CN104622888B - The new application of garden burnet tannin and astragalus polyose - Google Patents

The new application of garden burnet tannin and astragalus polyose Download PDF

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CN104622888B
CN104622888B CN201410626070.8A CN201410626070A CN104622888B CN 104622888 B CN104622888 B CN 104622888B CN 201410626070 A CN201410626070 A CN 201410626070A CN 104622888 B CN104622888 B CN 104622888B
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tannin
garden burnet
astragalus polyose
bone marrow
group
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CN104622888A (en
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苏柘僮
熊永爱
张帅杰
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Guangxi Yingluweite Pharmaceutical Co ltd
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CHENGDU BAICAO HEJI TECHNOLOGY Co Ltd
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Abstract

The invention provides purposes of the garden burnet tannin in preparation and astragalus polyose drug combination are treated or/and prevent the medicine of bone marrow suppression.After garden burnet tannin and astragalus polyose are used in combination the present invention, synergistic function are played, its drug activity is significantly improved, new selection is provided for clinical application.

Description

The new application of garden burnet tannin and astragalus polyose
Technical field
The invention provides garden burnet tannin and the new application of astragalus polyose.
Background technology
Bone marrow suppression is the most common and important complication of tumor chemoradiotherapy.Its peripheral white blood cells, it is hematoblastic substantially Decline, lethal infection and bleeding can be triggered, process and the prognosis of oncotherapy is seriously limited.In worldwide and severe The relevant treatment related mortality of bone marrow suppression is up to 4%~12%.Its reason overwhelming majority is that, because of serious bone marrow suppression, grain is thin Various unmanageable infection caused by born of the same parents lack.In addition, stage of bone marrow heating, bleeding make patient to be in hospital the anti-sense of carry out system Dye treatment, and hemostasis, blood transfusion etc., the medical expense of tumour patient is added indirectly, also deteriorates the quality of life of patient.Cause This, bone marrow suppression is the dangerous obstacles for disturbing clinical tumor doctor to implement chemicotherapy therapeutic scheme, is also to hinder tumor patient health Multiple lethal challenge.
At present, clinically to bone marrow suppression drug therapy and non-drug therapy can not all reach that the medication of clinician is needed The need for summation is to patient's compliance.Either defeated component blood, or use Hemopoietic factor or peripheral stem cell transplantation, though Right curative effect affirmative, but it is required for high cost.Simultaneously there is also the danger that infection is infected, the leucocyte being input into is in recipient's body Occur that rejection is acted on, the time-to-live is shorter, and have the possibility for promoting cancerous swelling recurrence.And biological agent and chemicals all can only For a certain class cytopenia, it is acted on, and single and side effect is big, it is impossible to plan as a whole marrow DNA and haemocyte rise.It is middle into Medicine preparation works slow, it is impossible to meet after tumour patient chemicotherapy the need for the fast quick-recovery of constitution and secondary disease prevention.
Therefore, how to mitigate caused by radiotherapy and chemotherapy bone marrow suppression, promote hemopoietic function of bone marrow to recover, rise peripheral blood cells are Ensure that chemicotherapy smoothly completes, improved the key issue of clinical tumor curative effect.Research and development material base is clear, the mechanism of action Clearly, the little guarantor's marrow green blood natural drug of adverse reaction is extremely urgent.
Garden burnet is the rosaceous plant garden burnet Sanguisorba officinalis L. or garden burnet Sanguisorbad that comes into leaves Officinalis L.var.longifolia (Bert.) Yuet Li dry root, first recorded in《Sheng Nong's herbal classic》, it is listed in Middle product." its cold nature, bitter, acid, puckery, Return liver, large intestine channel ".With cooling blood and hemostasis, effect of removing toxic substances sore.Clinical data table Bright, garden burnet raw medicinal herbs is notable to the therapeutic effect of tumor patient leukopenia caused by chemicotherapy, the small (5mg of dose Work), Coming-of-Age Day takes maximum dose into only 60mg raw medicinal herbs, and modern study shows, the active material of garden burnet increasing leukocyte Basis is saponin(e and tannin constituents.
