CN105596324A - Application of naringenin to preparation of drugs for preventing and/or treating aortic dissection - Google Patents
Application of naringenin to preparation of drugs for preventing and/or treating aortic dissection Download PDFInfo
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- CN105596324A CN105596324A CN201510964906.XA CN201510964906A CN105596324A CN 105596324 A CN105596324 A CN 105596324A CN 201510964906 A CN201510964906 A CN 201510964906A CN 105596324 A CN105596324 A CN 105596324A
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- naringenin
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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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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Abstract
The invention provides application of naringenin to the preparation of products for preventing and/or treating aortic dissection. The drugs for preventing and/or treating aortic dissection are safe and low-toxic, and high in pharmacological action; the source of raw materials are rich and wide, the price is low, and the raw materials can be obtained from crude products or monomer of naringin through a hydrolysis method, obtained by extracting from medicinal materials containing naringenin, or obtained by synthesis through other chemical methods; the cost is low, the process is simple, and the yield is high; curative effect is definite, and the effective dose is low. The application provides a novel source of drugs for preventing, diagnosing, detecting, protecting, treating and researching aortic dissection diseases, is easy to promote and apply, and can produce huge social benefit and economic benefit within a short time.
Description
Technical field
The present invention relates to a kind of new medicine use of naringenin, be specifically related to naringenin and prevent and/or treat master in preparationApplication in the medicine of artery dissection.
Background technology
Dissection of aorta is one of high-risk disease of cardiovascular field, refers to that aortic tunica intima tears, the blood in circulationEnter in aorta wall by breach, cause the layering of vascular wall. This vascular wall of tearing is very weak, is easy to expandOr break, and the latter's lethal often. Untreated dissection of aorta patient approximately 36%～50% clinicallyRise in 48 hours after being ill dead, approximately 65%～75% death 2 weeks in, 1 annual death rate up to 90%, 10 year extremelyThe rate of dying almost 100% (the yellow winter, Liu Mingya, the mechanism of dissection of aorta and Strategy of Diagnosis, angiocardiology entersExhibition, 2007,28 (4): 631-635.). PCI and prosthetic vessel replacement are that treatment dissection of aorta breaks at presentMain method. Although art formula development, overall M & M do not improve (HellenthalFA,BuurmanWA,WodzigWK,SchurinkGW.BiomarkersofAAAprogression.Part1:Extracellularmatrixdegeneration.NatureReviewsCardiology; 2009:6,464-474.). Still at presentWithout developing of active drug control dissection of aorta.
Summary of the invention
The object of this invention is to provide a kind of new medicine use of naringenin.
The new purposes of naringenin provided by the present invention is: naringenin can be used for preparation and prevents and/or treats dissection of aortaProduct, specifically can be medicine and/or health products.
Described dissection of aorta is specifically produced by BAPN induction.
Described dissection of aorta is specifically produced by Angiotensin II induction.
Naringenin gavage is suppressed to the test of the generation of the underage mouse dissection of aorta of BAPN induction and find, shaddock pedElement high dose group (200mg/kg/d), middle dosage group (100mg/kg/d) and low dose group (50mg/kg/d) all can be brightGeneration and the aorta rupture death of the aobvious mouse aorta interlayer that suppresses BAPN induction, and along with naringenin administrationThe increase of dosage, the interlayer death rate of mouse reduces, dissection of aorta incidence reduces, and naringenin high dose group suppressesThe effect that the mouse aorta interlayer of BAPN induction occurs is the most obvious, the mouse aorta interlayer incidence of its processed groupBe only 33%, the interlayer death rate is 0%. Body weight, amount of drinking water, heart rate and systolic pressure to underage mouse are examinedExamine discovery, when the underage mouse dissection of aorta that utilizes naringenin to carry out gavage inhibition BAPN induction occurs,Body weight, amount of drinking water, heart rate and systolic pressure to mouse all do not make significant difference.
Naringenin gavage is suppressed to the test of the generation of the aged mouse dissection of aorta of Angiotensin II induction and find, shaddockThe mouse aorta interlayer that Pi Su (200mg/kg/d) can obviously suppress Angiotensin II induction occurs and aorta ruptureDead: the mouse aorta interlayer incidence of model control group and naringenin processed group is respectively 33% and 22%, modelThe dissection of aorta death rate of control group and naringenin processed group mouse is respectively 23% and 13%. Body weight to mouse,Heart rate, systolic pressure and twenty-four-hour urine albumin are investigated discovery, utilize naringenin to carry out gavage and suppress angiotensinsWhen II buries the mouse aorta interlayer generation of pump induction, body weight, heart rate, systolic pressure and 24 mouse retentions to mouseAlbumin does not all make significant difference.
