CN101732299A - Medicinal composition containing ferulic acid and matrine compounds and application thereof - Google Patents
Medicinal composition containing ferulic acid and matrine compounds and application thereof Download PDFInfo
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Abstract
The invention relates to a medicinal composition containing ferulic acid and matrine compounds. The medicinal composition of the invention is used for preparing medicaments for treating tumors, cardiovascular diseases, bone and joint diseases and the like.
Description
Technical field
The present invention relates to contain the medical composition and its use of ferulic acid and matrine compound.
The research background
The chemical name of ferulic acid is 4-hydroxyl-3-methoxy cinnamic acid, is the ubiquitous a kind of phenolic acid of plant kingdom, is one of Effective Components of Chinese Herb such as Radix Angelicae Sinensis, Rhizoma Chuanxiong, Resina Ferulae, extensively exists in the various plants.Can be by extracting or the acquisition of synthetic method.It has pharmacological action widely, and for example antiinflammatory, antibiotic, antioxidation, enhance immunity, antitumor, anti-cardiovascular disease, fibrosis, anti-senile dementia etc. all have report.Radix Sophorae Flavescentis is one of Chinese medicine of using always.It contains multiple alkaloid, based on matrine (matrine), oxymatrine (oxyma-trine), next has sophocarpine (l-sophocarpine), sophoridine (sophoridine), N-N-oxysophocarpine (N-oxysophocarpine) and Iosmatrine etc.The medicine of its exploitation has kurarinone, matrine, sophocarpine etc. to be mainly used in treatment, antiviral, antineoplastic treatment and the cardiovascular diseases's of chronic hepatopathy treatment clinically.Have antiviral, anti-hepatic fibrosis, immunoregulation effect and antiinflammatory, anti-allergy action etc.We discover, the pharmaceutical composition that contains ferulic acid and matrine compound can obviously increase the effect of matrine compound and/or ferulic acid, and/or the two has the obvious synergistic effect in vivo, and/or reduce the toxicity of matrine compound, and/or increase the water solublity and fat-soluble of the two.
Summary of the invention
Invention relates to the pharmaceutical composition that contains ferulic acid and matrine compound.
The present invention relates to contain the pharmaceutical composition of ferulic acid and matrine.
The present invention relates to contain the pharmaceutical composition of ferulic acid and kurarinone.
The present invention relates to contain the pharmaceutical composition of ferulic acid and sophocarpine.
The ferulic acid that the present invention relates to comprises positive ferulic acid and Hesperetic acid and their isomers and the inorganic salts chemical compound of being formed.Architectural feature is seen relevant document [Zhang Juan etc.Synthetic and the pharmacological research progress of ferulic acid and derivant thereof, grain and oils and fats, 2007 the 1st phases, 43-45].According to claim 1, matrine compound involved in the present invention mainly comprises isomer sophoridine, Iosmatrine of matrine, oxymatrine (kurarinone), sophocarpine, N-oxysophocarpine, sophoranol, supanine and matrine etc. and their isomers and/or their inorganic salts.Its basic structural feature is to have a tetracyclic quinolizine pyridine, as shown in the formula:
The basic structure of matrine alkaloid
The compositions that contains ferulic acid and matrine compound that the present invention relates to, its ferulic acid can be formed compositions with a kind of matrine alkaloid, also can send out the composition compositions with matrine alkaloid more than 2 kinds or 2 kinds, the compositions that preferred ferulic acid and matrine, ferulic acid and kurarinone are formed, the molecule mol ratio of its ferulic acid and matrine and/or kurarinone is 1: 1-50, preferred 1: 1-3.
The compositions that contains ferulic acid and matrine compound that the present invention relates to has the obvious synergistic effect, has not only increased the pharmacy effect of ferulic acid but also can increase the pharmacy effect of matrine compound.The effect of for example anti-internal organs fibrosis improves hemorheology, antivirus action, antiinflammatory action suppresses the effect of acetylcholine esterase, pain relieving and itching-relieving action, anti thrombotic action, antibacterial action, antitumor action, antioxidation, effect for reducing blood fat, arteriosclerosis, rheumatism, increase immunity, increase motility of sperm and motion, antihypertensive function etc.
