CN1246012C - Medicine for treating endometriosis and its preparing process - Google Patents

Medicine for treating endometriosis and its preparing process Download PDF

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Publication number
CN1246012C
CN1246012C CN 03131990 CN03131990A CN1246012C CN 1246012 C CN1246012 C CN 1246012C CN 03131990 CN03131990 CN 03131990 CN 03131990 A CN03131990 A CN 03131990A CN 1246012 C CN1246012 C CN 1246012C
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rhizoma corydalis
filtrate
herba leonuri
total alkali
medicine
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CN1565527A (en
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肖伟
戴翔翎
凌娅
廖正根
刘涛
詹永成
钟裔荣
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Jiangsu Kanion Pharmaceutical Co Ltd
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Jiangsu Kanion Pharmaceutical Co Ltd
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Abstract

The present invention relates to a medicine for curing endometriosis, which is characterized in that the medicine comprises the following materials of the proportion by weight: 10 to 20 of motherwort and 4 to 10 of rhizoma corydalis. The present invention also relates to a preparation method of the medicine, which is characterized in that motherwort total alkali and rhizoma-corydalis total alkali are respectively extracted and are then mixed; pharmaceutic adjuvant materials are added, and any preparation described in pharmacy is produced. The present invention can be used for curing endometriosis and has the advantages of good curative effect, few medicine in the prescription, no medicinal material with strong medical speciality and toxicity, safe clinical application and little side or adverse reaction.

Description

A kind of medicine for the treatment of endometriosis and preparation method thereof
Technical field
The present invention relates to a kind of medicine for the treatment of endometriosis, specifically a kind of is the Chinese patent medicine of feedstock production with the Chinese herbal medicine, the invention still further relates to the preparation method of this medicine.
Background technology
Endometriosis is by the caused a kind of pathological changes of endometrium that is grown in cavity of uterus position in addition.Because ectopic endometrium still is subjected to the influence of ovarian hormone, through preceding hyperemia, menstrual period are hemorrhage, and accumulation of blood can cause that focus occurs inflammatory reaction on every side and stimulates local organization symptoms such as dysmenorrhea to occur in tissue.According to statistics, the endometriosis sickness rate accounts for childbearing age women's 15%-20%, and it mainly shows as secondary dysmenorrhea, sexual intercourse tumor, pelvic pain, irregular menstruation, infertile etc.The generation rate of malignant tumour that endometriosis causes is about 0.7%~1%, and the main malignant tumor that forms grows on the ovary.
In the prior art, the medicine for the treatment of endometriosis both at home and abroad has hormonotherapy, surgical therapy and herbal treatment, and hormone manufacturer is more.Wherein more representational gonadal hormone has 18 monomethyl norethindrone, ethinylestradiol, danazol, GuRH-A, M monomethyl norgestrienone, gonadotherapy exists side reaction serious, many difficult acceptance of patient, and medicine is removed the shortcoming that subtracts difficult assurance; Adopt surgical therapy, its defective is that patient recovery is longer, and also brings huge misery to patient in therapeutic process.In view of this, be devoted to explore the mechanism that endometriosis takes place both at home and abroad always, so that find to have safe, effective, the active drug that toxic and side effects is few of the new mechanism of action, but, up to the present, endometriosis genesis mechanism aspect in uterus, Shang Weijian has breakthrough.Also not having breakthrough medicine emerges.
Summary of the invention
Technical problem to be solved by this invention is at the deficiencies in the prior art, proposes a kind of medicine of new treatment endometriosis, and this medicine is with blood circulation promoting and blood stasis dispelling, and treatment mechanism such as reducing swelling and alleviating pain realize the purpose for the treatment of.
Another technical problem to be solved by this invention is the preparation method that has proposed this medicine, and this method can be extracted its active ingredient effectively, and removes its inert matter.
Technical problem to be solved by this invention is to realize by following technical scheme.The present invention is a kind of medicine for the treatment of endometriosis, and it is made by raw material and pharmaceutic adjuvant, is characterized in, raw material is made up of the Chinese medicine of following weight proportion:
Herba Leonuri 10-20 Rhizoma Corydalis 4-10.
Technical problem to be solved by this invention can also further realize by following technical scheme.Above-described a kind of medicine for the treatment of endometriosis is characterized in that wherein the weight proportion of each raw material is:
Herba Leonuri 15 Rhizoma Corydalis 6.
Technical problem to be solved by this invention can also further realize by following technical scheme.Above-described a kind of medicine for the treatment of endometriosis is characterized in, described medicament is a said dosage form on any pharmaceutics.Wherein preferred dosage form is tablet or capsule or granule.Can make according to conventional methods.
Technical problem to be solved by this invention can also further realize by following technical scheme.Above-described a kind of medicine for the treatment of endometriosis, be characterized in, extract the Rhizoma Corydalis total alkali of the Herba Leonuri total alkali of Herba Leonuri and Rhizoma Corydalis respectively after, the Herba Leonuri total alkali is mixed with the Rhizoma Corydalis total alkali, add pharmaceutic adjuvant, make said any dosage form on the pharmaceutics.
