The present patent application is to divide an application, and original application is Chinese patent CN201010131832.9, and the applying date is on March 25th, 2010, and denomination of invention is: a kind of Chinese medicine composition for the treatment of chronic pelvic inflammatory disease and preparation method thereof.
Summary of the invention
The purpose of this invention is to provide a kind of medicine for the treatment of chronic pelvic inflammatory disease, another object of the present invention is to provide the preparation method of this medicine.
Medicine of the present invention is according to theory of Chinese medical science, develops for the pathomechanism of chronic pelvic inflammatory disease." chronic pelvic inflammatory disease " is commonly encountered diseases, the frequently-occurring disease on a kind of gynecological clinic, and prevalence is 30% left and right, and the multiple age is 30^-40 year crowd.Primary disease sporadically appears in Chinese medicine “ mass in the abdomen ", the disease such as " leukorrhagia, disease ", " dysmenorrhea ", " infertility ".Mostly be secondary to acute pelvic inflammatory disease, not thorough because for the treatment of, the state of an illness shows as chronic delay, outbreak repeatedly more, and produces a series of complication (as menoxenia, dysmenorrhea, infertile, pelvic veins congestion etc.) and cause; Or patient's body constitution is relatively poor, pathogen virulence a little less than, chronic from the beginning of being.Clinical common type has: chronic salpingitis and hydrosalpinx, adnexitis and tubo-ovarian cyst, inflammation of pelvic connective tissue.The primary disease state of an illness is more obstinate, and easily acute attack repeatedly is difficult for thoroughly curing, and causes very big misery to patient.The relatively poor area of vast sanitary conditions particularly, sickness rate is very high, has a strong impact on the physical and mental health of female patient.
Be used for the treatment of clinically at present chronic pelvic inflammatory disease, the western modern medicine treatment: with antimicrobial drug quinolones, cephalosporins, coordinate metronidazole etc.; Or naturopathy: be beneficial to the absorption of inflammation with promotion pelvic cavity blood circulation as ultrashort wave, infrared ray, medicine-inductiveness etc., but therapeutic effect is all not good enough; Severe patient is granted operation.Chinese medicine: to cold-damp silt combined symptoms type: method for the treatment of is dispelling cold by warming the meridian, Cleering damp and dissolving phlegm, and Ramuli Cinnamimi and Poriae Decoction commonly used, few abdomen are by the silt ball; Or Chinese medicine decoction coloclysis, Orally taken and externally etc., though effective in cure being difficult to promote; The combination of Chinese and Western medicine adds " bitter cold Chinese medicine " treatment with antibiotic and also just attempts; On Chinese patent medicine market, Amino-Cerv is more, and the Chinese patent medicine that can be exclusively used in the treatment chronic pelvic inflammatory disease is few in number again, far can not satisfy the demand, and therefore, the safe and effective medicine of many exploitation treatment chronic pelvic inflammatory diseases is needs of extensive patients.This medicine prescription derives from famous mountain, nest county, Anhui and the side handed down from one's ancestors of Shan Yangshi TCM Gynecology family, cures undergoing chronic pelvic inflammation and reaches thousands of examples, and is evident in efficacy.The party is comprised of 12 flavor Chinese medicines.Take clearing away heat-damp and promoting diuresis as curative mechanism, be applicable to the morbid leukorrhea of damp invasion of lower energizer and the undergoing chronic pelvic inflammation person that has the damp-heat syndrome, not only curative effect is high, and without obvious adverse reaction.In a single day the party succeeds in developing through the granule that the research of science is made, and market prospect is wide.
