CN106692136A - Application of composition of Harrisotone A derivatives in anti-acute-gout drug preparation - Google Patents
Application of composition of Harrisotone A derivatives in anti-acute-gout drug preparation Download PDFInfo
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- BCLSJHWBDUYDTR-UHFFFAOYSA-N CCCNCCO Chemical compound CCCNCCO BCLSJHWBDUYDTR-UHFFFAOYSA-N 0.000 description 3
- ZBCBWPMODOFKDW-UHFFFAOYSA-N OCCNCCO Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
- 0 CCCO[C@](CC)(C[C@](C1)C([C@@](CC(C)C=C(C)C)(*C=*(C)C)C(C)=C(C)C(C)=O)=[U])[C@](C)(CC2)[C@@]1(C)[C@]2(C)O Chemical compound CCCO[C@](CC)(C[C@](C1)C([C@@](CC(C)C=C(C)C)(*C=*(C)C)C(C)=C(C)C(C)=O)=[U])[C@](C)(CC2)[C@@]1(C)[C@]2(C)O 0.000 description 1
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- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
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- 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
- A61K31/133—Amines having hydroxy groups, e.g. sphingosine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
- C07C217/12—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a ring other than a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Abstract
The invention discloses an application of composition of Harrisotone A derivatives in anti-acute-gout drug preparation, namely, an application of composition of an O-(pyrrolidine) ethyl derivative and an O-(dihydroxyethylamino) ethyl derivative of Harrisotone A in anti-acute-gout drug preparation, relates to the field of organic synthesis and medicinal chemistry and particularly relates to the composition of the Harrisotone A derivatives, a preparation method and the application of the composition in anti-acute-gout drug preparation. The invention discloses the composition of the Harrisotone A derivatives and the preparation method of the composition. Pharmacological experiments prove that the composition of the Harrisotone A derivatives has an anti-acute-gout effect and has the value for developing anti-acute-gout drugs.
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
Gout (gouty), also known as urarthritis (gouty arthritis), caused by being internal purine metabolic disturbance
Disease, uric acid is excessive in showing as blood, it is easy to make lithate (MSU) joint etc. tissue separate out crystallization.The acute hair of gout
Work is to cause neutrophil leucocyte local infiltration and inflammatory reaction due to being deposited on the MSU in joint.
Western medicine selects three kinds of medicines in acute gout arthritis：Colchicin, NSAIDs and cortex hormone of aadrenaline.
The mechanism of action of colchicin is the tubulin binding with neutrophil leucocyte, so as to hinder the activity of granulocyte, suppresses grain thin
Born of the same parents infiltrate.NSAIDs such as Indomethacin, suppresses epoxidase (COX) activity and plays antiinflammatory action, and selectivity
COX2 depressants.Although the effect of their anti-inflammatory analgetics is fast, toxic and side effect also quite substantially, such as the effective dose of colchicin with
Producing the comparable doses of the gastrointestinal symptoms such as diarrhoea, NSAIDs is having active peptic ulcer, hemorrhage of gastrointestinal tract feelings
Definitely disabled under condition, and phenylbutazone medication is as short as also causing serious agranulocytosis or alpastic anemia in 3 weeks.
Compound or lead compound are found from natural products and structural modification is carried out and obtains its derivative, so as to obtain
The potential drug of high-efficiency low-toxicity most has important value.
Compound I of 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, obtain two new derivatives i.e. compound III and compound
IV, and composition is prepared for compound III and compound IV and the anti-acute gout activity of said composition is evaluated,
It has anti-acute gout 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 15% and 85%.
Composition disclosed by the invention can be made pharmaceutically acceptable salt or pharmaceutically acceptable carrier.
