 times of water gagings decocts three times, 2 hours for the first time, 1.5 hours for the second time, 1 hour for the third time, the medicinal liquid after decocting liquid and the distillation merged, and filters, be concentrated into relative density 1.14～1.16 (80 ℃), put coldly, add ethanol and make and contain alcohol amount and reach 65%, airtight, left standstill 24 hours, filter, filtrate recycling ethanol is concentrated into relative density 1.18～1.20 (60 ℃), add Aromatic water, make oral liquid.Perhaps Aromatic water is made the betacyclodextrin clathrate, made oral solid formulations such as granule.
The invention has the advantages that: selected Herba Leonuri has the effect of promoting blood flow to regulate menstruation in the medicine material, cooperates Radix Angelicae Sinensis, Radix Paeoniae Rubra, Radix Salviae Miltiorrhizae can strengthen the effect of promoting blood circulation to restore menstrual flow.Radix Curcumae and Radix Achyranthis Bidentatae, Fructus Aurantii, Radix Aucklandiae compatibility are brought into play the effect of promoting flow of QI and blood jointly.Share the hemostasis dissipating blood stasis with Radix Rubiae behind Herba Schizonepetae, the Rhizoma Zingiberis parch to black.Full side has demonstrated fully the rule of treatment of blood-activating and qi-promoting, blood-arresting catamenia-regulating.
Specific embodiments:
This medicine shows by pharmacological experiment study: the contraction movement in the body uterus has the obvious suppression effect to isolated rat uterus and rabbit; And can the antagonism oxytocin and acetylcholine to the excitation in uterus.Can also improve the hemorheology of " blood stasis " card rat, increase the blood flow of Mouse Uterus, and shorten bleeding time and clotting time.Ovary and developing womb to teenage female rats have facilitation, and can raise serum estradiol and progesterone levels.This medicine is at body rabbit duodenal administration, and the contraction movement of normal uterus is had the obvious suppression effect, and contraction movement power and rate of change are all reduced significantly, and effect can be kept more than the 1.5h.Can also increase the weight in teenage rat ovary and uterus, estradiol and progesterone level in the rising serum.Mice and rat ig administration can be shortened bleeding time and the clotting time of mice, and can shorten the level of blood plasma recalcification time (PRT) and kaolin activated partial thromboplastin time (KPTT) and the reduction serum fibrin degradation product (FDP) (FDP) of rat.
Following pharmacology and clinical experiment example can confirm further that the present invention treats the advantage of dysfunctional uterine bleeding, and used in the experiment " female peaceful oral liquid " is the preparation that makes by optimal case of the present invention:
Experimental example 1: pharmacodynamic experiment
One, test material
(1) be subjected to the reagent thing: female peaceful oral liquid (hereinafter to be referred as female peaceful liquid), lot number 920722 is every 10ml oral liquid, every ml contains crude drug 1.25g.Test dose calculates the benzoic acid that adjuvant contains 20% sucrose and 0.3% with the crude drug amount, uses the distilled water wiring solution-forming.
(2) positive control drug: WUJI BAIFENG KOUFUYE (hereinafter to be referred as Gallus Domesticus liquid), to produce by White Cloud Mountain, Guangzhou pharmaceutical factory and Chaozhou, Guangdong Province Hong Xing pharmaceutical factory, lot number is respectively 920207 and 941235.YUNNAN BAIYAO is produced by Chinese yunnan white pharmaceutical factory and Dali pharmaceutical factory, and lot number is respectively 9307-163 and 950649.Above medicine faces the time spent and all uses distilled water diluting.
(3) other reagent: oxytocin (Oxy), the biochemical-pharmaceutical factory, Maanshan City produces, lot number 920216; Diethylstilbestrol injection, aminoacid company in Tianjin produces, lot number 911017.PGF2 α is put and is exempted from medicine box, is provided by Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences.Serum estradiol and progesterone are put and are exempted from medicine box, are provided by Tianjin nine ancient cooking vessel medical biotechnology company limiteies.960741), kaolin partial thromboplastin (lot number 960711), thrombin (lot number: 960711), (lot number: 961122), be Beite Biological Technology Co., Ltd., Shanghai provides two D immunity emulsion reagent box calcic thromboplastin (lot number:.(lot number: 950471), U.S. Sigma provides weary X factor frozen dry blood plasma test kit.
