CN1147303C - Application of Breviscapine in preparing medicine - Google Patents
Application of Breviscapine in preparing medicineInfo
- Publication number
- CN1147303C CN1147303C CNB001174762A CN00117476A CN1147303C CN 1147303 C CN1147303 C CN 1147303C CN B001174762 A CNB001174762 A CN B001174762A CN 00117476 A CN00117476 A CN 00117476A CN 1147303 C CN1147303 C CN 1147303C
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- China
- Prior art keywords
- breviscapine
- diabetes
- diabetic
- complication
- application
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Abstract
The present invention relates to a new purpose in the medicine preparation of 4, 5, 6-trihydroxyflavone-7-O-glucuronic acid glucoside which is also called breviscapine. The substance has the functions of tunica intima and vascular smooth muscle functional lesion when preventing and treating diabetes; thereby, diabetic complication caused by vascular functional lesion such as diabetic nephropathy, an eye disease, a coronary heart disease, sexual impotence, stomach motion retardation, etc. can be obviously prevented and treated. The substance obviously prevents and treats the diabetic complication under the condition that the blood sugar level of diabetics is not affected, and the functional target point is used for blocking a signal conduction system in a cell of the complication caused by hyperglycemia.
Description
The present invention relates to the extract-4` of Herba Erigerontis, 5,6-trihydroxyflavone-7-O-glucuronide has another name called the purposes of breviscapine, relates in particular to the purposes in pharmaceutical field.
Its chemical structural formula is:
Molecular formula is C
25H
24O
12, light khaki is Powdered, and molecular weight is 462.21, dissolves in alkaline water.
Herba Erigerontis is the herb of the short booth Herba Erigerontis aceris of Compositae, has activating blood circulation to dissipate blood stasis, the effect of regulating QI to relieve pain.Its treatment cerebrovascular disease of motherland's medical use, evident in efficacy.Breviscapine is that Herba Erigerontis is through the concise effective ingredient of special processes.Existing clinically treat sequela due to cerebral blood supply insufficiency, cerebral thrombosis, the cerebral hemorrhage, high blood viscosity with it.
At present for treatment of diabetes, though effectively control of diabetes patient's blood sugar level of many medicines is arranged clinically, but diabetics is dead mostly in the complication relevant with it, and especially cardiovascular and renal complication have become the diabetics main causes of death.For the treatment of diabetic complications, still lack effective medicine at present clinically.Can in the world complication such as diabetic nephropathy there be certainly effectively medicine (even ACEI) at present in particular.Though synthetic drug aminoguanidine (registered patent) has been developed nearly four more than ten years, because its side effect still fails to be used for clinical at present.Breviscapine is compared with aminoguanidine, and the effect of its prevention complication is stronger than aminoguanidine, and do not have aminoguanidine side effect, so its curative effect is very definite.
The object of the present invention is to provide the new purposes of breviscapine, i.e. new application in pharmacy.
In fact, the present invention relates to the application of breviscapine in the medicine of preparation treatment or prevent diabetes complication.
The present invention relates to breviscapine as the application in the medicine of preparation treatment or diabetes and nephropathy preventing complication.
Relate to breviscapine as the application in the medicine of preparation treatment or prevent diabetes oculopathy complication.
Relate to breviscapine as the application in the medicine of preparation treatment or prevent diabetes coronary heart disease complication.
Also relate to breviscapine as the application in the medicine of preparation treatment or prevent diabetes reproductive system complication.
Also relate to breviscapine as the application in the medicine of preparation treatment or prevent diabetes gastrointestinal complication.
Also relate to breviscapine as the application in the medicine of preparation treatment or prevent diabetes nervous system complication.
Essence for a better understanding of the present invention will illustrate its new purposes in pharmaceutical field with the pharmacological evaluation and the result of breviscapine below.
Fig. 1 is the myocardium vessel ring experiment sketch map of breviscapine;
Fig. 2 is in the body blood vessel experiment of breviscapine, tunica intima dependent vasorelaxation sketch map;
Fig. 3 is in the body blood vessel experiment of breviscapine, vascular smooth muscle stretching reaction sketch map.
1. the acute toxicity testing of white mice
A. oral administration: 10 of healthy male white mouses, body weight 17-24g irritates stomach by breviscapine 10g/kg and did not see death in three days.
B. drug administration by injection: 10 of healthy male white mouses, body weight 17-24g with breviscapine dissolving back drug administration by injection, calculates by simplifying probit method, records
LD50(iv)＝1300+160mg/kg。
2. the long term toxicity test of rat
30 of Wistar male white rats, body weight 200-250g is divided into 3 groups, 10 every group.Breviscapine is irritated stomach respectively by 1g/kg, 0.5g/kg, 0.1g/kg dosage and is detected after 3 months and learn, hepatic and renal function, surrounding hemogram, behavior, defecation routine all there are not obvious influence, also no abnormal to the pathological examination of vitals such as the heart, liver, lung.