Technical problem to be solved by this invention can also further realize by following technical scheme.Above-described a kind of medicine for the treatment of endometriosis is characterized in that its step is as follows:
(1) gets the water that Herba Leonuri is doubly measured with 5-15, extract 2-4 time, each 1-3 hour; With the water extract be concentrated to contain crude drug 1-3 grams per milliliter after, add ethanol after the cold preservation and be 50-70% to containing alcohol amount, cold preservation 20-30 hour, filter, filtrate is reclaimed alcohol fully, adds ethanol and is 70-90% to containing the alcohol amount, cold preservation 20-30 hour again, filters filtrate for later use;
(2) with after 1-3 times of the above-mentioned filtrate dilution, transfer PH, cold preservation 20-30 hour, filter filtrate for later use to 1-2;
(3) filtrate is added in the cation exchange resin column of having handled well, water wash to PH be 6-7, discard water liquid, the back is soaked resin column and is carried out eluting with the ammonia spirit of 5-15mol/L, collect eluent, be transferred to neutrality with 1-3mol/L hydrochloric acid, concentrating under reduced pressure obtains solid, go out wherein alkaloid with ethanol extraction, obtain the Herba Leonuri total alkali;
(4) get Rhizoma Corydalis with 0.5-2%HAC solution percolation or merceration, collect solution, reclaim ethanol, adding acid accent PH is 3-4, cold preservation 20-30 hour, to filter, it is 9-10 that filtrate transfers to PH with ammonia, cold preservation 20-30 hour again, filter, get precipitation, filter with less ammonia flushing back dissolve with ethanol, get filtrate concentrating, obtain the Rhizoma Corydalis total alkali;
(5) with the Herba Leonuri total alkali with after the Rhizoma Corydalis total alkali mixes, add pharmaceutic adjuvant, make said any dosage form on the pharmaceutics, promptly.
Technical problem to be solved by this invention can also further realize by following technical scheme.The present invention is a kind of medicine for the treatment of endometriosis, and it is made by raw material and pharmaceutic adjuvant, is characterized in, raw material is made up of the Chinese medicine of following weight proportion:
Herba Leonuri 10-20 Rhizoma Corydalis 4-10 Radix Paeoniae Rubra 8-20.
Technical problem to be solved by this invention can also further realize by following technical scheme.Above-described a kind of medicine for the treatment of endometriosis is characterized in that wherein the weight proportion of each raw material is:
Herba Leonuri 15 Rhizoma Corydalis 6 Radix Paeoniae Rubra 12.
Technical problem to be solved by this invention can also further realize by following technical scheme.Above-described a kind of medicine for the treatment of endometriosis, be characterized in, after extracting the peoniflorin of the Rhizoma Corydalis total alkali of Herba Leonuri total alkali, Rhizoma Corydalis of Herba Leonuri and Radix Paeoniae Rubra respectively, Herba Leonuri total alkali, Rhizoma Corydalis total alkali and peoniflorin are mixed, add pharmaceutic adjuvant, make said any dosage form on the pharmaceutics.
Technical problem to be solved by this invention can also further realize by following technical scheme.Above-described a kind of medicine for the treatment of endometriosis is characterized in that its step is as follows:
(1) gets the water that Herba Leonuri is doubly measured with 5-15, extract 2-4 time, each 1-3 hour; With the water extract be concentrated to contain crude drug 1-3 grams per milliliter after, add ethanol after the cold preservation and be 50-70% to containing alcohol amount, cold preservation 20-30 hour, filter, filtrate is reclaimed alcohol fully, adds ethanol and is 70-90% to containing the alcohol amount, cold preservation 20-30 hour again, filters filtrate for later use;
(2) with after 1-3 times of the above-mentioned filtrate dilution, transfer PH, cold preservation 20-30 hour, filter filtrate for later use to 1-2;
(3) filtrate is added in the cation exchange resin column of having handled well, water wash to PH be 6-7, discard water liquid, the back is soaked resin column and is carried out eluting with the ammonia spirit of 5-15mol/L, collect eluent, be transferred to neutrality with 1-3mol/L hydrochloric acid, concentrating under reduced pressure obtains solid, go out wherein alkaloid with ethanol extraction, obtain the Herba Leonuri total alkali;
(4) get Rhizoma Corydalis with 0.5-2%HAC solution percolation or merceration, collect solution, reclaim ethanol, adding acid accent PH is 3-4, cold preservation 20-30 hour, to filter, it is 9-10 that filtrate transfers to PH with ammonia, cold preservation 20-30 hour again, filter, get precipitation, filter with less ammonia flushing back dissolve with ethanol, get filtrate concentrating, obtain the Rhizoma Corydalis total alkali;
(5) get Radix Paeoniae Rubra with 60-80% alcohol reflux twice, each 1-3 hour, each consumption 3-7 doubly measured, merge extractive liquid, reclaims ethanol to there not being the alcohol flavor, is concentrated into every milliliter of medicinal liquid and contains 0.5-2 gram raw medicinal herbs, after centrifugal,, negative to the Molish reaction with water flushing macroporous resin column by D101 macroporous resin column adsorption treatment, use 15-25% alcoholic solution eluting then, collect eluent, reclaim ethanol, concentrate, drying gets extract product of paeoniflorin;
(6) with after Herba Leonuri total alkali, Rhizoma Corydalis total alkali and the peoniflorin mixing, add pharmaceutic adjuvant, make said any dosage form on the pharmaceutics, promptly.