(4) instrument: FF-613 calculates 1251 ria-determination instrument automatically, and the Beijing Nuclear Instrument Factory produces; XJY-1 type hydrogen is removed formula tissue blood analyzer; DC-001 type isolated organ analyzer, analytical tool factory in Nanjing produces; LMS-2B two road physiology monitors, Chengdu Instruement Factory produces; The muscle tone pick off, the Ministry of Aerospace's the 634 institute production: FJ-2107 type liquid scintillation counter, Xi'an 262 factories produce; XN-5 type capillary type viscosity apparatus and power supply instrument, Shanghai Medical Univ produces; ST4BIO type blood coagulation instrument, French Diagnosticastago factory produces.
(5) animal: Kunming mouse, Wistar rat, by Anhui Province Institute for Medical Research and the supply of Medical University Of Anhui animal center, the quality certification number: real moving accurate No. 01 and No. 03 of Anhui doctor.Rabbit is provided by Anhui Chinese Medicine College animal housing.
Two, test method and result
(1) to the influence of animal blood coagulation aspect
1, to the influence in mice bleeding time
100 of healthy mices, body weight 23～26g, male and female half and half are divided into 5 groups, by the table in shown in dosage ig administration, capacity 0.3ml/10g, once a day, continuous 6 days.40min after time administration does not measure the mice bleeding time with cutting the tail method, the results are shown in Table 1.
The female peaceful liquid of table 1. is to the influence in mice bleeding time
| Group | Dosage (g/kg) | Number of animals (only) | Bleeding time (min) | Rate of change (%) |
| The adjuvant group | Deng capacity | ????20 | ??8.59±2.94 | ????0 |
| The YUNNAN BAIYAO group | ????0.6 | ????20 | ??6.27±2.25 * | ????-26.37 |
| Female peaceful liquid group (low) | ????11.2 | ????20 | ??7.17±2.42 | ????-14.83 |
| Female peaceful liquid group (in) | ????22.5 | ????20 | ??6.09±2.44 * | ????-27.41 |
| Female peaceful liquid group (height) | ????33.8 | ????20 | ??7.38±2.44 | ????-14.1 |
Annotate: * represents p＜0.05 with the comparison of adjuvant group.The variation percentage rate of rate of change for comparing with adjuvant.
Table 1 shows that female peaceful liquid can shorten the bleeding time of mice, and is especially with the effect of middle dosage group better (p＜0.05), similar to YUNNAN BAIYAO: and the diversity not statistically significant (p＞0.05) between low, high dose group and the adjuvant.
2, to the influence of clotting time of mice
18～23g mice, male and female half and half are divided into 6 groups (10 every group) at random: matched group (waiting the capacity adjuvant), YUNNAN BAIYAO group (0.3g/kg), Gallus Domesticus liquid group (3ml/kg), basic, normal, high three the dosage groups of female peaceful liquid clear paste (5,10,20g/kg).Ig administration, capacity are 0.2ml/10g, qd * 5d.1h after the last administration inserts mice ophthalmic corner of the eyes ball rear vein beard with glass capillary (internal diameter 1mm, long 8cm), rotates withdrawal more gently, and blood is filled with the back and taken out.Observed and recorded fractures to pipe from blood inflow blood capillary and the time of blood clotting silk occurs, and this time is clotting time.Result and matched group relatively, female peaceful liquid clear paste (5,10,20g/kg) same YUNNAN BAIYAO (0.3g/kg) is the same with Gallus Domesticus liquid (3ml/kg), can obviously shorten clotting time (P＜0.05 or P＜0.01), sees Table 2.Illustrate that female peaceful liquid has certain blood coagulation enhancing effect.
The female peaceful liquid of table 2. is to the influence of clotting time of mice
| Group | Dosage (g/kg) | Number of animals (only) | Clotting time (s) |
| Matched group | The equivalent adjuvant | ????10 | ????71.2±18.4 |
| The YUNNAN BAIYAO group | ????0.3 | ????10 | ????42.9±10.5 ** |
| Gallus Domesticus liquid group | ????3ml | ????10 | ????43.4±13.6 ** |
| Female peaceful liquid group (low) | ????5 | ????10 | ????52.1±15.4 * |
| Female peaceful liquid group (in) | ????10 | ????10 | ????45.4±10.1 ** |
| Female peaceful liquid group (height) | ????20 | ????10 | ????40.1±12.7 ** |
Annotate: compare * p＜0.5, * * P＜0.01 with matched group.