3. myocardium vessel ring experiment
As shown in Figure 1, in the tunica intima functional experiment: Control, expression matched group.Diabetic, the expression diabetic groups.EB+treated, expression diabetes+breviscapine treatment group.
*Compare with diabetic groups.
The Wistar male rat, body weight 200-250g, the injection of chain urine rhzomorph (65mg/kg) disposable celiac.Injection 1 week of back, get one of tail blood, judge its hyperglycemia (contrast 5.0+0.5mM, diabetes 22+5mM) with the Bao Lingman blood glucose meter.Diabetic groups is further divided into: diabetic groups, diabetes+breviscapine group.Respectively in the 2nd, 6 weeks of experiment, rat broken end is got the aortic annulus observation that experimentizes.The result: in the 2nd week of experiment, under the phyenlephrinium preshrinking, the stretching reaction of Ach is when low concentration, and diabetic groups obviously weakens, but maximum stretching reaction does not have significant change compared with the control.When the 6th week, the concentration dependent inner membrance stretching reaction curve of diabetic groups acetylcholine all obviously weakens compared with the control in each concentration point, maximum stretching reaction has reduced about 60%[10uM Ach, diabetic groups 57.4 ± 14.4% (n=6) vs matched group 0% (n=6), P＜0.001], yet in breviscapine treatment group, though when the acetylcholine low concentration, still weaken to some extent, but maximum stretching reaction is approaching with contrast, and the stretching reaction of comparing acetylcholine with diabetic groups all obviously increases.[0.01 and 0.03uM Ach; Breviscapine treatment group 80.5 ± 4.2% and 58.8 ± 7.3% (n=6) vs matched group, 45.8 ± 9.2%and, 20.1 ± 4.1% (n=6), p＜0.01.].
4. test at the body blood vessel
A, as shown in Figure 2, Control represents matched group, and DM represents diabetic groups, and BT represents breviscapine treatment group.Tunica intima dependent vasorelaxation: 50 of Wistar male rats, body weight 200-250g, the injection of chain urine rhzomorph (65mg/kg) disposable celiac.Injection 1 week of back, get one of tail blood, judge its hyperglycemia (contrast 5.0+0.5mM, diabetes 20+3.5mM) with the Bao Lingman blood glucose meter.Diabetic groups is further divided into: diabetic groups, diabetes+breviscapine group.In the 12 week, row common carotid artery and femoral venous catheter behind the rat anesthesia are pressed the acetylcholine that 0.5ml/kg injects variable concentrations, observe the variation of blood pressure.Found that: the acetylcholine of 0.001uM can cause the blood pressure drops of normal rat, and the acetylcholine of 0.1uM just can cause the blood pressure drops of diabetes rat, at the diabetes rat of taking the 0.1g/kg breviscapine, the acetylcholine of 0.001uM also can cause the blood pressure drops of diabetes rat.Decline curve is very approaching in diabetic groups of taking breviscapine and normal control.
B, as shown in Figure 3, Control represents matched group, and DM represents diabetic groups, and BT represents breviscapine treatment group.The vascular smooth muscle stretching reaction: other condition is the same.In the 12 week, row common carotid artery and femoral venous catheter behind the rat anesthesia are pressed the nitre spectrum sodium that 0.5ml/kg injects variable concentrations, observe the variation of blood pressure.Found that: the nitre spectrum sodium of 0.001uM can cause the blood pressure drops of normal rat, yet, compose sodium at the nitre of diabetic groups 10uM and just can cause blood pressure drops.Taking the diabetes rat of breviscapine, the nitre spectrum sodium of 0.001uM also can cause the blood pressure drops of diabetes rat.
5. biochemical indicator measurement result
Table one is in the 12 week, and each organizes biochemical indicator result (n=8, x ± sd).
*Compare with diabetic groups.
| Blood NAG enzyme (IU/L) | Serum creatinine (umol/L) | Urine amount (ml) | Urine protein (g/L) | Crystalline lens AR (U/mg/min) | |
| Matched group | 106.3±18.5 | ?61.2±11.5 | 6±2.7 | 13.4±5.1 | 24.2±13.8 |
| Diabetic groups | 200±19.6 | ?85.4±11.8 | 50.6±14.2 | 34.4±6.4 | 92.4±22.3 |
| The breviscapine group | 124±17.2 * | ?54.0±46.3 * | 19.5±9.3 * | 17.2±8.7 * | 42.5±15.4 |
| The P value | ＜0.01 | ?＜0.05 | ＜0.05 | ＜0.01 | ＜0.01 |
Can illustrate from above result and the invention has the advantages that:
(1) the present invention is to compound known-4`, and 5,6-trihydroxyflavone-7-O-glucuronide-breviscapine has been excavated new medical application, has opened up a new application.
(2) 4` of the present invention, 5,6-trihydroxyflavone-7-O-glucuronide raw material sources are abundant, can make peroral dosage form, injection type, tablet etc., and are easy to use.
