Summary of the invention
The object of the invention provides a kind of compound Chinese medicinal preparation of treating anaphylactoid purpura, and the present invention has heat-clearing and toxic substances removing, removing heat from blood, blood stasis dispelling effect, and allergic purpura is had good curative effect.
Another object of the present invention provides a kind of method for preparing the Chinese medicine compound preparation of treating anaphylactoid purpura.
The technical scheme that adopts is:
A kind of compound Chinese medicinal preparation of treating anaphylactoid purpura is to be prepared into by Chinese crude drug Radix Arnebiae (Radix Lithospermi) 100-370g, Herba Taraxaci 100-500g, Cortex Moutan 100-250g, Cortex Dictamni 100-230g, Radix Paeoniae Alba 100-300g, Herba Ecliptae 100-300g, Herba Cirsii 100-500g, Radix Achyranthis Bidentatae 75-300g, Radix Glycyrrhizae 50-240g, Radix Rehmanniae 100-400g and Poria 100-400g.
A kind of method for preparing of treating the compound Chinese medicinal preparation of anaphylactoid purpura comprises following processing step:
1, gets Radix Rehmanniae 100-400g and Poria 100-400g decocte with water 2-3 time, add 6-8 times of water gaging at every turn, decocted 1-1.5 hour at every turn, merge decoction liquor, filter, the clear paste that it is 1.05-1.10 that filtrating is concentrated into 60 ℃ of following relative densities;
2, getting Radix Arnebiae (Radix Lithospermi) 100-370g, Herba Taraxaci 100-500g, Cortex Moutan 100-250g, Cortex Dictamni 100-230g, Radix Paeoniae Alba 100-300g, Herba Ecliptae 100-300g, Herba Cirsii 100-500g, Radix Achyranthis Bidentatae 75-300g and Radix Glycyrrhizae 50-240g, to use mass concentration be 90% ethanol extraction 2-3 time; Add 6-8 at every turn and doubly measure ethanol; Reflux, extract, is 1-1.5 hour respectively; Merge extractive liquid, filters, and is concentrated into behind the filtrating backflow ethanol that relative density is the clear paste of 1.05-1.10 under 60 ℃ of temperature;
3, the clear paste of combining step 1 and step 2 gained is evaporated to that relative density is the thick paste of 1.15-1.25 under 60 ℃ of temperature, adds an amount of dextrin and aspartame again, mixing, and drying is ground into fine powder, granulates by setting granularity, promptly gets.
Function: heat-clearing and toxic substances removing blood stasis dispelling.
Cure mainly: anaphylactoid purpura.
Dose: below 10 years old, each 10g, every day 3 times, more than 10 years old, each 20g, every day 3 times.
Beneficial effect of the present invention:
Anaphylactoid purpura has become the important multiple disease of serious harm child and juvenile healthy and life because sickness rate is high, renal damage is serious.Though the domestic bibliographical information that employing Chinese medicine compound decoction or decoct treatment anaphylactoid purpura are arranged has been developed into not seeing as yet of new Chinese medicine (VI class).Clinical treatment that we are engaged in anaphylactoid purpura and nearly 30 years of research based on the understanding of motherland's medical science to primary disease, have been established the method for the ruling by law treatment anaphylactoid purpura of detoxifcation, removing heat from blood, blood stasis dispelling; And the screening active drug is distinguished the flavor of on the basis of having carried out a large amount of clinical applications, forms effectively fixedly experience prescription, and on the basis of Chinese medicine decoction, has carried out technological innovation; Process Tournefortia monrana granules preparation, and carried out scientific and normal multicenter clinical observation, confirm that this Chinese medicine compound has detoxifcation, removing heat from blood, blood stasis dispelling effect clinical; Relief of symptoms shortens the course of treatment in the short period of time, reduces the state of an illness repeatedly; Reduce the probability of happening of renal damage, and do not have the disconnected effect in rank of hormone.The present invention has good application prospects, has great social benefit and economic benefit.
