CN103169803A - Traditional Chinese medicine composition with functions of tonifiying qi, nourishing yin and activating blood for treating myelodysplastic syndrome and preparation method thereof - Google Patents
Traditional Chinese medicine composition with functions of tonifiying qi, nourishing yin and activating blood for treating myelodysplastic syndrome and preparation method thereof Download PDFInfo
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Abstract
The invention provides a traditional Chinese medicine composition with functions of tonifiying qi, nourishing yin and activating blood, which is capable of improving peripheral hemogram of myelodysplastic syndrome sufferer, releasing marrow dyshaematopoiesis, improving clinical symptoms, improving the life quality and prolonging the lifetime, and a preparation method thereof. The traditional Chinese medicine composition provided by the invention is prepared from the crude drugs of 1-120 parts of astragalus mongholicus, 1-120 parts of codonopsis pilosula, 1-120 parts of dried rhizome of rehmannia, 1-120 parts of prepared rehmannia root, 1-120 parts of colla corii asini, 1-120 parts of tortoise plastic, 1-120 parts of flowers carthami, 1-120 parts of semen cuscutae, 1-120 parts of root of red-rooted salvia, and 1-120 parts of caulis spatholobi. The traditional Chinese medicine composition is prepared into the clinically acceptable mixture, concentrated pills, capsules, dropping pills, granules, tablets, pills, soft capsules, controlled release formulations, oral liquid preparations or injection preparations according to the conventional medical preparation process.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation method thereof, be specifically related to a kind ofly can promote the Patients With Myelodysplastic Syndrome peripheral hemogram, alleviate the bone marrow DH, improve life in patients, extend supplementing QI and nourishing YIN Chinese medical composition capable of invigorating blood circulation of survival of patients phase and preparation method thereof.
Background technology
Myelodysplastic syndrome (Myelodysplastic Syndromes, MDS) be one group of malignant clone hematopathy that originates from the marrow hemopoietic stem cells level, clinical active or obviously active with myelosis, with invalid and DH, and the surrounding hemogram different series is in various degree and reduces, and causes thus anemia, hemorrhage and infect and be feature.
In MDS pathological changes organic growth process, two kinds of conversion trend are arranged, the one, cause clinical death owing to the factor such as infecting, hemorrhage; The 2nd, be converted into acute leukemia.According to FAB cooperative groups statistics, RA, RAS, RAEB, RAEB-T, the various leukemia conversion ratio of CMML are respectively 12.5%, 11.5%, 42%, 59%, 29%.As seen the high risk that transforms of the oriented leukemia of MDS.For the MDS clinical treatment, except the supporting treatment of suiting the medicine to the illness, because primary disease has leukemoid clinical, the morphocytology of a lot of classes and molecular biological characteristics, and some cases develops into typical leukemia the most at last.Therefore everyly be used for the treatment of leukemic the whole bag of tricks and all be used for clinically, comprise and induce differentiation agent, hemopoietic to organize medicine, small dose chemotherapy, combined chemotherapy and bone marrow transplantation etc.Although clinically can obtain certain curative effect.But compare with the leukemia clinical efficacy, differ greatly.Various cytokines only have temporary curative effect, clinical as adjuvant therapy medicaments still can, can't be as MDS primary treatment method; Heavy dose of combined chemotherapy is enough to cause Bone Marrow of Patients to suppress, and might accelerate patient's death in advance; After bone marrow transplantation, though some patients can be able to clinical remission, long term follow-up, relapse rate is higher, and somewhat expensive, applies at present to also have certain difficulty.Therefore, how to remove the malignant clone of MDS patient self growth, there is no at present therapeutic regimen.
Summary of the invention
The invention provides a kind of Chinese medicine composition for the treatment of myelodysplastic syndrome and preparation method thereof.The present invention seeks to be achieved through the following technical solutions:
1. pharmaceutical composition crude drug composition of the present invention with dosage is
Radix Astragali 1-120 weight portion, Radix Codonopsis 1-120 weight portion, Radix Rehmanniae 1-120 weight portion, Radix Rehmanniae Preparata 1-120 weight portion, Colla Corii Asini 1-120 weight portion, Colla Plastri Testudinis 1-120 weight portion, Flos Carthami 1-120 weight portion, Semen Cuscutae 1-120 weight portion, Radix Salviae Miltiorrhizae 1-120 weight portion, Caulis Spatholobi 1-120 weight portion.
2. pharmaceutical composition crude drug composition of the present invention is preferably with dosage
Radix Astragali 10-30 weight portion, Radix Codonopsis 10-30 weight portion, Radix Rehmanniae 10-30 weight portion, Radix Rehmanniae Preparata 10-30 weight portion, Colla Corii Asini 10-30 weight portion, Colla Plastri Testudinis 10-30 weight portion, Flos Carthami 10-30 weight portion, Semen Cuscutae 10-30 weight portion, Radix Salviae Miltiorrhizae 10-30 weight portion, Caulis Spatholobi 10-30 weight portion.
3. pharmaceutical composition crude drug composition of the present invention is preferably with dosage
The Radix Astragali 10 weight portions, Radix Codonopsis 30 weight portions, the Radix Rehmanniae 35 weight portions, Radix Rehmanniae Preparata 60 weight portions, Colla Corii Asini 20 weight portions, Colla Plastri Testudinis 60 weight portions, Flos Carthami 45 weight portions, Semen Cuscutae 55 weight portions, Radix Salviae Miltiorrhizae 70 weight portions, Caulis Spatholobi 20 weight portions.
4. pharmaceutical composition crude drug composition of the present invention is preferably with dosage
The Radix Astragali 10 weight portions, Radix Codonopsis 60 weight portions, the Radix Rehmanniae 60 weight portions, Radix Rehmanniae Preparata 20 weight portions, Colla Corii Asini 70 weight portions, Colla Plastri Testudinis 100 weight portions, Flos Carthami 15 weight portions, Semen Cuscutae 80 weight portions, Radix Salviae Miltiorrhizae 25 weight portions, Caulis Spatholobi 60 weight portions.
5. pharmaceutical composition crude drug composition of the present invention is preferably with dosage
The Radix Astragali 30 weight portions, Radix Codonopsis 10 weight portions, the Radix Rehmanniae 60 weight portions, Radix Rehmanniae Preparata 20 weight portions, Colla Corii Asini 70 weight portions, Colla Plastri Testudinis 100 weight portions, Flos Carthami 15 weight portions, Semen Cuscutae 80 weight portions, Radix Salviae Miltiorrhizae 25 weight portions, Caulis Spatholobi 60 weight portions.