Monosodium urate (MSU) of the invention causes the acute gout model evaluation that human vascular endothelial (HUVEC) is damaged to show,
The present composition causes HUVEC to damage to MSU has protective effect, and suppresses ICAM-1 expression, can be used for preparation treatment acute
Gout anti-inflammatory drugs.New application it is an object of the invention to provide the present composition in medical science, concretely relates to
Application of the present composition in treatment acute gout medicine is prepared.
The purpose of the present invention is realized by following technical scheme：
Modern medicine pathological study illustrates that urarthritis is that MSU causes neutrophil leucocyte local infiltration and inflammatory anti-
Should, the essence that acute gout is produced is that neutrophil leucocyte (PMN)-vascular endothelial cell (HUVEC) is adhered enhancing (Terkeltaub
R, et al.The murine homolog of the interleukin-8 receptorcxcr-2is essential
for the occurrence of neutrophilic inflammation in air pouch model of acute
urate crystal-induced gouty synovitis.Arthritis Rheum,1998,41(5):900-909.),
HUVEC is damaged, and its molecular biology mechanism is interaction (FujiwaraY, the et of PMN and HUVEC surface adhesion molecules
al.Interleukin-8stimulates leukocyte migration across amonolayer of cultured
rabbit NF-α,IL-1β,IL-8,and IL-1 rain Monosodium Urate Crystal induced rabbit
arthritis.Labinvest,19998,78(5):559-569.), wherein ICAM-1 (ICAM-1) with adhesion
Functional relationship is most close, is that (Zhang Chun, Tang Yi, Liu Jun wait gout spirit sides to uric acid to one of important indicator of acute gout inflammation
Sodium causes the influence of rat model soft tissue of joint ICAM-1 expression, Chongqing Medical, 2002,31 (12)：1211-1213.).
Therefore, HUVEC is caused to damage for acute gout MSU, the pathological characters that ICAM-1 expression increases, present invention MSU
(Yang Yanhua, Yin Lian, Wang Mingyan wait Monosodium urates to induce the acute of HUVEC damages to the external acute gout model that cause HUVEC is damaged
Gout Model is studied, Chinese traditional Chinese medicine academic periodical, 2010,28 (3)：592-594.), the anti-acute gout of the present composition is evaluated scorching
Disease activity.MSU causes the acute gout model evaluation that human vascular endothelial (HUVEC) is damaged to show that the present composition is to MSU
Causing HUVEC to damage has protective effect, and suppresses ICAM-1 expression.
Beneficial effect
Result of study shows that the acute gout model evaluation for causing HUVEC damages with MSU shows that the present composition can be protected
Shield MSU causes HUVEC to damage, and reduces Apoptosis, improves cytoactive, suppresses ICAM-1 expression, with anti-acute gout inflammation
Activity, the present composition can be used for prepare treatment acute gout anti-inflammatory drugs.
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 Harrisotone A of embodiment 1
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- bromoethyls derivative (II) of the Harrisotone A of embodiment 2
Compound I (472mg, 1.00mmol) is dissolved in 15mL benzene, to addition TBAB (TBAB) in solution
50% sodium hydroxide solution of (0.08g), 1,2- Bromofume (3.760g, 20.00mmol) and 6mL.Mixture is Celsius 35
Degree stirring 3h.Reaction solution is poured into frozen water after 3h, is extracted twice with dichloromethane immediately, merge organic phase solution.Then
To organic phase solution successively with water and saturated common salt water washing 2 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=100:1.5, v/v), receive
Collection brown concentrates elution band and flings 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),
(m, the 6H) of 1.51 (s, 1H), 1.25 (d, J=58.1Hz, 1H), 1.15-0.75
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 the O- (nafoxidine base) ethyl derivative (III) of the Harrisotone A of embodiment 3
Compound II (396mg, 0.5mmol) is dissolved in the middle of 15mL acetonitriles, be added thereto to Anhydrous potassium carbonate (345mg,
2.5mmol), KI (84mg, 0.5mmol) and pyrrolidines (2840mg, 40mmol), mixture is heated to reflux 3h.Reaction knot
Reaction solution is poured into frozen water after beam, is extracted 2 times with equivalent dichloromethane, merge organic phase.Water and saturated aqueous common salt are used successively
Washing merge after organic phase, then with anhydrous sodium sulfate drying, removal solvent concentrated under reduced pressure obtains product crude product.Product crude product
Purify that (mobile phase is with silica gel column chromatography：Petroleum ether/acetone=100:1.0, v/v), collect light brown and concentrate elution band, concentration
Obtain the yellow solid (293.8mg, 77%) of compound III.