Flos Lonicerae merit tool heat-clearing and toxic substances removing wherein, the effect of dispelling wind and heat pathogens, nature and flavor are sweet, cold.Return lung, the heart, stomach warp.The tall and erect title with the card of controlling pyretic toxicity.Studies have shown that in recent years this product has obvious antiinflammatory and refrigeration function.Multiple pathogenic microorganisms there is inhibitory action.The Fructus Forsythiae nature and flavor are bitter, are slightly cold.Return lung, the heart, gallbladder meridian.Merit tool heat-clearing and toxic substances removing, eliminating carbuncle eliminating stagnation, the effect of dispelling wind and heat pathogens.Multiplex in sore swollen toxin and to affection due to external wind and heat.Studies confirm that in recent years this product has broad-spectrum antiseptic and antiinflammatory action.Two flavors share and focus on heat-clearing and toxic substances removing.The Rhizoma Dioscoreae Collettii nature and flavor are bitter, are slightly cold.Return liver, stomach warp.Merit tool dampness removing goes turbid, the effect of expelling wind and removing dampness.Multiplexly demonstrate,prove in the married woman leucorrhea.The Poria nature and flavor are sweet, light, flat.GUIXIN, spleen, kidney channel.Merit tool promoting diuresis to eliminate damp pathogen.The effect of spleen-benefiting mind-tranquilizing.Be used for the wet insufficiency of the spleen card of water.The seed of Jobs tears nature and flavor are sweet, light, be slightly cold.Return the taste lung meridian.Clinical in the wet card of water.Polyporus property slightly sweet flavor, flat.Return stomach, wing moon bright warp.The effect of merit tool promoting diuresis to eliminate damp pathogen.The Semen Plantaginis nature and flavor are sweet, cold.Return kidney, liver, lung meridian.The effect of merit tool inducing diuresis for treating stranguria syndrome, eliminating dampness by diuresis antidiarrheal.Multiplex in the wet card of water.The Rhizoma Alismatis nature and flavor are sweet, lightly tremble with fear, return kidney, wing skin warp.Merit tool promoting diuresis to eliminate damp pathogen, the effect that expels the heat-evil.Multiplex in drenching drop, band purgation card.Caulis Akebiae nature and flavor bitter cold.GUIXIN, small intestinal, urinary bladder channel.The effect of merit tool diuresis promoting, the stimulating milk secretion of stimulating the menstrual flow.Also multiplex in drenching drop, band purgation disease.Psychotria rubra (Lour.) Poir. Chang is the good person that ancient literature claims Rhizoma Acori Graminei.The nature and flavor acrid, bitter, warm.GUIXIN, stomach warp.The effect of merit tool removing dampness to restore normal function of the stomach.The hot fragrant removing dampness of this product is turbid, and bitter temperature is with the stomach of being amusing.Pericarpium Citri Reticulatae, Rhizoma Pinelliae Preparata two flavors are regulated the flow of vital energy and are reduced phlegm wet.
Chinese medicine composition of the present invention is made by following raw materials according:
The formula optimization weight proportion scope of preparation Chinese medicine composition of the present invention is:
The optimum weight proportioning of preparation Chinese medicine composition of the present invention is:
The preparation method that above-mentioned each component is made Chinese medicine composition of the present invention is:
Semen Coicis adds 3-10 doubly to measure with 40%~90% ethanol extraction 1-3 time at every turn, and backflow 1-3 hour, filter, merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 40%~90% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.10~1.30 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 2-8 times of water gaging and soaked 1~2 hour, with extraction by steam distillation volatile oil 2-7 hour, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 1-3 time, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.10~1.30, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Traditional Chinese medicine composition for treating chronic pelvic inflammatory disease of the present invention has good curative effect.For showing Chinese medicine composition of the present invention to the therapeutical effect of chronic pelvic inflammatory disease, we have done a large amount of experimentatioies, below experimental example be used for further illustrating the present invention.
The Pharmacodynamic test of active extract data of preparation of the present invention
1 tested medicine:
Medicine of the present invention: supplier: Jiangsu JumpCan Medicines Co., Ltd., lot number: 020910.
FULE KELI: Hangzhou Tianmushan Pharmaceutical Co., Ltd., 20022701,2 times/d of lot number, 2 bags/time, other medicines of 6g/ bag are commercially available qualified medicine
4. experimental animal: Kunming mouse and Wistar rat provide by Anhui Prov. Medical Science Inst.'s animal center,
2 experimental techniques and result:
2.1 the therapeutic test to the chronic pelvic inflammatory disease rat model
2.1.1 the Pyrogentisinic Acid causes the therapeutic test of rat chronic pelvic inflammatory disease model
[1]
2.1.1.1 test method
1. the preparation of phenol rubber cement: get phenol 5ml, tragakanta 19, glycerol 4ml, adding distil water are made into to 20ml the rubber cement that contains 25% phenol.
2. copying of chronic pelvic inflammatory disease model: animal ether inhalation anesthesia, the abdominal part routine disinfection, median incision of lower abdomen is 0.8~1cm approximately, expose the uterus, at the careful inserting needle of uterus crotch, slowly inject phenol rubber cement 0.04ml to the ovary direction with No. 4 syringe needles, then abdomen is closed in layering, separately get 10 and open abdomen and do not inject the phenol rubber cement, as Sham-operated control group in sterilization art district.