3, to the influence of P of Rats RT, PT, KPTT, TT, X:C and D-dimer content
48 of body weight 195～230g rats, male and female half and half, grouping and medication are tested ig capacity 1ml/100g with clotting time of mice.1h after the last administration, femoral artery is got blood.(1) blood adds 3.8% sodium citrate (9: 1), and mixing with the centrifugal 10min of 1000r, is drawn supernatant for being rich in platelet blood plasma (PRP); With the centrifugal 20min of 3000r, be platelet-poor plasma (PPP) again.Blood plasma (PRP) 100 μ l behind (2) 37 ℃ of incubation 1min add the CaCl2 liquid 100 μ l of 0.025mol/L, measure blood plasma recalcification time (PRT).Do blood plasma (PPP) 50 μ l behind (3) 37 ℃ of incubations add the Neoplastine that 100 μ l contain thromboplastin and Ca2+?, measure prothrombin time (PT, one-step method).(4) 50 μ l blood plasma (PPP) add PTT-LA reagent 50 μ l, the CaCl2 50 μ l of incubation (s) back adding in 180 seconds 0.025mol/L, and mixing is measured KPTT (KPTT).Do blood plasma (PPP) 100 μ l behind (5) 37 ℃ of incubations add Thrombin Prest? reagent 100 μ l measure thrombin time (TT).(6) 1: 10 diluting plasma (PPP) 50 μ l add weary X blood plasma 50 μ l, does mixing add Neoplastine behind the incubation 1min? reagent 100 μ l measure plasma coagulation factors X activity (X:C).(7) blood plasma (PPP) 10 μ l add the two D immunity of 10 μ l latex, measure the D-dimer content behind the mixing 3min.Result and matched group relatively, YUNNAN BAIYAO (0.3g/kg), Gallus Domesticus liquid (3ml/kg), female peaceful liquid clear paste (10,20g/kg) all obviously shorten PRT (P＜0.05 or P＜0.01); Three kinds of medicines all obviously shorten KPTT (P＜0.01); YUNNAN BAIYAO can obviously shorten TT (P＜0.05), but Gallus Domesticus liquid and female peaceful liquid clear paste there is no have a significant effect (P＞0.05) to TT.See Table 3.
Observe the influence of medicine to rat plasma D-dimer content and X:C, by the rank test of grade classified data, H-number is respectively 2.09 and 1.22, P＞0.05, and the rank test difference is described between six groups, and there are no significant, sees Table 4.
The female peaceful liquid of table 3. is to the influence of P of Rats RT, PT, KPTT and TT
| Group | Dosage (g/kg) | PRT(s) | PT(s) | KPTT(s) | TT(s) |
| Matched group | The equivalent adjuvant | 169.5±58.5 | 15.9±2.3 | 40.7±3.4 | 53.7±7.0 |
| YUNNAN BAIYAO | ??0.3g | 109.1±30.2 * | 18.4±2.7 | 26.8±5.8 ** | 43.6±8.8 |
| Gallus Domesticus liquid group | ??3ml | 85.2±23.1 ** | 17.1±1.3 | 28.5±2.0 ** | 50.2±3.2 |
| Female peaceful liquid group | ??5 | 134.3±39.7 | 17.8±3.0 | 25.9±1.7 ** | 55.6±4.4 |
| ??100 | 118.2±27.1 * | 17.5±2.3 | 27.3±1.8 ** | 54.9±6.8 | |
| ??20 | 115.2±31.2 * | 17.0±1.4 | 25.7±1.2 ** | 57.2±9.1 |
Annotate: compare * P＜0.05, * * P＜0.01 with matched group.
The female peaceful liquid of table 4. is to the influence of rat plasma D-dimer content and X:C
| Group | Dosage | ??? The D-dimer content??? (ug/ml) | ??? X:C | ||||
| ????(g/kg) | ????＜0.5 | ????＞4 | ????＞8 | ????＞16 | ????＜200％ | ??≥200％ | |
| Matched group | The equivalent adjuvant | ????2 | ????2 | ????0 | ????4 | ????1 | ??7 |
| YUNNAN BAIYAO | ????0.3g | ????4 | ????0 | ????0 | ????4 | ????0 | ??8 |
| Gallus Domesticus liquid group | ????3ml | ????5 | ????0 | ????0 | ????3 | ????2 | ??6 |
| Female peaceful liquid group | ????5 | ????4 | ????1 | ????0 | ????3 | ????2 | ??6 |
| ????10 | ????2 | ????1 | ????0 | ????5 | ????2 | ??6 | |
| ????20 | ????2 | ????3 | ????1 | ????2 | ????1 | ??7 | |
Annotate: between six groups respectively through rank test, p＞0.05.