1H NMR(500MHz,DMSO-d6)δ5.17(s,2H),4.27(s,2H),3.58(s,2H),3.56(s,2H),
3.23(s,2H),3.09(s,2H),2.90(s,1H),2.75(s,2H),2.65(s,2H),2.58–2.45(m,13H),2.43
(s, 2H), 2.39 (s, 3H), 1.92 (s, 1H), 1.85-1.72 (m, 14H), 1.68 (t, J=12.5Hz, 13H), 1.58 (s,
1H), 1.48 (d, J=3.0Hz, 2H), 1.14 (d, J=1.5Hz, 7H)
13C NMR(125MHz,DMSO-d6)δ206.54(s),198.31(s),195.54(s),190.33(s),135.36
(s),119.99(s),115.10(s),84.52(s),76.68(s),66.96(s),62.83(s),60.46(s),60.21
(s), 54.68 (d, J=13.9Hz), 54.13 (s), 51.02 (s), 45.31 (s), 39.77 (s), 36.69 (s), 30.88 (d, J
=8.9Hz), 28.87 (s), 25.41 (d, J=13.8Hz), 24.18 (d, J=19.2Hz), 22.85 (s), 18.28 (s)
HRMS(ESI):m/z[M+H]+calcd for C46H74N3O6:764.5578；found:764.5572.
The synthesis of O- (two hydroxyethylamines) ethyl derivative of the Harrisotone A of embodiment 4
Compound II (396mg, 0.5mmol) is dissolved in the middle of 22mL acetonitriles, be added thereto to Anhydrous potassium carbonate (690mg,
5.0mmol), KI (252mg, 1.5mmol) and diethanol amine (1051mg, 10mmol), mixture is heated to reflux 3h.Reaction
Reaction solution is poured into 25mL frozen water after end, is extracted 3 times with equivalent dichloromethane, merge organic phase.Water and saturation are used successively
Brine It merge after organic phase, then with anhydrous sodium sulfate drying, removal solvent concentrated under reduced pressure obtains product crude product.Produce
(mobile phase is the purifying of thing crude product silica gel column chromatography：Petroleum ether/acetone=100:0.5, v/v), collect light brown and concentrate wash-out
Band obtains the brown solid (324.4mg, 75%) of compound IV.
1H NMR (500MHz, DMSO-d6) δ 5.17 (s, 2H), 4.27 (s, 2H), 3.56 (d, J=2.7Hz, 4H), 3.38
(d, J=83.1Hz, 14H), 3.08 (s, 2H), 3.04 (s, 4H), 2.76-2.66 (m, 5H), 2.61 (s, 12H), 2.57 (s,
2H), 2.40 (s, 3H), 2.05 (s, 1H), 1.93 (s, 1H), 1.91-1.81 (m, 8H), 1.76 (d, J=15.5Hz, 7H),
(d, J=12.0Hz, the 7H) of 1.68 (s, 1H), 1.61 (s, 1H), 1.51 (s, 1H), 1.28 (s, 2H), 1.18
13C NMR(125MHz,DMSO-d6)δ206.46(s),198.23(s),195.44(s),190.26(s),135.27
(s),120.08(s),115.02(s),84.44(s),76.58(s),66.89(s),62.74(s),60.37(s),60.13
(s),59.31(s),56.85(s),53.89(s),53.08(s),50.95(s),45.22(s),39.68(s),36.61(s),
30.80 (d, J=8.9Hz), 28.77 (s), 25.29 (s), 24.09 (d, J=19.2Hz), 22.76 (s), 18.20 (s)
HRMS(ESI):m/z[M+H]+calcd for C46H80N3O12:866.5742；found:866.5737.