Can remove invalid components in the crude drug in a large number by above-mentioned formulation method, keep and its effective ingredient of enrichment comprises Herba Leonuri total alkali, Rhizoma Corydalis total alkali and peoniflorin etc., can guarantee that preparation has the advantages that dose is few, curative effect is high.
Be the zoopery that the inventor does the pharmacological effect of medicine of the present invention below.
One, experiment material:
1, animal, SD kind rat, female, body weight 250-280 gram, the SPF level, the animal quality certification number: SCXK (capital) 2002-2003, available from Beijing Vital River Experimental Animals Technology Co., Ltd..
2, medicine: A: the dilution of Herba Leonuri extract, every gram contain extract 0.3684 gram, are equivalent to crude drug 52.63 grams; B: the dilution of Rhizoma Corydalis extract, every gram contain extract 0.2315 gram, are equivalent to crude drug 46.3 grams; C: Radix Paeoniae Rubra extract, be equivalent to crude drug 20 grams, be made into respective concentration with before adding an amount of distilled water.Following side 1 is: the preparation of Herba Leonuri and Rhizoma Corydalis extract, be called for short A+B; Side 2 is: the preparation of Herba Leonuri, Rhizoma Corydalis and Radix Paeoniae Rubra extract, be called for short A+B+C.
3, experimental technique and result
(1) to the influence of rat endometrium dystopy model
The animal adaptability is raised a week back subcutaneous injection diethylstilbestrol 0.1ml/100g, once a day, injected continuously 3 days, the 4th day with 3% pentobarbital sodium intraperitoneal injection of anesthesia, 0.1mg/100g, open abdomen, cut the uterus, left side and be about 2cm, the row end-to-end anastomosis, the endometrial tissue of peeling off is cut into the inner membrance piece of 33mm size with the slide calliper rule amount, be sewn on respectively right side cornua uteri, right side fallopian tube just in and near the right ovary, stitching thread is No. 6 nylon monofilament lines of not damaged, closes abdomen.Rat was divided into 8 groups at random in the 3rd after the moulding, be normal control group, model control group, side 1 (A+B) and the large, medium and small dosage group of side 2 (A+B+C), every group 10, according to table 1 dosage difference gastric infusion, the administration volume is 1ml/100g (body weight), successive administration 30 days, the 31st day execution animal behind the medicine, get uterus and ectopic tissue, the general form of perusal uterus and uterine veil; 10% formaldehyde fixed, paraffin embedding, section, HE dyeing, high power microscope is observed endometrial tissue morphology down, adds up according to the grade scale of lesion degree, and compares between organizing.
(2) perusal result
The rats in normal control group uterus is not seen morphological changes of various tissue components, and not seeing has color change, and the uterus tube chamber is not seen to be had hypertrophy, increase or thicken, and inner membrance is not seen hyperemia and blood stasis phenomenon.
Model group rat dystopy endometrium thickens, the inner membrance bright shape that takes on a red color, and there is cyst on the surface, uterus, and cyst differs in size, and the mutual fusion that has forms the Fructus Mori spline structure, part Ectopic Endometrium and adhesion on every side, the individual animal adhesion is heavier.
The dystopy uterus of side 1 and the large and small dosage group of side's 2 administrations rat is brown focus, endometrium thickens, inner membrance color and luster and symptoms such as inner membrance and its surrounding tissue adhesion all have than model group and alleviate to some extent, wherein the change of the heavy dose of group of side 1 (A+B) is more obvious, obviously is better than model group and is subjected to each dosage group of reagent with the change of symptom such as its surrounding tissue adhesion.
(3) pathological tissue observed result (longitudinal section tissue morphology)
The endometrial epithelium of rats in normal control group is not seen hypertrophy, and not seeing has inflammatory cell infiltration, and body of gland is not seen the expansion that atrophy is arranged, and the full nothing of glandular epithelium comes off, and organizational structure is normal.
The dystopy endometrium of model group rat has cyst to form, the cyst wall liner columnar epithelium of cyst, and the glandular epithelium like Ectopic Endometrium is atrophing state.Dystopy body of gland blister cavities size is inhomogeneous, and form is irregular, is expansion state, forms false body of gland.Matter has remote hemorrhage between the Ectopic Endometrium of individual animal, and inflammatory cell infiltration is arranged, based on lymphocyte.