The compositions that contains ferulic acid and matrine compound that the present invention relates to can obviously increase the water solublity of ferulic acid and matrine alkaloid and fat-soluble.
The compositions that contains ferulic acid and matrine compound that the present invention relates to, can adopt the method preparation prevention of pharmaceutics and treatment tumor, arteriosclerosis, the heart, cerebrovascular, joint disease, flu, senile dementia, the inflammation of skin, eczema, acne, maculopapule, urticaria, psoriasis, gastrointestinal tract dynamia low, the medicine of the acute and chronic inflammation that the inflammation of internal organs such as hepatitis, nephritis and internal organs fibrosis and whole body and/or internal organs take place, its preparation can be an oral formulations, also can injection and the mucocutaneous preparation of using.
Specific embodiment:
Embodiment one ferulic acid kurarinone compound recipe freeze-dried powder preparation
With a little dissolve with ethanol of ferulic acid, add equimolar kurarinone aqueous solution, make freeze-dried powder according to conventional method.
The preparation of embodiment two ferulic acid sophocarpine tablets
After ferulic acid and 1: 2 mole of mixing of sophocarpine, make tablet according to the method for conventional dose, every 100mg.
The preparation of embodiment three ferulic acid matrine gels
Get 1: 1 mole ferulic acid matrine, behind the dissolved in distilled water, add in the carbomer gel after the swelling, conventional filling and sealing promptly.
The analgesic activity of embodiment four several drugs compositionss and with the comparison of the effect of kurarinone and ferulic acid
Table 1. several drugs compositions preparation table
| The compositions code name | Ferulic acid (molal quantity) | Matrine (molal quantity) | Kurarinone (molal quantity) | Sophocarpine (molal quantity) |
| ??I | ??1 | ??1 | ??0 | ??0 |
| ??II | ??1 | ??2 | ??0 | ??0 |
| ??III | ??1 | ??1 | ??1 | ??0 |
| ??IV | ??1 | ??0 | ??1 | ??0 |
| ??V | ??1 | ??0 | ??0 | ??2 |
Choose healthy mice, 10 every group.Gastric infusion 20mg/kg, for three days on end, behind the last administration 30min, lumbar injection 0.6% acetic acid 10ml/kg, the writhing response number of times appears in mice in the record 15min.Calculate medicine analgesia percentage rate.
Medicine analgesia percentage rate (%)=(matched group is turned round body number of times treatment group and turned round the body number of times)/matched group is turned round body number of times * 100%
Table 2. chemical compound compares the analgesic activity of mice acetic acid twisting
| Group | ??N | Analgesia percentage rate (%) |
| The blank group | ??10 | ??-- |
| Kurarinone | ??10 | ??29.98 |
| Ferulic acid | ??10 | ??18.30 |
| ??I | ??10 | ??88.86 |
| ??II | ??10 | ??98.29 |
| ??III | ??10 | ??87.42 |
| ??IV | ??10 | ??99.36 |
| ??V | ??10 | ??78.13 |
The antiinflammatory action of embodiment five several drugs compositionss and with the comparison of the effect of kurarinone and ferulic acid
Dosage and chemical compound are with embodiment four, 10 every group of mices are behind the labelling of weighing, with the auris dextra of mice dimethylbenzene cotton balls contact 5sec, left side ear in contrast, after causing scorching 10min, causing on the scorching auricular concha respectively, applying and giving drug level is 1% to be subjected to the reagent thing, the blank group is given normal saline, behind the 30min mouse carotid dislocation is put to death, with diameter 6mm card punch get an equivalance left side (own control), auris dextra (dimethylbenzene processing) is weighed, calculating ear swelling rate.Ear swelling rate (%)=auris dextra weight-left ear weight/left ear weight * 100%. the results are shown in Table 4.
