CN103463001B - Application of Neonectrolide A to preparation of medicament for treating acute gout - Google Patents
Application of Neonectrolide A to preparation of medicament for treating acute gout Download PDFInfo
- Publication number
- CN103463001B CN103463001B CN201310360636.2A CN201310360636A CN103463001B CN 103463001 B CN103463001 B CN 103463001B CN 201310360636 A CN201310360636 A CN 201310360636A CN 103463001 B CN103463001 B CN 103463001B
- Authority
- CN
- China
- Prior art keywords
- neonectrolide
- acute gout
- msu
- preparation
- application
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 201000005569 Gout Diseases 0.000 title claims abstract description 34
- 230000001154 acute effect Effects 0.000 title claims abstract description 26
- 239000003814 drug Substances 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 abstract description 13
- 230000006378 damage Effects 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 3
- 210000002889 endothelial cell Anatomy 0.000 abstract description 3
- 210000003606 umbilical vein Anatomy 0.000 abstract description 2
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 abstract 1
- 208000027418 Wounds and injury Diseases 0.000 abstract 1
- 208000014674 injury Diseases 0.000 abstract 1
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 13
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000012531 culture fluid Substances 0.000 description 8
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 244000309466 calf Species 0.000 description 4
- 230000003833 cell viability Effects 0.000 description 4
- 229960000905 indomethacin Drugs 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 206010018634 Gouty Arthritis Diseases 0.000 description 3
- 241001335047 Neonectria sp. Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 229940124599 anti-inflammatory drug Drugs 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000003714 granulocyte Anatomy 0.000 description 3
- 230000003448 neutrophilic effect Effects 0.000 description 3
- 210000003556 vascular endothelial cell Anatomy 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 241000204031 Mycoplasma Species 0.000 description 2
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 229940116269 uric acid Drugs 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000009514 concussion Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- NAFSTSRULRIERK-UHFFFAOYSA-M monosodium urate Chemical compound [Na+].N1C([O-])=NC(=O)C2=C1NC(=O)N2 NAFSTSRULRIERK-UHFFFAOYSA-M 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention provides novel application of a compound Neonectrolide A in medicine, in particular to application of the compound Neonectrolide A to preparation of a medicament for treating acute gout. An experimental research result shows that the Neonectrolide A has a protection effect on an MSU-induced HUVEC (Human Umbilical Vein Endothelial Cells) injury acute gout model and inhibits expression of ICAM-1, and thus, the compound Neonectrolide A can be used for application to preparation of the medicament for treating the acute gout.
Description
Technical field
The present invention relates to the novelty teabag of compound N eonectrolide A, particularly relate to the application of Neonectrolide A in preparation treatment acute gout medicine.
Background technology
Gout (gouty), also known as gouty arthritis (gouty arthritis), is the disease in body caused by purine metabolic disturbance, shows as uric acid in blood too much, is easy to make urate (MSU) organize crystallization in joint etc.The acute attack of gout is that the MSU owing to being deposited on joint causes neutrophilic granulocyte local infiltration and inflammatory reaction.
The compound N eonectrolide A that the present invention relates to is one and delivers (Jinwei Ren in 2012, et al., Neonectrolide A, a New Oxaphenalenone Spiroketal from the Fungus Neonectria sp.Organic Letters, 2012, 14(24) 6226 – 6229.) noval chemical compound, this compound has brand-new framework types, current purposes only relates to antitumor cell increment (Jinwei Ren, et al., Neonectrolide A, a NewOxaphenalenone Spiroketal from the Fungus Neonectria sp.Organic Letters, 2012, 14(24) 6226 – 6229.), the purposes of the Neonectrolide A that the present invention relates in preparation treatment acute gout medicine is belonged to first public.
Summary of the invention
The present invention MSU causes the acute gout model evaluation display that human vascular endothelial (HUVEC) damages, and causes HUVEC damage and has protective effect, and suppress ICAM-1 to express to MSU, can be used for preparation treatment acute gout anti-inflammatory drugs.The object of the present invention is to provide the novelty teabag of Neonectrolide A in medical science, specifically relate to the application of Neonectrolide A in preparation treatment acute gout medicine.
