CN102614160B - Use of shikimic acid in preparation of antihypertensive drug - Google Patents
Use of shikimic acid in preparation of antihypertensive drug Download PDFInfo
- Publication number
- CN102614160B CN102614160B CN 201110031013 CN201110031013A CN102614160B CN 102614160 B CN102614160 B CN 102614160B CN 201110031013 CN201110031013 CN 201110031013 CN 201110031013 A CN201110031013 A CN 201110031013A CN 102614160 B CN102614160 B CN 102614160B
- Authority
- CN
- China
- Prior art keywords
- shikimic acid
- hypertension
- rat
- shr
- preparation
- 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.)
- Active
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to the medicine field, especially to application of shikimic acid in preparation of an antihypertensive drug. The invention employs primary hypertension rats as animal models for experiment, and proves that the shikimic acid has depressurization effect. Through the inventive technology scheme, the invention provides drug selection which is low in cost and available as well as low in toxic and side effect for wide hypertension patients.
Description
Technical field
The present invention relates to medical usage, the particularly application of shikimic acid in preparation treatment hypertension drug.
Background technology
Hypertension be a kind of be feature with the arterial pressure rising, can be functional with heart, blood vessel, brain and kidney and other organs or the systemic disease of organic change.Do not using under the situation of antihypertensive, non-3 measurements on the same day, systolic pressure 〉=140mmHg and (or) diastolic pressure 〉=90mmHg, diagnosable is hypertension [Liu Lisheng, Wang Wen, Yao Chonghua etc., China's hypertension prevention and control guide (basic unit's version in 2009), China's hypertension magazine, 2010,1 (18): 11-30].
Along with China's rapid economic development and growth in the living standard, bigger variation has taken place in people's life style.In recent years, China resident hypertension prevalence persistence increases, show according to relevant epidemiology survey result: in the period of 1980 to 1991 10, population of China hypertension prevalence rises to 11.88%[China hypertension prevention and control guide revision committee by 7.73%, China's hypertension prevention and control guide (revised edition in 2005), the 8th page].By 2009, estimate to suffer from the hypertension number and reached 200,000,000 people, it is hypertension [Liu Lisheng, Wang Wen, Yao Chonghua etc., Chinese hypertension prevention and control guide (basic unit's version in 2009), Chinese hypertension magazine, 2010,1 (18): 11-30] that 2 people are just arranged among per 10 adults.Hypertension is to cause heart disease, cerebrovascular, nephropathy to take place and dead topmost risk factor.Cardiovascular and cerebrovascular disease death at present occupies China resident's cause of death first place, has become the major disease that threatens China's residents ' health, and the generation of cardiovascular and cerebrovascular disease is with dead over half relevant with hypertension.In addition, hypertension is occupied important function in apoplexy and incidence of coronary heart disease mechanism.There are some researches show that the every rising 10mmHg of baseline systolic pressure, apoplexy generation relative risk increase by 49% (Ischemic Stroke increases by 47%, and hemorrhagic apoplexy increases by 54%); The every rising 5mmHg of diastolic pressure, apoplexy is dangerous to increase by 46%.And systolic pressure is when 120～139mmHg, and coronary heart disease relative risk ratio＜120mmHg person increases 40%, 140～149mmHg person and increases by 1.3 times.[Chinese hypertension prevention and control guide is revised committee, Chinese hypertension prevention and control guide (revised edition in 2005), the 15th page].Therefore, control hypertension is the key of preventing and treating coronary heart disease, cerebro-vascular diseases.