The specific embodiment
Embodiment one
A kind of compound Chinese medicinal preparation of treating anaphylactoid purpura is to be prepared into by Chinese crude drug Radix Arnebiae (Radix Lithospermi) 367g, Herba Taraxaci 239g, Cortex Moutan 239g, Cortex Dictamni 239g, Radix Paeoniae Alba 239g, Herba Ecliptae 239g, Herba Cirsii 239g, Radix Achyranthis Bidentatae 184g, Radix Glycyrrhizae 239g, Radix Rehmanniae 239g and Poria 239g.
Embodiment two
A kind of compound Chinese medicinal preparation of treating anaphylactoid purpura is to be prepared into by Chinese crude drug Radix Arnebiae (Radix Lithospermi) 370g, Herba Taraxaci 500g, Cortex Moutan 250g, Cortex Dictamni 230g, Radix Paeoniae Alba 300g, Herba Ecliptae 300g, Herba Cirsii 500g, Radix Achyranthis Bidentatae 300g, Radix Glycyrrhizae 200g, Radix Rehmanniae 400g and Poria 400g.
Embodiment three
A kind of compound Chinese medicinal preparation of treating anaphylactoid purpura is to be prepared into by Chinese crude drug Radix Arnebiae (Radix Lithospermi) 100g, Herba Taraxaci 100g, Cortex Moutan 100g, Cortex Dictamni 100g, Radix Paeoniae Alba 100g, Herba Ecliptae 100g, Herba Cirsii 100g, Radix Achyranthis Bidentatae 75g, Radix Glycyrrhizae 50g, Radix Rehmanniae 100g and Poria 100g.
Embodiment four
A kind of compound Chinese medicinal preparation of treating anaphylactoid purpura is to get SHENGHUANG ground 239g and Poria 239g decocte with water secondary, adds 8 times of water gagings at every turn; Each decocted 1.0 hours, and collecting decoction filters; Being concentrated into relative density is the clear paste of 1.05-1.10 (60 ℃), and device is collected in addition.Get Radix Arnebiae (Radix Lithospermi) 367g, Herba Taraxaci 239g, Cortex Moutan 239g, Cortex Dictamni 239g, Radix Paeoniae Alba 239g, Herba Ecliptae 239g, Herba Cirsii 239g, Radix Achyranthis Bidentatae 184g and Radix Glycyrrhizae 239g with 90% ethanol extraction secondary, add 8 times of amounts at every turn, each reflux, extract, 1 hour; Merge extractive liquid, filters, and filtrate recycling ethanol also is concentrated into the clear paste that relative density is 1.05-1.10 (60 ℃); Merge with above-mentioned clear paste, being evaporated to relative density is the thick paste of 1.15~1.25 (60 ℃), adds dextrin an amount of (about 550g), aspartame an amount of (about 20g); Mixing, drying is ground into fine powder; Granulate, process 1000g, promptly get.
Clinical research:
The 75 routine clinical analysiss of clearing away heat and cooling blood blood stasis dispelling treatment anaphylactoid purpura.
1 data and method
1.1 the whole cases of clinical data are in January, 2008~2009 year December hospital outpatient case.Man's 45 examples, women 30 examples, M-F is 1.5: 1.5-7 year 21 examples, 7-14 year 49 examples,>14 years old 5 example.22 examples of falling ill spring, summers 25 example, autumns 9 example, winters 19 example.
1.2 case is selected
(1) Western medicine diagnose standard: formulate with reference to the diagnostic criteria about anaphylactoid purpura in " practical paidonosology "
[1]
(2) tcm diagnosis and dialectical standard: with reference to formulating about the diagnostic criteria of purpura in State Administration of Traditional Chinese Medicine's " traditional Chinese medical science disease diagnosis criterion of therapeutical effect "
[2]
Wind heat is hindered the network type: disease sees that onset is anxious, and the ecchymosis color is scarlet, and two lower limb are symmetrically distributed, or gargalesthesia is arranged, with heating, excessive thirst etc., red tip of the tongue, yellow and thin fur, floating and rapid pulse.
