CN106727573A - The piperazinyl and 1H tetrazole radical derivatives composition of Psiguadial A are used for increasing leukocyte - Google Patents
The piperazinyl and 1H tetrazole radical derivatives composition of Psiguadial A are used for increasing leukocyte Download PDFInfo
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- CN106727573A CN106727573A CN201611183492.8A CN201611183492A CN106727573A CN 106727573 A CN106727573 A CN 106727573A CN 201611183492 A CN201611183492 A CN 201611183492A CN 106727573 A CN106727573 A CN 106727573A
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- 239000000203 mixture Substances 0.000 title claims abstract description 51
- 210000000265 leukocyte Anatomy 0.000 title claims abstract description 17
- AXYPZJGNRHOELX-UHFFFAOYSA-N psiguadial A Natural products CC1CCC(C2(C)C)C2C2C3(C)CCC12OC1=C(C=O)C(O)=C(C=O)C(O)=C1C3C1=CC=CC=C1 AXYPZJGNRHOELX-UHFFFAOYSA-N 0.000 title abstract description 12
- 125000004193 piperazinyl group Chemical class 0.000 title abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 13
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 11
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 11
- 210000004369 blood Anatomy 0.000 claims description 8
- 239000008280 blood Substances 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 8
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical class C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 3
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 7
- 238000010828 elution Methods 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000002504 physiological saline solution Substances 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000000610 leukopenic effect Effects 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- -1 phosphate amine Chemical class 0.000 description 3
- 208000032467 Aplastic anaemia Diseases 0.000 description 2
- 240000001679 Psidium guajava Species 0.000 description 2
- 235000013929 Psidium pyriferum Nutrition 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 210000002798 bone marrow cell Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 230000002008 hemorrhagic effect Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 229930188068 psiguadial Natural products 0.000 description 2
- 229930184353 psiguadials Natural products 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 1
- 206010041660 Splenomegaly Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000018631 connective tissue disease Diseases 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 229910000437 dibromine pentoxide Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
- C07D313/02—Seven-membered rings
- C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Piperazinyl and 1H tetrazole radical derivatives composition the invention discloses Psiguadial A are used for increasing leukocyte, O (piperazinyl) ethyls of i.e. a kind of Psiguadial A and application of the composition of O (1H tetrazoles base) ethyl derivative in the medicine of increasing leukocyte, the present invention relates to organic synthesis and medicinal chemistry art, and in particular to the piperazinyl and 1H tetrazole radical derivatives composition, preparation method and its purposes on increasing leukocyte medicine is prepared of Psiguadial A.Piperazinyl and 1H tetrazole radical derivative compositions the invention discloses a kind of Psiguadial A and preparation method thereof.Pharmacological experiment shows that the piperazinyl and 1H tetrazole radical derivative compositions of Psiguadial A of the invention have the effect of increasing leukocyte, the value with exploitation increasing leukocyte medicine.
Description
Technical field
The present invention relates to organic synthesis and medicinal chemistry art, and in particular to composition, preparation method and its usage.
Background technology
Leukopenia is because reason is not clear and secondary to the disease caused after other diseases, is divided into primary
With the major class of Secondary cases two.Primary person's reason is failed to understand；Secondary cases person think its cause of disease can by acute infection, physics, chemical factor,
Disease in the blood system, the disease of companion's splenomegaly, connective tissue disease, anaphylactia, genetic disease etc., acquired or reason
Not clear property granulocyte reduction etc..
Existing medicine has that toxicity is big, security is low at present for leukopenic treatment, from natural products
Find compound or lead compound and carry out structural modification and obtain its derivative, so as to the potential drug for obtaining high-efficiency low-toxicity has
Important value.
Compound I of the present invention is one and delivers within 2011 (Meng Shao et al., 2010.Psiguadials
A and B,Two Novel Meroterpenoids with Unusual Skeletons from the Leaves of
Psidium guajava.Organic Letters 12 (2010) 5040-5043) compound, we are carried out to compound I
Structural modification, obtains two new derivatives i.e. compound III and compound IV, and with compound III and compound IV
It is prepared for composition and said composition increasing leukocyte activity is evaluated, it has increasing leukocyte activity.
