CN106580944A

CN106580944A - Application of OrthosipholB in preparation of drugs for treating gout

Info

Publication number: CN106580944A
Application number: CN201611225723.7A
Authority: CN
Inventors: 蒋敏捷; 林彩霞; 许立拔; 巫玲玲; 蒋伟哲
Original assignee: Guangxi Medical University
Current assignee: Guangxi Medical University
Priority date: 2016-12-27
Filing date: 2016-12-27
Publication date: 2017-04-26

Abstract

The invention discloses application of OrthosipholB in preparation of drugs for treating gout, belongs to the technical field of medicines and particularly relates to application of the OrthosipholB in preparation of drugs for treating primary gout and application of the OrthosipholB in preparation of drugs for treating secondary gout. The OrthosipholB is used for preparing anti-gout drugs, new therapeutic drugs can be provided for patients suffering from the gout, and various side effects brought by currently used anti-gout drugs can be reduced. The OrthosipholB has the advantages of being small in dosage and good in treating effect.

Description

Applications of the OrthosipholB in treatment gout medicine is prepared

Technical field

The present invention relates to pharmaceutical technology field, is specifically related to OrthosipholB answering in treatment gout medicine is prepared With.

Background technology

Hyperuricemia and gout have become one of ciril disease of the modern life, be one kind due to internal purine anabolism Increase, uric acid produces excess or causes uric acid in blood to raise because urate excretion is bad, and hyperuricemia is gout One biochemical marker.The clinical manifestation of gout is often divided into acute stage, intermission, chronic phase and nephropathy etc., is mainly shown as Gouty arthritises and gouty nephropathy.Nephropathy is the result of long-term hyperuricemia development, hyperuricemia Kidneys of patients pathologic finding almost has different degrees of infringement, and renal symptom occurs in the course of disease in about 1/3 patient.With regard to height Lithemic treatment, secondary hyperuricemia is treated mainly for its underlying diseases, and primary hyperuricemia Treatment, typically using diet, motor control Drug therapy in addition.Suppress uricopoiesis medicine main mechanism to suppress xanthine Oxidase（XO）Activity.Allopurinol is the representative of this kind of medicine, is all the time the clinical first-line drug of gout, and the medicine can Suppress xanthine oxidase, affect uricopoiesis, reduce uric acid in blood, prevent ventilation outbreak.But, the side effect of the medicine compared with Greatly, although uric acid resisting effect is significant, it is but very weak to the defencive function of kidney, or even hepatic insufficiency, renal failure etc. can be caused.

Compound OrthosipholB according to the present invention, can extract from kidney tea and obtain, with hypoglycemic effect.This It is first public that invention is used as preparing anti-ventilation medicine.

The content of the invention

It is an object of the invention to provide applications of the OrthosipholB in treatment gout medicine is prepared, in order to realize this The purpose of invention, adopts the following technical scheme that：

OrthosipholB treats the application in gout medicine in preparation, and the structural formula of the OrthosipholB is：

In above-mentioned technical proposal, preferably, described medicine includes or does not include other active component.

In above-mentioned technical proposal, preferably, described medicine does not contain other active component, also containing pharmaceutically can connecing The adjuvant received.

In above-mentioned technical proposal, preferably, the OrthosipholB is in treatment primary gout medicine is prepared Using.

In above-mentioned technical proposal, preferably, the OrthosipholB is in treatment secondary gout medicine is prepared Using.

In upper technical scheme, the dosage form of the medicine is liquid preparation.

In above-mentioned technical proposal, preferably, the concentration of OrthosipholB is 2.5 ~ 250 micrograms/milli in the medicine Rise.

In above-mentioned technical proposal, preferably, the concentration of OrthosipholB is 20 ~ 50 mcg/mls in the medicine.

In above-mentioned technical proposal, preferably, the concentration of OrthosipholB is 25 mcg/mls in the medicine.