Heat in blood is hindered the network type: disease sees that the erythra color is scarlet, and two lower limb are symmetrically distributed, and are many and intensive, a bit merges in flakes, and an awful ache in the belly, dysphoria, and constipation, oliguria with reddish urine can be with epistaxis, red tongue, tongue fur is white thick greasy or yellow greasy.
All case all meets the Chinese and western medicine diagnostic criteria.
1.3 Therapeutic Method
Chinese traditional treatment: the heat-clearing and toxic substances removing blood stasis dispelling, the side is with purple red water decoction, and medicine is formed: Radix Arnebiae (Radix Lithospermi), Herba Taraxaci, Cortex Moutan, Cortex Dictamni, the Radix Paeoniae Alba, Herba Ecliptae, Herba Cirsii, Radix Achyranthis Bidentatae, Radix Glycyrrhizae, Radix Rehmanniae, Poria etc.5
+-7 years old, each 50ml, twice of every day is oral, and 7
+-10 years old, each 80ml, twice of every day is oral; 10
+More than year, each 100ml, twice of every day is oral.And cooperate oral vitamin C, rutin etc., one month course of treatment.Use hormonotherapy in the outer court, then continued oral prednisone, 1mg/kg.d, gradation is oral, and decrement is to drug withdrawal.
1.4 efficacy assessment standard
Judge with reference to State Administration of Traditional Chinese Medicine's " traditional Chinese medical science disease diagnosis criterion of therapeutical effect "
[2]Cure: purpura is all disappeared, and simultaneous phenomenon disappears, and it is normal that lab testing each item index is recovered; Produce effects: the skin purpura disappears or obviously reduces, and General Symptoms alleviates, and laboratory each item index is clearly better; Invalid: the skin purpura does not move back or moves back and recurs, and lab testing does not have improvement.Total effective rate=(curing routine number+produce effects example number)/total routine number.
1.5 follow-up method
Finish the course of treatment in 3 months, check routine urinalysis weekly 1 time, routine urinalysis of per 2 weeks check was followed up a case by regular visits to 6 months after three months, was the terminal point incident of evaluation of renal infringement with hematuria, albuminuria.
2 results
2.1 clinical treatment is clinical cure 55 examples as a result, produce effects 14 examples, and invalid 6 examples, cure rate 73.3%, obvious effective rate 18.7%, effective percentage are 92%.
2.2 urine examination abnormal change 7 examples appear in Follow-up results, asymptomatic proteinuria 1 example wherein, and simple hematuria 5 examples, asymptomatic proteinuria, albuminuria 1 example, the secondary kidney damage is 9%.
The result shows: adopt the purple red water decoction of Chinese medicine of detoxifcation cooling blood and removing stasis method screening, to the treatment of anaphylactoid purpura, determined curative effect.The probability of happening of its Follow-up results renal damage is starkly lower than bibliographical information.National industry public welfare project has been listed in research in, is carrying out the RCT research of the red granule therapy anaphylactoid purpura of clinical purple.
List of references
[1] Hu Yamei, Jiang Zaifang, Zhu Futang, etc.Practical paidonosology [M] .7 version.Beijing: People's Health Publisher, 2002:689.
[2] State Administration of Traditional Chinese Medicine.Traditional Chinese medical science disease diagnosis criterion of therapeutical effect [S]. Nanjing: publishing house of Nanjing University, 1994:18.
Experimentation:
Purple red granule Expermental research on main pharmacodynamics
The summary purpose to the red granule of purple main pharmacodynamics effect study.Method adopts models of passive skin irritability of rats reaction experiment, the experiment of DNBC induced mice delayed hypersensitive reaction, observes purple red granule to allergic influence; Purple red granule antiinflammatory action is observed in rat paw edema experiment due to the abdominal cavity capillary permeability experiment of employing acetic acid induced mice, the Ovum Gallus domesticus album.The purple red granule of result can obviously suppress the models of passive skin irritability of rats reaction, suppresses DNBC induced mice delayed hypersensitive reaction; Rat paw edema due to the reduction acetic acid induced mice capillary permeability, inhibition Ovum Gallus domesticus album.The purple red granule of conclusion has antiallergic action, antiinflammatory action.