4, to the influence of rat blood serum fibrin degradation product (FDP) (FDP)
45 of rats, body weight 200～250g, the male and female dual-purpose is divided into 5 groups.Press table 5 dosage ig administration, capacity 1ml/100g, once a day, logotype 7 days.45min after the last administration, 20% urethane solutions i p anaesthetizes (1g/kg), and serum is got in the ventral aorta blood drawing, uses the normal saline doubling dilution.Micropipet is drawn one of each diluent (25 μ l), is added in the V-type blood-coagulation-board aperture, adds one of lyophilizing FDP preparing Diagnostic Erythrocyte (25 μ l) again.Put on the micro-stirrer jolting 30 seconds, and put 37 ℃ of water-bath 0.5h, take out cooling 10min.Pressing indirect hemagglutination method measures.The result with female peaceful liquid after, levels of fdp content reduces, especially in the dosage group the same with YUNNAN BAIYAO, with the adjuvant group relatively, significant difference is all arranged, illustrate that they can suppress fibrinolytic process (seeing Table 5).
The female peaceful liquid of table 5. is to the influence of rat blood serum FDP
| Group dosage (g/kg) | Number of animals (only) | FDP measures (ug/ml) |
| Matched group equivalent adjuvant | ????9 | ????5.00±0.63 |
| YUNNAN BAIYAO 0.6 | ????9 | ????4.30±1.54 * |
| Female peaceful liquid group 11.2 | ????9 | ????4.72±1.04 |
| ????????????22.5 | ????9 | ????3.75±l.08 ** |
| ????????????33.8 | ????9 | ????4.68±1.21 |
Annotate: compare * P＜0.05, * * P＜0.01 with matched group.
(2) to the influence of " blood stasis " card rat blood rheological characteristic
Healthy rat, body weight 230～250g, random packet, according to the form below dosage gastric infusion, capacity 1.4ml/100g once a day, continuous 5 days, gave rat skin lower injection 0.1% epinephrine 0.2ml totally 2 times on the 5th day, and soaks stimulation 5min with frozen water betwixt.Inferior morning, abdominal aortic blood was surveyed hemorheological property.As seen the result can cause rat " blood stasis " card, whole blood contrast viscosity, plasma viscosity and packed cell volume are increased with epinephrine+frozen water stimulation.Female peaceful liquid and Gallus Domesticus liquid all can reduce " blood stasis " card rat whole blood contrast viscosity, plasma viscosity and packed cell volume (table 6).Show that female peaceful liquid has certain function of promoting blood circulation to disperse blood clots.
The female peaceful liquid of table 6. is to the influence of " blood stasis " card rat blood rheological characteristic
| Group | Dosage (g/kg) | ????????? Whole blood contrast viscosityHeight is cut low cutting | Plasma viscosity (ratio) | Packed cell volume (%) | Erythrocyte electrophoretic time (S) | |
| Normal group | - | 6.75±0.25 | 8.28±0.88 | 1.74±0.03 | 42.8±0.76 | 17.01+0.92 |
| Model+normal saline group | Deng capacity | 8.13±0.52 | 15.71±1.61 | 2.01±0.09 | 47.0±1.73 | 17.51±1.81 |
| Model+Gallus Domesticus liquid group | 5.4ml | 6.85±0.34 ** | 10.41±1.84 ** | 1.84±0.06 ** | 40.3±2.08 ** | 16.93±0.93 |
| Model+female peaceful liquid (height) group | 22.5 | 7.14±0.65 ** | 9.75±1.49 ** | 1.72±0.09 ** | 44.6±2.29 ** | 16.95±0.81 |
| Model+female peaceful liquid (low) group | 11.2 | 7.26±0.77 ** | 10.48±1.86 ** | 1.82±0.04 ** | 43.3±3.51 ** | 18.2±1.66 |
Annotate: compare with model group: * * P＜0.01
(3) to the influence of Mouse Uterus blood flow
Get 40 of female mices, body weight 25 ± 2g is divided into 4 groups, irritates stomach by the listed dosage of table 7 respectively and gives female peaceful liquid low dosage and high dose, Gallus Domesticus liquid (positive controls) and normal saline (negative control group).The medicine distilled water diluting, every Mus gavages 0.6ml, every day 1 time, logotype 5d.50min after the last administration, the abdominal cavity is opened in urethane anesthesia, surveys uterine blood flow with hydrogen removing method. the result as seen, female peaceful liquid can increase the blood flow of Mouse Uterus very significantly, and increases with dosage and to act on enhancing.Its effect and Gallus Domesticus liquid phase are seemingly.