Table 4. chemical compound is to the effect of mice ear
| Group | Swelling rate (%) |
| The blank group | ??173.72 |
| Matrine | ??133.4 |
| Ferulic acid | ??164.6 |
| ??I | ??74.9 |
| ??II | ??98.9 |
| ??III | ??36.4 |
| ??IV | ??111.2 |
| Group | Swelling rate (%) |
| ??V | ??96.7 |
Embodiment six several compositionss to liver hepatic stellate cell increment and secreting type I collagen protein effect
Material and reagent: rat type i collagen protein ELISA kit, trypsin, hyclone etc.
Method: (hepatic stellate cell HSC) is seeded in the 100mL plastic culture bottle after the recovery rat liver hepatic stellate cell, cultivates in the CO2 incubator of 5%CO2,95% humidity.After treating that cell grows up to monolayer in the culture bottle, discard culture fluid, add 0.25% tryptic Digestive system, collect Digestive system, the centrifugal 7min of 2200rPmin, abandon supernatant, the washing of reuse DMEM medium centrifugal once, 20% hyclone DMEM culture fluid suspends cell mass and counting with containing, with containing DMEM culture fluid diluting cells suspension, be inoculated in 96 well culture plates, every hole 100 μ l, inhale behind the 48h and go the culture fluid reuse to contain the DMEM culture fluid synchronization cell of 10% calf serum, make cell synchronization resting stage.Experiment grouping (normal saline), add medicine and make that respectively organizing culture fluid Chinese medicine concentration is respectively 50 μ mol/L, every group 6 hole repeats to cultivate 3 times, behind the effect 48h, stop cultivating, add 5mg/L tetrazolium bromide (MTT) 20 μ L in every hole respectively, cultivate 4h again, add the 10min that vibrates behind the DMSO, with microplate reader (wavelength 570nm)
Measure the HSC absorbance.Get the cell behind the drug effect, after cultivating according to the method described above, draw supernatant, measure the type i collagen protein content according to the test kit description.The results are shown in Table 5
Table 5 chemical compound is to increment of rats'liver hepatic stellate cell and type i collagen protein content
The comparison of the anticholinesterasic effect of embodiment seven several compositionss
Get blood 5ml from healthy rat, put into the test tube that is added with anticoagulant, with 10 times of normal saline dilutions, stand-by.
Medicine diluted respectively with normal saline be 0,5,10,20,40,80,160,320, the solution to be measured of 640mg/L.Get in the different solution to be measured of 0.05ml and to add in the whole blood that 0.5ml diluted, fully behind the mixing, put 37 ℃ of environment and incubate 1h in advance.Measure the activity of whole blood acetylcholinesterase then according to acetylcholinesterase test kit description.Calculation of half inhibitory concentration (IC
50).The result shows that Compound I-X has the effect that suppresses whole blood acetylcholine ester, and wherein the inhibitory action of compound III is the strongest.
Several chemical compounds of table 6 are to the IC of choline esterase inhibition
50
| The chemical compound title | ??IC 50(mg/L) |
| Blank | ??-- |
| Kurarinone | ??735.5 |
| Matrine | ??-- |
| Ferulic acid | ??-- |
| Neostigmine | ??365.7 |
| ??I | ??223.4 |
| ??II | ??86.5 |
| ??III | ??58.8 |
| ??IV | ??433.9 |
| ??V | ??567.1 |
Embodiment eight several compositionss are to the comparison of mice intestinal motive force effect
Medicine and reagent Matrine Injection, Shandong XinHua Pharmacy stock Co., Ltd produces (lot number: 0306003); Methyl-sulfuric acid neostigmine injection, sky, Shandong good fortune pharmaceutical factory produces (lot number: 0404131); Atropine sulfate injection, sky, Shandong good fortune pharmaceutical factory produces (lot number: 0409271); Contenton, Beijing are sprouted base of a fruit pharmaceutical Co. Ltd and are produced (lot number: 04082312).
The healthy kunming mice of animal and feeding environment, the SPF level, male and female half and half, body weight 18-22g is provided by Shandong Green Leaf Pharmaceutical Co., Ltd zoopery center.The quality certification number: SYXK (Shandong) 20030020.10 placements of animal per cage.Feedstuff is provided by Shandong Province's Experimental Animal Center.Barrier system is raised, and filters air-supply, indoor temperature 18-22 ℃; Humidity 50-60%; Illumination 12 hours.
