CN106420736A - Application of berberine in preparation of drug for treating fibrinolysis system disorder related diseases - Google Patents
Application of berberine in preparation of drug for treating fibrinolysis system disorder related diseases Download PDFInfo
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- CN106420736A CN106420736A CN201611001038.6A CN201611001038A CN106420736A CN 106420736 A CN106420736 A CN 106420736A CN 201611001038 A CN201611001038 A CN 201611001038A CN 106420736 A CN106420736 A CN 106420736A
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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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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Abstract
The invention discloses an application of berberine in preparation of a drug for treating fibrinolysis system disorder related diseases. The prepared drug can be a single ingredient of berberine and can also be a drug mixture or composition with berberine as a main active ingredient or a modifier of berberine, wherein the drug mixture is obtained by mixing an effective dosage of berberine and pharmaceutically acceptable drugs; the drug composition is a compound preparation with berberine as the main active ingredient or a drug packaged by a carrier; the modifier is a compound obtained through a series of chemical modification on the basis of the basic structure of berberine. The invention further discloses an application of the drug as an oral preparation, an injection and spray in treatment of the fibrinolysis system disorder related diseases.
Description
Technical field
The present invention relates to application of the berberine in treatment fibrinolytic system obstacle relevant disease medicine is prepared, belongs to biological doctor
Medicine field.
Background technology
Fibrinolytic system (fibrinolytic system), mainly by fibrinoclase (fibrinolysin), Plasminogen activation
3 parts of thing and plasminogen activator inhibitor constitute, and activator of plasminogen produces fibrinolysin in order to plasminogen activation,
Including u-PA (urinePlasminogen Activator, u-PA) and tissue plasminogen activator
(tissue Plasminogen Activator, t-PA), u-PA is primarily present in urine, thin by kidney and urothelium
Intracrine, t-PA is released into blood mainly by vascular endothelial cell synthesis secretion, is widely present in the various tissues of body.I
Type tissue plasminogen activator inhibitor (Plasminogen Activator Inhibitor 1, PAI-1) is u-PA and t-
The major inhibitors of PA, mainly by vascular endothelial cell, fatty tissue and hepatic secretion.Fibrinolytic system is not only responsible in self-loopa
Remove and defibrinate, and multiple other biological processes are also assisted in, including ovulation, embryo's generation, neointimal hyperplasia, blood vessel life
Become, tumor occurs and atherosclerosiss.T-PA due to being widely present in the vascular endothelial cell of blood circulation, its increase
Fibrinolytic System can be significantly activated, the reduction of PAI-1 can similarly activate fibrinolytic system.
Fibrinolytic System obstacle includes the minimizing of t-PA, u-PA, the rising of PAI-1, and their unconventionality expression is multiple
Disease is found in developing, and is damaged including fibrinolytic system, thrombosiss and thromboembolism cause local organization ischemia,
Anoxia, necrosis, auricular fibrillation, apoplexy, cardiovascular disease, extracellular matrix build-up has related disorders, atherosclerosiss
Speckle, the increase of PAI-1 abnormal expression can affect angiogenesiss, diabetes, Alzheimer, inflammatory diseasess and cancer etc.,
Also the rising that there are some researches show PAI-1 expression in postmenopausal women's blood increased the risk for suffering from cardiovascular disease.
Berberine (Berberine, BBR) molecular formula is C20H18NO4, act on significant anti-inflammatory, antibacterial, facing at present
Treatment bacillary dysentery and enteritis is widely used on bed, and numerous studies had been carried out to the pharmacological mechanism of berberine further in recent years
Probing into, berberine is found in addition to above-mentioned functions, can be also used for treating cardiovascular system diseases, anticancer, improves hyperlipidemia and sugar
Urine disease, due to its wide material sources, safe, low cost, has extensive application in clinic.We accidentally send out under study for action
Existing, berberine can significantly activate t-PA, the expression of suppression PAI-1, thus it is presumed that, berberine can be used as fibrinolytic system
Activator is studied in this respect and has no report at present in clinical practice in the relevant disease of Fibrinolytic System exception.
Content of the invention
The present invention demonstrates the function of Radix Berberidis Amurensis alkaline activity fibrinolytic system using multiple technologies means, main including activation blood vessel
The expression of endotheliocyte t-PA, suppresses the expression of vascular endothelial cell PAI-1, and finally determining berberine can control as preparation
Treat the effective ingredient of Fibrinolytic System obstacle relevant disease.
Described berberine molecular formula is C20H18NO4, its structure is as shown in following formula I：
In the present invention, described Fibrinolytic System obstacle relevant disease include fibrinolytic system damage, thrombosiss and
The ischemia of the local organization that blood coagulation system obstacle causes, anoxia, necrosis, auricular fibrillation, apoplexy, diabetes, cardiovascular
Disease, extracellular matrix build-up has related disorders, angiogenesis-related disease, atheromatous plaque, Alzheimer, inflammation
Property disease and cancer.