The female peaceful liquid of table 7. is to the influence of Mouse Uterus blood flow
| Group | Number of animals (only) | Dosage (g/kg) | Uterine blood flow (ml/100gmin -1) |
| Female peaceful liquid group (low) | ????100 | ????11.2 | ????226.18±22.78 ** |
| Female peaceful liquid group (height) | ????10 | ????22.5 | ????337.58±38.46 ** |
| Gallus Domesticus liquid group | ????10 | ????5.4ml | ????334.20±66.62 ** |
| The normal saline group | ????10 | Deng capacity | ????195.82±8.13 |
Annotate: compare * * P＜0.01 with the normal saline group
Experimental example 2: clinical research test
Clinical trial protocol is formulated according to " the clinical research guideline of new Chinese medicine treatment menoxenia ", " the clinical research guideline of new Chinese medicine treatment dysfunctional uterine bleeding " in " new Chinese medicine clinical research guideline ", and clinical trial two stages promptly contrast the therapeutic test stage and enlarge the contrast therapeutic test stage carries out simultaneously.Set up treatment group and matched group at random in 1: 1 ratio, and establish open case group.Observe patient's 482 examples altogether, wherein 302 examples are organized in treatment, matched group 180 examples, (each disease is respectively observed treatment group 100～101 examples, matched group 60 examples).Result of the test shows, the hemostatic healing efficacy of this product treatment metrorrhagia (syndrome of qi stagnation and blood stasis): total obvious effective rate 83.2%, total effective rate 90.1%; Regulating menstruation curative effect: total obvious effective rate 70.3%, total effective rate 83.2%.The hemostatic healing efficacy of treatment menorrhagia (syndrome of qi stagnation and blood stasis): total obvious effective rate 82.2%, total effective rate 93.1%; Regulating menstruation curative effect: total obvious effective rate 77.2%, total effective rate 89.1%.The hemostatic healing efficacy of treatment menostaxis (syndrome of qi stagnation and blood stasis): total obvious effective rate 77.0%, total effective rate 93.0%: regulating menstruation curative effect: total obvious effective rate 73.0%, total effective rate 89.0%.Demonstrate good curative effect.
Rewrite embodiment:
Embodiment:
Below in conjunction with specific embodiment treatment menorrhagia of the present invention is described in further detail, the preparation method of the medicine of menostaxis:
EXAMPLE l: the preparation of oral liquid
Prescription is formed: 30 kilograms of Herba Leonuris, 30 kilograms of Radix Angelicae Sinensis, 30 kilograms of Radix Paeoniae Rubra, 30 kilograms of Radix Salviae Miltiorrhizaes, 20 kilograms of Radix Curcumaes, 30 kilograms of Radix Achyranthis Bidentataes, 20 kilograms of Fructus Aurantiis, 10 kilograms of the Radix Aucklandiae, 20 kilograms of Herba Schizonepetae (parch to black), 10 kilograms of Rhizoma Zingiberiss (parch to black), 20 kilograms in Radix Rubiae
Technical process: get Radix Angelicae Sinensis, Radix Curcumae, Fructus Aurantii, the Radix Aucklandiae and add the water distillation, collect Aromatic water, cold preservation is standby.Medicinal residues and Herba Leonuri, Radix Paeoniae Rubra, Radix Salviae Miltiorrhizae, Radix Achyranthis Bidentatae, Herba Schizonepetae charcoal, carbonized Rhizoma Zingiberis, after Radix Rubiae is soaked 2.5 hours, add 8 times of water gagings respectively and decoct 3 times, 2 hours for the first time, 1.5 hours for the second time, 1 hour for the third time, the medicinal liquid after decocting liquid and the distillation merged, filter, be concentrated into relative density 1.14～1.16 (80 ℃), put cold, adding ethanol makes and contains alcohol amount and reach 65%, airtight, left standstill 24 hours, filter, decompression filtrate recycling ethanol, and be concentrated into the clear paste of relative density 1.18～1.20 (60 ℃), add Aromatic water, simple syrup and sodium benzoate add water and transfer pH to 4.5, stir evenly, standing over night filters embedding, oral liquid is made in sterilization.Be applicable to the dysfunctional uterine bleeding patient.Its instructions of taking is every day three times, each 20ml.