When (3) medicine that is mixed with of material of the present invention has remarkable treatment and prevent diabetes: the effect of the effect .b. vascular smooth muscle functional lesion of a. tunica intima functional lesion.
The effect of glomerule, tubular injury when (4) medicine that is mixed with of material of the present invention has remarkable treatment and prevent diabetes, because the significantly rising of serum creatinine, blood NAG enzyme during prevent diabetes, significantly reduce the urine amount and the urine protein of diabetes rat, showing has significant preventive and therapeutic effect to diabetic nephropathy.
(5) because the medicine that material of the present invention is mixed with has the effect that crystalline aldose reductase raises when significantly preventing and treating diabetes, can be used for treating the diabetic ophthalmopathy complication.
(6) because the medicine that material of the present invention is mixed with has the effect that aldose reductase raises when significantly preventing and treating diabetes, can be used for preventing and treating the diabetes nerve complication.
(7) show through clinical trial: the injection that material of the present invention is mixed with, tablet take effect rapidly, and be evident in efficacy.In diabetic nephropathy patient (5 example), use Drug therapy (10mg/kg) week that material of the present invention is mixed with, found that: urine protein reduces rapidly.Studies show that through the kidney biopsy treatment group obvious diabetic nephropathy not only do not occur and changes, and stoped the generation of diabetic nephropathy early lesion-nephron hypertrophy (hypertrophy).In diabetic eye patient (7 example), use two weeks of Drug therapy (12mg/kg) that material of the present invention is mixed with, found that: treatment group vision on average improves 25%, and ophthalmofundoscopy finds that the optical fundus circulation has clear improvement.
(8) medicine that is mixed with of material of the present invention in biggest advantage aspect the control diabetic complications is: under the situation that does not influence blood sugar level, and significantly treatment and prevent diabetes complication.Its action target spot has been to block signal transducting system in the cell after the hyperglycemia.Therefore, can be used for preventing and treating each system's complication that diabetes cause.Share with antidiabetic drug, can significantly treat diabetes, obviously prolong patient's life.
Embodiment of various details, but content of the present invention is not limited to this fully.
Embodiment
Adopt Compositae Herba Erigerontis aceris platymiscium Herba Erigerontis (Erigeron breviscapus (Vant) Hand-Mazz) whole plant 10kg, extract 4` by commonsense method, 5,6-trihydroxyflavone-7-O-glucuronide is prepared into tablet by the existing method of those skilled in the art.Wherein the content of tablet can strengthen or minimizing by actual needs.
Claims (4)
1, the application of breviscapine in the medicine of preparation treatment or prevent diabetes complication.
2, the application of breviscapine in the medicine of preparation treatment or diabetes and nephropathy preventing.
3, the application of breviscapine in the medicine of preparation treatment or prevent diabetes oculopathy.
4, the application of breviscapine in the medicine of preparation treatment or prevent diabetes nervous system complication.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001174762A CN1147303C (en) | 2000-10-09 | 2000-10-09 | Application of Breviscapine in preparing medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001174762A CN1147303C (en) | 2000-10-09 | 2000-10-09 | Application of Breviscapine in preparing medicine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1318373A CN1318373A (en) | 2001-10-24 |
| CN1147303C true CN1147303C (en) | 2004-04-28 |
Family
ID=4586841
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB001174762A Expired - Fee Related CN1147303C (en) | 2000-10-09 | 2000-10-09 | Application of Breviscapine in preparing medicine |
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| CN (1) | CN1147303C (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100344290C (en) * | 2002-11-29 | 2007-10-24 | 北京天衡药物研究院 | Breviscapine dispersing tablet and its prepn |
| CN1823798A (en) * | 2005-02-22 | 2006-08-30 | 史关正 | Application of isobaicalin in preparation of medicine |
| CN100333741C (en) * | 2005-07-11 | 2007-08-29 | 中山大学中山医学院科技开发中心 | Medicine for preventing and treating diabets and kidney disease and preparing method |
| CN102512435B (en) * | 2012-01-05 | 2014-02-05 | 昆明制药集团股份有限公司 | Application of scutellarin methyl ester and medicinal composition as well as preparation thereof |
| CN102875620B (en) * | 2012-10-16 | 2015-02-04 | 昆明龙津药业股份有限公司 | New derivatives of myricetin and application of derivatives to medicine preparation |
| CN103893196B (en) * | 2014-04-02 | 2015-07-22 | 闫莹 | Medical application of sedoisoprosan and pharmaceutical composition of sedoisoprosan |
| CN113304161A (en) * | 2021-05-27 | 2021-08-27 | 昆明医科大学 | Application of scutellarin in preparation of drug for stent coating |
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2000
- 2000-10-09 CN CNB001174762A patent/CN1147303C/en not_active Expired - Fee Related
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| Publication number | Publication date |
|---|---|
| CN1318373A (en) | 2001-10-24 |
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Granted publication date: 20040428 Termination date: 20131009 |