6. pharmaceutical composition crude drug composition of the present invention is preferably with dosage
The Radix Astragali 70 weight portions, Radix Codonopsis 10 weight portions, the Radix Rehmanniae 20 weight portions, Radix Rehmanniae Preparata 40 weight portions, Colla Corii Asini 55 weight portions, Colla Plastri Testudinis 30 weight portions, Flos Carthami 60 weight portions, Semen Cuscutae 20 weight portions, Radix Salviae Miltiorrhizae 45 weight portions, Caulis Spatholobi 35 weight portions.
7. pharmaceutical composition crude drug composition of the present invention is preferably with dosage
The Radix Astragali 70 weight portions, Radix Codonopsis 10 weight portions, the Radix Rehmanniae 20 weight portions, Radix Rehmanniae Preparata 40 weight portions, Colla Corii Asini 55 weight portions, Colla Plastri Testudinis 30 weight portions, Flos Carthami 60 weight portions, Semen Cuscutae 20 weight portions, Radix Salviae Miltiorrhizae 120 weight portions, Caulis Spatholobi 35 weight portions.
Pharmaceutical composition of the present invention adds conventional adjuvant pharmaceutically to make the dosage form of clinical acceptance according to common process, as any one in powder (comprising granule), capsule (comprising soft capsule, slow releasing capsule), tablet (comprising dispersible tablet), pill (comprising the watered pill, honeyed pill, micropill), granule.
The preparation method of pharmaceutical composition of the present invention can also be:
Radix Salviae Miltiorrhizae and Semen Cuscutae add 60-85% ethanol extraction 1-3 time, add for the first time ethanol 6-10 times of weight, and reflux 1-2 hour, filter, medicinal residues add ethanol again, and reflux 1-2 hour, filter, merging filtrate reclaims ethanol, and medicinal liquid and medicinal liquid are standby respectively; The Radix Astragali and Radix Codonopsis decoct with water 1-3 time, add for the first time water 6-10 times of weight, decoct 1-2 hour, add later on water 4-8 times of weight at every turn, decoct 1-2 hour, merge each decocting liquid, are concentrated into thick paste, and be standby; Medicinal residues after Radix Rehmanniae, Radix Rehmanniae Preparata, Flos Carthami, Caulis Spatholobi four Chinese medicine and Radix Salviae Miltiorrhizae and Semen Cuscutae alcohol extraction decoct with water 1-3 time together, add for the first time water 6-10 times of weight, decocted 1-2 hour, add later on water 4-8 times of weight at every turn, decocted 1-2 hour, and merged each decocting liquid, being concentrated into relative density is that 50 ℃ of heat are surveyed 1.13 clear paste, let cool, add ethanol and make the alcohol amount of containing be 60-70%; Standing 26 hours, incline and get supernatant, reclaim ethanol, standby; Above three kinds of medicinal liquids are merged, be concentrated into thick paste, dry below 85-80 ℃, pulverize, cross 100 mesh sieves, with Colla Corii Asini after freezing and pulverizing and Colla Plastri Testudinis mixing, and make mixture, concentrated pill, capsule, drop pill, granule, tablet, pill, soft capsule, slow releasing agent, oral liquid or the ejection preparation of clinical acceptance according to common process.
The preparation method of pharmaceutical composition of the present invention is preferably:
Radix Salviae Miltiorrhizae and Semen Cuscutae add 80% ethanol extraction 2 times, add for the first time 80% ethanol 8 times of weight, and reflux 2 hours filters, and medicinal residues add 80% ethanol 6 times of weight again, and reflux 1.5 hours filters, and merging filtrate reclaims ethanol, and medicinal liquid and medicinal liquid are standby respectively.The Radix Astragali and Radix Codonopsis decoct with water twice, add for the first time water 8 times of weight, decoct 1.5 hours, add for the second time water 6 times of weight, decoct 1.0 hours, merge twice decocting liquid, are concentrated into thick paste, and be standby.Medicinal residues after Radix Rehmanniae, Radix Rehmanniae Preparata, Flos Carthami, Caulis Spatholobi four Chinese medicine and Radix Salviae Miltiorrhizae and Semen Cuscutae alcohol extraction decoct with water twice together, add for the first time water 8 times of weight, decocted 1.5 hours, add for the second time water 6 times of weight, decocted 1.0 hours, merge twice decocting liquid, being concentrated into relative density is the clear paste of 1.13 (50 ℃ of heat are surveyed), let cool, adding ethanol, to make the alcohol amount of containing be 65% (the limit edged stirs, and slowly adds).Standing 26 hours, incline and get supernatant, reclaim ethanol, standby.Above three kinds of medicinal liquids are merged, be concentrated into thick paste, dry below 80 ℃, pulverize, cross 100 mesh sieves, with mistake 100 purpose Colla Corii Asini and Colla Plastri Testudinis mixing after freezing and pulverizing, and by mixture, concentrated pill, capsule, drop pill, granule, tablet, pill, soft capsule, slow releasing agent, oral liquid or the ejection preparation of making clinical acceptance according to common process.
Radix Astragali Preparata of the present invention is Radix Astragali (processed with Mel).
The inventor passes through MDS patient clinical symptom preliminary observation, think that many kinds of paathogenic factors of MDS undermine negative and positive of qi and blood, not enough or the deficient blood stasis internal resistance traditional Chinese medical science pathogenesis that causes due to negative and positive of qi and blood, the simulataneous insufficiency and excessive syndrome of clinical common " cloudy (blood) two void of gas, blood stasis internal resistance ".Medicine of the present invention is take " supplementing QI and nourishing YIN activating blood circulation method " as MDS Chinese traditional treatment principle, take Radix Astragali Preparata, Radix Codonopsis, the Radix Rehmanniae, Radix Rehmanniae Preparata, Colla Corii Asini, Colla Plastri Testudinis, Flos Carthami, Semen Cuscutae, Radix Salviae Miltiorrhizae, Caulis Spatholobi as principal agent, with the treatment of disease plus-minus.The clinical research result shows, the party can obviously improve patient clinical subjective symptoms and bleeding, and peripheral blood in patients Lactoferrin, leukocyte, platelet are also had certain castering action.
Description of drawings:
Fig. 1 is the HI-Meg cytological map;
Fig. 2 is matched group HI-Meg cytological map;
Fig. 3 is (YSL) HI-Meg cytological map after medication.
Following test (experiment) example and embodiment are used for further illustrating but being not limited to the present invention.