The experimental technique mouse stomach is given relative medicine or normal saline, for three days on end, water 16h is can't help in fasting before the last administration, behind administration 30min, every mouse stomach gives 5% Insta-Char 0.2ml, mice is put to death in dislocation behind the 20min, opens the abdominal cavity and separates mesentery, and the clip pylorus is to the intestinal tube of ileocecus, place on the pallet, gently small intestinal is pulled into straight line, measures intestinal tube length as the small intestinal total length, from pylorus to charcoal the distance in forward position, end as the charcoal end at the enteral advance distance.Calculate charcoal end propelling rate with following formula.Charcoal end propelling rate (%)=charcoal end is at enteral advance distance/small intestinal total length * 100%
Several chemical compounds of table 7 are to the influence of small intestine movement of mice charcoal end propelling rate
| Chemical compound | Dosage (mg/kg) | ??N | Charcoal end propelling rate (%) |
| Blank | ??-- | ??10 | ??57.26±9.10 |
| Kurarinone | ??10 | ??10 | ??58.85±13.22 |
| Kurarinone | ??20 | ??10 | ??67.49±11.68* |
| Ferulic acid | ??20 | ??10 | ??54.33±10.22 |
| Neostigmine | ??4 | ??10 | ??68.55±4.80** |
| ??I | ??10 | ??10 | ??71.20±8.11** |
| ??II | ??10 | ??10 | ??78.54±12.42* |
| ??III | ??10 | ??10 | ??72.36±8.77** |
| ??IV | ??10 | ??10 | ??75.12±13.35* |
| ??V | ??10 | ??10 | ??79.01±6.88** |
Compare with matched group: * P＜0.05; * P＜0.01.
The experimental data of embodiment nine several chemical compound acute toxicities
Experimental technique: get mice, 1 gastric infusion was observed 72 hours, and the record death condition the results are shown in Table 8.
Several chemical compounds of table 8 are to the observation of mouse toxicity
| Chemical compound | Dosage (mg/kg) | ??N | The dead animal number |
| Matrine | ??500 | ??10 | ??10 |
| Ferulic acid | ??1000 | ??10 | ??0 |
| Sophocarpine | ??500 | ??10 | ??10 |
| ??I | ??800 | ??10 | ??0 |
| ??II | ??800 | ??10 | ??0 |
| ??III | ??800 | ??10 | ??0 |
| ??IV | ??800 | ??10 | ??0 |
| ??V | ??800 | ??10 | ??0 |
The observation of embodiment ten, ferulic acid kurarinone compositions arteriosclerosis
Test method:
Medication preparation: with the ferulic acid kurarinone with wiring solution-forming after 1: 1 molecule mixed in molar ratio.
Carry out [Liu Zhantao, Liu Sai, Wang Shoulan, Zhang Jian, Zhong Weizhen according to literature method.The comprehensive extract of seashells is to the therapeutical effect of experimental atherosclerosis.2005 the 13rd the 3rd phases of volume of China's arteriosclerosis magazine; 305308].
Get 140 of male Carnis Coturnicis japonicaes, be divided into 7 groups at random, normal control group, model group, positive controls (sieve cut down its fourth 10mg/kg), the high, medium and low dosage group of oral matched group of ferulic acid (40mg/kg) and medicine (administration 10,20 respectively, 40mg/kg).Except that the normal control group is fed normal feedstuff, set up high fat bait arteriosclerosis model according to literature method for all the other 5 groups.
Each medication group gastric infusion, once a day, 4 weeks of continuous use.Respectively at the 4th weekend after the medication, get 10 its serum lipids of zoometry for every group.Carnis Coturnicis japonicae to survival when experiment finishes carries out the pathology detection.
The serum lipids assay: each organizes the 2nd, 4 weekend after medication, and fasting 12h is after jugular vein is got blood 2mL, and separation of serum adopts enzymatic assays serum cholesterol (TC), triglyceride (TG) level.