Purple red granule is made up of 11 flavor medical materials such as Radix Arnebiae (Radix Lithospermi), Cortex Moutan, the Radix Rehmanniae, has the detoxifcation removing heat from blood, the blood stasis dispelling effect.Be used to treat anaphylactoid purpura.This paper has carried out Pharmacodynamic test of active extract to its effect and clinical practice to this medicine.
One, experiment purpose
Observe purple red granule and cure mainly relevant main pharmacodynamics effect, for the clinical practice of this medicine provides reference with function.
Two, experiment material
Receive the reagent thing: purple red granule is provided lot number by Shenyang Pharmaceutical University:; Specification: 9g/ bag, 2.702g crude drug/g, Chinese medicine positive control drug Callicarpa nudiflora sheet, Hainan Jiuzhitang Maedicine Co., Ltd produces; Lot number: 900820, specification: 24/close, 0.5g (dry extract)/sheet; Western medicine positive control drug prednisone acetate tablets, Tianjin Tianyao Pharmaceutical Co., Ltd. produces, lot number: 090603, specification: 20 slices/bottle, the 50mg/ sheet.
Animal subject: SPF level white mice, purchase Experimental Animal Center in Chinese Medical Sciences University; Credit number: SCXK-(the Liao Dynasty) 2008-0005; SPF level rat is purchased in Test Animal Centre, Academy of Military Medical Sciences, P.L.A credit number: SCXK-(army) 2007-004.
Experimental situation: Liaoning Chinese Medicine Institute's Experimental Animal Center.Credit number: SYXK (the Liao Dynasty) 2007-0010.Laboratory temperature: 20 ℃~23 ℃, laboratory humidity: 50%~60%.
Instrument: 721 spectrophotometers, Shanghai the 3rd analytical tool factory produces.PV-200 toes volumetric measurement appearance, Chengdu TME Technology Co., Ltd. produces.
Reagent: azovan blue, lot number: 20070207, Chemical Reagent Co., Ltd., Sinopharm Group produces.2.4-dinitrochlorobenzene, Military Medical Science Institute MED SUP station provides lot number: 991223.Acetone, Tianjin chemical industry all generations company limited produces.Lot number: 20050408.Acetic acid, chemical reagent factory in Kaiyuan produces, lot number: 900812.
Statistical method: all data are represented with mean ± standard deviation
.Relatively check between group with t.
Three, test method and result
1 purple red granule is to the influence (1) of models of passive skin irritability of rats reaction (PCA)
1.1 Antiserum Preparation: get 10 of body weight 100~120g male rats, except that 3 intravenous injection normal saline, all the other 7 intravenous injections, 1% fresh-laid egg clear liquids are pressed 50mg/kg, simultaneously lumbar injection 4%A1
2(SO
4)
3Gel 2mL/, the 12nd day venous blood collection is centrifugal after the sensitization, separation of serum, and-20 ℃ of preservations, subsequent use in 2 weeks.
1.2 antiserum inoculation and antigen challenge
Get 70 of body weight 180~220g male rats; Divide 7 groups at random by body weight; Blank (equal-volume distilled water), model control group (equal-volume distilled water), the basic, normal, high dose groups of purple red granule (6.57g crude drug/kg, 13.13g crude drug/kg, 26.26g crude drug/kg); Western medicine positive control drug prednisone acetate tablets group (3.6mg/kg), and Chinese medicine positive control drug Callicarpa nudiflora sheet group (the 0.54g dry extract/kg).Gastric infusion, every day 1 time, continuous 7 days; Administration the 6th day, respectively in back part of animal center line both sides depilations, above-mentioned antiserum is diluted to the 1:8 dilution factor with normal saline after; At each group rat back depilation place intradermal injection antiserum 0.1ml/ point, 48h after the sensitization (30min after the last administration) carries out antigen challenge, and each only organizes rat intravenous injection 0.5% azovan blue protein injection liquid (including 1ml% fresh-laid egg clear liquid) 1ml/; Take off neck behind the 30min and put to death rat, skin of back locus coeruleus skin graft is cut, shred; Add among acetone one physiology saline (7: 3) the mixed solution 5mL and soak, next day is centrifugal, gets supernatant; Measure its trap (0D value) with 721 spectrophotometers in the 610nm wavelength, the significance of comparing difference between group calculates the inhibition percentage rate.The result sees table 1.