Test example one: the clinical research of pharmaceutical composition of the present invention (embodiment 1 preparation) treatment MDS
1. diagnostic criteria
(1) MDS diagnostic criteria: carry out with reference to " diagnosis of hematological diseases and criterion of therapeutical effect " third edition (south, Shen Ti chief editor, Science Press, 2007).1. clinical manifestation: take Anemia as main, can have heating or hemorrhage concurrently.2. hemogram: pancytopenia, or arbitrary, two be Leukopenia, the DHs performances such as gigantocyte, Giant platelet, erythroblast are arranged.3. bone marrow smear: have three be or two be or arbitrary be the DH of hemocyte.4. disease except: except other with the DH disease, as chronic myelocytic leukemia, myelofibrosis, erythroleukemia, primary thrombocytosis, acute nonlymphocytic leukemia (M2b type), non-hematopoietic neoplasm etc.; Except other red be proliferative disease, as hemolytic anemia, megaloblastic anemia etc.; Except other pancytopenia diseases, as aplastic anemia, PNH etc.
(2) morbidity of MDS Clinical typing: MDS and progress are dynamic continuous process, nineteen eighty-two method, American and Britain (FAB) cooperative groups what are counted according to MDS peripheral blood in patients and bone marrow blast it have been carried out Clinical typing (phase).That is: 1. refractory anemia (Refractory anemia, RA): bone marrow blast＜5%, peripheral blood germinal cell＜1%; 2. refractory anemia (the Refractory anemia with ring sideroblasts that increases of annular sideroblast, RAS): bone marrow and peripheral blood germinal cell number are with the RA type, but, ring-type sideroblast in bone marrow＞full bone marrow nucleated cell 15%; 3. the refractory anemia (Refractory anemia with excess of blasts, RAEB) that increases of germinal cell: bone marrow blast is counted 5%-20%, peripheral blood germinal cell＜5%; 4. refractory anemia (the Refractory anemia with excess of blasts in transformation of original cytosis in changing, RAEB-t): when peripheral blood germinal cell 〉=5%, bone marrow blast 20%-30% or to see that one of 3 kinds of phenomenons such as Auer body appear in juvenile cell namely diagnosable.Because RA, RAS have the low AL of conversion risk, be called again low danger crowd; It is that AL is dangerous that RAEB, RAEB-t have high-degree of conversion, is called again the high-risk group.
(3) Standards of Chinese Medical Syndrome Differentiation: 1. cardinal symptom: spiritlessness and sparing of words, fatigue and asthenia, hectic fever night sweat, dysphoria with feverish sensation in the chest palms and soles, the parched throat xerostomia, body has ecchymosis, petechia or sees the lower long-pending piece of the side of body; 2. minor symptom: inappetence, abdominal distention after meal, cardiopalmus is nervous, defecates uncomfortable; 3. light red tongue is dark, and ecchymosis is arranged, and pulse condition is thin and delicate.Meeting cardinal symptom, possess two of minor symptoms, can dialectically be " deficiency of both QI and YIN, blood stasis internal resistance " syndrome in conjunction with the tongue arteries and veins.
2. case choice criteria
(1) enter the group standard: meeting following standard can diagnose: 1. meet the MDS diagnostic criteria; 2. meet the dialectical standard of deficiency of both QI and YIN; 3. the age is between 18～80 years old; 4. liver, renal function are good; 5. accept voluntarily this group Drug therapy.
(2) exclusion standard: have following one to belong to Excluded cases: the disease that 1. other pancytopenia that cause as aplastic anemia, PNH etc. are arranged; 2. age＜18 year old,＞80 years old person; 3. gestation and women breast-feeding their children; 4. suffer from mental disease or other state of an illness and can not partner treatment and monitoring requirement; 5. be associated with the serious primary disease such as cardiovascular, cerebrovascular, liver, kidney, wherein ALT is higher than the person more than 2 times of Upper Limit of Normal Value, the abnormal person of Bun, Cr; 6. MDS-RAEB and the MDS-RAEB-t patient in FAB cooperative groups Clinical typing; 7. known to some drugs allergy sufferers in said composition.
(3) reject the case standard: 1. not medication in accordance with regulations, can't judge curative effect, or data is not congruent affects the treatment or safety judgement person; 2. be converted into MDS-RAEB, MDS-RAEB-t and acute leukemia by MDS-RA or RAS in therapeutic process; 3. treated less than 1 month and death.
3. research method
(1) clinical grouping: adopt practicality random method (pragmatic randomized controlled trials, pragmatic clinical trials), with 60 routine MDS patients according to 5: 1 minutes two groups, wherein, treatment group 50 examples (male's 28 examples, women's 22 examples, 66.5 years old mean age); Matched group 10 examples (male's 6 examples, women's 4 examples, 58.5 years old mean age).
(2) Therapeutic Method: treatment group is prepared into granule with pharmaceutical composition of the present invention, every twice-daily, each 2 bags; Matched group adopts the each 2mg of stanozolol, every day 2 times.Identical (hemoglobin＜35g/L the support of being transfused blood of two groups of case Primary Cares; Platelet＜30 * 10
9/ L gives platelet transfusion; Leukemia＜1.5 * 10
9/ L gives granulocyte stimulating factor).45 days is a course for the treatment of, check hemogram after finishing the course for the treatment of, and bone marrow smear, and continue to observe 6 months, the check hemogram carries out evaluation of clinical curative effect after bone marrow smear.
(3) observation index: treated 6 months, and observed 12 months assessment curative effects, dynamically observed afterwards 5 years.Observe clinical effective rate, median survival interval, leukemia conversion ratio, year interior accumulative total infection rate.
4. criterion of therapeutical effect
(1) curative effect of disease: (the 3rd edition, love and respect one's elder brother in south, Shen, Beijing: Science Press) formulate: 1. substantially alleviate: anemia, bleeding disappear, and hemoglobin reaches female 100g/l, and leukocyte reaches 4.0 * 10 according to " diagnosis of hematological diseases and criterion of therapeutical effect "
9/ L, platelet reaches 80 * 10
9More than/L, classification is without juvenile cell.Original in bone marrow+prorubricyte＜5% is maintained until not a half year.2. partial rcsponse: anemia, bleeding disappear, and three is that hemocyte has certain recovery, and blood Central Plains+prorubricyte＜5%, bone marrow Central Plains+prorubricyte reduce 50% before, keep at least 3 months.3. progressive: anemia and bleeding take a turn for the better, and do not transfuse blood and modal value that hemoglobin was treated in previous month increases 30g/L, and former+prorubricyte number reduces.4. invalid: as can not to reach above-mentioned standard person through abundant treatment.
(3) other criterions of therapeutical effect: 1. median survival interval: from begin treatment to the death time; 2. leukemia conversion ratio: observe leukemia and transform case load and also calculate conversion ratio; 3. infection rate: calculate 1 year accumulative total infection rate from begin treatment.