The result: ferulic acid kurarinone ether can obviously reduce arteriosclerosis model Carnis Coturnicis japonicae serum TC, TG level, and it acts on than the obvious enhancing of ferulic acid (table 9).The most aortas of model group have tangible pathological changes, and most As pathological changes are more than 2 grades, and ferulic acid kurarinone ether group atherosclerosis of aorta lesion degree is lighter, how below 1～2 grade (table 10).Visible most arteries inner membrance is complete under the mirror, and part has slight lipid to soak into, and includes and is dispersed in foam cell.
Table 9. ferulic acid kurarinone is to the influence of high blood lipid model Carnis Coturnicis japonicae blood fat
Table 10. ferulic acid kurarinone is to the influence of high blood lipid model Carnis Coturnicis japonicae aorta artery sclerosis pathological changes
Embodiment nine, ferulic acid matrine gel are to the influence of acute rheumatic arthritis.
Medication preparation: the ferulic acid matrine with after 1: 1 molecule mixed in molar ratio, is made ointment according to practice of pharmacy.
30 couples of rheumatic arthritis patients, wherein 30 examples are matched group, 30 examples are test group.The independent oral naproxen 200g of matched group, ferulic acid matrine ketone emulsifiable paste, every day 1 time, continuous use 5 days are smeared in treatment group affected part.
Observation of curative effect: swelling and pain disappear substantially, are produce effects; Mild swelling, pain disappear substantially for effectively; Swelling and pain all do not take a turn for the better, for invalid.
The result: test group produce effects 21 examples, effective 8 examples, total effective rate is 96.7%.Matched group produce effects 12 examples, effective 11 examples, total effective rate is 76.7%.
Tens kinds of chemical compounds of embodiment are to the therapeutical effect of erythra
Case is selected: the age is in 18-25 year, health bilateral erythra, male or female, every kind of drug study 10 examples.Partial smearing 1% medicine is returned the ginseng emulsifiable paste on erythra, the blind contrast of self list, and left limb is smeared medicine, and right side limbs normal saline is smeared and was carried out evaluation of result in back 10 minutes.
Evaluation of result: the detumescence itching-relieving action is estimated.Produce effects: erythra obviously disappears, and itching-relieving action is obvious.Effectively: certain itching-relieving action is arranged, and pimple has disappearing to a certain degree.Invalid: as not see obvious effect.
The results are shown in following table.
Several chemical compounds of table 11. are to the therapeutical effect therapeutic evaluation of erythra
Embodiment 11, Compound I I, III, V are to the therapeutical effect of rat senile dementia
1. medicine and reagent: kurarinone, matrine and sophocarpine are produced by Ningxia Boertaili Pharmaceutical Co., Ltd, and the huperzine A sheet is produced by Shanghai red flag pharmaceutical factory.The D-galactose is that reagent two factories in Shanghai produce, and amino-(3-hydroxy-5-isoxazolyl)acetic acid. (IBO) is analytical pure available from Sigma company.Whole blood and cerebral tissue TChE (TchE) detection kit are built up bio-engineering research by Nanjing to be provided.
2. animal grouping, modeling and administration: 57 of 15 monthly age young old female Wistar rats, body weight 300～450g provides by Qingdao City medicine inspecting institute animal center.Conventional sub-cage rearing, natural illumination is arbitrarily drunk water and is got food.Be divided into 6 groups at random, normal control group (abbreviation normal group) wherein, Meynert nuclear injecting normal saline in 6 weeks of intraperitoneal injection of saline and the brain, AD model group (abbreviation model group), bilateral Meynert nuclear injection IBO in lumbar injection D_ galactose (48mg/kg/d) 6 week and the brain, huperzine A matched group (abbreviation huperzine A group) and tried all same model group of thing observation group modeling.Intracerebral injection carries out with reference to relevant document behind lumbar injection
[1]After modeling finished, the huperzine A group was irritated stomach and is given huperzine A 50ug/kg, and Compound I I, III, X group are irritated stomach medicine 50mg/kg respectively.Normal group, model group give the normal saline with volume.Successive administration 7 days, carries out learning capacity and detects after 1 hour in the last administration, rat is anaesthetized with pentobarbital then, ventral aorta blood sampling 5ml on the ice platform, the rapid taking-up of dissection cerebral cortex as the homogenate medium, is made the homogenate of 10% (W/V) brain cortical tissue with normal saline.According to the mensuration of test kit explanation carrying out acetylcholine esterase active, the mensuration of the acetylcholine esterase active of whole blood is carried out according to literature method
[2]
3. detection index: animal memory behavior test: the passive avoidance step down test, rat is put reaction chamber endoadaptation environment 3min.Pass to the 50V alternating current then.After rat is shocked by electricity.Escape reaction is for jumping onto platform to hide noxious stimulation.Record be subjected in the 5min number of shocks (errors number) as school grade with the response learning ability.Directly rat is placed on the platform behind the 24h.Write down incubation period of jumping off for the 1st time with errors number in reaction memory ability and the 5min, surpass 5min person incubation period in 5min.