Embodiment 2: the preparation of granule
Prescription is formed: 25 kilograms of Herba Leonuris, 25 kilograms of Radix Angelicae Sinensis, 25 kilograms of Radix Paeoniae Rubra, 25 kilograms of Radix Salviae Miltiorrhizaes, 15 kilograms of Radix Curcumaes, 25 kilograms of Radix Achyranthis Bidentataes, 15 kilograms of Fructus Aurantiis, 5 kilograms of the Radix Aucklandiae, 15 kilograms of Herba Schizonepetae, 5 kilograms of Rhizoma Zingiberiss, 15 kilograms in Radix Rubiae
Technical process: get Radix Angelicae Sinensis, Radix Curcumae, Fructus Aurantii, the Radix Aucklandiae and add the water distillation, collect Aromatic water, cold preservation divides and gets volatile oil, makes the betacyclodextrin clathrate.After medicinal residues after the distillation and Herba Leonuri, Radix Paeoniae Rubra, Radix Salviae Miltiorrhizae, Radix Achyranthis Bidentatae, Herba Schizonepetae, Rhizoma Zingiberis, Radix Rubiae are soaked 2 hours, adding 6 times of water gagings respectively decocts 2 times, each 1 hour, medicinal liquid after decocting liquid and the distillation merges, and filters, and is concentrated into relative density 1.10～1.12 (80 ℃), put cold, add ethanol and make and contain alcohol amount and reach 60%, airtight, left standstill 24 hours, filter, decompression filtrate recycling ethanol, and be concentrated into the clear paste of relative density 1.15～1.17 (60 ℃), add the betacyclodextrin clathrate, spray drying, spray powder reenters an amount of dextrin, and dry-pressing is granulated, and makes granule.Be applicable to the dysfunctional uterine bleeding patient.Its instructions of taking is every day three times, each 5g.
Embodiment 3: the preparation of tablet
Prescription is formed: 35 kilograms of Herba Leonuris, 35 kilograms of Radix Angelicae Sinensis, 35 kilograms of Radix Paeoniae Rubra, 35 kilograms of Radix Salviae Miltiorrhizaes, 25 kilograms of Radix Curcumaes, 35 kilograms of Radix Achyranthis Bidentataes, 25 kilograms of Fructus Aurantiis, 15 kilograms of the Radix Aucklandiae, 35 kilograms of Herba Schizonepetae, 15 kilograms of Rhizoma Zingiberiss, 25 kilograms in Radix Rubiae
Technical process: get Radix Angelicae Sinensis, Radix Curcumae, Fructus Aurantii, the Radix Aucklandiae and add the water distillation, collect Aromatic water, cold preservation divides and gets volatile oil, makes the betacyclodextrin clathrate.Medicinal residues after the distillation and Herba Leonuri, Radix Paeoniae Rubra, Radix Salviae Miltiorrhizae, Radix Achyranthis Bidentatae, Herba Schizonepetae, Rhizoma Zingiberis, after Radix Rubiae is soaked 4 hours, add 10 times of water gagings respectively and decoct 3 times, each 2 hours, the medicinal liquid after decocting liquid and the distillation merged, filter, be concentrated into relative density 1.18～1.20 (80 ℃), put coldly, add ethanol and make and contain alcohol amount and reach 70%, airtight, left standstill 48 hours, and filtered decompression filtrate recycling ethanol, and be concentrated into the clear paste of relative density 1.20～1.22 (60 ℃), add the betacyclodextrin clathrate, spray drying, spray powder adds 10 kilograms of microcrystalline Cellulose, 3 kilograms of carboxymethyl starch sodium, add starch to 76 kilogram, make wetting agent, the system granule with 60% ethanol, dry, tabletting, the bag film-coat, promptly.Its instructions of taking is every day three times, each 4 (0.4g/ sheet).
Embodiment 4: the preparation of capsule
Prescription is formed: 35 kilograms of Herba Leonuris, 30 kilograms of Radix Angelicae Sinensis, 30 kilograms of Radix Paeoniae Rubra, 25 kilograms of Radix Salviae Miltiorrhizaes, 20 kilograms of Radix Curcumaes, 25 kilograms of Radix Achyranthis Bidentataes, 15 kilograms of Fructus Aurantiis, 15 kilograms of the Radix Aucklandiae, 30 kilograms of Herba Schizonepetae (parch to black), 10 kilograms of Rhizoma Zingiberiss (parch to black), 15 kilograms in Radix Rubiae
Technical process: get Radix Angelicae Sinensis, Radix Curcumae, Fructus Aurantii, the Radix Aucklandiae and add the water distillation, collect Aromatic water, cold preservation divides and gets volatile oil, makes the betacyclodextrin clathrate.Medicinal residues after the distillation and Herba Leonuri, Radix Paeoniae Rubra, Radix Salviae Miltiorrhizae, Radix Achyranthis Bidentatae, Herba Schizonepetae charcoal, carbonized Rhizoma Zingiberis, after Radix Rubiae is soaked 3 hours, adding 8 times of water gagings respectively decocts 3 times, each 1.5 hours, the medicinal liquid after decocting liquid and the distillation merged, and filters, be concentrated into relative density 1.13～1.15 (80 ℃), put coldly, add ethanol and make and contain alcohol amount and reach 65%, airtight, left standstill 24 hours, filter, decompression filtrate recycling ethanol, and be concentrated into the clear paste of relative density 1.18～1.20 (60 ℃), add the betacyclodextrin clathrate, spray drying, spray powder add starch to 66 kilogram, and Pulvis Talci is an amount of, filled capsules, promptly.Its instructions of taking is every day three times, each 4 (0.33g/ grain).