The content of the invention
The invention discloses a new composition, said composition is made up of compound III and compound IV, said composition
The mass percent of middle compound III and compound IV is respectively 35% and 65%.
Composition disclosed by the invention can be made pharmaceutically acceptable salt or pharmaceutically acceptable carrier.
It is an object of the invention to provide application of the composition in increasing leukocyte medicine is prepared.The present composition can be with
Significantly raise the leucocyte reduction lost blood and cause with chemical substance.
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not by specific real
Any limitation of example is applied, but is defined in the claims.
Specific embodiment
The preparation of the compound Psiguadial A of embodiment 1
Document (the Meng Shao that the preparation method of compound Psiguadial A (I) is delivered with reference to Meng Shao et al.
et al.,2010.Psiguadials A and B,Two Novel Meroterpenoids with Unusual
Skeletons from the Leaves of Psidium guajava.Organic Letters 12(2010)5040–
5043) method.
The synthesis of O- bromoethyls derivative (II) of the Psiguadial A of embodiment 2
Compound I (474mg, 1.00mmol) is dissolved in 20mL benzene, to addition TBAB (TBAB) in solution
50% sodium hydroxide solution of (0.16g), 1,2- Bromofume (7.520g, 40.00mmol) and 12mL.Mixture is Celsius 35
Degree stirring 8h.Reaction solution is poured into frozen water after 8h, is extracted twice with dichloromethane immediately, merge organic phase solution.Then
To organic phase solution successively with water and saturated common salt water washing 3 times, then with anhydrous sodium sulfate drying, the removal that is finally concentrated under reduced pressure is molten
Agent obtains product crude product.(mobile phase is the purifying of product crude product silica gel column chromatography：Petroleum ether/acetone=100:0.5, v/v), receive
Collection brown concentrates elution band and flings to the brown ceramic powder (502mg, 73%) that solvent obtains compound II.
1H NMR(500MHz,DMSO-d6) δ 10.44 (s, 2H), 7.24 (s, 2H), 7.20 (d, J=10.0Hz, 3H),
4.31(s,4H),3.89(s,1H),3.74(s,4H),2.30(s,1H),2.12(s,1H),2.02(s,1H),1.92(s,1H),
1.79 (s, 1H), 1.73 (s, 1H), 1.51 (d, J=19.8Hz, 3H), 0.99 (s, 3H), 0.95 (d, J=4.7Hz, 7H),
0.85(s,3H),0.53(s,1H),0.43(s,1H).
13C NMR(125MHz,DMSO-d6)δ188.69(s),170.54(s),165.42(s),163.38(s),142.72
(s),129.71(s),127.96(s),127.08(s),118.00(s),116.82(s),114.82(s),72.73(s),
40.19(s),34.75(s),34.32(s),31.75(s),30.93(s),28.09(s),26.43(s),24.48(s),23.74
(s),21.18(s),20.77(s),19.99(s),14.39(s).
HRMS(ESI)m/z[M+H]+calcd for C34H41Br2O5:689.1300；found 689.1303.
The synthesis of O- (piperazinyl) ethyl derivative (III) of the Psiguadial A of embodiment 3
Compound II (344mg, 0.5mmol) is dissolved in the middle of 25mL acetonitriles, be added thereto to Anhydrous potassium carbonate (690mg,
5.0mmol), KI (168mg, 1.0mmol) and Piperazine anhydrous (3446mg, 40mmol), mixture is heated to reflux 4h.Reaction
Reaction solution is poured into frozen water after end, is extracted 3 times with equivalent dichloromethane, merge organic phase.Water and saturated common salt are used successively
Water washing merge after organic phase, then with anhydrous sodium sulfate drying, removal solvent concentrated under reduced pressure obtains product crude product.Product is thick
(mobile phase is the purifying of product silica gel column chromatography：Petroleum ether/acetone=100:1.0, v/v) yellow, is collected to concentrate elution band and wave
Solvent is gone to obtain the yellow powder (254.8mg, 73%) of compound III.