The purple red granule of table 1 is to the influence
of PCA reaction
* * * P<0.01, P<0.05 (comparing) (with the model control group ratio) with model control group
Visible by table 1, (13.13g crude drug/kg, the 26.26g crude drug/kg) OD value is starkly lower than model control group to the middle and high dose groups of purple red granule, compares difference significance (P<0.05) with model control group.Show that purple red granule can reduce locus coeruleus and form, suppress the models of passive skin irritability of rats reaction and take place.
2 purple red granules are to the influence of DNCB induced mice delayed hypersensitive reaction
(1)
Get 60 of white mice, male.Divide 6 groups at random by body weight; Blank group (equal-volume distilled water); The basic, normal, high dose groups of purple red granule (9.48g crude drug/kg, 18.96g crude drug/kg, 37.92g crude drug/kg); Western medicine positive control drug prednisone acetate tablets group (5.2mg/kg), and Chinese medicine positive control drug Callicarpa nudiflora sheet group (0.78 dry extract/kg).Gastric infusion, successive administration 9 days.First administration mouse back subcutaneous injection on the secondth 1.25%2.4 dinitrochlorobenzene acetone soln (DNCB) 20 a μ l/ sensitization; After the last administration 1 hour, smear 1.25%DNBC acetone solution 20 μ l/ on the mouse right ear two sides only, attack back 24h; Mice is put to death in the cervical vertebra dislocation; With diameter 8mm card punch in the left and right sides ear same area lay auricle, weigh, be the swelling degree with the weight difference of left and right sides auricle.The difference of each administration group of statistical disposition and model control group.The result sees table 2.
The purple red granule of table 2 is to the influence
of DNCB induced mice delayed hypersensitive reaction
* * * P<0.01, P<0.05 (comparing) (with blank group ratio) with the blank group
Visible by table 2, (9.48 crude drugs/kg, 18.96g crude drug/kg, the 37.92g crude drug/kg) the ear swelling degree is starkly lower than the blank group to the basic, normal, high dose groups of purple red granule, compares difference significance (P<0.05) with the blank group.Show that purple red granule can suppress DNBC induced mice ear swelling.
The influence of 3 purple red granule Dichlorodiphenyl Acetate induced mice abdominal cavity capillary permeabilities
(2)
Get 60 of white mice, body weight 18~22g, female, hero half and half divides into groups and dosage experiment 2 together; Gastric infusion, every day 1 time, continuous 7 days, behind the last administration 30min; Equal tail vein injection 0.5% azovan blue normal saline solution 0.1ml/10g body weight, every lumbar injection 0.6% acetic acid 0.2ml takes off neck and puts to death behind the 20min immediately, cuts off abdominal part; Divide several to wash the abdominal cavity with the 6ml normal saline, suction pipe sucking-off cleaning mixture merges the back and adds normal saline to 10ml.Put into the centrifugal 15min of centrifuge 3000rpm, get supernatant and measure OD value, the significance of comparing difference between group at the 590nm place with spectrophotometer.And obtain suppression ratio.
The result sees table 3.