Ectopic Endometrium cyst wall and the smooth muscle layer attenuation of each group of administration (side 1 and side's 2 large and small dosage groups) rat, false body of gland reduces, superficial epithelium and Interstitial cell rareness, the obvious attenuation of Ectopic Endometrium cyst wall and smooth muscle layer, the obvious atrophy of false body of gland, superficial epithelium and interstitial cell hyperplasia alleviate, add up according to grade scale (seeing Table 1 time), the endometrial pathologic of each dosage group rat dystopy of administration changes all than model group alleviating in various degree, false body of gland number reduces, the transverse diameter of false body of gland and perpendicular footpath reduce, and lumen of gland diminishes.Wherein the side 1 (A+B) the effect side of being better than 2 (A+B+C); The effect of side's 1 big or middle dosage group and side's 2 heavy dose of groups is more obvious.See table 1,2 for details.
Table 1, to the influence (n=10) of rat uterus Ectopic Endometrium histopathology
Group Dosage (g/Kg) +++ ++ + -
Normally 0 0 0 10
Model 5 # 5 # 0 # 0 ##
A+B 0.43 0 * 0 * 4 * 6 *
A+B 0.29 0 * 0 * 5 * 5 *
A+B is little 0.145 0 * 0 * 7 * 3 *
A+B+C is big 1.03 0 * 0 * 5 * 5 *
Among the A+B+C 0.69 0 * 0 * 8 * 2 *
A+B+C is little 0.345 0 * 2 * 6 * 2 *
Annotate: X 2 test: compare with the normal control group: #P<0.05; ##P<0.01;
Compare with model control group: * P<0.05; * P<0.01.
Grade scale:
++ the false body of gland of+dystopy endometrium is more, and cell infiltration and hemorrhagic focus are arranged.
++ the false body of gland of dystopy endometrium reduces cell infiltration and hemorrhage alleviating.
The basic atrophy of the false body of gland of+dystopy endometrium, cell infiltration and hemorrhagely obviously alleviate.
-dystopy endometrium is not seen false body of gland, does not see cell infiltration and hemorrhage.
Table 2, to the influence (X ± S of rat uterus Ectopic Endometrium body of gland; N=10)
Group Dosage (g/Kg) Quantity (individual) False body of gland
Transverse diameter Perpendicular footpath
Normally 0 - -
Model 3.7±2.4 ## 10.16±3.23 7.45±1.79
A+B is big 0.43 1.3±0.48 ** 4.75±0.75 ** 3.05±0.16 **
Among the A+B 0.29 1.7±0.67 * 6.13±1.66 ** 4.15±1.17 **
A+B is little 0.145 2.3±1.06 8.97±2.68 5.66±1.48 *
A+B+C is big 1.03 1.6±0.70 * 5.08±0.60 ** 3.53±0.44 **
Among the A+B+C 0.69 2.6±0.70 * 6.47±0.56 ** 4.23±0.35 **
A+B+C is little 0.345 2.9±1.20 8.59±1.52 5.15±0.84 **
Annotate: t check between group: compare with the normal control group: ##P<0.01;
Compare with model control group: * * P<0.01.
The unit in false body of gland transverse diameter and perpendicular footpath is the little lattice number (16 * 16) of micrometer under the light microscopic eyepiece
(4) acute toxicity test
Getting body weight is 20 of 20-22 gram Kunming mouses, male and female half and half, behind the fasting 16h respectively to the mouse stomach administration, the administration concentration side of being 1 (A+B) 1.3g (extract)/ml, side 2 (A+B+C) 1.1g (extract)/ml, the administration volume is 0.4ml/10g, accumulation the administration side of being 1:52g (extract)/Kg, square 2:44g (extract)/Kg, be equivalent to 121 times and 43 times of pharmacodynamics heavy dose respectively, observed 7 days continuously behind the medicine, Non Apparent Abnormality does not have dead.
Show that through the maximum dosage-feeding result of the test mice does not see the overt toxicity reaction under this dosage.Point out the toxicity of these two kinds of extracts lower, and the safety range between pharmacodynamics dosage is bigger.Pharmacodynamics test shows, side 1:21,14,7g (crude drug)/Kg, contain extract 0.43,0.29,0.145, g/Kg and square 2:33,22,11g (crude drug)/Kg, contain extract 1.03,0.69,0.34g/Kg, be equivalent to 60,40,20 times of clinical dosage, the pathological tissue of endometriosis rat model is changed all have certain inhibitory action.Side's onset dosage of 1 is 0.43,0.29g/Kg; The onset dosage of side 2 is 1.03g/Kg.