5. therapeutic outcome
(1) clinical curative effect analysis: find through clinical observation: 1. the clinical obvious effective rate for the treatment of group, total effective rate are respectively 62%, 86%; Matched group obvious effective rate, total effective rate are respectively 3/10 (30%), 5/10 (50%), two group relatively, and statistical significance (P＜0.05) is arranged.2. treatment group 20 examples long term follow-up more than 5 years, surpass 56 months middle several life cycles, obviously is better than 26 months of matched group (5 example).3. 5 years leukemia conversion ratios for the treatment of group are 15%.Be starkly lower than 50% of matched group.4. a year interior accumulative total infection rate is respectively 46% (treatment group) and 100% (matched group).
(2) safety is observed: treatment and viewing duration, without overt toxicity reaction (darling renal function is no abnormal); Matched group 7/10 example is all seen the hepatic and renal function injure that has in various degree.
The research that experimental example two, pharmaceutical composition of the present invention (embodiment 1 preparation) affect HI-Meg
1 method
Selecting megakaryocytic leukemia is that HI-Meg is target cell, by short-term and longer-term liquid culture, observes Chinese medicine pharmaceutical composition of the present invention and the side of tearing open thereof to the impact of HI-Meg cell proliferation and differentiation.1. short term culture: get the HI-Meg cell suspension that went down to posterity 24 hours, after RPMI-1640 culture fluid washing 1 time, hang with appropriate RPMI-1640, be inoculated in 24 orifice plates (Nunc), every hole 1 * 10
5Individual cell, 20% calf serum, every group of three holes; Appropriate liquid hangs, and respectively adds this pharmaceutical composition of equivalent, and concentration is 1: 1000, and matched group adds equivalent RPMI-1640 culture fluid, puts 37 ℃, 5%CO
2, saturated humidity cultivates, and gets 0 o'clock cell and does contrast, counts respectively each cell concentration and the experiment of row trypan blue exclusion in 24 hours, 48 hours, 72 hours in cultivating, and centrifugal smear carries out light microscopy checking after doing Switzerland's dyeing.2. longer-term liquid culture: use the 5ml culture bottle, minute contrast, pharmaceutical composition group, every group of cell concentration is 1 * 10
5/ ml, drug level 1: 1000, cultural method is the same.Took out in the 2nd, 4,6 day after cultivating and organize respectively that cell is counted and the trypan blue exclusion test, and centrifugal smear.Each organize cell with fresh RPMI-1640 culture fluid washing 1 time after, still be made into 1 * 10
5/ ml cell concentration suspension by 1: 1000 drug level, adds 20% calf serum to continue to cultivate.Observe pharmaceutical composition of the present invention to the impact of HI-Meg cell proliferation and differentiation.
2. result
The Short-term cell culture demonstration, cell counting pharmaceutical composition group cell is starkly lower than matched group; 24, division cells was observed demonstration, matched group＞pharmaceutical composition group in 48,72 hours.Longer-term is cultivated and is shown, YSL group＜matched group; After cultivating the 4th day, each is organized cell division and is mutually matched group＞pharmaceutical composition group.Short-term and longer-term liquid culture cell smear om observation cellular morphology show: the pharmaceutical composition group all occurs than double-core, multinuclear megalokaryocyte more than matched group, but ratio still be can not determine; After longer-term liquid culture the 4th day, YSL group cell double-core, apocyte, cell space increases, and endochylema is shallow, and without obvious cavity, nucleolar fraction is smudgy, also finds that the similar cell that withers and falls is arranged (referring to Fig. 1-Fig. 3).
3. conclusion
Pharmaceutical composition compound recipe of the present invention shows as obvious inhibition propagation and promotes the differentiation dual function, and non-toxic reaction.
Experimental example three, pharmaceutical composition of the present invention (embodiment 1 preparation) are to the HI-Meg Gene Expression
1. method
Get 80～120 generation HI-Meg cells, recovery is rear with 1 * 10
5The concentration of individual/ml is inoculated in 24 orifice plates, every hole 1ml, and medication group drug regimen substrate concentration is 0.1%, matched group adds the culture fluid with the pharmaceutical composition equal volume.Each 6 holes of two lines, 37 ℃, 5%CO
2, saturated humidity is cultivated.Got 0 o'clock and 48 hours HI-Meg cells, row life or death cell counting is to observe the growth conditions of HI-Meg cell, the cell proliferation vigor is surveyed in the MTT test, carries out morphological observation after the cell smear Wright's staining and surveys to determine its differentiation degree with times health check-up of flow cytometer (FACS) row cell.Adopt biotin to lack the galloping note probe (BRL) of singing, through Streptavidin-alkaline phosphatase assay system (BRL) show nucleic acid molecular hybridization signal, carry out cell smear CDNA-MRNA in situ hybridization by the magnificent laboratory modification method of Song Yu.Cytoplasm black-and-blue granule occurs or flocky precipitate is that hybridization signal is positive.Positive cell number, positive percentage and integrated value under the oil mirror in 200 cells of counting.The hybridization signal response strength is divided into Pyatyi: "-" is for reactionless; "+" positive reflection accounts for endochylema area 1/4; " ++ " positive reaction accounts for endochylema area 1/2; " +++" positive reaction accounts for endochylema area 3/4; " ++ ++ " positive reaction is abound with endochylema.Integrated value is calculated: each response strength multiply by the algebraical sum of cell number.
2. result
HI-Meg propagation after the pharmaceutical composition effect is compared with matched group with differentiation state, and the pharmaceutical composition effect is after 48 hours, and the HI-Meg cell counting descends, and further looks into the shared percentage rate of its division cells low, and MTT test showed cell proliferation activity descends; Medication group cell cell space increases, and profile is irregularity very, and endochylema increases, and the caryoplasm ratio descends, and double-core is the apocyte showed increased especially; The flow cytometer test shows 4 times of somatic cell showed increased; Increasing with expansion of transmission electron microscope showed cell device showed increased, especially rough endoplasmic reticulum is obvious.The above results shows, the HI-Meg cell is bred suppressed under the pharmaceutical composition effect, and differentiation degree is obviously strengthened.Medication group LIF gene expression is generally strengthened, and sees especially that volume is large, endochylema irregularity, the shallow cell of nucleus dyeing, and most cell effect intensity are ++～+++, a small amount of cell reaches ++ ++; Matched group and medication group positive rate difference 40% and 80%, integration is respectively 108 and 318.When LIF expressed enhancing, medication group cell myc gene also strengthened, and is mainly seen in volume large, the cell of endochylema irregularity; Matched group and medication group positive rate are respectively 20% and 48%, and integration is respectively 42 and 148.
3. conclusion
Can suppress the HI-Meg cell proliferation and promote it to break up on the basis at definite pharmaceutical composition of the present invention, observe with the CDNA-mRNA hybridization in situ technique, the HI-Meg cell is induced the rear LIF of differentiation, myc gene expression that enhancing is in various degree arranged by YSL, and positive reaction is positioned in the higher megalokaryocyte of differentiation degree.
