CN106420748A - Application of Harrisotone A lignocaine and piperazine-based derivative composition in medicine for raising white blood cells - Google Patents
Application of Harrisotone A lignocaine and piperazine-based derivative composition in medicine for raising white blood cells Download PDFInfo
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- 239000000203 mixture Substances 0.000 title claims abstract description 52
- 210000000265 leukocyte Anatomy 0.000 title claims abstract description 15
- 239000003814 drug Substances 0.000 title claims abstract description 14
- BMTORNFHNMDAAJ-UHFFFAOYSA-N harrisotone A Natural products CC(=CCC1(CC=C(C)C)C(=C(C(=O)C)C(=O)C2(CC3C(CCC3(C)O)C(C)(O)C2)C1=O)O)C BMTORNFHNMDAAJ-UHFFFAOYSA-N 0.000 title description 7
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 title description 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 title description 3
- 229960004194 lidocaine Drugs 0.000 title description 3
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- 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 14
- 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 13
- 210000004369 blood Anatomy 0.000 claims description 8
- 239000008280 blood Substances 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 4
- 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
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 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
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 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
- 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
- 239000000047 product Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- -1 Piperazino Chemical group 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 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
- 239000003208 petroleum Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 208000032467 Aplastic anaemia Diseases 0.000 description 2
- 240000006015 Harrisonia perforata Species 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
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 229930191860 harrisotone Natural products 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
- 125000000830 polyketide group Chemical group 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 239000007787 solid Substances 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
- NQRYJNQNLNOLGT-UHFFFAOYSA-N C1CCNCC1 Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N CCN(CC)CCO Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 238000012449 Kunming mouse Methods 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
- 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
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 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
- 230000000630 rising effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 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
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 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
- A61K31/13—Amines
- A61K31/132—Amines having two or more amino groups, e.g. spermidine, putrescine
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (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
The invention relates to the field of organic synthesis and medicinal chemistry, in particular to a composition, a preparation method and application of the composition in preparation of medicine for raising white blood cells. The invention discloses a composition and a preparation method thereof. Pharmacological experiments show that the composition has the effect of raising the white blood cells and has development value for the medicine for raising the white blood cells.
Description
Technical field
The present invention relates to organic synthesis and medicinal chemistry art are and in particular to composition, preparation method and its usage.
Background technology
Leukopenia is the disease failed to understand and caused after being secondary to other diseases due to reason, is divided into primary
With Secondary cases two big class.Primary person's reason is failed to understand；Secondary cases person thinks that its cause of disease can be by acute infection, physics, chemical factor,
Disease in the blood system, with the disease of splenomegaly, connective tissue disease, anaphylactia, genetic disease etc., acquired or reason
Not clear property granulocyte minimizing etc..
Existing medicine has that toxicity is big, security is low, from natural products at present for leukopenic treatment
Find compound or lead compound and carry out structural modification and obtain its derivative, thus the potential drug obtaining high-efficiency low-toxicity has
Important value.
Compound I according to the present invention be one deliver within 2009 (Sheng Yin et al.,
2009.Harrisotones A–E,five novel prenylated polyketides with a rare
spirocyclic skeleton from Harrisonia perforata.Tetrahedron 65(2009)1147–1152)
Compound, we have carried out structural modification to compound I, and obtaining two new derivatives is compound III and compound
IV, and be prepared for composition with compound III and compound IV and said composition increasing leukocyte activity is evaluated, its
There is increasing leukocyte activity.
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 make pharmaceutically acceptable salt or pharmaceutically acceptable carrier.
It is an object of the invention to provide application in preparing increasing leukocyte medicine for the composition.The present composition is permissible
The notable leucocyte causing with chemical substance of losing blood that raises reduces.
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subject to concrete reality
Apply any restriction of example, but be defined in the claims.