The present invention has also further comprised the product that prevents and/or treats dissection of aorta taking naringenin as active component,As medicine and/or health products.
Described medicine can be by the method for injection, injection, collunarium, eye drip, infiltration, absorption, physics or chemistry mediationImport body as muscle, intracutaneous, subcutaneous, vein, mucosal tissue; Or mixed by other materials or wrap up after importBody.
When needs, in above-mentioned medicine, can also add one or more pharmaceutically acceptable carriers. Described yearBody comprises that diluent, excipient, filler, adhesive, wetting agent, disintegrant, the absorption of pharmaceutical field routine is shortEnter agent, surfactant, absorption carrier, lubricant etc.
Described medicine can be made the various ways such as parenteral solution, suspending agent, pulvis, tablet, granule. Above-mentioned variousThe medicine of formulation all can be according to the conventional method preparation of pharmaceutical field.
The present invention adopt two kinds to clinical relevant aorta clamp layer model: the mouse aorta folder of BAPN gavage inductionLayer and (1000ng/kg/min) the subcutaneous pump inducing mouse dissection of aorta that buries of Angiotensin II (AngiotensinII). RealVerify brightly, by naringenin oral administration gavage, can obviously suppress BAPN gavage and AngII and bury the mouse aorta of pump inductionDeveloping of interlayer, may be applied to the patient who treats dissection of aorta.
The drug safety low toxicity that prevents and/or treats dissection of aorta provided by the invention, pharmacological action is stronger; Its raw materialOriginate abundant, extensive, inexpensive, can be obtained by the method for hydrolysis by aurantiin (Naringin) crude product or monomer,Or from obtaining containing extracting the various medicinal materials of naringenin, or obtain by other chemical methodes are synthetic; Cost effects a permanent cureCheap, technique is simple, yield is high; And determined curative effect, effective dose is low. The present invention for prevention, diagnosis, detect,Protection, treatment and research dissection of aorta disease provide a kind of new medicament sources, and easily apply, canHave a tremendous social and economic benefits in the short period of time.
Brief description of the drawings
Fig. 1 is model control group and the teenage C57 of various dose naringenin gavage to BAPN induction in embodiment 1The impact of mouse death rate.
Fig. 2 is model control group and the teenage C57 of various dose naringenin gavage to BAPN induction in embodiment 1The impact of mouse interlayer incidence.
Fig. 3 is model control group and the large volume image of naringenin high dose group mouse aorta in embodiment 1.
Fig. 4 is model control group and the teenage C57 of various dose naringenin gavage to BAPN induction in embodiment 1The impact of Mouse Weight.
Fig. 5 is model control group and the teenage C57 of various dose naringenin gavage to BAPN induction in embodiment 1The impact of mouse amount of drinking water.
Fig. 6 is model control group and the teenage C57 of various dose naringenin gavage to BAPN induction in embodiment 1The impact of mouse heart rate.
Fig. 7 is model control group and the teenage C57 of various dose naringenin gavage to BAPN induction in embodiment 1The impact of mouse systolic pressure.
Fig. 8 is model control group and the old C57 mouse of naringenin gavage to Angiotensin II induction in embodiment 2The impact of dissection of aorta incidence.
Fig. 9 is the large volume image of mouse aorta of model control group and naringenin processed group in embodiment 2.
Figure 10 is model control group and the old C57 of naringenin processed group to Angiotensin II induction in embodiment 2The impact of Mouse Weight.
Figure 11 is model control group and the old C57 of naringenin processed group to Angiotensin II induction in embodiment 2The impact of mouse heart rate.
Figure 12 is model control group and the old C57 of naringenin processed group to Angiotensin II induction in embodiment 2The impact of mouse systolic pressure.
Figure 13 is model control group and the old C57 of naringenin processed group to Angiotensin II induction in embodiment 2The albuminous impact of mouse twenty-four-hour urine.
Detailed description of the invention
The experimental technique using in following embodiment if no special instructions, is conventional method.
Material, reagent etc. used in following embodiment, if no special instructions, all can obtain from commercial channels.