1H NMR (500MHz, DMSO-d6) δ 10.46 (s, 2H), 7.23 (s, 2H), 7.20 (d, J=10.0Hz, 3H),
4.02 (s, 4H), 3.96 (s, 1H), 2.62 (d, J=8.0Hz, 12H), 2.31 (s, 8H), 2.10 (s, 1H), 2.01-1.85 (m,
3H),1.79(s,1H),1.66(s,1H),1.44(s,2H),1.38(s,1H),1.27(s,1H),1.05(s,2H),1.03(d,
J=45.8Hz, 3H), 0.93-0.70 (m, 9H), 0.52 (s, 1H), 0.23 (s, 1H)
13C NMR(125MHz,DMSO-d6)δ188.62(s),170.44(s),165.27(s),163.22(s),142.59
(s),129.52(s),127.80(s),126.91(s),117.86(s),116.67(s),114.65(s),69.34(s),
54.61(s),54.05(s),45.17(s),40.02(s),34.61(s),34.17(s),30.77(s),27.92(s),26.29
(s),24.33(s),23.57(s),21.00(s),20.62(s),19.84(s),14.21(s).
HRMS(ESI):m/z[M+H]+calcd for C42H59N4O5:699.4485；found:699.4480.
The synthesis of O- (1H- tetrazoles base) ethyl derivative (IV) of the Psiguadial A of embodiment 4
Compound II (344mg, 0.5mmol) is dissolved in the middle of 20mL acetonitriles, be added thereto to Anhydrous potassium carbonate (690mg,
5.0mmol), KI (168mg, 1.0mmol) and 1H- tetrazoles (1401mg, 20mmol), mixture is heated to reflux 2h.Instead
Reaction solution is poured into 20mL frozen water after should terminating, is extracted 2 times with equivalent dichloromethane, merge organic phase.Water is used successively and is satisfied
Organic phase after merging with brine It, then with anhydrous sodium sulfate drying, removal solvent concentrated under reduced pressure obtains product crude product.
Because tautomerization, two kinds of substitution products of 1H- tetrazoles base and 2H- tetrazoles base can be generated at reaction conditions.Product
(mobile phase is the purifying of crude product silica gel column chromatography：Petroleum ether/acetone=100:1, v/v), collect yellow and concentrate elution band, then will
Elution band is concentrated, and purifies that (mobile phase is with silica gel column chromatography：Petroleum ether/acetone=100:0.5, v/v), collection two is light successively
The elution band of yellow, it is the faint yellow solid (89.9mg, 27%) for obtaining compound IV to concentrate preceding 1 elution band.
1H NMR(500MHz,DMSO-d6)δ10.47(s,2H),10.40(s,1H),10.26(s,1H),7.24(s,
2H), 7.21 (d, J=10.0Hz, 3H), 4.65 (s, 1H), 4.60 (s, 1H), 4.45 (d, J=2.6Hz, 5H), 4.42 (s,
1H),4.07(s,1H),2.20(s,1H),1.93–1.84(m,4H),1.72(s,1H),1.60–1.21(m,4H),0.99(s,
3H),0.92–0.71(m,9H),0.55(s,1H),0.25(s,1H).
13C NMR(125MHz,DMSO-d6)δ188.53(s),170.35(s),165.18(s),163.13(s),144.94
(s),142.48(s),129.45(s),127.69(s),126.84(s),117.75(s),116.60(s),114.54(s),
67.03(s),47.04(s),39.95(s),34.52(s),34.10(s),30.66(s),27.85(s),26.18(s),24.26
(s),23.46(s),20.93(s),20.51(s),19.77(s),14.10(s).
HRMS(ESI):m/z[M+H]+calcd for C36H43N8O5:667.3356；found:667.3352.
The composition increasing leukocyte of embodiment 5 activity
First, therapeutic action of the composition to post hemorrhagic mice
Influence ICR mouse 50 to post hemorrhagic mice, ♀ ♂ half and half are divided into 5 groups (n=10).In addition to physiological saline group,
Other every mouse of group take blood from orbital vein bloodletting 0.5ml, after 24h and survey whole each group leucocyte indexs again, then continuous to fill
Stomach is administered 1 week, after last dose 1h, takes the full whole bliid platelet analyzers of blood F-800 from orbital venous plexus and surveys leucocyte index.