The anti-acute gout inflammation test of the composition of embodiment 5
1st, solution is prepared
5g uric acid adds 1000ml distilled water to boil, plus 5%NaOH solution adjusts PH 7.4, stirring, cooling crystallization to be made uric acid
Sodium crystallizes (MSU).The MSU 10mg autoclavings that will be made, plus the DMEM nutrient solution 10ml without serum, grinding are made into 1mg/
The DMEM solution of ml.During experiment, this solution adds DMEM nutrient solutions to be made into the MSU solution of various concentrations DMEM again.
The preparation of composition：The powder of the 15mg compounds III of 200 mesh nets will be crossed after grinding and 200 will be crossed after grinding
The powder of the 85mg 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.
Composition, compound III or compound IV 2.5mg, are dissolved, DMSO final concentrations with dimethyl sulfoxide (DMSO) (DMSO)<
0.02%, then add the DMEM nutrient solutions of serum-free, it is configured to concentration 25ug/ml.
2nd, the in vitro culture of vascular endothelial cell
Human umbilical vein endothelial cell HUVEC plants is provided by preclinical medicine institute of Nanjing University of Traditional Chinese Medicine, and cell is former through branch
Physical examination is surveyed, and without mycoplasma contamination, cell is neutralized through 0.25% Trypsin Induced, the DMEM nutrient solutions containing 10% calf serum,
Centrifugation (1000r/min × 6min), removes supernatant, plus the DMEM nutrient solutions containing 10% calf serum, in immigration Tissue Culture Flask,
Put 37 DEG C, 5%CO2Secondary Culture in incubator.
3rd, the influence of HUVEC vigor is stimulated MSU
HUVEC is cultivated in blake bottle, it is to be grown to 70%~80% fusion when, with 0.25% Trypsin Induced, from
The heart, 10% calf serum DMEM nutrient solutions are washed 3 times, and 4 × 10 are tuned into 10% calf serum DMEM nutrient solutions4/ ml cells hang
Liquid, 96 orifice plates of implantation (per hole 200ul), culture gently suctions out original fluid after 24 hours, carries out following experiment, every group of each 8 hole, tool
Body is grouped and liquid feeding is as follows：Control group (200ul DMEM nutrient solutions), model group (100ug/ml MSU solution), intervention group
(composition or compound of 100ug/ml MSU solution+25ug/ml), continues to put 37 DEG C, 5%CO after liquid feeding2In incubator
Culture 24 hours, collects supernatant, and remaining HUVEC is used to determine cytoactive, per Kong Zaijia 5mg/ml MTT liquid 20ul, after
It is continuous to put 37 DEG C, 5%CO2After being cultivated 4 hours in incubator, MTT liquid is abandoned, add dimethyl sulfoxide (DMSO) 200ul dissolvings, concussion, in enzyme
Mark instrument reads absorbance, wavelength 490nm.
Statistical data treatment, cell viability (%)=experimental group absorbance/control group absorbance × 100%, knot
Fruit is shown in Table 1.
Compared with control group, model group cell viability is substantially reduced (P<0.05) cell viability is notable after, composition is intervened
Improve (P<0.05), and it is better than control group, and compound III and compound IV is without this activity.