Experimental example four, pharmaceutical composition of the present invention (embodiment 1 preparation) are on HI-Meg proliferation and differentiation impact research
1. method
Get patients with chronic myelocytic leukemia peripheral blood (Ph ' chromatin-positive) and set up HI-Meg cell line, get the 178th generation HI-Meg cell suspension that went down to posterity 24 hours, after RPMI-1640 culture fluid washing 1 time, hang with appropriate RPMI-1640 again, be inoculated in 24 orifice plates (Nunc), every hole 1 * 10
5Individual cell, 20% calf serum, every group of three holes; If the former concentration of pharmaceutical composition is 1, the experimental drug substrate concentration is followed successively by 1: 1000,1: 5000,1: 25000 (because the non-specific cell toxic effect being arranged higher than 1: 400 o'clock, therefore in this research, the drug level scope is selected in 10
-3～10
-5); The experiment contrast group only adds the RPMI-1640 culture fluid, puts 37 ℃, 5%CO
2, saturated humidity cultivates; Do contrast in 0 o'clock with 0 o'clock cell, counted respectively each cell concentration and the blue active somatic cell Coloration experiment of row platform dish in 24 hours, 48 hours, 72 hours in cultivating, and centrifugal smear is done Switzerland's dyeing.Calculate cell proliferation speed, carry out division cells ratio mensuration and MTT experiment, observation of cell morphology and flow cytometer are measured HI-Meg cell cycle and DNA content.
2. result
Pharmaceutical composition is respectively organized the more corresponding matched group of each time period cell counting and is obviously reduced, and be time and drug level dependence, Switzerland's 1: 1000 group and 1: 5000 group cell division of dyeing Image Display is less than matched group, 1: 25000 group of division stage cells ratio rise, sometimes a little more than matched group, illustrate that medicine effective concentration is 1: 1000 (seeing Table 1); Cultivate the HI-Meg matched group of 48 hours, the cell optical density value of 1: 5000 group, 1: 25000 group, 1: 1000 group is followed successively by 1.364,1.256,1.260,1.090, illustrates that the HI-Meg cell proliferation vigor after the pharmaceutical composition effect descends; Under the pharmaceutical composition effect, HI-Meg cell S phase (DNA synthesis stage) cells ratio obviously reduces, G
2+ M phase (DNA post-synthetic phase add cell division stage) cells ratio significantly increases, and obvious temporal correlation is arranged, with matched group relatively, 4 times of somatic cells obviously increase.Obviously low in conjunction with aforementioned pharmaceutical composition effect group division stage cells ratio, show that pharmaceutical composition descends HI-Meg cell proliferation vigor, the core polyploidization is strengthened (seeing Table 2); Wright's staining specimen oil Microscopic observation, with compare with non-medication group of time, pharmaceutical composition is made the HI-Meg cell volume and is increased, form is irregularity more, and projection increases and is large lamellar, and nucleocytoplasmic ratio descends, the cell qualitative change is abundant, but endochylema color and matched group are without obvious difference, and double-core and apocyte increase, and be proportionate with incubation time and drug level (seeing Table 3).
HI-Meg under the effect of table 1. pharmaceutical composition divides compare (‰)
Compare χ with matched group
2Check,
★P＜0005
Table 2. pharmaceutical composition is on HI-Meg cell cycle and times body impact (FACS)
Compare with 0 o'clock matched group, chi-square criterion,
*P＜001
HI-Meg metamorphosis (‰) under the effect of table 3. pharmaceutical composition
Compare chi-square criterion, * P＜0005 with matched group
3. conclusion
Experimentation proof pharmaceutical composition of the present invention has obvious inhibition propagation and promotes it to the dual function of ripe direction differentiation human leukemia megakaryocytic series HI-Meg.
Experimental example five, pharmaceutical composition of the present invention (embodiment 1 preparation) are on IL-2 and the impact of NK cytoactive
1. method
Get Balb/c mouse boosting cell suspension, be seeded in 24 well culture plates, be divided into 4 groups, 10 parts every group, every part of 1ml, front 3 groups of experimental grouies add the pharmaceutical composition medicinal liquid of variable concentrations, and add simultaneously the ConA of 5.0 μ g/ml in 4 groups.Measure IL-2 and NK cytoactive.
2. result
Result of study prompting, pharmaceutical composition of the present invention can increase mouse boosting cell IL-2 and NK cytoactive, and its effect degree and Drug level have substantial connection, and the pharmaceutical composition drug level is 0.1% the time, and IL-2 and NK cytoactive are the highest, the results are shown in Table.
The impact of pharmaceutical composition on mouse spleen cell IL-2 activity and NK cytoactive
Compare with matched group,
★P＜0.02,
★ ★P＜0.001
3. conclusion
Pharmaceutical composition of the present invention can make mouse boosting cell IL-2 and NK cytoactive increase, and with Drug level, certain relation is arranged, and the Drug level of prove out may be shaped with regulating action to immunization machine.
Experimental example six, pharmaceutical composition of the present invention (embodiment 1 preparation) are to CD
4 +CD
25 +Foxp
3 +Treg cell and correlation factor impact research
1. method
Get 40 Balb/c mices and be divided at random normal group, model group, Prednisone Therapy group, medicine composite for curing group, except normal group, all the other are respectively organized equal the next day once by 100 μ l/20g lumbar injection 1: the 4 anti-mouse platelets serum of Cavia porcellus (GP-APS) and set up the ITP mouse model, and each group of modeling beginning in the 8th day is all by 0.2ml/10gd
-1The volume gavage, normal group, model group gavage normal saline, and medicine composite for curing is pressed 0.3g/10gd
-1Gavage, after continuous 8 days, eyeball is got blood system from serum, and the ELISA method detects TGF-β 1, gets spleen and prepares the spleen single cell suspension, detects spleen Treg with flow cytometer.
2. result
Model group mice Treg cell proportion, TGF-β 1 level are starkly lower than normal group, (); Prednisone and medicine composite for curing group Treg cell proportion and TGF-β 1 level, all higher than model group, but Treg does not reach normal level yet, there are differences than still with normal group, and TGF-β 1 with normal group than the not obvious not statistically significant of difference.See table for details.
Pharmaceutical composition is to ITP mouse spleen CD
4 +CD
25 +Foxp
3 +The impact of Treg, serum TG F-β 1 level
With the normal group ratio,
●P＞0.05,
△P＜0.05,
△ △P＜0.001; With the model group ratio,
★P＜0.05,
★ ★P＜0.001
3. conclusion
ITP mice Treg cell proportion reduces, TGF-β 1 level reduces may be relevant to the cellular immunization imbalance of ITP, the ratio that pharmaceutical composition can be by raising ITP mice Treg cell and serum TG F-β 1 level and to the cellular immunization of the ITP regulating action of having lacked of proper care.