The preparation of composition：The powder of the 35mg compounds III of 200 mesh nets will be crossed after grinding and 200 will be crossed after grinding
The powder of the 65mg compounds IV of mesh net is fitted into tubule with cover and obtains 100mg compositions with the mixing of turbine stirring instrument,
The solution of composition is obtained when using with the composition of water dissolves this 100mg.
The composition of table 1 is to because of caused leukopenic therapeutic action (10 of losing blood9/L)
Compare with model group：*p<0.05
Result shows that after taking composition treatment 7 days, composition administration group compares bloodletting mouse with model group, white thin
Born of the same parents are significantly higher than model group, close to physiological saline group.And compound III and compound IV is without this activity.
2nd, composition causes leukopenic therapeutic action to endoxan
The preventive and therapeutic effect ICR mouse 50 damaged to mouse bone marrow cells hematopoiesis function, ♀ ♂ dual-purposes are divided into 5 groups (n=10),
That is physiological saline group, modeling group, composition 1.2mg/kg groups, compound III 1.2mg/kg groups and compound IV 1.2mg/kg
Group, is administered orally, once a day.Other each group mouse distinguished intraperitoneal injection cycli phosphate amine in addition to physiological saline group on 0th, 5,10th
80mg/kg, then proceedes to administration 3 days.In 1h after last dose, blood is taken from orbital venous plexus, survey leucocyte.
The composition of table 2 is to the leukopenic therapeutic action (10 of caused by cyclophosphamide9/L)
Compare with model group：*p<0.05
Result shows, compares with physiological saline group that cycli phosphate amine can damage mouse bone marrow cells, under causing PBC
Drop, composition group compares with model group, can substantially resist the decline of cycli phosphate amine induced mice leucocyte.And compound III and
Compound IV is without this activity.
3rd, composition is to leukopenic therapeutic action caused by benzene
Influence to Induced Aplastic Anemia Mice：Kunming mouse 50, ♀ ♂ dual-purposes are divided into 5 groups (n=10), remove
Outside physiological saline group, other groups mouse subcutaneous injection benzene 0.5ml/kg, continuous 12 days, the same day of modeling, while be administered orally, often
It 1 time, totally 18 days, 1h after last dose, orbital venous plexus took blood, surveyed leucocyte.
The therapeutic action (10 that the composition of table 3 is reduced to haemocyte caused by benzene9/L)
Compare with model group：*p<0.05
Result shows that composition group compares with model group, and Induced Aplastic Anemia Mice caused by can substantially resisting benzene is thin in vain
The decline of born of the same parents.And compound III and compound IV is without this activity.
Conclusion：Composition can notable increasing leukocyte, can be used to prepare anti-leucocyte reduction medicine.And compound
Activity of the III and compound IV without notable increasing leukocyte, it is not possible to for preparing anti-leucocyte reduction medicine.
The preparation of the composition tablet involved in the present invention of embodiment 6
2 grams of compositions are taken, addition prepares 18 grams of the customary adjuvant of tablet, mixed, conventional tablet presses are made 100.
The preparation of the composition capsule involved in the present invention of embodiment 7
2 grams of compositions are taken, addition prepares customary adjuvant such as 18 grams of the starch of capsule, mixed, it is encapsulated to be made 100.
Claims (7)
1. a kind of composition, it is characterized by said composition is made up of compound III and compound IV, compound in said composition
The mass percent of III and compound IV is respectively 35% and 65%,
2. the preparation method of composition as claimed in claim 1, it is characterized by：By the powder of compound III and compound IV
Powder be respectively 35% and 65% according to mass percent and be sufficiently mixed.
3. application of a kind of composition as claimed in claim 1 in increasing leukocyte medicine.
4. application of the composition as claimed in claim 3 in increasing leukocyte medicine, it is characterised in that the composition liter
Height is lost blood the reduction of caused leucocyte.
5. application of the composition as claimed in claim 3 in increasing leukocyte medicine, it is characterised in that the composition liter
The reduction of leucocyte caused by chemicals high.
6. application of the composition as claimed in claim 5 in increasing leukocyte medicine, it is characterised in that the chemicals is
Endoxan.
7. application of the composition as claimed in claim 5 in increasing leukocyte medicine, it is characterised in that the chemicals is
Benzene.
Priority Applications (1)
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|---|---|---|---|
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