Relatively t check between date processing employing group, with p＜0.05 as the statistical significance index.
4. result: 3 kinds of chemical compounds all can reduce whole blood and cerebral tissue acetylcholine esterase level, improve learning and memory in rats achievement (table 12,13)
Table 12 Compound I I, III, V are to the influence of TChE level in rat whole blood and the cerebral tissue
| Group | ??N | Whole blood TchE (mmol/L) | Suppression ratio | Cerebral tissue TchE (umol/g) | Suppression ratio |
| Normal control | ??10 | ??76±28 | ??- | ??3.4±0.7 | ??- |
| The model contrast | ??10 | ??84±32 | ??- | ??3.8±0.9 | ??- |
| The huperzine A group | ??8 | ??48±35* | ??42.86％ | ??2.0±0.6* | ??41.18％ |
| ??II | ??10 | ??37±29* | ??55.95％ | ??1.4±0.7** | ??58.82％ |
| ??III | ??9 | ??26±35* | ??69.05％ | ??1.6±0.8** | ??52.94％ |
| ??V | ??10 | ??33±27* | ??60.71％ | ??1.8±0.9** | ??47.06％ |
Compare * p＜0.05 with model group; * p＜0.01
Table 13 Compound I I, III, V are to the influence of rat step down test learning and memory ability
| Group | Errors number in the 5min | Incubation period (s) | Errors number in the 5min behind the 24h |
| Normal control | ??0.9±0.7 | ??237±86 | ??0.3±0.2 |
| The model contrast | ??16±7.6 | ??78±27 | ??9±4.2 |
| The huperzine A contrast | ??4±2.3* | ??135±55* | ??2±1.6* |
| ??II | ??5±1.9* | ??187±43* | ??4±2.1* |
| ??III | ??3±2.2* | ??222±78* | ??3±1.0* |
| ??V | ??4±2.7* | ??112±41* | ??2±1.5* |
Compare * p＜0.05 with model group.
Claims (10)
1. the present invention relates to contain the pharmaceutical composition of ferulic acid and matrine compound.
2. the present invention relates to contain the pharmaceutical composition of ferulic acid and matrine.
3. the present invention relates to contain the pharmaceutical composition of ferulic acid and kurarinone.
4. the present invention relates to contain the pharmaceutical composition of ferulic acid and sophocarpine.
5. according to claim 1-4, the ferulic acid that the present invention relates to comprises positive ferulic acid and Hesperetic acid and their isomers and the inorganic salts chemical compound of being formed.Architectural feature is seen relevant document [Zhang Juan etc.Synthetic and the pharmacological research progress of ferulic acid and derivant thereof, grain and oils and fats, 2007 the 1st phases, 43-45].
6. according to claim 1, matrine compound involved in the present invention mainly comprises isomer sophoridine, Iosmatrine of matrine, oxymatrine (kurarinone), sophocarpine, N-oxysophocarpine, sophoranol, supanine and matrine etc. and their isomers and/or their inorganic salts.Its basic structural feature is to have a tetracyclic quinolizine pyridine, as shown in the formula:
The basic structure of matrine alkaloid.
7. according to claim 1-6, ferulic acid can be formed compositions with a kind of matrine alkaloid, also can form compositions with matrine alkaloid more than 2 kinds or 2 kinds, the compositions that preferred ferulic acid and matrine, ferulic acid and kurarinone are formed, the molecule mol ratio of its ferulic acid and matrine and/or kurarinone is 1: 1-50, preferred 1: 1-3.