The Radix Astragali is legume astragalus mongolicus Astragalus membranaceus (Fisch.) Bge.var.mongholicus (Bge.) Hsiao or Astragalus membranacus Astragalus membranaceus (Fisch.) Bge.'s Dry root, with multiple efficacies such as element culturing fixed folder, tonifying middle-Jiao and Qis.Modern study shows the Radix Astragali to leucocyte caused by a variety of causes Disease is reduced, such as, due to tumor radiotherapy chemotherapy, by x-ray and the radiation of other radioactive substances, benzene poisoning, takes some antipyretic-antalgics Medicine, leukopenia caused by the leukopenia caused by reason such as some infectious diseases and some unknown causes has Good therapeutic action, its principle active component is astragalus polyose.
It there is no at present by the relevant report of the active component compatibility in the active component and the Radix Astragali in garden burnet.
The content of the invention
Modern study of the inventor based on garden burnet and Radix Astragali increasing leukocyte material base, it is theoretical and clinical in modern medicine Under medication experience is instructed, based on clinical experience, using effect experiment as means, draft and being made up of garden burnet tannin and astragalus polyose Pharmaceutical composition be the basic prescription of myelosuppresive therapy, then protect marrow according to astragalus polyose and garden burnet tannin and rise white clinical use Amount is carried out etc. than baseline design as factor level, using quantity of leucocyte as MAIN OUTCOME MEASURES, observation different ratio dosage Garden burnet tannin-influence of the astragalus polyose composition to endoxan inducing mouse bone marrow suppression, filters out optimal prescription and optimal Proportion relation, the tcm componentses for research treatment bone marrow suppression lay the foundation.
It is an object of the invention to provide garden burnet tannin and the new application of astragalus polyose.Another object of the present invention is to carry For a kind of pharmaceutical composition for treating or preventing bone marrow suppression.
Treated the invention provides garden burnet tannin in preparation and astragalus polyose drug combination or/and prevent the medicine of bone marrow suppression Purposes in thing.
Further, garden burnet tannin and the weight of astragalus polyose ratio are 1~50:1~160.
Further, garden burnet tannin and the weight of astragalus polyose ratio are 25~30:55~60.
Preferably, garden burnet tannin and the weight of astragalus polyose ratio are 27:57.
Present invention also offers a kind of pharmaceutical composition treated or/and prevent bone marrow suppression, it is containing following weight The preparation that the raw material of proportioning is prepared from:
Garden burnet tannin and the weight of astragalus polyose ratio are 1~50:1~160.
Further, garden burnet tannin and the weight of astragalus polyose ratio are 25~30:55~60.
Preferably, garden burnet tannin and the weight of astragalus polyose ratio are 27:57.
Wherein, content of tannin is 50~99% in the garden burnet tannin;Polyoses content is 50~99% in astragalus polyose.
Wherein, the preparation is oral formulations.
Present invention also offers purposes of the aforementioned pharmaceutical compositions in the medicine for treating or preventing bone marrow suppression is prepared.
Present invention also offers purposes of the aforementioned pharmaceutical compositions in the medicine with function of increasing leukocyte is prepared.
After garden burnet tannin and astragalus polyose are used in combination the present invention, synergistic function is played, its drug activity shows Write and improve, new selection is provided for clinical application.
Brief description of the drawings
Each experimental mice peripheral white blood cell amounts of Fig. 1 (note:Compared with model group, * P<0.05, * * P<0.01;With ground Elm tannin group group compares,P<0.05,△△P<0.01;Compared with astragalus polyose group,P<0.05,▲▲P<0.01。)
Each experimental mice marrow DNA contents of Fig. 2(note:Compared with model group, * P<0.05, * * P<0.01;With Garden burnet group compares,P<0.05,△△P<0.01;Compared with Radix Astragali group,P<0.05,▲▲P<0.01。)
Each experimental mice candidate stem cell quantity of Fig. 3(note:Compared with model group, * P<0.05, * * P< 0.01;Compared with garden burnet group,P<0.05,△△P<0.01;Compared with Radix Astragali group,P<0.05,▲▲P<0.01。)
Each experimental mice hematopoietic tissue capacity of Fig. 4(note:Compared with model group, * P<0.05, * * P<0.01; Compared with garden burnet group,P<0.05,△△P<0.01;Compared with Radix Astragali group,P<0.05,▲▲P<0.01。)
Embodiment
The tablet of embodiment 1
【Preparation method】Recipe quantity astragalus polyose and garden burnet tannin are taken, is added after auxiliary materials and mixing, 80 mesh sieves are crossed, then adds 95% second Alcohol softwood, the granulation of 16 mesh nets;Whole grain after 60 DEG C of temperature are dried, then adds magnesium stearate 50g, mixes, and is pressed into 1000, bag Clothing is produced.
The capsule of embodiment 2
【Preparation method】Recipe quantity astragalus polyose and garden burnet tannin are taken, is added after auxiliary materials and mixing, 80 mesh sieves are crossed, then adds 95% second Alcohol softwood, the granulation of 16 mesh nets;Whole grain after 60 DEG C of temperature are dried, it is encapsulated, 1000 are made altogether.