Compared with prior art, the present invention uses the blood circulation promoting and blood stasis dispelling of theory of Chinese medical science, and the theory of reducing swelling and alleviating pain is carried out prescription, and animal experiment shows that this product has obvious suppression endometrial gland proliferative effect, can be used for treating endometriosis, and its curative effect is better.Side's taste of Chinese medicine is less, high violent, the toxicity medical material of the no property of medicine, and clinical application safety, side effect and untoward reaction are less.Preparation method of the present invention has used membrane separation technique, macroporous adsorption resin technology, cation exchange technology to wait the effective constituent that mainly contains among the other side to extract, the Main Ingredients and Appearance of the side's of making Chinese medicine is comparatively clear and definite, the effective constituent that mainly contains in the Chinese crude drug is extracted and give enrichment, and can remove its invalid components.This product active ingredient is clear and definite, technology advanced person, and dose is little, and quality is easy to control, has improved the looks of Chinese medicine " big (dose is many), thick (active ingredient not being made with extra care), black (outward appearance is relatively poor) " greatly.This product can be treated endometriosis effectively, can overcome the misery that the shortcoming that there is big toxic and side effects in gonadal hormone preparation for treating endometriosis maybe can allow the patient avoid performing the operation and bring again effectively, thereby can greatly improve patient's life quality, existing deep social meaning has huge market prospect again.
The specific embodiment
The following examples can make those skilled in the art more fully understand the present invention, but do not limit the present invention in any way.
Embodiment 1.A kind of medicine for the treatment of endometriosis, it is the medicament of being made by the raw material of following weight proportioning (unit: restrain):
Herba Leonuri 15 Rhizoma Corydalis 6
Decoction according to a conventional method.
Embodiment 2.A kind of medicine for the treatment of endometriosis, it is the medicament of being made by the raw material of following weight proportioning (unit: kilogram):
Herba Leonuri 10 Rhizoma Corydalis 8
Extract active ingredient according to a conventional method, add adjuvant, make capsule.
Embodiment 3.A kind of medicine for the treatment of endometriosis, it is the medicament of being made by the raw material of following weight proportioning (unit: kilogram):
Herba Leonuri 20 Rhizoma Corydalis 10
Its preparation method is as follows:
(1) gets the water of Herba Leonuri by above-mentioned weight, extract each 1 hour 2 times with 5 times of amounts; With the water extract be concentrated to contain crude drug 1 grams per milliliter after, adding ethanol after the cold preservation is 50% to the alcohol amount of containing, cold preservation 20 hours is filtered, filtrate is reclaimed alcohol fully, adding ethanol is 70% to containing the alcohol amount, cold preservation is 20 hours again, filters filtrate for later use;
(2) with after 1 times of the above-mentioned filtrate dilution, transfer PH to 1, filtrate for later use is filtered in cold preservation 20 hours;
(3) filtrate is added in the cation exchange resin column of having handled well, water wash to PH be 6, discard water liquid, the back is soaked resin column and is carried out eluting with the ammonia spirit of 5mol/L, collect eluent, be transferred to neutrality with 1mol/L hydrochloric acid, concentrating under reduced pressure obtains solid, go out wherein alkaloid with ethanol extraction, obtain the Herba Leonuri total alkali;
(4) get Rhizoma Corydalis with 0.5%HAC solution percolation or merceration, collect solution, reclaim ethanol, adding acid accent PH is 3, cold preservation 20 hours is filtered, and it is 9 that filtrate transfers to PH with ammonia, cold preservation is 20 hours again, filter, get precipitation, filter with less ammonia flushing back dissolve with ethanol, get filtrate concentrating, obtain the Rhizoma Corydalis total alkali;
(5) with the Herba Leonuri total alkali with after the Rhizoma Corydalis total alkali mixes, add pharmaceutic adjuvant, make granule, promptly.
Embodiment 4.A kind of medicine for the treatment of endometriosis, it is the medicament of being made by the raw material of following weight proportioning (unit: kilogram):
Herba Leonuri 12 Rhizoma Corydalis 4
Its preparation method is as follows:
(1) gets the water of Herba Leonuri, extract each 2 hours 3 times with 10 times of amounts; With the water extract be concentrated to contain crude drug 2 grams per milliliters after, adding ethanol after the cold preservation is 60% to the alcohol amount of containing, cold preservation 25 hours is filtered, filtrate is reclaimed alcohol fully, adding ethanol is 80% to containing the alcohol amount, cold preservation is 25 hours again, filters filtrate for later use;
(2) with after 2 times of the above-mentioned filtrate dilutions, transfer PH to 1.5, filtrate for later use is filtered in cold preservation 25 hours;
(3) filtrate is added in the cation exchange resin column of having handled well, water wash to PH be 6.5, discard water liquid, the back is soaked resin column and is carried out eluting with the ammonia spirit of 10mol/L, collect eluent, be transferred to neutrality with 2mol/L hydrochloric acid, concentrating under reduced pressure obtains solid, go out wherein alkaloid with ethanol extraction, obtain the Herba Leonuri total alkali;
(4) get Rhizoma Corydalis with 1%HAC solution percolation or merceration, collect solution, reclaim ethanol, adding acid accent PH is 3.5, cold preservation 25 hours is filtered, and it is 9.5 that filtrate transfers to PH with ammonia, cold preservation is 25 hours again, filter, get precipitation, filter with less ammonia flushing back dissolve with ethanol, get filtrate concentrating, obtain the Rhizoma Corydalis total alkali;
(5) with the Herba Leonuri total alkali with after the Rhizoma Corydalis total alkali mixes, add pharmaceutic adjuvant, make capsule, promptly.