Wherein, the diabetes are non-insulin-dependent diabetes mellitus；The cardiovascular disease include with coronary artery and
The relevant thrombotic disease of cerebrovascular disease；The extracellular matrix build-up have related disorders include but is not limited to renal fibrosiss,
Chronic obstructive pulmonary disease, pulmonary fibrosiss, polycystic ovarian syndrome, renal vascular and organ rejection response；The angiogenesiss
Related disorders are had to include but is not limited to diabetic retinopathy；The inflammatory diseasess include but is not limited to septic shock and with
The relevant blood vessel injury of infection；The cancer includes but is not limited to leukemia, breast carcinoma and ovarian cancer.
The application of berberine proposed by the invention in treatment fibrinolytic system obstacle relevant disease medicine is prepared, the medicine
Thing is berberine single component or the medicinal mixture containing effective dose berberine, pharmaceutical composition or molecular structure alteration thing.
Wherein, the medicinal mixture is that the berberine of the medicine and effective dose for pharmaceutically receiving is mixed；Described
Pharmaceutical composition is the compound preparation containing effective dose berberine or the medicine after carrier package, and the feature of the carrier is
Microsphere, liposome, microemulsion, high molecular surfactant, nanoparticle, implant；The molecular structure alteration thing be little
On the basis of bark of a cork tree alkali basic structure, a series of compounds being chemically modified to obtain are carried out, wherein chemical modification mode includes into salt
Modification, esterification and amidatioon modification, the modification of ammonia firstization, etherificate modification, open loop and cyclisation modification.
In the present invention, it is preferred that described medicinal mixture, pharmaceutical composition and molecular structure alteration thing, according to medicine
The conventional method of preparation makes oral agents, injection, spray.
Description of the drawings
Fig. 1 is administered different time points HUVEC t-PA mRNA expression for berberine；
Fig. 2 is administered different time points HUVEC t-PA protein expression level for berberine；
Fig. 3 is administered different time points HUVEC PAI-1mRNA expression for berberine；
Fig. 4 is administered different time points HUVEC PAI-1 protein expression level for berberine；
Fig. 5 is variable concentrations Radix Berberidis Amurensis alkaline activity HUVEC t-PA mRNA expression；
Fig. 6 is variable concentrations Radix Berberidis Amurensis alkaline activity HUVEC t-PA protein expression situation；
Fig. 7 is variable concentrations Radix Berberidis Amurensis alkaline activity HUVEC PAI-1mRNA expression；
Fig. 8 is variable concentrations Radix Berberidis Amurensis alkaline activity HUVEC PAI-1 protein expression situation.
Specific embodiment
Checking is described further with reference to embodiment for the present invention, advantages of the present invention and feature will be with retouching
State and apparent.But these embodiments are only exemplary, do not constitute any restriction to the scope of the present invention.This area skill
Art personnel should be understood that can be to the details of technical solution of the present invention and shape under without departing from the spirit and scope of the present invention
Formula is modified or is replaced, but these modifications and replacement are each fallen within protection scope of the present invention.
The effect of 1 Radix Berberidis Amurensis alkaline activity fibrinolytic system of embodiment
Endothelial cells of human fetal umbilical vein in vitro HUVEC, culture fluid supernatant add berberine hydrochloride (Sigma,
1065210) so that final concentration of 500 μM, cell being collected after 0h, 0.5h, 3h, 6h, 9h, 12h, 24h respectively, uses respectively
Q-PCR and western blot method detection t-PA, PAI-1mRNA and protein expression situation.
As a result as shown in figure 1, after berberine administration 0.5h, t-PA mrna expression amount dramatically increases 5.6 times, and in administration
3h reaches peak value afterwards, and now t-PA mRNA expression increases to 6.4 times, and this significant facilitation continues to 12h, and t-PA
Protein expression content also starts to increase in 0.5h, continues 24h (Fig. 2).Then, we are detected to PAI-1 expression again, I
Find that berberine can significantly inhibit the expression (Fig. 3) of 80%PAI-1mRNA after administration 0.5h, protein expression similarly by
Suppression (Fig. 4), this inhibitory action can significantly continue 24h.Next, we are using different Radix Berberidis Amurensis alkali concns, respectively 0 μ
M, 20 μM, 100 μM, 500 μM, in HUVEC culture fluid effect 3h after, detect t-PA and PAI-1 expression, as a result show,
Berberine can promote t-PA mRNA (Fig. 5) and albumen (Fig. 6) expression with dose dependent, while with dose-dependent inhibition
PAI-1mRNA (Fig. 7) and albumen (Fig. 8) expression.