Experimental example seven, pharmaceutical composition of the present invention (embodiment 1 preparation) affects splenic lymphocyte apoptosis and Bcl-2, the Bax protein expression is studied
1. method
40 Balb/c mices are divided into normal group, model group, Prednisone Therapy group and medicine composite for curing group at random, except normal group, all the other are respectively organized equal the next day once by 100 μ l/20g lumbar injection 1: the 4 anti-mouse platelets serum of Cavia porcellus (GP-APS) and set up the ITP mouse model, in modeling the 8th day, each group was all by 0.2ml/10gd
-1The volume gavage, wherein, normal group, model group gavage normal saline, and prednisone is pressed 0.0113mg/10gd
-1Gavage, pharmaceutical composition is pressed 0.3g/10gd
-1Gavage is put to death animal after continuous 8 days, the aseptic spleen of getting, and paraffin embedding, section 4 μ m detect the splenocyte apoptosis with original position end labelling (TUNEL) method, and Immunohistochemical Method detects Bcl-2, Bax protein expression.
2. result
Compare with normal group, model group splenocyte apoptosis reduces, and the Bcl-2 protein expression increases, and the Bax protein expression reduces (P＜0.05), and concrete data see Table 1; Compare with model group, prednisone and pharmaceutical composition group splenocyte increasing apoptosis are many, and the Bcl-2 protein expression reduces, and the Bax protein expression increases (P＜0.05), sees table 2 for details.
Table 1. is respectively organized ITP splenic lymphocyte apoptosis index
Table 2. is respectively organized ITP mouse spleen Bcl-2, Bax protein expression situation
3. conclusion
The ITP mice exists the immune dysfunction may be relevant to Lymphocyte Apoptosis and Bcl-2, Bax protein abnormal expression.Pharmaceutical composition can play regulating action to the ITP immune disorder by regulating Lymphocyte Apoptosis and Bcl-2, Bax protein expression.
Following embodiment all can realize technique effect of the present invention.The specific embodiment is as follows:
Embodiment 1
Radix Astragali Preparata 10kg, Radix Codonopsis 30kg, Radix Rehmanniae 35kg, Radix Rehmanniae Preparata 60kg, Colla Corii Asini 20kg, Colla Plastri Testudinis 60kg, Flos Carthami 45kg, Semen Cuscutae 55kg, Radix Salviae Miltiorrhizae 70kg, Caulis Spatholobi 20kg.Get the above-mentioned raw materials medicine, Radix Salviae Miltiorrhizae and Semen Cuscutae add 80% ethanol extraction 2 times, add for the first time 80% ethanol 8 times of weight, reflux 2 hours, filter, medicinal residues add 80% ethanol 6 times of weight again, and reflux 1.5 hours filters, merging filtrate reclaims ethanol, and medicinal liquid and medicinal liquid are standby respectively.The Radix Astragali and Radix Codonopsis decoct with water twice, add for the first time water 8 times of weight, decoct 1.5 hours, add for the second time water 6 times of weight, decoct 1.0 hours, merge twice decocting liquid, are concentrated into thick paste, and be standby.Medicinal residues after Radix Rehmanniae, Radix Rehmanniae Preparata, Flos Carthami, Caulis Spatholobi four Chinese medicine and Radix Salviae Miltiorrhizae and Semen Cuscutae alcohol extraction decoct with water twice together, add for the first time water 8 times of weight, decocted 1.5 hours, add for the second time water 6 times of weight, decocted 1.0 hours, merge twice decocting liquid, being concentrated into relative density is the clear paste of 1.13 (50 ℃ of heat are surveyed), let cool, adding ethanol, to make the alcohol amount of containing be 65% (the limit edged stirs, and slowly adds).Standing 26 hours, incline and get supernatant, reclaim ethanol, standby.Above three kinds of medicinal liquids are merged, be concentrated into thick paste, dry below 80 ℃, pulverize, cross 100 mesh sieves, and cross 100 purpose Colla Corii Asini and Colla Plastri Testudinis mixing after freezing and pulverizing, according to the granulation agent.
Embodiment 2
Radix Astragali Preparata 10kg, Radix Codonopsis 60kg, Radix Rehmanniae 60kg, Radix Rehmanniae Preparata 20kg, Colla Corii Asini 70kg, Colla Plastri Testudinis 100kg, Flos Carthami 15kg, Semen Cuscutae 80kg, Radix Salviae Miltiorrhizae 25kg, Caulis Spatholobi 60kg.Get the above-mentioned raw materials medicine, Radix Salviae Miltiorrhizae and Semen Cuscutae add 80% ethanol extraction 2 times, add for the first time 80% ethanol 8 times of weight, reflux 2 hours, filter, medicinal residues add 80% ethanol 6 times of weight again, and reflux 1.5 hours filters, merging filtrate reclaims ethanol, and medicinal liquid and medicinal liquid are standby respectively.The Radix Astragali and Radix Codonopsis decoct with water twice, add for the first time water 8 times of weight, decoct 1.5 hours, add for the second time water 6 times of weight, decoct 1.0 hours, merge twice decocting liquid, are concentrated into thick paste, and be standby.Medicinal residues after Radix Rehmanniae, Radix Rehmanniae Preparata, Flos Carthami, Caulis Spatholobi four Chinese medicine and Radix Salviae Miltiorrhizae and Semen Cuscutae alcohol extraction decoct with water twice together, add for the first time water 8 times of weight, decocted 1.5 hours, add for the second time water 6 times of weight, decocted 1.0 hours, merge twice decocting liquid, being concentrated into relative density is the clear paste of 1.13 (50 ℃ of heat are surveyed), let cool, adding ethanol, to make the alcohol amount of containing be 65% (the limit edged stirs, and slowly adds).Standing 26 hours, incline and get supernatant, reclaim ethanol, standby.Above three kinds of medicinal liquids are merged, be concentrated into thick paste, dry below 80 ℃, pulverize, cross 100 mesh sieves, and cross 100 purpose Colla Corii Asini and Colla Plastri Testudinis mixing after freezing and pulverizing, make powder.