Beneficial effect：OrthosipholB in the present invention can be extracted from kidney tea and obtained, and raw material is easily obtained, and has Hypoglycemic effect, to by congenital purine metabolic disturbance and（Or）Primary gout caused by uric acid excretion disorder and it is secondary to Uricopoiesis increase caused by underexcretion, myeloproliferative disease and chemotherapy of tumors caused by kidney disease or some drugses Secondary gout there is significant therapeutic effect.Therefore, OrthosipholB is used to prepare anti-gout drugs, can is pain Syndrome caused by wind pathogen people provides new medicine, can reduce the various side effect for using anti-gout drugs to occur at present.The present invention has Dosage is low, eutherapeutic feature.

Specific embodiment

If not specified, the conventional meanses that technological means used are well known to those skilled in the art in embodiment.

Its pharmaceutically active is further illustrated below by pharmacodynamic experiment.

Embodiment 1：

OrthosipholB gout inflammation tests：

Concrete grammar is as follows：

1. solution is prepared

1000ml distilled water is added to boil 5g uric acid, plus 5% NaOH solution adjusts pH7.4, stirring, cooling crystallization to make Monosodium urate crystallizes (MSU).By the MSU10mg autoclavings for making, plus the DMEM culture fluid 10ml without serum, grinding It is made into the DMEM solution of 1mg/ml.During experiment, this solution adds again DMEM culture fluid to be made into variable concentrations DMEM's MSU solution.

OrthosipholB 2.5mg, are dissolved, final concentration with ethanol<0.02%, then add the DMEM cultures of serum-free Liquid, is configured to concentration 2.5ug/ml, 25ug/ml, 250ug/ml.

Positive drug indomethacin 2.0mg, the same OrthosipholB of method, compound concentration 20ug/ml.

2. the In vitro culture of vascular endothelial cell

Human umbilical vein endothelial cell HUVEC strains, are provided, cell Jing detection of mycoplasma by Guangxi medical college, without an original Body pollution, the trypsinizations of cell Jing 0.25%, the neutralization of the DMEM culture fluid containing 10% calf serum is centrifuged (1000r/ Min × 6min), remove supernatant, plus the DMEM culture fluid containing 10% calf serum, in moving into Tissue Culture Flask, put 37 DEG C, 5% CO₂Secondary Culture in incubator.

3. the impact of HUVEC vigor is stimulated MSU

HUVEC is cultivated in culture bottle, to be grown when 70%～80% fusion, with 0.25% trypsinization, centrifugation, 10% calf serum DMEM culture fluid is washed 3 times, and with 10% calf serum DMEM culture fluid 4 × 104/ml is tuned into Cell suspension, 96 orifice plates of implantation (per hole 200ul), culture gently suctions out original fluid after 24 hours, carries out following experiment, Per group of each 8 hole, specifically packet and liquid feeding are as follows：Matched group (200ulDMEM culture fluid), (100ug/ml MSU are molten for model group Liquid), intervene A groups (100ug/ml MSU solution+2.5ug/ml OrthosipholB), intervene B group (100ug/ml MSU solution+25ug/ ml OrthosipholB), intervene C groups (100ug/ml MSU solution+250ug/ml OrthosipholB), continue to put 37 DEG C, 5% CO after liquid feeding₂Cultivate 24 hours in incubator, collect supernatant, it is remaining HUVEC be used to determine cytoactive, per Kong Zaijia 5mg/ml MTT liquid 20ul, continue to put 37 DEG C, 5% CO₂Culture After cultivating 4 hours in case, MTT liquid is abandoned, add dimethyl sulfoxide 200ul dissolvings, concussion to read extinction in microplate reader Angle value, wavelength 490nm.

Positive drug group liquid feeding (100ug/ml MSU solution+20ug/ml indomethacins), additive method is ibid.

Statistical data process, cell viability (%)=experimental group absorbance/matched group absorbance × 100%, the results are shown in Table 1.