The object of the invention is to be realized by following technical scheme:
The explanation of modern medicine pathological study, gouty arthritis is that MSU causes neutrophilic granulocyte local infiltration and inflammatory reaction, the essence that acute gout produces is that neutrophilic granulocyte (PMN)-vascular endothelial cell (HUVEC) is adhered enhancing, HUVEC damages, its molecular biology mechanism is the interaction of PMN and HUVEC surface adhesion molecule, wherein ICAM-1 (ICAM-1) is the closest with adhesion function relation, is one of important indicator of acute gout inflammation.
Therefore, cause HUVEC damage for acute gout MSU, the pathological characters of ICAM-1 increasing expression, the present invention MSU causes the external acute gout model of HUVEC damage, evaluates the anti-acute gout inflammatory activity of Neonectrolide A.MSU causes the acute gout model evaluation display that human vascular endothelial (HUVEC) damages, and causes HUVEC damage and has protective effect, and suppress ICAM-1 to express to MSU.
The present invention proposes the application of Neonectrolide A in preparation treatment acute gout medicine.Find out from pharmacological evaluation, Neonectrolide A has treatment acute pain wind action preferably.Due to the pharmacological action of the first public Neonectrolide A of the present invention in treatment acute gout.
Described compound N eonectrolide A structure is as shown in formula I:
Result of study shows; the acute gout model evaluation display of HUVEC damage is caused with MSU; Neonectrolide A can protect MSU to cause HUVEC damage; reduce apoptosis; improve cytoactive; suppress ICAM-1 to express, have the activity of anti-acute gout inflammation, Neonectrolide A can be used for preparation treatment acute gout anti-inflammatory drugs.
The purposes of the Neonectrolide A that the present invention relates in preparation treatment acute gout medicine belongs to first public, because framework types belongs to brand-new framework types, and its control for acute gout is active unexpectedly strong, there is not the possibility being provided any enlightenment by other compounds, possess outstanding substantive distinguishing features, the control simultaneously for acute gout obviously has significant progress.
Detailed description of the invention
The preparation method of compound N eonectrolide A involved in the present invention is see document (Jinwei Ren, et al., Neonectrolide A, a New Oxaphenalenone Spiroketal from the Fungus Neonectria sp.Organic Letters, 2012,14(24) 6226 – 6229.)
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not by any restriction of specific embodiment, but be limited by claim.
Embodiment 1: the preparation of compound N eonectrolide A tablet involved in the present invention:
Get 5 g of compound Neonectrolide A, add 195 grams, dextrin, mixing, Conventional compression makes 1000.
Embodiment 2: the preparation of compound N eonectrolide A capsule involved in the present invention:
Get 5 g of compound Neonectrolide A, add starch 195 grams, mixing, encapsulatedly makes 1000.
Its pharmaceutically active is further illustrated below by pharmacodynamic experiment.
The anti-acute gout inflammation test of experimental example 1:Neonectrolide A:
1: method
1. solution preparation
5g uric acid adds 1000ml distilled water and boils, and add 5%NaOH solution and adjust PH7.4, stir, cooling crystallization makes Monosodium urate crystallization (MSU).By the MSU10mg autoclaving made, add not containing the DMEM culture fluid 10ml of serum, grinding is made into the DMEM solution of 1mg/ml.During experiment, this solution adds the MSU solution that DMEM culture fluid is made into variable concentrations DMEM again.
Neonectrolide A2.5mg, dissolve with dimethyl sulfoxide (DMSO), DMSO final concentration <0.02%, then the DMEM culture fluid adding serum-free, be mixed with concentration 2.5ug/ml, 25ug/ml, 250ug/ml.
Positive drug indomethacin 2.0mg, method with Neonectrolide A, compound concentration 20ug/ml.
2. the In vitro culture of vascular endothelial cell
Human umbilical vein endothelial cell HUVEC strain, thered is provided by preclinical medicine institute of Nanjing University of Traditional Chinese Medicine, cell is through detection of mycoplasma, and without mycoplasma contamination, cell is through 0.25% trypsinization, DMEM culture fluid containing 10% calf serum neutralizes, centrifugal (1000r/min × 6min), removes supernatant, adds the DMEM culture fluid containing 10% calf serum, move in Tissue Culture Flask, put 37 DEG C, 5%CO
2secondary Culture in incubator.