Embodiment 3
Radix Astragali Preparata 30kg, Radix Codonopsis 10kg, Radix Rehmanniae 60kg, Radix Rehmanniae Preparata 20kg, Colla Corii Asini 70kg, Colla Plastri Testudinis 100kg, Flos Carthami 15kg, Semen Cuscutae 80kg, Radix Salviae Miltiorrhizae 25kg, Caulis Spatholobi 60kg.Get the above-mentioned raw materials medicine, Radix Salviae Miltiorrhizae and Semen Cuscutae add 80% ethanol extraction 2 times, add for the first time 80% ethanol 8 times of weight, reflux 2 hours, filter, medicinal residues add 80% ethanol 6 times of weight again, and reflux 1.5 hours filters, merging filtrate reclaims ethanol, and medicinal liquid and medicinal liquid are standby respectively.The Radix Astragali and Radix Codonopsis decoct with water twice, add for the first time water 8 times of weight, decoct 1.5 hours, add for the second time water 6 times of weight, decoct 1.0 hours, merge twice decocting liquid, are concentrated into thick paste, and be standby.Medicinal residues after Radix Rehmanniae, Radix Rehmanniae Preparata, Flos Carthami, Caulis Spatholobi four Chinese medicine and Radix Salviae Miltiorrhizae and Semen Cuscutae alcohol extraction decoct with water twice together, add for the first time water 8 times of weight, decocted 1.5 hours, add for the second time water 6 times of weight, decocted 1.0 hours, merge twice decocting liquid, being concentrated into relative density is the clear paste of 1.13 (50 ℃ of heat are surveyed), let cool, adding ethanol, to make the alcohol amount of containing be 65% (the limit edged stirs, and slowly adds).Standing 26 hours, incline and get supernatant, reclaim ethanol, standby.Above three kinds of medicinal liquids are merged, be concentrated into thick paste, dry below 80 ℃, pulverize, cross 100 mesh sieves, and cross 100 purpose Colla Corii Asini and Colla Plastri Testudinis mixing after freezing and pulverizing, make capsule.
Embodiment 4
Radix Astragali Preparata 70kg, Radix Codonopsis 10kg, Radix Rehmanniae 20kg, Radix Rehmanniae Preparata 40kg, Colla Corii Asini 55kg, Colla Plastri Testudinis 30kg, Flos Carthami 60kg, Semen Cuscutae 20kg, Radix Salviae Miltiorrhizae 45kg, Caulis Spatholobi 35kg.Get the above-mentioned raw materials medicine, make tablet according to the preparation technology of routine.
Embodiment 5
Radix Astragali Preparata 70kg, Radix Codonopsis 10kg, Radix Rehmanniae 20kg, Radix Rehmanniae Preparata 40kg, Colla Corii Asini 55kg, Colla Plastri Testudinis 30kg, Flos Carthami 60kg, Semen Cuscutae 20kg, Radix Salviae Miltiorrhizae 120kg, Caulis Spatholobi 35kg.Get the above-mentioned raw materials medicine, make sublimed preparation according to the preparation technology of routine.
Embodiment 6
Radix Astragali Preparata 70kg, Radix Codonopsis 10kg, Radix Rehmanniae 20kg, Radix Rehmanniae Preparata 40kg, Colla Corii Asini 55kg, Colla Plastri Testudinis 30kg, Flos Carthami 60kg, Semen Cuscutae 20kg, Radix Salviae Miltiorrhizae 45kg, Caulis Spatholobi 35kg.Get the above-mentioned raw materials medicine, make slow releasing agent according to the preparation technology of routine.
Embodiment 7
Radix Astragali Preparata 10kg, Radix Codonopsis 30kg, Radix Rehmanniae 35kg, Radix Rehmanniae Preparata 60kg, Colla Corii Asini 20kg, Colla Plastri Testudinis 60kg, Flos Carthami 45kg, Semen Cuscutae 55kg, Radix Salviae Miltiorrhizae 70kg, Caulis Spatholobi 20kg.Get the above-mentioned raw materials medicine, make pill according to the preparation technology of routine.
Claims (10)
1. pharmaceutical composition for the treatment of myelodysplastic syndrome is characterized in that this pharmaceutical composition crude drug forms with dosage and is:
Radix Astragali 1-120 weight portion, Radix Codonopsis 1-120 weight portion, Radix Rehmanniae 1-120 weight portion, Radix Rehmanniae Preparata 1-120 weight portion, Colla Corii Asini 1-120 weight portion, Colla Plastri Testudinis 1-120 weight portion, Flos Carthami 1-120 weight portion, Semen Cuscutae 1-120 weight portion, Radix Salviae Miltiorrhizae 1-120 weight portion, Caulis Spatholobi 1-120 weight portion.
2. pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition crude drug forms with dosage and is:
Radix Astragali 10-30 weight portion, Radix Codonopsis 10-30 weight portion, Radix Rehmanniae 10-30 weight portion, Radix Rehmanniae Preparata 10-30 weight portion, Colla Corii Asini 10-30 weight portion, Colla Plastri Testudinis 10-30 weight portion, Flos Carthami 10-30 weight portion, Semen Cuscutae 10-30 weight portion, Radix Salviae Miltiorrhizae 10-30 weight portion, Caulis Spatholobi 10-30 weight portion.
3. pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition crude drug forms with dosage and is:
The Radix Astragali 10 weight portions, Radix Codonopsis 30 weight portions, the Radix Rehmanniae 35 weight portions, Radix Rehmanniae Preparata 60 weight portions, Colla Corii Asini 20 weight portions, Colla Plastri Testudinis 60 weight portions, Flos Carthami 45 weight portions, Semen Cuscutae 55 weight portions, Radix Salviae Miltiorrhizae 70 weight portions, Caulis Spatholobi 20 weight portions;
The Radix Astragali 10 weight portions, Radix Codonopsis 60 weight portions, the Radix Rehmanniae 60 weight portions, Radix Rehmanniae Preparata 20 weight portions, Colla Corii Asini 70 weight portions, Colla Plastri Testudinis 100 weight portions, Flos Carthami 15 weight portions, Semen Cuscutae 80 weight portions, Radix Salviae Miltiorrhizae 25 weight portions, Caulis Spatholobi 60 weight portions;
The Radix Astragali 30 weight portions, Radix Codonopsis 10 weight portions, the Radix Rehmanniae 60 weight portions, Radix Rehmanniae Preparata 20 weight portions, Colla Corii Asini 70 weight portions, Colla Plastri Testudinis 100 weight portions, Flos Carthami 15 weight portions, Semen Cuscutae 80 weight portions, Radix Salviae Miltiorrhizae 25 weight portions, Caulis Spatholobi 60 weight portions;
The Radix Astragali 70 weight portions, Radix Codonopsis 10 weight portions, the Radix Rehmanniae 20 weight portions, Radix Rehmanniae Preparata 40 weight portions, Colla Corii Asini 55 weight portions, Colla Plastri Testudinis 30 weight portions, Flos Carthami 60 weight portions, Semen Cuscutae 20 weight portions, Radix Salviae Miltiorrhizae 45 weight portions, Caulis Spatholobi 35 weight portions;
Perhaps, the Radix Astragali 70 weight portions, Radix Codonopsis 10 weight portions, the Radix Rehmanniae 20 weight portions, Radix Rehmanniae Preparata 40 weight portions, Colla Corii Asini 55 weight portions, Colla Plastri Testudinis 30 weight portions, Flos Carthami 60 weight portions, Semen Cuscutae 20 weight portions, Radix Salviae Miltiorrhizae 120 weight portions, Caulis Spatholobi 35 weight portions.