Specific embodiment
The preparation of embodiment 1 compound Harrisotone A
Document (the Sheng Yin that the preparation method of compound Harrisotone A (I) is delivered with reference to Sheng Yin et al.
et al.,2009.Harrisotones A–E,five novel prenylated polyketides with a rare
spirocyclic skeleton from Harrisonia perforata.Tetrahedron 65(2009)1147–1152)
Method.
The synthesis of O- bromoethyl derivative (II) of embodiment 2 Harrisotone A
Compound I (472mg, 1.00mmol) is dissolved in 15mL benzene, adds TBAB (TBAB) in solution
(0.08g), 50% sodium hydroxide solution of 1,2- Bromofume (3.760g, 20.00mmol) and 6mL.Mixture is Celsius 35
Degree stirring 3h.After 3h, reactant liquor is poured in frozen water, be extracted twice with dichloromethane immediately, merge organic phase solution.Then
Successively water and saturated common salt water washing 2 times are used to organic phase solution, then uses anhydrous sodium sulfate drying, last reduced pressure concentration removal is molten
Agent obtains product crude product.Product crude product silica gel column chromatography purifies that (mobile phase is：Petroleum ether/acetone=100:1.5, v/v), receive
Collection brown is concentrated elution band and is flung to the yellow powder (602mg, 76%) that solvent obtains compound II.
1H NMR(500MHz,DMSO-d6) δ 5.18 (s, 2H), 4.56 (s, 2H), 3.93 (d, J=16.7Hz, 4H), 3.79
(s, 2H), 3.62 (d, J=0.9Hz, 4H), 3.15 (s, 2H), 2.48 (s, 2H), 2.41 (d, J=9.4Hz, 4H), 2.27 (s,
1H), 1.95 (s, 1H), 1.88 1.80 (m, 8H), 1.77 (d, J=15.5Hz, 7H), 1.68 (s, 1H), 1.61 (s, 1H),
1.51 (s, 1H), 1.25 (d, J=58.1Hz, 1H), 1.15 0.75 (m, 6H).
13C NMR(125MHz,DMSO-d6)δ206.46(s),198.24(s),195.44(s),190.27(s),135.27
(s),120.09(s),115.02(s),84.45(s),76.58(s),74.12(s),63.67(s),62.76(s), 60.36
(s), 50.96 (s), 45.22 (s), 39.69 (s), 36.61 (s), 34.40 (s), 32.63 (s), 30.81 (d, J=8.9Hz),
28.77 (s), 25.30 (s), 24.09 (d, J=19.2Hz), 22.77 (s), 18.20 (s).
HRMS(ESI)m/z[M+H]+calcd for C34H50Br3O6:793.1137；found 793.1134.
The synthesis of O- (lignocaine) ethyl derivative (III) of embodiment 3 Harrisotone A
Compound II (396mg, 0.5mmol) is dissolved in the middle of 15mL acetonitrile, be added thereto to Anhydrous potassium carbonate (345mg,
2.5mmol), KI (84mg, 0.5mmol) and diethylamine (2920mg, 40mmol), mixture is heated to reflux 3h.Reaction knot
After bundle, reactant liquor is poured in frozen water, extracted 2 times with equivalent dichloromethane, merge organic phase.Use water and saturated aqueous common salt successively
Washing merge after organic phase, then use anhydrous sodium sulfate drying, reduced pressure concentration removal solvent obtain product crude product.Product crude product
Purify that (mobile phase is with silica gel column chromatography：Petroleum ether/acetone=100:1.5, v/v), collect brown and concentrate elution band, concentration is
Obtain the faint yellow solid (246.1mg, 64%) of compound III.
1H NMR (500MHz, DMSO-d6) δ 5.13 (s, 2H), 4.19 (s, 2H), 3.52 (d, J=5.3Hz, 4H), 3.21
(s, 2H), 3.04 (s, 2H), 2.85 (s, 12H), 2.64 (d, J=13.5Hz, 4H), 2.33 (s, 3H), 2.18 (s, 1H), 2.11
(s, 2H), 2.04 (s, 1H), 1.98 (s, 1H), 1.88 (s, 1H), 1.77 (d, J=5.0Hz, 7H), 1.70 (d, J=15.5Hz,
7H),1.61(s,1H),1.54(s,1H),1.44(s,1H),1.37(s,1H),1.10(s,24H).