The soft capsule of embodiment 3
【Preparation method】Recipe quantity astragalus polyose and garden burnet tannin are taken, 60 DEG C of dryings are ground into subdivision after being sufficiently mixed, add big Soya-bean oil is mixed, and 1000 soft capsules are made.
The oral liquid of embodiment 4
【Preparation method】Recipe quantity astragalus polyose and garden burnet tannin are taken, adds the stirring of 1000ml pure water molten after being well mixed with auxiliary material Solution, is mixed, and filtering is filling into 1000 bottles of oral liquids, sterilizing, thus obtaining the product.
The dripping pill of embodiment 5
【Preparation method】Take recipe quantity astragalus polyose and garden burnet tannin well mixed, add molten PEG-4000 and PEG- 6000, stir and evenly mix, instill dimethicone condensation shaping, 1000 balls are made in drop altogether.
The granule of embodiment 6
【Preparation method】Recipe quantity astragalus polyose and garden burnet tannin are taken, is added after auxiliary materials and mixing, 80 mesh sieves are crossed, then adds 95% second Alcohol softwood, the granulation of 16 mesh nets;Whole grain after 60 DEG C of temperature are dried, packing dresses up 1000 bags altogether.
Beneficial effects of the present invention are illustrated below by way of test example.
The test of pesticide effectiveness of the drug therapy bone marrow suppression of the present invention of test example 1
1 experiment material
1.1 medicinal material
(1) garden burnet tannin (content is 50%~99%).
(2) astragalus polyose (content is 50%~99%).
1.2 positive drug:Recombinant humangranulocyte shoots down stimulating factor.
1.3 SPF grades of experimental animal KM mouse.
1.4 chemical reagent
(1) endoxan.(2) physiological saline.(3) absolute ethyl alcohol.(4) DMEM culture mediums.(5) hyclone.(6) it is dual anti- (penicillin+streptomysin).
1.5 laboratory apparatus
(1) full-automatic blood cell analysis machine.(2) ultraviolet specrophotometer.(3) global function ELIASA.(4) constant-temperature table.(5) Refiner.(6) refrigerated centrifuge.(7) flow cytometer.
2 experimental methods
2.1 medicine groups pair
Fully and effectively to carry out the screening of optimal drug compatibility and optimum dose proportion relation to primary election prescription, and as far as possible Test number (TN) is reduced, this experiment use etc. carries out Formulation than base-line method.It is thin in vain with reference to garden burnet tannin and Effect of APS in Treating Born of the same parents reduce the effective dose of disease for distribution rate baseline (garden burnet tannin:5~50mg, 40~160mg of astragalus polyose), the Radix Astragali is more therebetween Sugared agent amount is successively decreased with 10~30%, and garden burnet tannin dosage is incremented by with 10~30%, or garden burnet tannin dosage is passed with 10~40% Subtract, astragalus polyose dosage is incremented by with 10~40% to be extended to both sides, is finally expanded to limit, both sides limit is respectively the simple Radix Astragali Polysaccharide and simple garden burnet tannin.With astragalus polyose and two kinds of medicines of garden burnet tannin it is several proportioning packet, according to research purpose with Two medicine main effects and secondary efficacy are evaluation index, are analyzed by integrated information, carry out the optimal screening of each proportioning.Two medicines are matched somebody with somebody 1 is shown in Table than ratio.
The ratio baseline proportion design table such as the astragalus polyose of table 1 and garden burnet tannin
The pharmacological evaluation screening of 2.2 optimal doses
2.2.1 the preparation of test medicine
Weigh the astragalus polyose and garden burnet tannin of 1~9 dosage group respectively by composition consumption in table 1, be separately added into certain The dissolved in purified water of volume is mixed, and obtains 1~9 group of medicinal composition solution.
2.2.2 experiment packet and administration
All Animal adaptabilities are randomly divided into after feeding 1 week by body weight:Normal group, model group, positive group (granular leukocyte colony Stimulating factor group);1~9 group of extract, every group 12.Each experimental group is given by 0.2ml/kg dosage gavages since the experimental day Give relative medicine, normal group and the isometric pure water of model group mouse stomach, continuous 10 days.
2.2.3 animal model is prepared and collection of specimens
Test the 4th day, in addition to blank group, remaining each group mouse presses 100mgkg-1Dosage intraperitoneal injection of cyclophosphamide physiology Saline solution, continuous 4 days, isometric physiological saline was injected intraperitoneally in naive mice.Test the 10th day, each experimental mice eye socket Blood is taken, collects to be measured with the 0.5mlEP pipes equipped with EDTA anti-coagulants;Disconnected neck puts to death mouse, takes left and right sides femur in ultra-clean work Make on platform, cleared muscle and connective tissue.
2.2.4 Testing index and method
1. peripheral hemogram is detected:Each experimental mice peripheral white blood cells (WBC) are entered using full-automatic blood counting instrument Row is counted.
