CN101491516B - Use of tanshinone compound in preparing analgesic - Google Patents
Use of tanshinone compound in preparing analgesic Download PDFInfo
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- CN101491516B CN101491516B CN2008100331013A CN200810033101A CN101491516B CN 101491516 B CN101491516 B CN 101491516B CN 2008100331013 A CN2008100331013 A CN 2008100331013A CN 200810033101 A CN200810033101 A CN 200810033101A CN 101491516 B CN101491516 B CN 101491516B
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Abstract
The invention discloses application of a tanshinone compound in preparation of an analgesic drug. The tanshinone compound is dihydrotanshinone which can be used only or can be made into oral or non-oral preparations by adding pharmaceutically acceptable excipients. An animal experiment shows that the substances have analgesic effect and can be used for preparing the analgesic drug.
Description
Technical field
The present invention is field of medicaments, especially natural medicine field, is specifically related to the application of tanshinone compound in the preparation analgesic.
Background technology
Pain has become one of important diseases that influences people's live and work.Investigation shows, headache, toothache, muscle and arthralgia are the pain of normal experience, secondly pain and dysmenorrhoea for caused by athletic injury of China resident.Wherein, the generation ratio of all ages and classes paragraph header pain has all surpassed half; Below 30 years old and 30-45 year crowd have a headache incidence rate all above 70%; The generation ratio of muscle arthralgia and toothache is also improving.
Present stage, analgesic commonly used mainly contained two big classes: the opiates narcosis analgesic is representative with the morphine; Nonsteroidal antiinflammatory drug is representative with aspirin.Opium kind analgesics is a depressor of nerve centre, though the obvious easily addiction and produce toleration of effect.Nonsteroidal antiinflammatory drug acts on peripheral nervous system, is the purpose that synthesizes with the blocking-up prostaglandin, and such drug side effect is bigger, takes for a long time to cause allergy, gastrorrhagia and ulcer.Therefore, press for effective, the safe and reliable analgesic of searching.
Along with people become increasingly conspicuous to the understanding day by day of Chinese medicine unique advantage and chemical analgesic toxic and side effects and drug injury problem, the Chinese medicine analgesic has obtained paying attention to widely and using.From Chinese herbal medicine, seek and development has the medicine of good analgesic activity, have little, and the many advantages such as safe and reliable of good effect, side effect, and more and more cause people's attention.
Radix Salviae Miltiorrhizae is the dry root and rhizome of labiate Radix Salviae Miltiorrhizae (Salvia miltiorrhiza Bunge), is recorded by the many editions Pharmacopoeias of the People's Republic of China.Radix Salviae Miltiorrhizae cold nature, bitter in the mouth.GUIXIN, Liver Channel.Has pain relieving, tranquilizing by nourishing the heart, blood circulation promoting and blood stasis dispelling, removing heat from blood, detumescence, functions such as regulating menstruation.Be used for the treatment of insomnia, pained, amenorrhea, coronary heart disease, dysmenorrhea, menoxenia, myocardial infarction, cerebral infarction, cerebral infarction, hypertension, diseases such as cerebral ischemia.Main chemical compositions is two big class, i.e. water solublity salvianolic acid and fat-soluble tanshinones.The latter mainly is to be the o-quinone structure tanshinone compound of representative with the tanshinone.The sodium sulfonate that obtains after tanshinone and its sulfonation is used for cardiovascular and cerebrovascular disease such as cerebral infarction, cerebral infarction, coronary heart disease, hypertension, the treatment of cerebral ischemia etc. clinically.But tanshinone compound and tanshinone extract do not have the report of analgesic activity.
Summary of the invention
The present invention aims to provide the novel medical use of tanshinone compound and total-tanshinone extract, promptly in the application of preparation in the analgesic, to obtain the analgesic that good effect, side effect are little, safe and reliable, can take for a long time.
Utilize tests such as mice acetic acid twisting, the extract of a large amount of natural medicinal plants is carried out the analgesic activities screening, and found that by the method that activity is followed the trail of tanshinone compound and total-tanshinone extract have analgesic activities, and do not demonstrate toxic and side effects.
With natural plants or Chinese crude drug, as Radix Salviae Miltiorrhizae is raw material, adopt one or more technologies in the technologies such as solvent extraction method, solvent extraction, resin adsorption method, carbon dioxide supercritical fluid extraction, and in conjunction with conventional drying method such as concentrate drying, drying under reduced pressure or lyophilizations, utilize again to comprise adsorbent resin column chromatography, vacuum liquid phase column chromatography, silica gel column chromatography, Sephadex gel filtration chromatography, mesolow column chromatography and preparation type high-pressure liquid phase (HPLC) column chromatography, and methods such as precipitation, crystallization obtain tanshinone compound or total-tanshinone extract.
In the solvent extraction method that is adopted, organic solvent or two or more mixed solvents that dissolve each other such as optional water or methanol, ethanol, propanol, butanols, amylalcohol, acetone, ethyl acetate, Ethyl formate, chloroform, dichloromethane, ether, petroleum ether, at room temperature dipping extracts or with the reflux, extract, under supersound extraction or the heated condition, extraction time can be once, also can be repeatedly.
In the solvent extraction that is adopted, the above-mentioned extract that obtains can be suspended in water and directly extract with suitable solvent (butanols, amylalcohol, ethyl acetate, Ethyl formate, chloroform, dichloromethane, ether, petroleum ether etc.), extraction times can be once, also can be repeatedly.
The resin method that is adopted is the macroporous adsorbent resin method, and water, alcohol or hydrous alcohol extraction thing can be handled with macroporous adsorbent resin, discard the water elution part, and all or part of collection alcohol eluting part promptly.