Hypertensive control method mainly is that Drug therapy combines with the adjustment of life style.At present, the antihypertensive drugs that is widely used clinically mainly contains 5 big class: a, diuretic antihypertensive medicine, as hydrochlorothiazide (hydrochlorothiazide); B, β1Shou Tizuzhiji are as propranolol; C, calcium ion antagonist are as amlodipine; D, angiotensin converting enzyme inhibitor (comprising angiotensin ii receptor antagonist) are as captopril; E, α 1 receptor blocking agent are as prazosin.Though existing depressor can make 90% above hyperpietic's blood pressure reduce to normally, but the present hypertensive control rate of China is very low, the compliance that major reason is exactly the patient is poor, and influences a untoward reaction that key factor is exactly medicine of patient's compliance.[Li Aihui, Li Xishan, Li Jing's ripple, the investigation of hyperpietic's drug compliance and nursing countermeasure, China's mistaken diagnosis magazine, 2010,29 (10): 7306] for example hydrochlorothiazide can cause blood sugar increasing, cholesterolemia and triglyceride raise, and blood uric acid rising and serum potassium reduction etc. can also make insulin sensitivity descend; That propranolol can cause is dizzy, tired, drowsiness, gastrointestinal dysfunction, bring out acute heart failure or bronchial asthma etc.; The topmost untoward reaction of captopril is cough; The common untoward reaction of prazosin be dizzy, headache, drowsiness, spirit is poor, cardiopalmus, nauseating.These untoward reaction have restricted the enthusiasm that the hyperpietic takes medicine.Therefore, the new hypertensive medicine for the treatment of safely and effectively of development has significance.
The shikimic acid molecular formula is C
7H
10O
5, relative molecular weight is 174.15, chemistry 3,4,5-trihydroxy by name-1-cyclohexene-1-carboxylic acid.Shikimic acid extensively is present in the natural plants such as Fructus Anisi Stellati, Radix Hyperici Monogyni (Herba Hyperici Monogyni), poisoned arrow wood, little rice dumpling, Radix Codonopsis Convolvulaceae, Pinus massoniana Lamb Folium Pini.Shikimic acid content higher relatively (about 8%～13%) in the Fructus Anisi Stellati wherein, and extraction process is simple.Because China's Fructus Anisi Stellati resource is very abundant, Fructus Anisi Stellati more than 90% stems from China [Liu Yongyou, Liao Xiaofeng in the tool report whole world, the progress of shikimic acid, print during chemical industry, 2007,21 (3): 54-57], Fructus Anisi Stellati has become the source material that enriches of suitability for industrialized production shikimic acid at present.Therefore, shikimic acid has wide material sources in China, and extraction process is simple, and has formed the advantage of suitability for industrialized production.
And people are when carrying out toxicity research to plant Folium illicii Lanceolati and wild anise, find to contain in the above-mentioned plant neurotoxic Sesquiterpene compounds, wherein sikimitoxin and shikimene toxicity are very strong, and separation obtains from plant shikimic acid toxicity less [Li Fafang, Ma Jinliang etc., the preliminary study of Folium illicii Lanceolati water cooking liquid bacteriostasis, the practical medical magazine of China, 2007,6 (7): 498-500; Yang Chunshu, Wang Jialin etc., the research of wild octagonal fruit toxic component, Acta Pharmaceutica Sinica, 1991,26 (2)].
Shikimic acid has antiinflammatory, analgesic activity, is the intermediate of antiviral and cancer therapy drug, also is the synthetic intermediate that effectively tackles mortality H1N1 type bird flu medicine " oseltamivir phosphate capsule ".CN1163104A discloses the purposes of shikimic acid in the formation of preparation antithrombotic and thrombolytic drug.CN101352427A discloses shikimic acid and has prevented and treated purposes in the ulcerative colitis medicine in preparation, and CN1874687A discloses a kind of extract from pine needles, contains shikimic acid in this extract, and this extract can be used for preparing medicine or the food with hypotensive activity.The applicant can be used in treatment hypertension through a large amount of surprised shikimic acids of learning of experimentation.
Summary of the invention
One of the problem to be solved in the present invention is exactly for numerous hyperpietics provide a kind of cheap and easy to get, and the novel drugs that toxic and side effects is low is selected.
In order to address the above problem, the invention provides the purposes of purposes, the especially shikimic acid of shikimic acid in preparation treatment hypertension drug in preparation treatment essential hypertension medicine.