2. marrow DNA content is determined:Mouse left rear limb femur is peeled off, is cut with ophthalmologic operation and cuts femur two ends, is revealed Go out ossis.With 10ml0.005mol/L CaCl2Marrow is rinsed into centrifuge tube, 4 DEG C of refrigerators place 30min, 2500r/min Centrifuge 15min.Supernatant is abandoned, 0.2mo1/L HClO are added4Solution 5ml, after vibration is mixed, 90 DEG C of heating 15min.It is cold with flowing water But to room temperature cooled and filtered, filtrate determines 268nm absorbance A value through ultraviolet specrophotometer.
3. Bone Marrow Hematopoietic Stem counts (HSPC, using candidate stem cell phenotype molecule CD34 as label) with containing bovine serum albumin White concentration goes out right side of mice femur bone marrow cell for 0.2% PBS, takes out 106Individual cell centrifugation, abandons supernatant, plus Enter 30 μ L Normal Mouse Serums to close unspecific binding sites, the rat anti-mouse CD34 for adding 10 μ L FITC marks resists Body, control tube adds the corresponding control antibodies of 10 μ L, and 4 DEG C of lucifuges react 30min.2mL erythrocyte cracked liquids are added, 5min is acted on, Wash cell 2 times, final concentration of 3 μ g/mL PI dye liquors are added, using flow cytomery bone marrow cell CD34+Antigen presentation.
4. marrow protection Morphology observation:Part marrow is taken, 10% neutral formalin is fixed, plastic embedding, femur stage casing Marrow hematopoietic capacity percentage change is observed under slices across, Giemsa dyeing, high power light microscopic.
2.3 statistical method
Statistical analysis is carried out using SPSS17.0 softwares, data are with mean ± standard deviationRepresent, using single between group LSD inspections are carried out between analysis of variance, the neat person's group of variance, heterogeneity of variance person carries out Tamhane ' sT2 and examined.
2.4 experimental result
2.4.1 the influence result to bone marrow suppression mouse peripheral blood cell quantity is shown in Fig. 1.
As shown in Figure 1, compared with normal group, model group mouse peripheral blood WBC has pole to significantly reduce (P<0.01);With model Group compares, and 1~9 group of mouse peripheral blood WBC of composition has significantly rise (P<0.05), wherein, 6 groups of composition has extremely notable liter Height (P<0.01);Compared with garden burnet tannin, astragalus polyose group, 1~9 group of mouse peripheral blood WBC of composition has rise trend, group 6 groups of mouse peripheral blood WBC of compound have significantly rise (P<0.05).
2.5.2 the influence result to bone marrow suppression mouse DNA content is shown in Fig. 2.
As shown in Figure 2, compared with normal group, model group mouse bone marrow cells DNA content has pole to significantly reduce (P<0.01);With mould Type group compares, and 1~9 group of mouse bone marrow cells DNA content of composition has significantly rise (P<0.05), wherein, 6 groups of composition have extremely show Write rise (P<0.01);Compared with garden burnet tannin, astragalus polyose group, 1~9 group of marrow DNA content of composition has rise trend, 6 groups of mouse bone marrow cells DNA contents of composition have significantly rise (P<0.05).
2.5.3 the influence result to bone marrow suppression mouse hematopoietic stem cell quantity is shown in Fig. 3.
From the figure 3, it may be seen that being compared with normal group, model group mouse hematopoietic stem cell quantity has pole to significantly reduce (P<0.01); Compared with model group, 1~9 group of mouse hematopoietic stem cell quantity of composition has significantly rise (P<0.05), wherein, composition 6 Group has extremely notable rise (P<0.01);Compared with garden burnet tannin, astragalus polyose group, 1~9 group of candidate stem cell quantity of composition is equal There is rise trend, 6 groups of mouse hematopoietic stem cell quantity of composition have significantly rise (P<0.05).
2.5.4 the influence result to bone marrow suppression mouse hemopoietic volume of tissue is shown in Fig. 4.
As shown in Figure 4, compared with normal group, model group mouse hemopoietic volume of tissue has pole to significantly reduce (P<0.01);With Model group compares, and 1~9 group of mouse hemopoietic volume of tissue of composition has significantly rise (P<0.05), wherein, 6 groups of composition has Extremely significantly rise (P<0.01);Compared with garden burnet tannin, astragalus polyose group, 1~9 group of composition, which makes hematopoietic tissue capacity, liter High trend, 6 groups of mouse hemopoietic volume of tissue of composition have significantly rise (P<0.05).
3 experiment conclusions
(1) 9 kinds of ratio compatibilities of astragalus polyose and garden burnet tannin suppress to be respectively provided with well to caused by cyclophosphamide mouse bone marrow cells Therapeutic action, and the therapeutic effect of various ratio compatibilities is superior to astragalus polyose and garden burnet tannin is alone.
(2) optimal proportion of Radix Astragali compatibility garden burnet treatment bone marrow suppression is 52mg:27mg.