13C NMR(125MHz,DMSO-d6)δ206.30(s),198.04(s),195.18(s),190.07(s),135.11
(s),119.89(s),114.86(s),84.15(s),76.42(s),66.70(s),62.58(s),60.18(s),59.97
(s),52.53(s),51.93(s),50.76(s),47.69(s),45.04(s),39.51(s),36.43(s), 30.63(d,J
=8.9Hz), 28.61 (s), 25.10 (s), 23.93 (d, J=19.2Hz), 22.57 (s), 18.04 (s), 12.27 (s).
HRMS(ESI):m/z[M+H]+calcd for C46H80N3O6:770.6047；found:770.6044.
The synthesis of O- (piperazinyl) ethyl derivative of embodiment 4 Harrisotone A
Compound II (396mg, 0.5mmol) is dissolved in the middle of 16mL acetonitrile, be added thereto to Anhydrous potassium carbonate (345mg,
2.5mmol), KI (84mg, 0.5mmol) and Piperazine anhydrous (6892mg, 80mmol), mixture is heated to reflux 1h.Reaction
After end, reactant liquor is poured in 15mL frozen water, extracted 2 times with equivalent dichloromethane, merge organic phase.Use water and saturation successively
Brine It merge after organic phase, then use anhydrous sodium sulfate drying, reduced pressure concentration removal solvent obtain product crude product.Produce
Thing crude product silica gel column chromatography purifies that (mobile phase is：Petroleum ether/acetone=100:1.5, v/v), collect light brown and concentrate wash-out
Band obtains the Light brown solid (286.9mg, 71%) of compound IV.
1H NMR (500MHz, DMSO-d6) δ 5.14 (s, 2H), 4.21 (s, 2H), 3.53 (d, J=6.2Hz, 4H), 3.09
(s, 2H), 3.05 (s, 2H), 2.66 (s, 12H), 2.57 2.53 (m, 4H), 2.33 (d, J=15.0Hz, 15H), 2.24 (s,
1H), 2.14 (s, 2H), 2.10 (s, 1H), 2.00 (s, 1H), 1.88 (d, J=10.5Hz, 3H), 1.79 (d, J=5.0Hz,
7H), 1.71 (d, J=15.5Hz, 7H), 1.63 (s, 1H), 1.55 (s, 1H), 1.46 (s, 1H), 1.15 1.05 (m, 8H).
13C NMR(125MHz,DMSO-d6)δ206.30(s),198.04(s),195.28(s),190.07(s),135.11
(s),119.89(s),114.86(s),84.25(s),76.42(s),66.70(s),62.58(s),60.18(s), 59.97
(s),54.35(s),54.16(s),53.66(s),50.78(s),45.24(s),45.06(s),39.49(s),36.45(s),
30.61 (d, J=8.9Hz), 28.61 (s), 25.10 (s), 23.93 (d, J=19.2Hz), 22.58 (s), 18.04 (s).
HRMS(ESI):m/z[M+H]+calcd for C46H77N6O6:809.5905；found:809.5901.
Embodiment 5 composition increasing leukocyte activity
First, the therapeutic action to post hemorrhagic mice for the composition
Impact ICR mouse 50 to post hemorrhagic mice, ♀ ♂ half and half, it is divided into 5 groups (n=10).In addition to physiological saline group,
Every mouse of other group, from orbital vein bloodletting 0.5ml, takes blood to survey whole each group leucocyte indexs again, then continuously fills after 24h
Stomach is administered 1 week, after last dose 1h, takes the full whole bliid platelet analyzer of blood F-800 to survey leucocyte index from orbital venous plexus.
The preparation of composition：Cross the powder of the 35mg compound III of 200 mesh nets after grinding and cross 200 after grinding
The powder of the 65mg compound IV of mesh net loads in tubule with cover and obtains 100mg composition with the mixing of turbine stirring instrument,
Obtain the solution of composition with the composition of this 100mg of water dissolves during use.