3. medication: after modeling 7d with 60 of animal patterns by being divided at random 5 groups, every group 10, positive controls (8.00g crude drug/kg wherein, be equivalent to 20 times of clinical people's consumption 24g), medicine a small amount of of the present invention (the 7.75g crude drug/kg), middle amount (the 15.50g crude drug/kg), (the 31.00g crude drug/kg) group (is calculated by kg body weight and is equivalent to 5 of clinical people's consumption 93g in a large number, 10 and 20 times), separately add totally 6 groups of Sham-operated control group (waiting the capacity distilled water), according to dosage administration (2.0ml/100g body weight) respectively, continuous 20d, 24h after the last medicine, press the 40mg/kg intraperitoneal anesthesia with pentobarbital sodium, perusal is also recorded the inflammation of uterus variation, win the uterus, take respectively both sides weight, and calculate its weight difference, then get and cause scorching Aconitum carmichaeli Debx. palace and put in 10% formalin solution fixing, conventional section, HE dyeing, observe the uterus morphological changes of various tissue components under light microscopic.
Uterus weight difference=left side uterus weight one right side uterus weight
2.1.1.2 result of the test the results are shown in Table 1,2
Table 1 medicine Pyrogentisinic Acid of the present invention rubber cement causes the impact (x scholar s) of chronic pelvic inflammatory disease rat model uterus weight
With sham operated rats than #P<0.05, ##P<0.01 with model group than * P<0.05**P<0.01
Table 2 medicine Pyrogentisinic Acid of the present invention rubber cement copies the uterus pathology integrated value of the therapeutical effect of rat chronic pelvic inflammatory disease model
With sham operated rats than well P<0.05, ##P<0.01 with model group than * P<0.05**P<0.01
Perusal: open the rat abdominal cavity naked eyes as seen, injection phenol rubber cement Aconitum carmichaeli Debx. palace obvious tumefaction, hyperemia, what have has a purulence thing.Do not inject phenol rubber cement Aconitum carmichaeli Debx. palace and sham operated rats uterus ratio, there is no notable difference.
By table 1,2 as seen: medicine Pyrogentisinic Acid rubber cement of the present invention causes pelvic inflammatory disease rat model uterus weight to be had obviously and alleviates; By the pathological replacement of uterine cancer cell as seen: it is inaccessible that the phenol rubber cement causes rat uterus chamber adhesion, and the pathological changes such as epithelial cell degeneration necrosis, chronic inflammatory cell infiltrations, inner membrance congestion and edema illustrates that copying rat with the phenol rubber cement overflows the establishment of property pelvic inflammatory disease model; After using medicine of the present invention, all pathological symptoms improve significantly, and illustrate that medicine Pyrogentisinic Acid rubber cement of the present invention causes the pelvic inflammatory disease rat model obvious therapeutical effect is arranged.
2.1.2 escherichia coli are caused the therapeutical effect of rat chronic pelvic inflammatory disease model
[2]
2.1.2.1 test method:
1. copying of chronic pelvic inflammatory disease model: get 60 rats, use ether inhalation anesthesia, the abdominal part routine disinfection, median incision of lower abdomen is 0.8~1cm approximately, expose the uterus, at the careful inserting needle of uterus crotch, slowly inject 0.2ml through the escherichia coli suspension (3 * 10 of trial test result from the uterus, left side to the ovary direction with No. 4 syringe needles
8CFU/ml), abdomen is closed in layering, sterilization art district, keeps 10 open abdomen not the Escherichia Coli Injection suspension as Sham-operated control group, with syringe mechanical damage endometrial tissue, sewed up the incision before injecting bacterium liquid, recover drinking-water, normal cleaning raising.
2. medication: after modeling, 7d begins the modeling animal is divided into 5 groups at random, every group 10, add Sham-operated control group, totally 6 groups, press dosed administration in table 2 (2.0ml/100g body weight), continuous 20d is after the last medicine after 24h, with animal pentobarbital sodium 40mg/kg intraperitoneal anesthesia, cut open the belly, perusal is also recorded the inflammation of uterus variation, wins the uterus, take respectively both sides weight, and calculate its weight difference, then get cause scorching Aconitum carmichaeli Debx. palace put in 10% formalin solution fixing, conventional section, the uterus morphological changes of various tissue components is observed in HE dyeing under light microscopic.Result
2.1.2.2 result of the test the results are shown in Table 3,4,
Table 3 medicine of the present invention causes the impact (x scholar s) of chronic pelvic inflammatory disease rat model uterus weight on escherichia coli
With sham operated rats than #P<0.05, ##P<0.01 with model group than * P<0.05**P<0.01
Table 4 pair escherichia coli are copied the uterus pathology integrated value (X ± s) of the therapeutical effect of rat chronic pelvic inflammatory disease model
With sham operated rats than #P<0.05, ##P<0.01 with model group than * P<0.05**P<0.01
Perusal: open the rat abdominal cavity naked eyes as seen, Escherichia Coli Injection Aconitum carmichaeli Debx. palace obvious tumefaction, hyperemia.There is no Escherichia Coli Injection Aconitum carmichaeli Debx. palace and sham operated rats uterus ratio, there is no notable difference.