Embodiment 5.A kind of medicine for the treatment of endometriosis, it is the medicament of being made by the raw material of following weight proportioning (unit: kilogram):
Herba Leonuri 15 Rhizoma Corydalis 6 Radix Paeoniae Rubra 12
Extract active ingredient wherein according to a conventional method, and add pharmaceutic adjuvant, make granule.
Embodiment 6.A kind of medicine for the treatment of endometriosis, it is the medicament of being made by the raw material of following weight proportioning (unit: kilogram):
Herba Leonuri 10 Rhizoma Corydalis 4 Radix Paeoniae Rubra 8
Extract active ingredient wherein according to a conventional method, and add pharmaceutic adjuvant, make tablet.
Embodiment 7.A kind of medicine for the treatment of endometriosis, it is the medicament of being made by the raw material of following weight proportioning (unit: kilogram):
Herba Leonuri 18 Rhizoma Corydalis 9 Radix Paeoniae Rubra 15
Its preparation method is as follows:
(1) gets the water of Herba Leonuri, extract each 3 hours 4 times with 15 times of amounts; With the water extract be concentrated to contain crude drug 3 grams per milliliters after, adding ethanol after the cold preservation is 70% to the alcohol amount of containing, cold preservation 30 hours is filtered, filtrate is reclaimed alcohol fully, adding ethanol is 90% to containing the alcohol amount, cold preservation is 30 hours again, filters filtrate for later use;
(2) with after 3 times of the above-mentioned filtrate dilutions, transfer PH to 2, filtrate for later use is filtered in cold preservation 30 hours;
(3) filtrate is added in the cation exchange resin column of having handled well, water wash to PH be 7, discard water liquid, the back is soaked resin column and is carried out eluting with the ammonia spirit of 15mol/L, collect eluent, be transferred to neutrality with 3mol/L hydrochloric acid, concentrating under reduced pressure obtains solid, go out wherein alkaloid with ethanol extraction, obtain the Herba Leonuri total alkali;
(4) get Rhizoma Corydalis with 2%HAC solution percolation or merceration, collect solution, reclaim ethanol, adding acid accent PH is 4, cold preservation 30 hours is filtered, and it is 10 that filtrate transfers to PH with ammonia, cold preservation is 30 hours again, filter, get precipitation, filter with less ammonia flushing back dissolve with ethanol, get filtrate concentrating, obtain the Rhizoma Corydalis total alkali;
(5) get Radix Paeoniae Rubra with 80% alcohol reflux twice, each 3 hours, each 3 times of amounts of consumption, merge extractive liquid, reclaims ethanol to there not being the alcohol flavor, is concentrated into every milliliter of medicinal liquid and contains 0.5 gram raw medicinal herbs, after centrifugal,, negative to the Molish reaction with water flushing macroporous resin column by D101 macroporous resin column adsorption treatment, use 15% alcoholic solution eluting then, collect eluent, reclaim ethanol, concentrate, drying gets extract product of paeoniflorin;
(6) with after Herba Leonuri total alkali, Rhizoma Corydalis total alkali and the peoniflorin mixing, add pharmaceutic adjuvant, make oral liquid, promptly.
Embodiment 8.A kind of medicine for the treatment of endometriosis, it is the medicament of being made by the raw material of following weight proportioning (unit: kilogram):
Herba Leonuri 13 Rhizoma Corydalis 5 Radix Paeoniae Rubra 10
Its preparation method is as follows:
(1) gets the water of Herba Leonuri, extract each 3 hours 3 times with 10 times of amounts; With the water extract be concentrated to contain crude drug 2 grams per milliliters after, adding ethanol after the cold preservation is 70% to the alcohol amount of containing, cold preservation 30 hours is filtered, filtrate is reclaimed alcohol fully, adding ethanol is 90% to containing the alcohol amount, cold preservation is 30 hours again, filters filtrate for later use;
(2) with after 3 times of the above-mentioned filtrate dilutions, transfer PH to 2, filtrate for later use is filtered in cold preservation 30 hours;
(3) filtrate is added in the cation exchange resin column of having handled well, water wash to PH be 6, discard water liquid, the back is soaked resin column and is carried out eluting with the ammonia spirit of 10mol/L, collect eluent, be transferred to neutrality with 2mol/L hydrochloric acid, concentrating under reduced pressure obtains solid, go out wherein alkaloid with ethanol extraction, obtain the Herba Leonuri total alkali;
(4) get Rhizoma Corydalis with 1%HAC solution percolation or merceration, collect solution, reclaim ethanol, adding acid accent PH is 4, cold preservation 30 hours is filtered, and it is 10 that filtrate transfers to PH with ammonia, cold preservation is 30 hours again, filter, get precipitation, filter with less ammonia flushing back dissolve with ethanol, get filtrate concentrating, obtain the Rhizoma Corydalis total alkali;
(5) get Radix Paeoniae Rubra with 80% alcohol reflux twice, each 3 hours, each 7 times of amounts of consumption, merge extractive liquid, reclaims ethanol to there not being the alcohol flavor, is concentrated into every milliliter of medicinal liquid and contains 2 gram raw medicinal herbs, after centrifugal,, negative to the Molish reaction with water flushing macroporous resin column by D101 macroporous resin column adsorption treatment, use 25% alcoholic solution eluting then, collect eluent, reclaim ethanol, concentrate, drying gets extract product of paeoniflorin;
(6) with after Herba Leonuri total alkali, Rhizoma Corydalis total alkali and the peoniflorin mixing, add pharmaceutic adjuvant, make tablet, promptly.