The carbon dioxide supercritical extraction method that is adopted can according to circumstances add suitable entrainer, as cyclohexane extraction, chloroform, ethyl acetate, methanol, ethanol etc.
Tanshinone compound of the present invention is dihydrotanshinone (dihydrotanshinone), and chemical compound can extract from plant or Chinese herbal medicine, also can be chemosynthesis.
Tanshinone compound described in the present invention can be used separately or share or combine with acceptable excipient etc. as the active ingredient of preparation analgesic, makes the medicine of the treatment pain of peroral dosage form or non-peroral dosage form according to conventional method.
Result of the test shows that above-mentioned tanshinone compound has tangible analgesic effect, can be used for preparing analgesic; And have obvious curative effects, side effect is little, and is safe and reliable, is fit to mild or moderate pain, can take for a long time.
The specific embodiment
Embodiment 1: the preparation of total-tanshinone extract
Get the decoction pieces 300g of Labiatae salvia Radix Salviae Miltiorrhizae, use 90% ethanol extraction, concentrated lixiviating solution gets ethanol extraction, and extract is scattered in the water, after low temperature is placed, filters, and drying promptly obtains total-tanshinone extract.Wherein total tanshinone content is 80%.
Embodiment 2: the extraction separation of tanshinone compound in the Radix Salviae Miltiorrhizae
Get total-tanshinone extract described in the embodiment 1, last silicagel column, petroleum ether chloroform gradient elution obtains tanshinone compounds such as Tanshinone I, Tanshinone I Ia, cryptotanshinone and Norshinone.
Embodiment 3: tanshinone compound is to the analgesic activity test of mice
Get the Tanshinone I, Tanshinone I Ia, cryptotanshinone and the dihydrotanshinone that obtain among the embodiment 2, oral administration is applied to the experiment of mice acetic acid twisting.
Operational approach is: get 30 of 18～22g mices, be divided into three groups at random, respectively by body weight 100mg/kg, 30mg/kg and 10mg/kg oral administration, administration group sample liquid 0.6ml/ only; Other establishes matched group and gives the equal-volume normal saline.After 60 minutes, each Mus lumbar injection 0.7% acetic acid 0.1ml/10g observes and writes down the number of animals of generation writhing response in 10 minutes or the number of times of every group of writhing response, compares its analgesic effect with matched group.Result such as table 1.
Get Tanshinone I Ia, oral administration is applied to experiment of mice formalin and hot plate experiment, result such as table 2.
Mice formalin experiment: get 30 of 25g～30g ICR mice, respectively by body weight 100mg/kg, 30mg/kg and 10mg/kg oral administration, administration group sample liquid 0.6ml/ only; Other establishes matched group and gives the equal-volume normal saline.20 μ l are in metapedes sole of the foot portion for injection of formalin after 60 minutes (2.5%, 0.9% normal saline).After formalin given in record, 0～5 minute (1 phase is represented with PI), 20～35 minutes (2 phases are represented with PII), interior mice licked the sufficient time.The reaction of 1 phase (PI) is relevant with acute pain, and the reaction of 2 phases (PII) is relevant with chronic pain.
Hot plate experiment: get 30 of 25g～30g ICR mice, respectively by body weight 100mg/kg, 30mg/kg and 10mg/kg oral administration, administration group sample liquid 0.6ml/ only; Other establishes matched group and gives the equal-volume normal saline.After 60 minutes, mice placed on 55 ℃ the hot plate, write down its vola contact hot plate to the time that occurs licking foot, playing back leg or jump, as threshold of pain index.
Table 1. mice acetic acid twisting experimental result
The analgesic test result of table 2. Tanshinone I Ia
Embodiment 4: total-tanshinone extract is to the analgesic activity test of mice
Get the total-tanshinone extract that obtains among the embodiment 1, oral administration is applied to the experiment of mice acetic acid twisting, formalin experiment and hot plate experiment, and the result is as shown in table 3.
Table 3. Headquarters of the General Staff ketone extract analgesic test result
Claims (1)
1. the application of tanshinone compound in the preparation analgesic, it is characterized in that described tanshinone compound is a dihydrotanshinone, described medicine with dihydrotanshinone as active component, use separately, perhaps add the oral or non-oral formulation that pharmaceutically acceptable excipient is made.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100331013A CN101491516B (en) | 2008-01-25 | 2008-01-25 | Use of tanshinone compound in preparing analgesic |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2008100331013A CN101491516B (en) | 2008-01-25 | 2008-01-25 | Use of tanshinone compound in preparing analgesic |
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| CN101491516A CN101491516A (en) | 2009-07-29 |
| CN101491516B true CN101491516B (en) | 2011-09-28 |
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| CN2008100331013A Expired - Fee Related CN101491516B (en) | 2008-01-25 | 2008-01-25 | Use of tanshinone compound in preparing analgesic |
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EA031561B1 (en) * | 2016-02-26 | 2019-01-31 | Тахир Аббасали оглы Сулейманов | Use of a mixture of lilac sage and hardy sage extracts as an analgesic agent |
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- 2008-01-25 CN CN2008100331013A patent/CN101491516B/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| 张富赓.轮叶婆婆纳生物有效化学成分的研究.《中国优秀博硕士学位论文全文数据库（硕士） 医药卫生科技辑》.2007,(第5期),E057-24. |
| 张富赓.轮叶婆婆纳生物有效化学成分的研究.《中国优秀博硕士学位论文全文数据库(硕士) 医药卫生科技辑》.2007,(第5期),E057-24. * |
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Granted publication date: 20110928 Termination date: 20140125 |