8. according to claim 1-7, the compositions that ferulic acid and matrine compound form that contains that the present invention relates to has the obvious synergistic effect, has not only increased the pharmacy effect of ferulic acid but also can increase the pharmacy effect of matrine compound.The effect of for example anti-internal organs fibrosis improves hemorheology, antivirus action, antiinflammatory action suppresses the effect of acetylcholine esterase, pain relieving and itching-relieving action, anti thrombotic action, antibacterial action, antitumor action, antioxidation, effect for reducing blood fat, arteriosclerosis, rheumatism, increase immunity, increase motility of sperm and motion, antihypertensive function etc.
9. what the present invention relates to contains ferulic acid and compositions that matrine compound forms and can obviously increase the water solublity of ferulic acid and matrine alkaloid and fat-soluble.
10. what the present invention relates to contains ferulic acid and compositions that matrine compound forms, can adopt method preparation treatment tumor, arteriosclerosis, the heart, cerebrovascular, joint disease, flu, senile dementia, the inflammation of skin, eczema, acne, maculopapule, urticaria, psoriasis, the gastrointestinal tract dynamia of pharmaceutics low, the medicine of the acute and chronic inflammation that the inflammation of internal organs such as hepatitis, nephritis and internal organs fibrosis and whole body and/or internal organs take place, its preparation can be an oral formulations, also can injection and the mucocutaneous preparation of using.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810305381A CN101732299A (en) | 2008-11-05 | 2008-11-05 | Medicinal composition containing ferulic acid and matrine compounds and application thereof |
| US13/058,738 US8785471B2 (en) | 2008-09-11 | 2009-09-09 | Pharmaceutical composition containing ferulic acid and matrine compounds, the preparation and the use thereof |
| EP09812662A EP2343065A4 (en) | 2008-09-11 | 2009-09-09 | The pharmaceutical composition containing ferulic acid and matrine compounds, the preparation and the use thereof |
| PCT/CN2009/073837 WO2010028596A1 (en) | 2008-09-11 | 2009-09-09 | The pharmaceutical composition containing ferulic acid and matrine compounds, the preparation and the use thereof |
| JP2011520315A JP5538386B2 (en) | 2008-09-11 | 2009-09-09 | Drug composition containing ferulic acid and matrine compounds, and production method and use thereof |
| CA2734309A CA2734309C (en) | 2008-09-11 | 2009-09-09 | Preparation and usage of a pharmaceutical composition containing ferulic acid and matrine compounds |
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| CN111166746A (en) * | 2019-09-16 | 2020-05-19 | 宁夏医科大学 | Application of oxysophocarpine in preparing medicine for dilating thoracic aorta blood vessel |
| CN112569219A (en) * | 2019-09-30 | 2021-03-30 | 中国科学院上海药物研究所 | Medicine for treating artery related diseases and application thereof |
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| WO2018228430A1 (en) * | 2017-06-13 | 2018-12-20 | 首都医科大学附属北京地坛医院 | Use of isoferulic acid, isoferulic acid-containing traditional chinese medicine extract and cimicifugae foetidae |
| CN111166746A (en) * | 2019-09-16 | 2020-05-19 | 宁夏医科大学 | Application of oxysophocarpine in preparing medicine for dilating thoracic aorta blood vessel |
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| CN112569219A (en) * | 2019-09-30 | 2021-03-30 | 中国科学院上海药物研究所 | Medicine for treating artery related diseases and application thereof |
| CN112569219B (en) * | 2019-09-30 | 2023-05-02 | 中国科学院上海药物研究所 | Medicine for treating artery related diseases and application thereof |
| CN114436822A (en) * | 2022-01-12 | 2022-05-06 | 厦门稀土材料研究所 | Compound salt of rupestonic acid and alkaloid, preparation method and application thereof |
| CN114436822B (en) * | 2022-01-12 | 2024-04-16 | 厦门稀土材料研究所 | Rupestonic acid and alkaloid double salt, and preparation method and application thereof |
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