By table 3,4 as seen: medicine of the present invention causes pelvic inflammatory disease rat model uterus weight to escherichia coli to be had obviously and alleviates; By the pathological replacement of uterine cancer cell as seen: it is inaccessible that escherichia coli cause the rat uterus intrauterine adhesion, and the pathological changes such as epithelial cell degeneration necrosis, chronic inflammatory cell infiltrations, inner membrance congestion and edema illustrates that copying rat with escherichia coli overflows the establishment of property pelvic inflammatory disease model; After using medicine of the present invention, all pathological symptoms improve significantly, and illustrate that medicine of the present invention causes the pelvic inflammatory disease rat model to escherichia coli obvious therapeutical effect is arranged.
2.2 antibacterial tests
2.2.1 In vitro Bactericidal Experiments
2.2.1.1 materials and methods
1. strain: Gartner Salmonella 8 strains, staphylococcus aureus 11 strains (containing type strain ATCC25923), staphylococcus epidermidis 9 strains, beta hemolytic streptococcus 8 strains, pneumobacillus 7 strains, escherichia coli 11 strains (containing reference culture ATCC25922), alpha streptococcus 8 strains, Bacillus proteus 10 strains, bacillus pyocyaneus 9 strains, Candida albicans 7 strains, above 8 kind of 68 strain bacterial strain, wherein reference culture is preserved the center from Beijing biological product checks institute strain, and all the other bacterial strains separate from clinical outer inspection specimen by Anhui Chinese Medicine College microorganism teaching and research room and obtain.Strain was write " national Clinical Laboratory rule of operation " in 1997 according to Ministry of Public Health Department of Medical Administration.
2. culture medium: select the MH culture medium; And add 5% calf serum; Fungus, Candida albicans are selected the Sabouraud culture medium.
3. MIC experiment
Preparation for examination bacterium liquid: individual strains tested is inoculated in respectively in above-mentioned corresponding culture medium, cultivate 24h for 37 ℃, wherein inoculate in second chain bacterium culture medium and add 5% calf serum, the Gartner Salmonella adds 5% human blood, cultivate 6h for 37 ℃, make standard bacterium colony subcultivation in fluid medium after 6h, adjusting bacterial concentration is 10
8CFU/ml, standby.
The preparation of pastille culture medium: add respectively medicine medicinal liquid of the present invention and the positive drug for preparing in advance in for the examination culture medium, make the drug level of culture medium be respectively 200mg, 100mg, 50mg, 25mg, 12.5mg, 6.25mg, 3.125mg, 1.56mg and 0.78mg/ml, separately establish a flat board that does not contain medicine and make negative control.
For examination strain inoculation: inoculating loop gets respectively that (bacteria containing amount is about 10 for examination bacterium liquid one ring
4CFU/ml) be inoculated on the culture medium of different pharmaceutical concentration, 37 ℃ of temperature are incubated, and Candida albicans is cultivated 48h, after other antibacterial culturing 24h, observed result is on the flat board of 2 the variable concentrations gradient medicines in front and back, make the concentration of the unexpected minimizing 80%~90% of bacterial number be MIC, the results are shown in Table 5.
Table 5 medicine of the present invention is to 68 strain antibacterial MIC measurement results
By as seen from Table 5, medicine of the present invention has certain bacteriostasis outward to above-mentioned various bacterial bodies.What wherein effect was the strongest is to staphylococcus aureus, its MIC
50Be 0.78mg/ml.
2.2.1.2 antibacterial tests in body
2.2.2.1 the protective effect to the candida albicans infection mice
Get 50 of body weight 18-22g mices, be divided at random by body weight that distilled water group, FULE KELI group, medicine of the present invention are little, the heavy dose of group of neutralization, each group is pressed respectively oral dose administration in table 6 (0.25ml/10g body weight), continuous 7d, (bacterial concentration is 4.0 * 10 in respectively organizing ip in mice Candida albicans suspension 0.4ml according to the trial test result after 40min on the 3rd day after administration
8CFU/ml) 0.1ml 5% yeast soln, the death condition of then observing mice in 7d, 9d, the results are shown in Table 6,7 altogether.