The influence of the vascular endothelial cell vigor that the composition of table 1 stimulates MSU
Note：Compared with model group, * P<0.05；Compared with control group,△P<0.05
4 express influence to ICAM-1
By the HUVEC in exponential phase with 0.25% Trypsin Induced, gently blow and beat, be made cell suspension,
Adjustment cell density is 5 × 109/ L, is inoculated in Tissue Culture Flask.After cell is covered with (about 24h), abandoning supernatant is divided into
Following group：Control group, model group (100ug/ml MSU solution), intervention group (100ug/ml MSU solution+25ug/ml compositions
Or compound), continuing to cultivate 24 hours, PBS collects cell, and supernatant is removed in centrifugation, adds CD54 monoclonal antibodies, after 30min,
PBS is washed, and re-suspended cell using its positive percentage (n=10000) of flow cytomery, is repeated 3 times, as a result sees
Table 2.
The influence of the ICAM-1 Expression in Vascular Endothelial Cells that the composition of table 2 stimulates MSU
Note：Compared with model group, * P<0.05；Compared with control group,△P<0.05
Result shows that blank group HUVEC is expressed almost without ICAM-1, the expression highest of model group ICAM-1, with model group
Compare, expression of the composition to ICAM-1 has significant inhibitory action, and compound III and compound IV suppresses to make without significant
With.
Conclusion：The acute gout model evaluation that HUVEC is damaged is caused to show with MSU, composition can protect MSU to cause HUVEC to damage
Wound, reduces Apoptosis, improves cytoactive, suppresses ICAM-1 and expresses, the activity with anti-acute gout inflammation, and composition can
For preparing treatment acute gout anti-inflammatory drugs.And compound III and compound IV can not protect MSU to cause HUVEC to damage, it is impossible to
Reduce Apoptosis, it is impossible to improve cytoactive, it is impossible to suppress ICAM-1 and express, the activity without anti-acute gout inflammation,
Cannot be used for preparing treatment acute gout anti-inflammatory drugs.
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 (6)
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 15% and 85%,
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 15% and 85% according to mass percent and be sufficiently mixed.
3. application of a kind of composition as claimed in claim 1 in acute gout medicine is treated.
4. application of the composition as claimed in claim 3 in acute gout medicine is treated, it is characterized by：The acute gout
It is to be induced by Monosodium urate.
5. application of the composition as claimed in claim 3 in acute gout medicine is treated, it is characterized by：Composition reduces people
The damage of vascular endothelial cell, improves the activity of human vascular endothelial.
6. application of the composition as claimed in claim 3 in acute gout medicine is treated, it is characterized by：Composition reduces anxious
The expression of ICAM-1 during property gout.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101646440A (en) * | 2007-01-19 | 2010-02-10 | 武田制药北美公司 | Methods for preventing or reducing the number of gout flares using xanthine oxidoreductase inhibitors and anti-inflammatory agents |
| CN106046017A (en) * | 2016-06-07 | 2016-10-26 | 黄芳 | Medicine composition containing huperzine-A and medical application of medicine composition |
-
2016
- 2016-12-16 CN CN201611168133.5A patent/CN106692136A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101646440A (en) * | 2007-01-19 | 2010-02-10 | 武田制药北美公司 | Methods for preventing or reducing the number of gout flares using xanthine oxidoreductase inhibitors and anti-inflammatory agents |
| CN106046017A (en) * | 2016-06-07 | 2016-10-26 | 黄芳 | Medicine composition containing huperzine-A and medical application of medicine composition |
Non-Patent Citations (5)
| Title |
|---|
| HUCHENG ZHU等: "Hyperascyrones A–H, polyprenylated spirocyclic acylphloroglucinol derivatives from Hypericum ascyron Linn.", 《PHYTOCHEMISTRY》 * |
| 吕江明 等: "黄海棠提取物抗炎镇痛效应的研究", 《实用中西医结合临床》 * |
| 国家食品药品监督管理局执业药师资格认证中心: "《药学综合知识与技能》", 30 April 2013, 中国医药科技出版社 * |
| 杨玺: "《专家谈痛风用药技巧》", 30 June 2012, 人民军医出版社 * |
| 武东 等: "痛风的治疗进展", 《临床荟萃》 * |
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