Claims (6)

1. purposes of the garden burnet tannin with astragalus polyose in the combination medicine for preparing treatment or/and prevention bone marrow suppression;Garden burnet Tannin and the weight of astragalus polyose ratio are 27:52.
2. a kind of pharmaceutical composition treated or/and prevent bone marrow suppression, it is characterised in that:It contains following weight proportion The preparation that bulk drug is prepared from:Garden burnet tannin and the weight of astragalus polyose compare 27:52.
3. pharmaceutical composition according to claim 2, it is characterised in that:In the garden burnet tannin content of tannin be 50~ 99%;Polyoses content is 50~99% in astragalus polyose.
4. the pharmaceutical composition according to Claims 2 or 3, it is characterised in that:The preparation is oral formulations.
5. Claims 2 or 3 described pharmaceutical composition is in the medicine for treating or preventing bone marrow suppression or increasing leukocyte is prepared Purposes.
6. use of claim 4 described pharmaceutical composition in the medicine for treating or preventing bone marrow suppression or increasing leukocyte is prepared On the way.
CN201410626070.8A 2013-11-08 2014-11-07 The new application of garden burnet tannin and astragalus polyose Active CN104622888B (en)

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CN201310554209 2013-11-08
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CN102406731B (en) * 2010-12-01 2013-12-11 成都科尔医药技术有限公司 Combination medicament for preventing or/and treating bone marrow suppression
CN102895515B (en) * 2011-06-29 2015-07-15 上海中医药大学附属龙华医院 Chinese medicinal composition for raising leucocytes and preparation method and application thereof

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Denomination of invention: New Applications of Tannins from Ulmus officinalis and Polysaccharides from Astragalus membranaceus

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