Table 6 medicine of the present invention is to candida albicans infection dead mouse distribution situation
The protective effect of table 7 medicine of the present invention to the candida albicans infection mice
2.8.1.2 to the protective effect in the coli-infection Mice Body
Get 50 of body weight 18~22g mices, be divided at random the happy positive group of distilled water group, woman and medicine of the present invention is little, in and heavy dose of group, according to the trial test result, each group is pressed respectively table 8 oral dose administration (0.25ml/10g body weight), continuous 7d, after administration 3d 40min, each organizes ip in mice Escherichia coli bacteria liquid 0.5ml (3 * 10
8CFU/ml), then observe the death condition of mice in 7d, 9d, the results are shown in Table 8,9 altogether.
Table 8 medicine of the present invention is to coli-infection dead mouse distribution situation
The protective effect of table 9 medicine of the present invention to the coli-infection mice
2.3.2 writhing method
Get 50 of body weight 18~22g mices, the male and female dual-purpose is divided into 5 groups at random, presses respectively oral dose administration in table 12 (0.25ml/10g body weight), successive administration 5d.40min lumbar injection 0.7% acetum 0.1ml/10g body weight after the last medicine, after record injection acetic acid, each organizes each mice 10min respectively, and writhing number of times in 20min the results are shown in Table 12.
Table 12 medicine of the present invention is to the inhibitory action of writhing method induced pain (n=10x ± s)
With the distilled water group than * P<0.05**P<0.01
By as seen from Table 12, the pain due to medicine Dichlorodiphenyl Acetate of the present invention stimulates has obvious inhibitory action, and with distilled water group ratio, its medium and small, heavy dose of group has significant difference.
2.4 antiinflammatory test
2.4.1 xylol causes the inhibitory action of mice ear
Get 50 of body weight 18~22g male mices, be divided at random 5 groups.Press dosed administration in table 13, (0.25ml/10g body weight), continuous use 5d, 40min after the last medicine, the left ear of every Mus is coated with dimethylbenzene 0.1ml, and auris dextra is coated with equivalent NS.Put to death mice after 1h, cut auricle and respectively get an auricle with the 0.8cm card punch in mice two ear same area, in scales/electronic balance weighing, as swelling, and calculate swelling resistance rate with two ear weight differences, the results are shown in Table 13.
It is heavy that swelling (g)=left auricle weighs an auris dextra sheet
Swelling rate (%)=(swelling/left auricle is heavy) * 100%
Swelling resistance rate (%)=(model group-administration group)/model group * 100%
Table 13 medicine xylol of the present invention causes the inhibitory action (n=10x ± s) of mice ear
With the distilled water group than * P<0.05**P<0.01
By as seen from Table 13, the mice ear due to medicine xylol of the present invention has obvious inhibitory action, with distilled water group ratio, significant difference is arranged.
2.4.2 Ovum Gallus domesticus album is caused the inhibitory action of rat paw edema
Get 50 of body weight 180~220g male rats, be divided at random 5 groups, press oral dose administration in table 14 (2.0ml/100g body weight), continuous use 7d.Survey right back sufficient volume with volumetric method, 40min after the last administration then, the subcutaneous injection of the right back sufficient intestinal of every Mus 0.1ml 100% Ovum Gallus domesticus album, and respectively at cause scorching after 0.5,1,1.5,2,3,4h surveys sufficient volume, deduct with this volume and cause scorching front foot volume as paw swelling, the results are shown in Table 14,15.
Table 14 medicine of the present invention causes the inhibitory action (n=10x ± s) of rat paw edema to Ovum Gallus domesticus album
With the distilled water group than * P<0.05**P<0.01
Table 15 medicine of the present invention causes the suppression ratio effect (n=10x ± s) of rat paw edema to Ovum Gallus domesticus album
By table 14,15 as seen, and medicine of the present invention causes rat paw edema to Ovum Gallus domesticus album obvious inhibitory action, it is medium and small, in, heavy dose of group of effect be obvious, middle amount group 0.5h just has obvious inhibitory action, and the inhibitory action of a large amount of groups remains to 4h always, with the distilled water group, significant difference is arranged.