Table 1 composition is to because of leukopenic therapeutic action (10 caused by losing blood9/L)
Compare with model group：*p<0.05
Result shows, after taking composition treatment 7 days, composition administration group is compared bloodletting mouse with model group, in vain carefully
Born of the same parents are significantly higher than model group, close to physiological saline group.And compound III and compound IV does not have this activity.
2nd, composition causes leukopenic therapeutic action to endoxan
The preventive and therapeutic effect ICR mouse 50 that mouse bone marrow cells hematopoiesis function is damaged, ♀ ♂ dual-purpose, it is divided into 5 groups (n=10),
I.e. physiological saline group, modeling group, composition 1.2mg/kg group, compound III 1.2mg/kg group and compound IV 1.2mg/kg
Group, oral administration, once a day.In addition to physiological saline group, other each group mouse distinguished lumbar injection cycli phosphate amine on 0th, 5,10th
80mg/kg, then proceedes to be administered 3 days.1h after last dose, takes blood from orbital venous plexus, surveys leucocyte.
The leukopenic therapeutic action (10 to caused by cyclophosphamide of table 2 composition9/L)
Compare with model group：*p<0.05
Result shows, compares with physiological saline group, and cycli phosphate amine can make mouse bone marrow cells damage, and causes under PBC
Fall, composition group is compared with model group, all can substantially resist cycli phosphate amine induced mice leucocyte and decline.And compound III and
Compound IV does not have this activity.
3rd, composition is to therapeutic action leukopenic caused by benzene
Impact to Induced Aplastic Anemia Mice：Kunming mouse 50, ♀ ♂ dual-purpose, it is divided into 5 groups (n=10), remove
Outside physiological saline group, other group mouse subcutaneous injection benzene 0.5ml/kg, continuous 12 days, the same day of modeling, oral administration simultaneously, often
It 1 time, totally 18 days, 1h after last dose, orbital venous plexus take blood, survey leucocyte.
The therapeutic action (10 that table 3 composition reduces to haemocyte caused by benzene9/L)
Compare with model group：*p<0.05
Result shows, composition group is compared with model group, and caused by can substantially resisting benzene, Induced Aplastic Anemia Mice is thin in vain
The decline of born of the same parents.And compound III and compound IV does not have this activity.
Conclusion：Composition can notable increasing leukocyte, can be used to prepare anti-leucocyte and reduce medicine.And compound
III and compound IV does not have the activity of notable increasing leukocyte it is not possible to reduce medicine for preparing anti-leucocyte.
The preparation of embodiment 6 composition tablet involved in the present invention
Take 2 grams of compositions, 18 grams of the customary adjuvant of tablet is prepared in addition, mix, conventional tablet presses make 100.
The preparation of embodiment 7 composition capsule involved in the present invention
Take 2 grams of compositions, customary adjuvant such as 18 grams of the starch of capsule is prepared in addition, mix, encapsulated make 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 according to mass percent and 35% and 65% be sufficiently mixed.
3. application in increasing leukocyte medicine for a kind of composition as claimed in claim 1.
4. application in increasing leukocyte medicine for the composition as claimed in claim 3 is it is characterised in that described composition liter
Height is lost blood the reduction of caused leucocyte.
5. application in increasing leukocyte medicine for the composition as claimed in claim 3 is it is characterised in that described composition liter
The reduction of leucocyte caused by high chemicals.
6. application in increasing leukocyte medicine for the composition as claimed in claim 5 is it is characterised in that described chemicals is
Endoxan.
7. application in increasing leukocyte medicine for the composition as claimed in claim 5 is it is characterised in that described chemicals is
Benzene.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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| CN (1) | CN106420748A (en) |
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2016
- 2016-10-18 CN CN201610907695.0A patent/CN106420748A/en not_active Withdrawn
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Application publication date: 20170222 |