Embodiment 9.A kind of medicine for the treatment of endometriosis, it is the medicament of being made by the raw material of following weight proportioning (unit: kilogram):
Herba Leonuri 16 Rhizoma Corydalis 7 Radix Paeoniae Rubra 20
Its preparation method is as follows:
(1) gets the water of Herba Leonuri, extract each 3 hours 3 times with 12 times of amounts; With the water extract be concentrated to contain crude drug 2.5 grams per milliliters after, adding ethanol after the cold preservation is 65% to the alcohol amount of containing, cold preservation 28 hours is filtered, filtrate is reclaimed alcohol fully, adding ethanol is 85% to containing the alcohol amount, cold preservation is 28 hours again, filters filtrate for later use;
(2) with after 2.5 times of the above-mentioned filtrate dilutions, transfer PH to 2, filtrate for later use is filtered in cold preservation 28 hours;
(3) filtrate is added in the cation exchange resin column of having handled well, water wash to PH be 7, discard water liquid, the back is soaked resin column and is carried out eluting with the ammonia spirit of 12mol/L, collect eluent, be transferred to neutrality with 2.5mol/L hydrochloric acid, concentrating under reduced pressure obtains solid, go out wherein alkaloid with ethanol extraction, obtain the Herba Leonuri total alkali;
(4) get Rhizoma Corydalis with 1.5%HAC solution percolation or merceration, collect solution, reclaim ethanol, adding acid accent PH is 4, cold preservation 28 hours is filtered, and it is 9.5 that filtrate transfers to PH with ammonia, cold preservation is 28 hours again, filter, get precipitation, filter with less ammonia flushing back dissolve with ethanol, get filtrate concentrating, obtain the Rhizoma Corydalis total alkali;
(5) get Radix Paeoniae Rubra with 70% alcohol reflux twice, each 2 hours, each 5 times of amounts of consumption, merge extractive liquid, reclaims ethanol to there not being the alcohol flavor, is concentrated into every milliliter of medicinal liquid and contains 1 gram raw medicinal herbs, after centrifugal,, negative to the Molish reaction with water flushing macroporous resin column by D101 macroporous resin column adsorption treatment, use 20% alcoholic solution eluting then, collect eluent, reclaim ethanol, concentrate, drying gets extract product of paeoniflorin;
(6) with after Herba Leonuri total alkali, Rhizoma Corydalis total alkali and the peoniflorin mixing, add pharmaceutic adjuvant, make injection, promptly.

Claims (10)

1, a kind of medicine for the treatment of endometriosis, it is made by raw material and pharmaceutic adjuvant, it is characterized in that, and raw material is made up of the Chinese medicine of following weight proportion:
Herba Leonuri 10-20 Rhizoma Corydalis 4-10.
2, a kind of medicine for the treatment of endometriosis according to claim 1 is characterized in that wherein the weight proportion of each raw material is:
Herba Leonuri 15 Rhizoma Corydalis 6.
3, a kind of medicine for the treatment of endometriosis according to claim 1 and 2 is characterized in that, described medicament is a said dosage form on any pharmaceutics.
4, a kind of medicine for the treatment of endometriosis according to claim 3 is characterized in that, described medicament is tablet or capsule or granule.
5, claim 1 or 2 described a kind of preparation methoies for the treatment of the medicine of endometriosis, it is characterized in that, after extracting the Rhizoma Corydalis total alkali of the Herba Leonuri total alkali of Herba Leonuri and Rhizoma Corydalis respectively, the Herba Leonuri total alkali is mixed with the Rhizoma Corydalis total alkali, add pharmaceutic adjuvant, make said any dosage form on the pharmaceutics.