Claims (4)
1.[document source] electronic application
2.[the message in-coming date] 2004-5-18
3.[application number]
4.[claim item]
[claim 1] a kind of pharmaceutical composition for the treatment of dysfunctional uterine bleeding, it is characterized in that: this pharmaceutical composition is made by following materials of weight proportions:
Herba Leonuri 25-35 weight portion Radix Angelicae Sinensis 25-35 weight portion Radix Paeoniae Rubra 25-35 weight portion
Radix Salviae Miltiorrhizae 25-35 weight portion Radix Curcumae 15-25 weight portion Radix Achyranthis Bidentatae 25-35 weight portion
Fructus Aurantii 15-25 weight portion Radix Aucklandiae 5-15 weight portion Herba Schizonepetae 15-25 weight portion
Rhizoma Zingiberis 5-15 weight portion Radix Rubiae 15-25 weight portion
The pharmaceutical composition of [claim 2] treatment dysfunctional uterine bleeding according to claim 1 is characterized in that: the weight proportion of said each crude drug is:
Herba Leonuri 30 weight portion Radix Angelicae Sinensis 30 weight portion Radix Paeoniae Rubra 30 weight portions
Radix Salviae Miltiorrhizae 30 weight portion Radix Curcumaes 20 weight portion Radix Achyranthis Bidentataes 30 weight portions
The Fructus Aurantii 20 weight portion Radix Aucklandiae 10 weight portion Herba Schizonepetae 20 weight portions
Rhizoma Zingiberis 10 weight portion Radix Rubiaes 20 weight portions
The pharmaceutical composition of [claim 3] treatment dysfunctional uterine bleeding according to claim 1 and 2 is characterized in that: said Herba Schizonepetae should be fried into charcoal, and Rhizoma Zingiberis should be fried into charcoal, and Radix Achyranthis Bidentatae is a Radix Cyathulae.
[claim 4] is characterized in that according to the pharmaceutical composition of claim 1,2 or 3 described treatment dysfunctional uterine bleedings: also contain the medicine correctives or/and drug excipient in the said medicament.
The pharmaceutical composition of [claim 5] treatment dysfunctional uterine bleeding according to claim 4 is characterized in that: said medicine correctives is one or more the combination in sucrose, simple syrup, sodium benzoate, stevioside, the protein sugar; Said drug excipient is one or more the combination in dextrin, magnesium stearate, microcrystalline Cellulose, carboxymethyl starch sodium, starch, Pulvis Talci, sodium bicarbonate, the citric acid.
[claim 6] is characterized in that as claim 1,2 or 3 described a kind of preparation methoies for the treatment of the medicine of dysfunctional uterine bleeding this method comprises the steps:
Get Radix Angelicae Sinensis, Radix Curcumae, Fructus Aurantii, the Radix Aucklandiae and add the water distillation, collect Aromatic water, cold preservation is standby.Or divide and get volatile oil, make the betacyclodextrin clathrate.Medicinal residues after the distillation and Herba Leonuri, Radix Paeoniae Rubra, Radix Salviae Miltiorrhizae, Radix Achyranthis Bidentatae, Herba Schizonepetae, Rhizoma Zingiberis, after medicines such as Radix Rubiae are soaked 2-4 hour, adding 6-10 times of water gaging decocts 2-3 time, each 1-2 hour, medicinal liquid after decocting liquid and the distillation merges, filter, relative density 1.10～1.20 when being concentrated into 80 ℃, put cold, adding ethanol makes the alcohol amount of containing reach 60-70%, airtight, left standstill 24-48 hour, filter, filtrate recycling ethanol, and relative density 1.15～1.22 when being concentrated into 60 ℃, according to the dosage form needs, add Aromatic water or betacyclodextrin clathrate, add an amount of medicine correctives again or/and drug excipient, make oral liquid, or granule, or tablet, or oral formulations such as capsule, promptly get described medicine.