2.4.3 cotton pellet method is caused the inhibitory action of rat granulation hyperplasia
Get 50 of body weight 200~220g male rats, be divided at random 5 groups, under the etherization aseptic condition, through autoclaving, each cotton balls adds ampicillin 1mg/0.1ml with the cotton balls of having weighed, and after 50 ℃ of oven dry, implants Rat Right flank butt crack subcutaneous.After animal is clear-headed, by the continuous 7d of above-mentioned oral dose administration (2.0ml/100g body weight).After the last administration, 40min puts to death rat, peels off and take out granulation tissue, claims its weight, and deduct the raw cotton ball weight and get the granulation weight in wet base, dry 24h in 90 ℃ of baking ovens then, then weigh, and deduct former cotton balls recuperation granulation dry weight, the results are shown in Table 16.
Table 16 medicine of the present invention causes the inhibitory action (n=10x ± s) of granulation hyperplasia to cotton pellet method
With model group than * P<0.05**P<0.01
By as seen from Table 16, medicine of the present invention can obviously suppress cotton balls and cause granulation hyperplasia, and granulation weight in wet base and dry weight are all obviously reduced, and with the model group ratio, highly significant difference is arranged.
2.5 the impact of medicine of the present invention on the hemorheology index of rat model
Get 250~350g rat, the male and female dual-purpose, be divided at random Normal group, model group, positive controls, medicine of the present invention little, in, a large amount of group, cause the modeling of rat chronic pelvic inflammatory disease method by phenol, oral dose administration in table 17 (2.0ml/100g body weight), continuous 20d, 24h after the last administration presses the 40mg/kg intraperitoneal anesthesia with pentobarbital sodium, the ventral aorta blood drawing, do the hemorheological property inspection, survey clotting time with slide method simultaneously.The results are shown in Table 17.
The impact (x ± s, n=10) of table 17 medicine of the present invention on chronic pelvic inflammatory disease rat whole blood viscosity ratio
With the distilled water group than ##p<0.01 with model group than * * p<0.01
By as seen from Table 17, the viscosity of the hemorheology index of rat model obviously increases; And after using medicine of the present invention, hemorheological property is obviously improved, and degree of killing reduces, and illustrates that medicine of the present invention obviously improves the hemorheological property of chronic pelvic inflammatory disease rat.
2.6 the impact of medicine of the present invention on the mda content of chronic pelvic inflammatory disease rat model
Get 250~350g rat, the male and female dual-purpose, be divided at random Sham-operated control group, model group, positive controls, woman's relaxation grain little, in, a large amount of group, cause the unrestrained property pelvic inflammatory disease method modeling of rat by escherichia coli, use continuously 20d by dosage in table 18,24h after the last medicine, abdominal aortic blood, (Biochemics Inc.'s lot number is built up in Nanjing: 20021230) illustrate, in 754 its traps of spectrophotometer 532nm place's detection, the results are shown in Table 18 by the Mda test kit.
The impact (x ± s, n=10) of table 18 medicine of the present invention on the mda content of chronic pelvic inflammatory disease rat model
With the distilled water group than ##p<0.01 with model group than * * p<0.01
By model group mda content as seen from Table 18 apparently higher than, with the distilled water group, significant difference is arranged, and obviously descends with mda content after medicine of the present invention.
2.7 the impact of medicine of the present invention on uterine myometrium
[3]
2.7.1 on the impact at the body uterine myometrium
Get 50 of female Sexual health unpregnancy rats, body weight 180~220g.Be divided at random Normal group, positive controls, medicine of the present invention little, in, a large amount of group, after 40mg/kg pentobarbital sodium iv anesthetized animal, face upward the position and be fixed in operating-table, be about 4^-5cm through median incision of lower abdomen and enter abdomen, find out an Aconitum carmichaeli Debx. palace.choose from cornua uteri and be about the 5cm section, in bring a cotton thread out into the open in succession on tonotransducer, and fix with special glass, that continues makes a kerf under xiphoid-process, find out duodenum, put a gavage syringe needle within it in order to administration, animal is incubated with the operating lamp irradiation, tonotransducer is connected in MedLab System of organism signal (Meiyi Science ﹠ Technology Co., Ltd., Nanjing's production), give the uterus preload, trace the normal uterus shrinkage curve after stable, then through duodenal administration (2ml/100g), observe respectively and record after administration 0.5, 1, 1.5, 2, 3, 4h uterine contraction situation, measurements and calculations administration front and back are in the variation of body uterine contraction amplitude and contraction frequency.The results are shown in Table 18,19,20.
Following embodiment is further openly the present invention, need to prove that these embodiment only for optimal way of the present invention, do not limit the scope of protection of present invention.