The specific embodiment
The hypotensive activity of embodiment 1 shikimic acid
Essential hypertension (SHR) rat is nineteen fifty-nine Okamoto and Aoky from the be commissioned to train rat model of the blood pressure stabilization rising that brings out of wistar capital of a country kind rat selectivity copulation 20, quite similar with human hypertension, be comparatively ideal animal model [Xu Shuyun of research hypertension pathogenesis and screening antihypertensive drugs, Bian Rulian, old repairing (chief editor), pharmacological experimental methodology, the third edition, Beijing, People's Health Publisher, 2001:953-954].Below the hypotensive effect of this animal model proof shikimic acid is adopted in experiment.
Medicine and reagent
Shikimic acid (Shikimic acid), buy the company in sigma, purity: 〉=99%, article No.: 138-59-0, specification: 5g/ bottle; During experiment shikimic acid is made as high, medium and low dosage group, presses 171.2mg/kg, 85.6mg/kg, 42.8mg/kg dosed administration respectively.
Animal
Essential hypertension (SHR) rat, male, SPF level, body weight 250～270g; The normal arterial pressure matched group is wistar capital of a country kind rat (WKY rat), and is male, no-special pathogen level (SPF level), and body weight 250～270g provides by Sichuan Academy of Medical Sciences institute of lab animals, the quality certification number: SCXK (river) 2008-24.Raise in animal after animal is bought and observe receptacle, natural lighting, well-ventilated, humidity 50～65%, 20～25 ℃ of temperature.
Key instrument
BP-6 animal non-invasive blood pressure tester, Chengdu TME Technology Co., Ltd.; The numerical control super constant temperature trough, the permanent instrument plant in sky, Ningbo.The statistical procedures method
The quantitative response data is represented with means standard deviation
Adopt the analysis of SPSS16.0 software statistics, relatively use one factor analysis of variance (One-WayANOVA) LSD method statistics between group, P＜0.05 is for having statistical significance.
Experimental technique
The SHR rat is measured blood pressure earlier and screens, and rejects defective rat, and then rat is divided at random: SHR model control group, the high, medium and low dosage group of shikimic acid, other establishes WKY blank group, 10 every group.The high, medium and low dosage group of shikimic acid is pressed 171.2mg/kg, 85.6mg/kg, 42.8mg/kg dosed administration respectively, administration volume 10ml/kg, model control group and blank group are irritated stomach isometric(al) distilled water, each is organized before the rat administration arteria caudalis manometry and surveys its systolic pressure and diastolic pressure 3 times, get separately meansigma methods as administration before pressure value.Behind the successive administration 7 days, measure systolic pressure and diastolic pressure in last administration 1 hour with method, reject unstable rat in the stipulated time.The same period is systolic pressure and diastolic pressure relatively, judges the medicine hypotensive effect.
Experimental result
1, shikimic acid is to the influence of SHR rat systolic pressure
Table 1 shikimic acid is to the influence of SHR rat systolic pressure
The WKY contrast is compared with the SHR contrast:
##P＜0.01; The medicine group is compared with the SHR contrast:
*P＜0.05,
*P＜0.01
Table 1 result shows: compare SHR matched group rat model systolic pressure obviously raise (P＜0.01) with the WKY matched group; With the same period SHR matched group compare, shikimic acid 171.2mg/kg, 85.6mg/kg dosage group can obviously reduce SHR rat systolic pressure (P＜0.01～0.05).
2, shikimic acid is to the influence of SHR rat diastolic pressure
Table 2 shikimic acid is to the influence of SHR rat diastolic pressure
The WKY contrast is compared with the SHR contrast:
##P＜0.01; The medicine group is compared with the SHR contrast:
*P＜0.05,
*P＜0.01
Table 2 result shows: compare with the WKY matched group, SHR matched group rat model diastolic pressure is obviously rising (P＜0.01) all; With the same period SHR matched group compare, shikimic acid 171.2mg/kg, 85.6mg/kg dosage group can obviously reduce SHR rat diastolic pressure (P＜0.01～0.05).
Table 1, table 2 result show: shikimic acid has hypotensive effect, systolic pressure and diastolic pressure are all had reduction, and hypotensive effect has obvious dose dependent.