The influence
of the purple red granule Dichlorodiphenyl Acetate induced mice of table 3 abdominal cavity capillary permeability
* * * P<0.01, P<0.05 (comparing) (with blank group ratio) with the blank group
Visible by table 3, (18.96g crude drug/kg, the 37.92g crude drug/kg) OD value is starkly lower than the blank group to the middle and high dose groups of purple red granule, compares difference significance (P<0.05) with the blank group.Show that purple red granule can obviously suppress the blue seepage discharge of ivens, reduces capillary permeability.
The influence of rat paw edema due to the 4 pairs of Ovum Gallus domesticus album
(1)
Get 60 of rats; Body weight 160~200g, male, be divided into 6 groups at random by body weight; Blank (equal-volume distilled water); The basic, normal, high dose groups of purple red granule (6.57g crude drug/kg, 13.13g crude drug/kg, 26.26g crude drug/kg), Western medicine positive control drug prednisone acetate tablets group (3.6mg/kg), Chinese medicine positive control drug Callicarpa nudiflora sheet group (the 0.54g dry extract/kg).Successive administration 7 days; Before the experiment every rat left hind paw ankle with oiliness stroke one clear horizontal line, measure the normal Mus corpus unguis of each Mus earlier and amass, behind the last administration 30min; Left back foot plantar subcutaneous injection 10% Ovum Gallus domesticus album solution 0.1ml/ only causes inflammation each Mus; Cause scorching afterwards 1h, 2h, 4h, 6h and measure each Mus toes volume, it is the swelling degree that each Mus causes the sufficient volume difference in scorching front and back, respectively organizes the difference of swelling degree.The result sees table 4.
The purple red granule of table 4 is to the influence
of rat paw edema due to the Ovum Gallus domesticus album
* * * P<0.01, P<0.05 (comparing) (with blank group ratio) with the blank group
Visible by table 4; (6.57g crude drug/kg, 13.13g crude drug/kg, 26.26g crude drug/kg) are starkly lower than model control group causing scorching back 1~6h paw swelling to the basic, normal, high dose groups of purple red granule; Compare difference significance (P<0.05, P<0.01) with model control group.Show that purple red granule has remarkable inhibitory action to rat paw edema due to the Ovum Gallus domesticus album.
3 conclusions
Models of passive skin irritability of rats (PCA) reaction experiment result shows, (13.13g crude drug/kg, the 26.26g crude drug/kg) OD value is starkly lower than model control group to the middle and high dose groups of purple red granule; Compare difference significance (P<0.05) with model control group; Show that purple red granule can reduce locus coeruleus and form; Suppress the models of passive skin irritability of rats reaction and take place, have the effect of anti-I type allergy.DNBC induced mice delayed hypersensitive reaction experimental result shows; (9.48 crude drugs/kg, 18.96g crude drug/kg, the 37.92g crude drug/kg) the ear swelling degree is starkly lower than the blank group to the basic, normal, high dose groups of purple red granule; Compare difference significance (P<0.05) with the blank group, show that purple red granule has anti-delayed (IV type) allergy effect.
Acetic acid induced mice abdominal cavity capillary permeability experimental result shows; (18.96g crude drug/kg, the 37.92g crude drug/kg) OD value is starkly lower than the blank group to the middle and high dose groups of purple red granule; Compare difference significance (P<0.05) with the blank group; Show that purple red granule can obviously suppress the azovan blue seepage discharge, reduce capillary permeability; The rat paw edema experimental result shows due to the Ovum Gallus domesticus album; (6.57g crude drug/kg, 13.13g crude drug/kg, 26.26g crude drug/kg) are starkly lower than model control group causing scorching back 1~6h paw swelling to the basic, normal, high dose groups of purple red granule; Compare difference significance (P<0.05 with model control group; P<0.01), shows that purple red granule can significantly suppress rat paw edema due to the Ovum Gallus domesticus album, has antiinflammatory action.
List of references
1. Li Yi Kui, etc. herbal pharmacology experimental methodology [M]. second edition. Shanghai science tech publishing house, 2006:744,875,774
2. Qi Chen. herbal pharmacology research methodology [M]. People's Health Publisher, 1993,305.