4. described pharmaceutical composition as arbitrary in claim 1-3, is characterized in that Radix Astragali Preparata wherein is Radix Astragali (processed with Mel).
5. pharmaceutical composition as claimed in claim 4, be characterised in that Radix Astragali Preparata wherein is Radix Astragali (processed with Mel).
6. as claim 1-3, the preparation method of 5 arbitrary described pharmaceutical compositions is characterized in that the method is:
Radix Salviae Miltiorrhizae and Semen Cuscutae add 60-85% ethanol extraction 1-3 time, add for the first time ethanol 6-10 times of weight, and reflux 1-2 hour, filter, medicinal residues add ethanol again, and reflux 1-2 hour, filter, merging filtrate reclaims ethanol, and medicinal liquid and medicinal liquid are standby respectively; The Radix Astragali and Radix Codonopsis decoct with water 1-3 time, add for the first time water 6-10 times of weight, decoct 1-2 hour, add later on water 4-8 times of weight at every turn, decoct 1-2 hour, merge each decocting liquid, are concentrated into thick paste, and be standby; Medicinal residues after Radix Rehmanniae, Radix Rehmanniae Preparata, Flos Carthami, Caulis Spatholobi four Chinese medicine and Radix Salviae Miltiorrhizae and Semen Cuscutae alcohol extraction decoct with water 1-3 time together, add for the first time water 6-10 times of weight, decocted 1-2 hour, add later on water 4-8 times of weight at every turn, decocted 1-2 hour, and merged each decocting liquid, being concentrated into relative density is that 50 ℃ of heat are surveyed 1.13 clear paste, let cool, add ethanol and make the alcohol amount of containing be 60-70%; Standing 26 hours, incline and get supernatant, reclaim ethanol, standby; Above three kinds of medicinal liquids are merged, be concentrated into thick paste, dry below 85-80 ℃, pulverize, cross 100 mesh sieves, with Colla Corii Asini and the Colla Plastri Testudinis mixing crossed after freezing and pulverizing, the mixture of clinical acceptance, concentrated pill, capsule, drop pill, granule, tablet, pill, soft capsule, slow releasing agent, oral liquid or ejection preparation.
7. the preparation method of pharmaceutical composition as claimed in claim 4 is characterized in that the method is:
Radix Salviae Miltiorrhizae and Semen Cuscutae add 60-85% ethanol extraction 1-3 time, add for the first time ethanol 6-10 times of weight, and reflux 1-2 hour, filter, medicinal residues add ethanol again, and reflux 1-2 hour, filter, merging filtrate reclaims ethanol, and medicinal liquid and medicinal liquid are standby respectively; The Radix Astragali and Radix Codonopsis decoct with water 1-3 time, add for the first time water 6-10 times of weight, decoct 1-2 hour, add later on water 4-8 times of weight at every turn, decoct 1-2 hour, merge each decocting liquid, are concentrated into thick paste, and be standby; Medicinal residues after Radix Rehmanniae, Radix Rehmanniae Preparata, Flos Carthami, Caulis Spatholobi four Chinese medicine and Radix Salviae Miltiorrhizae and Semen Cuscutae alcohol extraction decoct with water 1-3 time together, add for the first time water 6-10 times of weight, decocted 1-2 hour, add later on water 4-8 times of weight at every turn, decocted 1-2 hour, and merged each decocting liquid, being concentrated into relative density is that 50 ℃ of heat are surveyed 1.13 clear paste, let cool, add ethanol and make the alcohol amount of containing be 60-70%; Standing 26 hours, incline and get supernatant, reclaim ethanol, standby; Above three kinds of medicinal liquids are merged, be concentrated into thick paste, dry below 85-80 ℃, pulverize, cross 100 mesh sieves, with Colla Corii Asini and the Colla Plastri Testudinis mixing crossed after freezing and pulverizing, the mixture of clinical acceptance, concentrated pill, capsule, drop pill, granule, tablet, pill, soft capsule, slow releasing agent, oral liquid or ejection preparation.
8. as the preparation method of the arbitrary described pharmaceutical composition of claim 6-7, it is characterized in that the method is:
Radix Salviae Miltiorrhizae and Semen Cuscutae add 80% ethanol extraction 2 times, add for the first time 80% ethanol 8 times of weight, and reflux 2 hours filters, and medicinal residues add 80% ethanol 6 times of weight again, and reflux 1.5 hours filters, and merging filtrate reclaims ethanol, and medicinal liquid and medicinal liquid are standby respectively.The Radix Astragali and Radix Codonopsis decoct with water twice, add for the first time water 8 times of weight, decoct 1.5 hours, add for the second time water 6 times of weight, decoct 1.0 hours, merge twice decocting liquid, are concentrated into thick paste, and be standby.Medicinal residues after Radix Rehmanniae, Radix Rehmanniae Preparata, Flos Carthami, Caulis Spatholobi four Chinese medicine and Radix Salviae Miltiorrhizae and Semen Cuscutae alcohol extraction decoct with water twice together, add for the first time water 8 times of weight, decocted 1.5 hours, add for the second time water 6 times of weight, decocted 1.0 hours, merge twice decocting liquid, being concentrated into relative density is the clear paste of 1.13 (50 ℃ of heat are surveyed), let cool, adding ethanol, to make the alcohol amount of containing be 65% (the limit edged stirs, and slowly adds).Standing 26 hours, incline and get supernatant, reclaim ethanol, standby.Above three kinds of medicinal liquids are merged, be concentrated into thick paste, dry below 80 ℃, pulverize, cross 100 mesh sieves, with mistake 100 purpose Colla Corii Asini and Colla Plastri Testudinis mixing after freezing and pulverizing, and by mixture, concentrated pill, capsule, drop pill, granule, tablet, pill, soft capsule, slow releasing agent, oral liquid or the ejection preparation of making clinical acceptance according to common process.
9. as claim 1-3, the application of 5 arbitrary described pharmaceutical compositions in the medicine of preparation treatment myelodysplastic syndrome.
10. the application of pharmaceutical composition as claimed in claim 4 in the medicine of preparation treatment myelodysplastic syndrome.
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