The acute toxicity test of embodiment 2 shikimic acids
Medicine and reagent
Shikimic acid, specification: 1000913874, to purchase in sigma, the time spent is mixed with desired concn with normal saline.
Animal
SPF level Kunming mouse, credit number: SCXK (river) 2008-24 purchases in Sichuan Academy of Medical Sciences institute of lab animals.
Experimental technique
Get 110 of healthy mices, body weight 18～20g, male and female half and half are divided into intraperitoneal injection 1.5,2.0,2.25,2.5,2.8g/kg dosage group immediately; Gastric infusion 5.0,6.0,7.5,8.0g/kg dosage group, other establishes 2 groups of normal controls, fasting is 14 hours before the test, freely drink water, intraperitoneal injection group administration volume is 0.2ml/10g, and gastric infusion group administration volume is 0.4ml/10g, each organizes administration 1 time, after the administration, observe mice toxic reaction, general behavior in 14 days continuously, statistics dead mouse number.
Statistical method
Adopt spss 17.0 statistics computed in software LD
50And LD
5095% confidence interval.
Experimental result
A shot and gastric infusion (the various dose experiment and the results are shown in Table 3 and table 4) the back mice shows lethargy, the movable minimizing, part mice hair is vertical, amount of drinking water reduces, feces reduces, dead mice occurring the dyspnea phenomenon.Wherein mice was death in 8～10 hours behind the lumbar injection 2.8g/kg, and other dosage mices occurred dead in 30～60 hours; Death appearred in mice behind the gastric infusion 8.0g/kg in 2～10 hours, and other dosage group mices occurred dead in 10～18 hours; Not dead mice was at mental restoration on the 2nd, and it is normal that its activity, hair and color and luster, drinking-water, feces etc. all recover.
Behind the dead mouse, dissect immediately, the perusal mice has stomach swelling, assembles a large amount of content phenomenons, and no abnormal in the intestinal, all no abnormal discoveries of the heart, liver, lung, spleen, kidney; Dissect not dead mice on the 14th, the heart of perusal mice, liver, lung, spleen, kidney, intestinal are all no abnormal.
The measurement result that table 3 shikimic acid intraperitoneal injection causes death to the mice half
The measurement result that table 4 shikimic acid gastric infusion causes death to the mice half
The result of the test of table 3 and table 4 shows that the shikimic acid intraperitoneal injection is to mice median lethal dose(LD 50) LD
50Be 2.14g/kg, LD
5095% credibility interval be 1.95～2.29g/kg; The shikimic acid gastric infusion is to mice median lethal dose(LD 50) LD
50Be 7.14g/kg, LD
5095% credibility interval be 6.61～7.59g/kg.Two kinds of different approaches of above presentation of results shikimic acid lumbar injection and gastric infusion all can find LD
50, judge that from poisoning symptom and toxic dose the toxicity of shikimic acid is less, super large dosage may influence the digestive function of stomach, but central nervous system, respiratory system, blood circulation are not all had influence.
Claims (2)
1. shikimic acid is as the purposes of unique active component in preparation treatment hypertension drug.