3. MSU is stimulated to the impact of HUVEC vigor
HUVEC cultivates in culture bottle, and in time growing to 70% ~ 80% and merge, with 0.25% trypsinization, centrifugal, 10% calf serum DMEM culture fluid washs 3 times, with 10% calf serum DMEM culture fluid furnishing 4 × 10
4/ ml cell suspension, implant 96 orifice plates (every hole 200ul), cultivate light sucking-off original fluid after 24 hours, carry out following experiment, often organize each 8 holes, concrete grouping and liquid feeding as follows: matched group (200ulDMEM culture fluid), model group (100ug/ml MSU solution), intervene A group (100ug/ml MSU solution+2.5ug/ml Neonectrolide A), intervene B group (100ug/ml MSU solution+25ug/mlNeonectrolide A), intervene C group (100ug/ml MSU solution+250ug/ml Neonectrolide A), continue after liquid feeding to put 37 DEG C, 5%CO
2cultivate 24 hours in incubator, collect supernatant, remaining HUVEC is for measuring cytoactive, and every hole adds 5mg/ml MTT liquid 20ul again, continues to put 37 DEG C, 5%CO
2cultivate after 4 hours in incubator, abandon MTT liquid, add dimethyl sulfoxide 200ul and dissolve, concussion, read absorbance in microplate reader, wavelength 490nm.
Positive drug group liquid feeding (100ug/ml MSU solution+20ug/ml indomethacin), additive method is the same.
Data statistics processes, and cell viability (%)=experimental group absorbance/matched group absorbance × 100%, the results are shown in Table 1.
Compared with matched group, model group cell viability significantly reduces (P<0.01, P<0.05), after positive drug indomethacin and Neonectrolide A intervene, cell viability significantly improves (P<0.01, P<0.05), and be better than matched group, wherein, the cell viability of each concentration group of Neonectrolide A is better than positive drug indomethacin.
Table 1Neonectrolide A is on the impact (X ± s) of the vascular endothelial cell vigor that MSU stimulates
Compare with model group,
*p<0.01
*p<0.05, compares with matched group,
##p<0.01
#p<0.05
4. impact is expressed on ICAM-1
To be in the HUVEC trypsinization of 0.25% of exponential phase, and blow and beat gently, make cell suspension, adjustment cell density is 5 × 10
9/ L, is inoculated in Tissue Culture Flask.After cell covers with (about 24h), abandoning supernatant, is divided into following group: matched group, model group (100ug/ml MSU solution), Neonectrolide A group (100ug/ml MSU solution+25ug/mlNeonectrolide A), continue cultivation 24 hours, PBS collecting cell, centrifugally removes supernatant, adds CD54 monoclonal antibody, after 30min, PBS washs, re-suspended cell, application its positive percentage of flow cytomery (n=10000), repeat 3 times, the results are shown in Table 2.
Table 2Neonectrolide A is on the impact (X ± s) of the ICAM-1 Expression in Vascular Endothelial Cells that MSU stimulates
Compare with model group,
*p<0.01
*p<0.05, compares with matched group,
##p<0.01
#p<0.05
2, result result display, blank group HUVEC almost expresses without ICAM-1, and the expression of model group ICAM-1 is the highest, and compared with model group, the expression of Neonectrolide A to ICAM-1 has stronger inhibitory action.
Conclusion: the acute gout model evaluation display causing HUVEC damage with MSU; Neonectrolide A can protect MSU to cause HUVEC damage; reduce apoptosis; improve cytoactive; ICAM-1 is suppressed to express; have the activity of anti-acute gout inflammation, Neonectrolide A can be used for preparation treatment acute gout anti-inflammatory drugs.