Embodiment 1
Semen Coicis adds 10 times of amounts with 40% ethanol extraction 1 time at every turn, refluxes 2 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 40% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.15 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 2 times of water gagings and soaked 1 hour, with extraction by steam distillation volatile oil 2 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 1 time, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.10, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 2
Semen Coicis adds 10 times of amounts with 60% ethanol extraction 2 times at every turn, refluxes 3 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 90% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.10 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 8 times of water gagings and soaked 2 hours, with extraction by steam distillation volatile oil 7 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 3 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.30, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, pulverize, pill, and get final product.
Embodiment 3
Semen Coicis adds 6 times of amounts with 70% ethanol extraction 3 times at every turn, refluxes 2 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 90% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.30 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 4 times of water gagings and soaked 2 hours, with extraction by steam distillation volatile oil 4 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 1 time, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, capsule charge, and get final product.
Embodiment 4
Semen Coicis adds 8 times of amounts with 60% ethanol extraction 2 times at every turn, refluxes 1 hour, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 90% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.30 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 4 times of water gagings and soaked 2 hours, with extraction by steam distillation volatile oil 5 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 1 time, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, tabletting, and get final product.
Embodiment 5
Semen Coicis adds 6 times of amounts with 60% ethanol extraction 1 time at every turn, refluxes 2 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 50% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.15 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 6 times of water gagings and soaked 2 hours, with extraction by steam distillation volatile oil 6 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 3 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.15, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour in 1: 3 by ratio ethanol) for volatile oil, let cool, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing adds the water for injection dissolving, embedding, sterilization, and get final product.
Embodiment 6
Semen Coicis adds 5 times of amounts with 75% ethanol extraction 3 times at every turn, refluxes 1 hour, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 50% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.20 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 2-8 times of water gaging and soaked 1~2 hour, with extraction by steam distillation volatile oil 2-7 hour, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 2 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, pulverize, mixing namely gets powder.
And get final product.
Embodiment 7
Semen Coicis adds 6 times of amounts with 80% ethanol extraction 3 times at every turn, refluxes 2 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 60 alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.10~1.20 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 7 times of water gagings and soaked 1.5 hours, with extraction by steam distillation volatile oil 3 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 2 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.10~1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 8
Semen Coicis adds 3 times of amounts with 40% ethanol extraction 1 time at every turn, refluxes 1 hour, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 40% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.10 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 2 times of water gagings and soaked 1 hour, with extraction by steam distillation volatile oil 2 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 1 time, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.10, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 9
Semen Coicis adds 4 times of amounts with 45 ethanol extraction 2 times at every turn, refluxes 2 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 45 alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.20 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 3 times of water gagings and soaked 1.5 hours, with extraction by steam distillation volatile oil 3 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 2 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.10~1.30, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 10
Semen Coicis adds 5 times of amounts with 50% ethanol extraction 3 times at every turn, refluxes 3 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 50% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.30 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 4 times of water gagings and soaked 2 hours, with extraction by steam distillation volatile oil 4 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 3 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.30, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 11
Semen Coicis adds 6 times of amounts with 55% ethanol extraction 1 time at every turn, refluxes 1 hour, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 55% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.10 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 5 times of water gagings and soaked 1 hour, with extraction by steam distillation volatile oil 5 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 1 time, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.10, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 12
Semen Coicis adds 7 times of amounts with 60% ethanol extraction 2 times at every turn, refluxes 2 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 60% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.20 clear paste.Mixing that Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three is distinguished the flavor of adds 6 times of water gagings soaked 2 hours, used extraction by steam distillation volatile oil 6 hours, filtered, the another device of distillation rear solution is collected, and medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 3 times, add 12 times of water gagings at every turn, decocted collecting decoction 1 hour, filter, filtrate and above-mentioned aqueous solution merge, and are concentrated into the clear paste of relative density 1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 13
Semen Coicis adds 8 times of amounts with 70% ethanol extraction 1 time at every turn, refluxes 1 hour, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 60% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.30 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 8 times of water gagings and soaked 1 hour, with extraction by steam distillation volatile oil 7 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 1 time, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 14
Semen Coicis adds 6 times of amounts with 65% ethanol extraction 2 times at every turn, refluxes 2 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 65% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.30 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 7 times of water gagings and soaked 2 hours, with extraction by steam distillation volatile oil 5 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 2 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 15