[claim 7] a kind of preparation method for the treatment of the medicine of dysfunctional uterine bleeding as claimed in claim 6 is characterized in that this method comprises the steps:
Radix Angelicae Sinensis, Radix Curcumae, Fructus Aurantii, the Radix Aucklandiae add the water distillation, collect Aromatic water 400ml, and cold preservation is standby.Medicinal water logging bubble such as medicinal residues and Herba Leonuri, Radix Paeoniae Rubra, Radix Salviae Miltiorrhizae, Radix Achyranthis Bidentatae, Herba Schizonepetae, Rhizoma Zingiberis, Radix Rubiae added 8 times of water gagings and decocts three times, 2 hours for the first time after 2.5 hours, 1.5 hours for the second time, 1 hour for the third time, the medicinal liquid after decocting liquid and the distillation merged, filter, relative density 1.14～1.16 when being concentrated into 80 ℃, put cold, add ethanol and make and contain alcohol amount and reach 65%, airtight, left standstill 24 hours, filter, filtrate recycling ethanol, relative density 1.18～1.20 when being concentrated into 60 ℃, add Aromatic water, make oral liquid.Perhaps Aromatic water is made the betacyclodextrin clathrate, made oral solid formulations such as granule.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004101551031A CN1308032C (en) | 2004-05-18 | 2004-05-18 | Pharmaceutical composition for treating dysfunctional uterine bleeding and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2004101551031A CN1308032C (en) | 2004-05-18 | 2004-05-18 | Pharmaceutical composition for treating dysfunctional uterine bleeding and preparation method thereof |
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| Publication Number | Publication Date |
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| CN1589894A true CN1589894A (en) | 2005-03-09 |
| CN1308032C CN1308032C (en) | 2007-04-04 |
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| CNB2004101551031A Expired - Lifetime CN1308032C (en) | 2004-05-18 | 2004-05-18 | Pharmaceutical composition for treating dysfunctional uterine bleeding and preparation method thereof |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1814196B (en) * | 2005-12-05 | 2011-07-27 | 杨雄志 | Chinese medicine composition for treating functional metrorrhagia and preparation method thereof |
| CN104007221A (en) * | 2014-05-23 | 2014-08-27 | 荣昌制药(淄博)有限公司 | Detection method of traditional Chinese medicine composition for treating functional uterine bleeding |
| CN104374839A (en) * | 2014-10-31 | 2015-02-25 | 荣昌制药(淄博)有限公司 | Detection method for specific chromatogram of traditional-Chinese-medicine composition for treating irregular menstruation |
| CN104547720A (en) * | 2013-11-20 | 2015-04-29 | 田孝东 | Medicament for treating functional bleeding |
| CN105434877A (en) * | 2015-12-24 | 2016-03-30 | 青岛市第三人民医院 | Traditional Chinese medicine for treating dysfunctional uterine bleeding caused by internal heat due to yin deficiency and preparation method |
| CN108524904A (en) * | 2018-07-18 | 2018-09-14 | 天长亿帆制药有限公司 | A kind of preparation method of female peaceful particle |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1194749C (en) * | 2003-02-27 | 2005-03-30 | 张晴龙 | Medicine for treating functional metrorrhagia and preparing process thereof |
-
2004
- 2004-05-18 CN CNB2004101551031A patent/CN1308032C/en not_active Expired - Lifetime
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1814196B (en) * | 2005-12-05 | 2011-07-27 | 杨雄志 | Chinese medicine composition for treating functional metrorrhagia and preparation method thereof |
| CN104547720A (en) * | 2013-11-20 | 2015-04-29 | 田孝东 | Medicament for treating functional bleeding |
| CN104007221A (en) * | 2014-05-23 | 2014-08-27 | 荣昌制药(淄博)有限公司 | Detection method of traditional Chinese medicine composition for treating functional uterine bleeding |
| CN104374839A (en) * | 2014-10-31 | 2015-02-25 | 荣昌制药(淄博)有限公司 | Detection method for specific chromatogram of traditional-Chinese-medicine composition for treating irregular menstruation |
| CN104374839B (en) * | 2014-10-31 | 2016-03-23 | 荣昌制药(淄博)有限公司 | A kind of detection method for the treatment of irregular menstruation Chinese medicine composition feature |
| CN105434877A (en) * | 2015-12-24 | 2016-03-30 | 青岛市第三人民医院 | Traditional Chinese medicine for treating dysfunctional uterine bleeding caused by internal heat due to yin deficiency and preparation method |
| CN108524904A (en) * | 2018-07-18 | 2018-09-14 | 天长亿帆制药有限公司 | A kind of preparation method of female peaceful particle |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1308032C (en) | 2007-04-04 |
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