Claims (1)
- The application of 1.Neonectrolide A in preparation treatment acute gout medicine, described compound N eonectrolideA structure is as shown in formula I:Formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310360636.2A CN103463001B (en) | 2013-08-17 | 2013-08-17 | Application of Neonectrolide A to preparation of medicament for treating acute gout |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310360636.2A CN103463001B (en) | 2013-08-17 | 2013-08-17 | Application of Neonectrolide A to preparation of medicament for treating acute gout |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103463001A CN103463001A (en) | 2013-12-25 |
| CN103463001B true CN103463001B (en) | 2015-04-15 |
Family
ID=49788199
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310360636.2A Expired - Fee Related CN103463001B (en) | 2013-08-17 | 2013-08-17 | Application of Neonectrolide A to preparation of medicament for treating acute gout |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103463001B (en) |
-
2013
- 2013-08-17 CN CN201310360636.2A patent/CN103463001B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN103463001A (en) | 2013-12-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114028453A (en) | Broad-spectrum antiviral drug, and pharmaceutical composition and application thereof | |
| CN103462950B (en) | Application of scopariusins in preparation of medicine treating acute gout | |
| CN103463001B (en) | Application of Neonectrolide A to preparation of medicament for treating acute gout | |
| CN106491589A (en) | Applications of the Linderolide H in treatment acute gout medicine is prepared | |
| CN105250266A (en) | Application of Hirsutellone B in preparing medicine for curing acute gout | |
| CN103655551B (en) | Application of Manzamenone O in acute gout treatment medicines | |
| CN105287505A (en) | Application of Microphyllandiolide in preparation of acute gout treating medicine | |
| CN105476978A (en) | Application of Norsampsone A in preparing medicine for treating acute gout | |
| CN105456245A (en) | Application of Vulgarisin A in preparing medicine for treating acute gout | |
| CN103405426B (en) | Application of compound in preparation of medicines for treating acute gout | |
| CN103372010B (en) | The application of Chukrasone B in preparation treatment acute gout medicine | |
| CN102988384A (en) | Application of Houttuynoid C for preparing medicine for treating acute gout | |
| CN103127087A (en) | Application of Aphanamixoid A in medicines curing acute gout | |
| CN105412069A (en) | Application of Herqueioxazole in preparation of acute gout treatment drug | |
| CN105395529A (en) | Application of Dysidavarone A in preparation of drugs treating acute gouty | |
| CN104998270A (en) | Medicine for treating acute gout and application thereof | |
| CN105287451A (en) | Use of Foveoeudesmenone in preparation of drug for treating acute gout | |
| CN103381163B (en) | The application of Chukrasone A in preparation treatment acute gout medicine | |
| CN105078987A (en) | Composition 38083001030527 and application of composition 38083001030527 to drug for resisting acute gout | |
| CN102861030B (en) | Application of Gypensapogenin B in medicine for treating acute gout | |
| CN103768049B (en) | The application of Eryngiolide A in treatment acute gout medicine | |
| CN103462978A (en) | Application of spirooliganones B in preparation of medicine treating acute gout | |
| CN103463102A (en) | Application of Kadcoccitones A in preparing medicament for treating acute gout | |
| CN103463108A (en) | Application of Phyllanthoid A in preparing medicament for treating acute gout | |
| CN104825470A (en) | Application of cleistanone O-(benzimidazolyl) ethyl derivative in preparation of drugs for treating acute gout |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: ZHANG ZHEFU Free format text: FORMER OWNER: ZHANG SUFENG Effective date: 20150319 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| C53 | Correction of patent for invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhou Weidong Inventor after: Pan Feng Inventor after: Xu Qili Inventor after: Wang Lizhong Inventor after: Xu Zengliang Inventor after: Zhang Zhefu Inventor before: Zhang Sufeng |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: ZHANG SUFENG TO: ZHOU WEIDONG PAN FENG XU QILI WANG LIZHONG XU ZENGLIANG ZHANG ZHEFU Free format text: CORRECT: ADDRESS; FROM: 315016 NINGBO, ZHEJIANG PROVINCE TO: 325000 WENZHOU, ZHEJIANG PROVINCE |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20150319 Address after: The streets of Haicheng Dai Gang Lu Longwan District of Wenzhou City, Zhejiang Province, No. 15 325000 Applicant after: Zhang Zhefu Address before: 315016 Hai Guang building, No. 298 West Zhongshan Road, Haishu District, Zhejiang, Ningbo Applicant before: Zhang Sufeng |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: JIANGSU BAIJIAN PHARMACENTICAL TECHNOLOGY CO., LTD Free format text: FORMER OWNER: ZHANG ZHEFU Effective date: 20150427 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 325000 WENZHOU, ZHEJIANG PROVINCE TO: 226500 NANTONG, JIANGSU PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20150427 Address after: 226500, No. 999, Wanshou South Road, Chengnan street, Rugao City, Jiangsu province (room 3A08-26, building 8, Rugao hi tech Zone) Patentee after: Jiangsu hundred sword Pharmaceutical Technology Co., Ltd. Address before: The streets of Haicheng Dai Gang Lu Longwan District of Wenzhou City, Zhejiang Province, No. 15 325000 Patentee before: Zhang Zhefu |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150415 Termination date: 20190817 |