The underage mouse dissection of aorta of embodiment 1, naringenin gavage inhibition BAPN (BAPN) inductionOccur
1, the model of the underage mouse dissection of aorta of BAPN induction
The male C57 mouse that uses 3 week age, is divided into four groups, is respectively model control group (BAPN0.8g/kg/d drinkWater+physiological saline gavage), naringenin low dose group (BAPN0.8g/kg/d drinking-water+naringenin 50mg/kg/d gavage),Dosage group in naringenin (BAPN0.8g/kg/d drinking-water+naringenin 100mg/kg/d gavage) and naringenin high dose group(BAPN0.8g/kg/d drinking-water+naringenin 200mg/kg/d gavage), gives gavage when BAPN drinking-water. ExperimentIn process, observe mouse ordinary circumstance and the death rate, after BAPN drinking-water surrounding, draw materials, observe mouse aorta interlayer and send outRaw rate.
2, naringenin gavage suppresses the generation of the underage mouse dissection of aorta of BAPN induction
The impact of model control group and the each dosage group gavage teenage C57 mouse death rate on BAPN induction is as Fig. 1Described, the impact of model control group and the each dosage group gavage teenage C57 mouse interlayer incidence on BAPN inductionAs shown in Figure 2, the large volume image of sustainer of model control group and naringenin high dose group mouse as shown in Figure 3, by scheming1, Fig. 2 and Fig. 3 are known, and the incidence of BAPN inducing mouse dissection of aorta reaches 79%, BAPN inducing mouse masterThe artery dissection death rate of breaking reaches 30%, naringenin is high, in and low dose group all can obviously suppress the little of BAPN inductionThe generation of mouse dissection of aorta and aorta rupture death, and along with the increase of naringenin dosage, the folder of mouseThe layer death rate reduces, dissection of aorta incidence reduces, and naringenin high dose group suppresses the mouse active of BAPN inductionThe effect that arteries and veins interlayer occurs is the most obvious, and the mouse aorta interlayer incidence of its processed group is only 33%, the interlayer death rateBe 0%.
The impact of model control group and the various dose naringenin gavage teenage C57 Mouse Weight on BAPN induction asShown in Fig. 4, model control group and the various dose naringenin gavage teenage C57 mouse amount of drinking water to BAPN inductionImpact as shown in Figure 5, model control group and various dose naringenin gavage are little to the teenage C57 of BAPN inductionAs shown in Figure 6, model control group and various dose naringenin gavage are teenage to BAPN induction in the impact of mouse heart rateThe impact of C57 mouse systolic pressure as shown in Figure 7. From the result of Fig. 4-Fig. 7, utilize naringenin to carry out gavage and press downWhen the underage mouse dissection of aorta of BAPN processed induction occurs, body weight to mouse, amount of drinking water, heart rate andSystolic pressure does not all make significant difference.
Embodiment 2, naringenin gavage suppress the generation of the aged mouse dissection of aorta of Angiotensin II induction
1, the model of the aged mouse dissection of aorta of Angiotensin II induction
Use 8～9 the monthly age male C57 mouse, be divided into two groups, give respectively Angiotensin II 2500ng/kg/minBury pump+physiological saline gavage (model control group) and give Angiotensin II 2500ng/kg/min and bury pump+naringenin200mg/kg/d gavage (naringenin processed group), buries pump and starts gavage the last week. In experimentation, observe mouse generalSituation and the death rate, draw materials after burying pump for 14 days, observes mouse aorta interlayer incidence.
2, naringenin gavage suppresses the generation of the aged mouse dissection of aorta of Angiotensin II induction
Model control group and naringenin processed group occur the old C57 mouse aorta interlayer of Angiotensin II inductionThe impact of rate as shown in Figure 8, the large volume image of mouse aorta of model control group and naringenin processed group as shown in Figure 9,The body weight of old C57 mouse that model control group is induced Angiotensin II and the impact of systolic pressure are respectively as Figure 10Shown in Figure 12, can be found out by Fig. 8, Fig. 9, Figure 10 and Figure 12, Angiotensin II buries pump can make Mice BodyHeavily alleviate, systolic pressure rising, mouse death rate and interlayer incidence increase, and naringenin can obviously suppress vasotoniaThe mouse aorta interlayer of element II induction occurs and aorta rupture death: the mouse of model control group and naringenin processed groupDissection of aorta incidence is respectively 33% and 22%, the dissection of aorta of model control group and naringenin processed group mouseThe death rate is respectively 23% and 13%.
Model control group and naringenin processed group on the impact of the old C57 Mouse Weight on Angiotensin II induction asDescribed in Figure 10, model control group and the naringenin processed group old C57 mouse heart rate to Angiotensin II inductionAffect as described in Figure 11 model control group and the naringenin processed group old C57 mouse to Angiotensin II inductionSystolic pressure affects as shown in figure 12, model control group and the naringenin processed group old C57 to Angiotensin II inductionThe albuminous impact of mouse twenty-four-hour urine as shown in figure 13, from the result of Figure 10-Figure 13, utilizes naringenin to enterWhen row gavage inhibition Angiotensin II buries the mouse aorta interlayer generation of pump induction, the body weight to mouse, the heartRate, systolic pressure and 24 mouse retention albumin all do not make significant difference.