2. according to the described purposes of claim 1, it is characterized in that described hypertension is essential hypertension.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110031013 CN102614160B (en) | 2011-01-28 | 2011-01-28 | Use of shikimic acid in preparation of antihypertensive drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110031013 CN102614160B (en) | 2011-01-28 | 2011-01-28 | Use of shikimic acid in preparation of antihypertensive drug |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102614160A CN102614160A (en) | 2012-08-01 |
| CN102614160B true CN102614160B (en) | 2013-08-14 |
Family
ID=46554614
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110031013 Active CN102614160B (en) | 2011-01-28 | 2011-01-28 | Use of shikimic acid in preparation of antihypertensive drug |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102614160B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115998723A (en) * | 2022-12-26 | 2023-04-25 | 肇庆大华农生物药品有限公司 | Application of shikimic acid in preparation of medicine for preventing and/or treating white spot syndrome of aquatic animals |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1965870A (en) * | 2005-11-18 | 2007-05-23 | 北京天新园医药科技开发有限公司 | Pharmaceutical composition containing ligustrazine and effective component of ginkgo leaf and formulation thereof |
| CN101352427A (en) * | 2008-09-12 | 2009-01-28 | 西安交通大学 | Use of shikimic acid in preparing medicament for treating ulcerative colitis |
| CN101940552A (en) * | 2008-09-16 | 2011-01-12 | 倪健 | Chinese medicament shikimic acid powder injection |
-
2011
- 2011-01-28 CN CN 201110031013 patent/CN102614160B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1965870A (en) * | 2005-11-18 | 2007-05-23 | 北京天新园医药科技开发有限公司 | Pharmaceutical composition containing ligustrazine and effective component of ginkgo leaf and formulation thereof |
| CN101352427A (en) * | 2008-09-12 | 2009-01-28 | 西安交通大学 | Use of shikimic acid in preparing medicament for treating ulcerative colitis |
| CN101940552A (en) * | 2008-09-16 | 2011-01-12 | 倪健 | Chinese medicament shikimic acid powder injection |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102614160A (en) | 2012-08-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104688782B (en) | A kind of method of the high efficiency extraction triterpene active component from fuling peel | |
| CN101810659A (en) | Total saponins of salvia chinensis benth, and medical application and preparation method thereof | |
| CN102994350B (en) | Preparation method of tartary buckwheat wine with function of reducing blood fat | |
| CN102228539B (en) | Rosa davurica total flavone extract, its extracting method and its medical use | |
| CN102014931A (en) | Use and preparation of paeoniflorin and the composition thereof | |
| CN101199581B (en) | Chick-pea embryo and bean sprout valid part, preparing method and application thereof | |
| CN102266407A (en) | Traditional Chinese medicinal composition for treating hypertension and preparation method thereof | |
| CN102614160B (en) | Use of shikimic acid in preparation of antihypertensive drug | |
| CN105085534B (en) | A kind of alkaloid compound and its extraction separation method | |
| CN106236834A (en) | The preparation method of Cortex Cinnamomi extract, Cortex Cinnamomi extract, a combination thereof thing and application | |
| KR101722165B1 (en) | A method of preparation of neohesperidin dihydrochalcone from citrus peel by using supercritical fluid extraction | |
| CN104224863B (en) | Lysimachia herb total flavone is preparing the application in treating antihyperuricemic disease drug | |
| CN101756965A (en) | Application of maca imidazole alkaloid in preparation of cardiovascular drugs | |
| CN106822331A (en) | To lock application of the lichee bark extract based on shape polymer polyphenol in treatment antihyperuricemic disease drug or health products are prepared | |
| CN107537028B (en) | Formula for simultaneously assisting in reducing blood sugar and blood pressure and preparation method thereof | |
| CN106928376B (en) | The separation method of skunk bush polysaccharide and its application | |
| CN1188406C (en) | Cattail pollen extract and preparation process and use thereof | |
| CN101623437A (en) | Pulse-activating preparation for injection and preparation method thereof | |
| Hermilasari et al. | Study in vitro and in silico on effectiveness noni fruit extract (Morinda citrifolia) to reducing hypertension | |
| CN101934044B (en) | Novel application of ginseng, tuckahoe and atractylodes preparation | |
| CN101804083B (en) | Application of pollen pini and extract thereof in treating inflammatory bowel disease and method for preparing extract | |
| CN1895540A (en) | Medicinal composition for treating cardiovascular disease, its making method and use | |
| CN102336795A (en) | Eucommia ulmoides Oliv active monomer compound and preparation method thereof as well as medicament composition and application thereof | |
| CN1935201B (en) | Radix aconiti carmichaeli extract and its preparing method | |
| CN103083408B (en) | Composition of traditional Chinese medicine extracts, and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20120801 Assignee: Sichuan Jishengtang Pharmaceutical Co., Ltd. Assignor: Kanghong Pharmaceutical Co., Ltd., Chengdu Contract record no.: 2017510000030 Denomination of invention: Use of shikimic acid in preparation of antihypertensive drug Granted publication date: 20130814 License type: Common License Record date: 20171018 |