Semen Coicis adds 8 times of amounts with 70% ethanol extraction 3 times at every turn, refluxes 3 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 70% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.20 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 2-8 times of water gaging and soaked 2 hours, with extraction by steam distillation volatile oil 2-7 hour, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 2 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.30, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 16
Semen Coicis adds 7 times of amounts with 75% ethanol extraction 2 times at every turn, refluxes 2 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 75% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.10 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 5 times of water gagings and soaked 2 hours, with extraction by steam distillation volatile oil 6 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 2 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.30, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 17
Semen Coicis adds 4 times of amounts with 80% ethanol extraction 1 time at every turn, refluxes 2 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 80% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.10~1.20 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 5 times of water gagings and soaked 1 hour, with extraction by steam distillation volatile oil 2 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 1-3 time, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.10~1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 18
Semen Coicis adds 7 times of amounts with 85% ethanol extraction 2 times at every turn, refluxes 3 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 85% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.20~1.30 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 6 times of water gagings and soaked 2 hours, with extraction by steam distillation volatile oil 2-7 hour, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 3 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.20~1.30, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 19
Semen Coicis adds 8 times of amounts with 90% ethanol extraction 2 times at every turn, refluxes 3 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 90% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.10~1.20 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 7 times of water gagings and soaked 2 hours, with extraction by steam distillation volatile oil 6 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 2 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.10~1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 20
Semen Coicis adds 5 times of amounts with 50% ethanol extraction 1 time at every turn, refluxes 2 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 60% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.10~1.20 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 6 times of water gagings and soaked 2 hours, with extraction by steam distillation volatile oil 2-7 hour, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 2 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.10~1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 21
Semen Coicis adds 5 times of amounts with 75% ethanol extraction 3 times at every turn, refluxes 2 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 50% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.10~1.20 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 5 times of water gagings and soaked 1~2 hour, with extraction by steam distillation volatile oil 2-7 hour, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 3 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.10~1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 22
Semen Coicis adds 6 times of amounts with 75% ethanol extraction 2 times at every turn, refluxes 2 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 50% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.20~1.30 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 5 times of water gagings and soaked 1~2 hour, with extraction by steam distillation volatile oil 3 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 3 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.20~1.30, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 23
Semen Coicis adds 7 times of amounts with 70% ethanol extraction 3 times at every turn, refluxes 2 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 60% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.10~1.20 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 6 times of water gagings and soaked 1 hour, with extraction by steam distillation volatile oil 4 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 2 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.10~1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 24
Semen Coicis adds 5 times of amounts with 75% ethanol extraction 3 times at every turn, refluxes 3 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 50% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.10~1.20 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 5 times of water gagings and soaked 1~2 hour, with extraction by steam distillation volatile oil 5 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 3 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.10~1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 25
Semen Coicis adds 8 times of amounts with 60% ethanol extraction 2 times at every turn, refluxes 2 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 70% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.20~1.30 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 6 times of water gagings and soaked 1~2 hour, with extraction by steam distillation volatile oil 4 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 3 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.10~1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.
Embodiment 25
Semen Coicis adds 9 times of amounts with 60% ethanol extraction 3 times at every turn, refluxes 1.5 hours, filter, and merging filtrate, decompression recycling ethanol, low-temperature vacuum drying is pulverized, and is standby.Pericarpium Citri Reticulatae adds 60% alcohol reflux 3 times, and alcohol adding amount is respectively 12 times, 10 times and 8 times, and each 1 hour, merge backflow, filter, decompression recycling ethanol is concentrated into relative density and is 1.10~1.20 clear paste.Flos Lonicerae, Fructus Forsythiae are criticized, Rhizoma Anemones Altaicae three flavor mixing add 7 times of water gagings and soaked 1~2 hour, with extraction by steam distillation volatile oil 5 hours, filter, the another device of distillation rear solution is collected, medicinal residues merge with seven flavors such as remaining Semen Plantaginis, decoct with water 3 times, add 12 times of water gagings at every turn, decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned aqueous solution merge, be concentrated into the clear paste of relative density 1.10~1.20, merge above-mentioned clear paste, Semen Coicis extract adds appropriate dextrin and protein sugar, mixing, spraying one step pelletize, standby.The volatile oil of collecting adopts β-CD saturated water solution method enclose.(β-CD and volatile oil proportioning are 4g: 0.75ml), add water appropriate, heating makes dissolving, is down to 45 ℃ to get β-CD.(oil: with dehydrated alcohol dilute, slowly inject the β-CD solution of 45 ℃, constant temperature stir 2 hour, let cool in 1: 3 by ratio ethanol) for volatile oil, put refrigerator (below 10 ℃) vacuum drying, pulverize, sieve, be added in above-mentioned granule, mixing, and get final product.