6, a kind of preparation method for the treatment of the medicine of endometriosis according to claim 5 is characterized in that its step is as follows:
(1) gets the water that Herba Leonuri is doubly measured with 5-15, extract 2-4 time, each 1-3 hour; With the water extract be concentrated to contain crude drug 1-3 grams per milliliter after, add ethanol after the cold preservation and be 50-70% to containing alcohol amount, cold preservation 20-30 hour, filter, filtrate is reclaimed alcohol fully, adds ethanol and is 70-90% to containing the alcohol amount, cold preservation 20-30 hour again, filters filtrate for later use;
(2) with after 1-3 times of the above-mentioned filtrate dilution, transfer PH, cold preservation 20-30 hour, filter filtrate for later use to 1-2;
(3) filtrate is added in the cation exchange resin column of having handled well, water wash to PH be 6-7, discard water liquid, the back is soaked resin column and is carried out eluting with the ammonia spirit of 5-15mol/L, collect eluent, be transferred to neutrality with 1-3mol/L hydrochloric acid, concentrating under reduced pressure obtains solid, go out wherein alkaloid with ethanol extraction, obtain the Herba Leonuri total alkali;
(4) get Rhizoma Corydalis with 0.5-2%HAC solution percolation or merceration, collect solution, reclaim ethanol, adding acid accent PH is 3-4, cold preservation 20-30 hour, to filter, it is 9-10 that filtrate transfers to PH with ammonia, cold preservation 20-30 hour again, filter, get precipitation, filter with less ammonia flushing back dissolve with ethanol, get filtrate concentrating, obtain the Rhizoma Corydalis total alkali;
(5) with the Herba Leonuri total alkali with after the Rhizoma Corydalis total alkali mixes, add pharmaceutic adjuvant, make said any dosage form on the pharmaceutics, promptly.
7, a kind of medicine for the treatment of endometriosis, it is made by raw material and pharmaceutic adjuvant, it is characterized in that, and raw material is made up of the Chinese medicine of following weight proportion:
Herba Leonuri 10-20 Rhizoma Corydalis 4-10 Radix Paeoniae Rubra 8-20.
8, a kind of medicine for the treatment of endometriosis according to claim 7 is characterized in that wherein the weight proportion of each raw material is:
Herba Leonuri 15 Rhizoma Corydalis 6 Radix Paeoniae Rubra 12.
9, the described a kind of preparation method for the treatment of the medicine of endometriosis of claim 7, it is characterized in that, after extracting the peoniflorin of the Rhizoma Corydalis total alkali of Herba Leonuri total alkali, Rhizoma Corydalis of Herba Leonuri and Radix Paeoniae Rubra respectively, Herba Leonuri total alkali, Rhizoma Corydalis total alkali and peoniflorin are mixed, add pharmaceutic adjuvant, make said any dosage form on the pharmaceutics.
10, a kind of preparation method for the treatment of endometriosis according to claim 9 is characterized in that its step is as follows:
(1) gets the water that Herba Leonuri is doubly measured with 5-15, extract 2-4 time, each 1-3 hour; With the water extract be concentrated to contain crude drug 1-3 grams per milliliter after, add ethanol after the cold preservation and be 50-70% to containing alcohol amount, cold preservation 20-30 hour, filter, filtrate is reclaimed alcohol fully, adds ethanol and is 70-90% to containing the alcohol amount, cold preservation 20-30 hour again, filters filtrate for later use;
(2) with after 1-3 times of the above-mentioned filtrate dilution, transfer PH, cold preservation 20-30 hour, filter filtrate for later use to 1-2;
(3) filtrate is added in the cation exchange resin column of having handled well, water wash to PH be 6-7, discard water liquid, the back is soaked resin column and is carried out eluting with the ammonia spirit of 5-15mol/L, collect eluent, be transferred to neutrality with 1-3mol/L hydrochloric acid, concentrating under reduced pressure obtains solid, go out wherein alkaloid with ethanol extraction, obtain the Herba Leonuri total alkali;
(4) get Rhizoma Corydalis with 0.5-2%HAC solution percolation or merceration, collect solution, reclaim ethanol, adding acid accent PH is 3-4, cold preservation 20-30 hour, to filter, it is 9-10 that filtrate transfers to PH with ammonia, cold preservation 20-30 hour again, filter, get precipitation, filter with less ammonia flushing back dissolve with ethanol, get filtrate concentrating, obtain the Rhizoma Corydalis total alkali;
(5) get Radix Paeoniae Rubra with 60-80% alcohol reflux twice, each 1-3 hour, each consumption 3-7 doubly measured, merge extractive liquid, reclaims ethanol to there not being the alcohol flavor, is concentrated into every milliliter of medicinal liquid and contains 0.5-2 gram raw medicinal herbs, after centrifugal,, negative to the Molish reaction with water flushing macroporous resin column by D101 macroporous resin column adsorption treatment, use 15-25% alcoholic solution eluting then, collect eluent, reclaim ethanol, concentrate, drying gets extract product of paeoniflorin;
(6) with after Herba Leonuri total alkali, Rhizoma Corydalis total alkali and the peoniflorin mixing, add pharmaceutic adjuvant, make said any dosage form on the pharmaceutics, promptly.
CN 03131990 2003-06-22 2003-06-22 Medicine for treating endometriosis and its preparing process Expired - Lifetime CN1246012C (en)

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CN102188497B (en) * 2010-03-19 2013-08-07 傅宏征 Preparation method of total alkali of corydalis tuber, and corydalis tuber preparation and use thereof
CN105250619A (en) * 2015-09-30 2016-01-20 杜秀春 Traditional Chinese medicine for treating intrinsic endometriosis and preparation method thereof

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