Claims (6)
1. naringenin prevents and/or treats the application in the product of dissection of aorta in preparation.
2. application according to claim 1, is characterized in that: described product is medicine and/or health products.
3. application according to claim 1 and 2, is characterized in that: described dissection of aorta is by beta-amino thirdNitrile induction produces.
4. application according to claim 1 and 2, is characterized in that: described dissection of aorta is by vasotoniaElement II induction produces.
5. prevent and/or treat a product for dissection of aorta, its active component is naringenin.
6. product according to claim 5, is characterized in that: described product is medicine and/or health products.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201510964906.XA CN105596324A (en) | 2015-12-21 | 2015-12-21 | Application of naringenin to preparation of drugs for preventing and/or treating aortic dissection |
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| CN201510964906.XA CN105596324A (en) | 2015-12-21 | 2015-12-21 | Application of naringenin to preparation of drugs for preventing and/or treating aortic dissection |
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| CN105596324A true CN105596324A (en) | 2016-05-25 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109771412A (en) * | 2018-12-29 | 2019-05-21 | 遵义医学院 | The drug and rat model construction method of reangiostenosis after mitigation balloon injured |
| CN110583569A (en) * | 2019-08-26 | 2019-12-20 | 华中科技大学同济医学院附属同济医院 | Method for establishing mouse model with obstructive sleep apnea accompanied by aortic dissection |
| CN113750085A (en) * | 2020-06-02 | 2021-12-07 | 中国科学院上海药物研究所 | Application of natural compound and derivative thereof in treating arterial lesion |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103340849A (en) * | 2013-06-27 | 2013-10-09 | 北京大学 | Application of naringenin in preparing medicament for preventing and/or treating abdominal aortic aneurysm |
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2015
- 2015-12-21 CN CN201510964906.XA patent/CN105596324A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103340849A (en) * | 2013-06-27 | 2013-10-09 | 北京大学 | Application of naringenin in preparing medicament for preventing and/or treating abdominal aortic aneurysm |
Non-Patent Citations (3)
| Title |
|---|
| BRIAN C. TIEU ET AL.: "An adventitial IL-6/MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice", 《THE JOURNAL OF CLINICAL INVESTIGATION》 * |
| 彭静等: "主动脉夹层免疫炎症机制研究进展", 《中国循环杂志》 * |
| 李飞等: "MMP-2及MMP-9与主动脉疾病相关性的研究进展", 《现代生物医学进展》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109771412A (en) * | 2018-12-29 | 2019-05-21 | 遵义医学院 | The drug and rat model construction method of reangiostenosis after mitigation balloon injured |
| CN110583569A (en) * | 2019-08-26 | 2019-12-20 | 华中科技大学同济医学院附属同济医院 | Method for establishing mouse model with obstructive sleep apnea accompanied by aortic dissection |
| CN110583569B (en) * | 2019-08-26 | 2022-02-15 | 华中科技大学同济医学院附属同济医院 | Method for establishing mouse model with obstructive sleep apnea accompanied by aortic dissection |
| CN113750085A (en) * | 2020-06-02 | 2021-12-07 | 中国科学院上海药物研究所 | Application of natural compound and derivative thereof in treating arterial lesion |
| WO2021244547A1 (en) * | 2020-06-02 | 2021-12-09 | 中国科学院上海药物研究所 | Application of natural compound and derivative thereof in treating arterial lesions |
| CN113750085B (en) * | 2020-06-02 | 2023-08-29 | 中国科学院上海药物研究所 | Use of natural compounds and derivatives thereof for the treatment of arterial lesions |
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| C06 | Publication | ||
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| TA01 | Transfer of patent application right |
Effective date of registration: 20180103 Address after: Room 217, Department of clinical medicine, China-Japan Friendship Hospital, No. 2, East Cherry East Street, Chaoyang District, Beijing, Beijing Applicant after: Zheng Jingang Applicant after: Kong Wei Applicant after: Gao Yanxiang Address before: Room 217, Department of clinical medicine, China-Japan Friendship Hospital, No. 2, East Cherry East Street, Chaoyang District, Beijing, Beijing Applicant before: Zheng Jingang Applicant before: Kong Wei |
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| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160525 |