Above test result indicate that, berberine can significantly activate the expression of vascular endothelial cell t-PA, notable in 0.5h
The expression of suppression PAI-1, plays a part of acute activation fibrinolytic system.
Claims (10)
1. berberine is in the purposes of the medicine for preparing treatment fibrinolytic system obstacle relevant disease, and described berberine molecular formula is
C20H18NO4, molecular structure is shown in formula I：
2. application as claimed in claim 1, it is characterised in that the medicine is berberine single component or little containing effective dose
The medicinal mixture of bark of a cork tree alkali, pharmaceutical composition or molecular structure alteration thing.
3. application as claimed in claim 2, it is characterised in that the medicinal mixture be the medicine that pharmaceutically receives with effective
The berberine of dosage is mixed；Described pharmaceutical composition is the compound preparation containing effective dose berberine or through carrier package
Medicine afterwards, the feature of the carrier is microsphere, liposome, microemulsion, high molecular surfactant, nanoparticle, implant；
The molecular structure alteration thing is on the basis of berberine basic structure, carries out a series of compounds being chemically modified to obtain,
Wherein chemical modification mode includes into salt modification, esterification and amidatioon modification, the modification of ammonia firstization, etherificate modification, open loop and cyclisation
Modification.
4. application as claimed in claim 3, it is characterised in that the medicinal mixture, pharmaceutical composition and molecular structure are repaiied
Jewelry is oral agents, injection or spray.
5. the application as described in any one of claim 1-4, it is characterised in that the fibrinolytic system obstacle relevant disease includes：
Fibrinolytic system is damaged, and thrombosiss and blood coagulation system obstacle cause to obtain the ischemia of local organization, anoxia, necrosis, atrial fibrillation
Vibration, apoplexy, diabetes, cardiovascular disease, extracellular matrix build-up has related disorders, angiogenesis-related disease, and tremulous pulse is athero-
Plaque, Alzheimer, inflammatory diseasess and cancer.
6. application as claimed in claim 5, it is characterised in that the diabetes are non-insulin-dependent diabetes mellitus.
7. application as claimed in claim 5, it is characterised in that the cardiovascular disease includes and coronary artery and cerebrovascular disease
The relevant thrombotic disease of disease.
8. application as claimed in claim 5, it is characterised in that the extracellular matrix build-up has related disorders to include but is not limited to
Renal fibrosiss, chronic obstructive pulmonary disease, pulmonary fibrosiss, polycystic ovarian syndrome, renal vascular and organ rejection response.
9. application as claimed in claim 5, it is characterised in that the angiogenesis-related disease includes but is not limited to diabetes
Property retinopathy.
10. application as claimed in claim 5, it is characterised in that the inflammatory diseasess include but is not limited to septic shock and
The blood vessel injury relevant with infection, the cancer includes but is not limited to leukemia, breast carcinoma and ovarian cancer.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201611001038.6A CN106420736A (en) | 2016-11-14 | 2016-11-14 | Application of berberine in preparation of drug for treating fibrinolysis system disorder related diseases |
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| CN201611001038.6A CN106420736A (en) | 2016-11-14 | 2016-11-14 | Application of berberine in preparation of drug for treating fibrinolysis system disorder related diseases |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114177174A (en) * | 2021-12-06 | 2022-03-15 | 山东中医药大学 | Application of berberine in treating pulmonary fibrosis |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101816653A (en) * | 2010-04-29 | 2010-09-01 | 苏州基莫夫药物开发有限公司 | Application of berberine in preparing tumor radio sensitization medicine |
| CN104906088A (en) * | 2015-02-16 | 2015-09-16 | 上海交通大学医学院附属瑞金医院 | Application of berberine in preparation of medicine for treating T cell lymjphoma |
-
2016
- 2016-11-14 CN CN201611001038.6A patent/CN106420736A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101816653A (en) * | 2010-04-29 | 2010-09-01 | 苏州基莫夫药物开发有限公司 | Application of berberine in preparing tumor radio sensitization medicine |
| CN104906088A (en) * | 2015-02-16 | 2015-09-16 | 上海交通大学医学院附属瑞金医院 | Application of berberine in preparation of medicine for treating T cell lymjphoma |
Non-Patent Citations (1)
| Title |
|---|
| 赵晓华 等: "黄连素和牛磺酸对胰岛素抵抗大鼠脂肪组织PAI-lmRNA表达的影响", 《临床医药实践杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114177174A (en) * | 2021-12-06 | 2022-03-15 | 山东中医药大学 | Application of berberine in treating pulmonary fibrosis |
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Application publication date: 20170222 |