Table 1 is the impact (X ± s) of the vascular endothelial cell vigor that OrthosipholB stimulates MSU.

Table 1

Group	Drug level（Mcg/ml）	N/ holes	Cell viability（%）
				Matched group	0	8	100
Model group	0	8	86
				Positive drug	20	8	107
Intervene A groups	2.5	8	176
				Intervene B groups	25	8	209
Intervene C groups	250	8	195

As can be seen from Table 1, compared with matched group, model group cell viability is substantially reduced (P<0.01, P<0.05), positive drug Cell viability significantly improves (P after indomethacin and OrthosipholB intervene<0.01, P<0.05), and matched group is better than, its In, the cell viability of each concentration groups of OrthosipholB is better than positive drug indomethacin.

4. ICAM-1 expression is affected

By the HUVEC in exponential phase with 0.25% trypsinization, gently blow and beat, make cell suspension, adjust Whole cell density is 5 × 109/L, in being inoculated in Tissue Culture Flask.After cell is covered with (about 24h), abandoning supernatant is divided into Following group：Matched group, model group (100ug/ml MSU solution), OrthosipholB groups (100ug/ml MSU solution+ 25ug/ml OrthosipholB), continue to cultivate 24 hours, PBS collects cell, and supernatant is removed in centrifugation, adds CD54 Dan Ke Grand antibody, after 30min, PBS washings, re-suspended cell, using flow cytomery its positive percentage (n= 10000), repeat 3 times, the results are shown in Table 2.

Table 2 be OrthosipholB vascular endothelial cell ICAM-1 that MSU is stimulated express impact (X ± s)。

Table 2

Group	Drug level	ICAM is expressed
			Matched group	0	15±4
Model group	0	233±49
			OrthosipholB groups	25	188±46

Compare with model group, * * P<0.01*P<0.05, compare with matched group, ##P<0.01#P<0.05 .

2nd, result

As a result show, blank group HUVEC is expressed almost without ICAM-1, the expression highest of model group ICAM-1, with model Group is compared, and expression of the OrthosipholB to ICAM-1 has stronger inhibitory action.

Conclusion：The Gout Model evaluation that HUVEC is damaged is caused to show that OrthosipholB can protect MSU to cause with MSU HUVEC is damaged, and reduces apoptosis, improves cytoactive, suppresses ICAM-1 expression, with gout activity, OrthosipholB can be used to prepare treatment gout anti-inflammatory drugs.

The above is the preferred embodiments of the present invention, it is noted that for those skilled in the art come Say, on the premise of without departing from principle of the present invention, some improvements and modifications can also be made, these improvements and modifications also should It is considered as protection scope of the present invention.

Claims

Applications of the 1.OrthosipholB in treatment gout medicine is prepared, it is characterised in that the knot of the OrthosipholB Structure formula is：

。
2. the application according to claim 1, it is characterised in that：Described medicine includes or does not include other activity Composition.
3. application according to claim 2, it is characterised in that：Described medicine does not contain other active component, also contains There is pharmaceutically acceptable adjuvant.
4. the application according to claim 1, it is characterised in that：The OrthosipholB is preparing treatment constitutional pain Application in expelling wind drug thing.
5. the application according to claim 1, it is characterised in that：The OrthosipholB is preparing treatment Secondary cases pain Application in expelling wind drug thing.
6. the application according to any one of claim 1 to 5, it is characterised in that：The dosage form of the medicine is liquid preparation.
7. application according to claim 6, it is characterised in that：In the medicine concentration of OrthosipholB be 2.5 ~ 250 mcg/mls.
8. application according to claim 7, it is characterised in that：The concentration of OrthosipholB is 20 ~ 50 in the medicine Mcg/ml.
9. application according to claim 8, it is characterised in that：The concentration of OrthosipholB is 25 micro- in the medicine Grams per milliliter.