CN102920726B - Medicinal composition for preventing and treating neuropathic pain - Google Patents
Medicinal composition for preventing and treating neuropathic pain Download PDFInfo
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- 208000021722 neuropathic pain Diseases 0.000 title claims abstract description 37
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Abstract
The invention discloses a medicinal composition for preventing and treating neuropathic pain. The medicine is prepared from magnoflorine and ranunculin which are used as bulk pharmaceuticals in a certain proportion; the medicine can be prepared into various preparations by the conventional preparation process; the defects in the prior art are overcome; the medicinal composition which is used for treating neuropathic pain and is obvious in curative effect and safe is provided; the provided medicine is easy to prepare and low in cost; and the clinical test proves that the medicine has an obvious clinical effect on neuropathic pain comprising prosopalgia, ischialgia, sciatica of nerve roots, postherpetic neuralgia and diabetic peripheral polyneuritis and the like.
Description
Technical field
The invention belongs to the field of Chinese medicines, particularly relate to a kind of pharmaceutical composition preventing and treating neuropathic pain.
Background technology
Neuropathic pain refers to the pain syndrome caused by central or peripheral nervous system novo lesions or dysfunction.Can by wound or/and disease cause peripheral nerve, spinal cord after root, spinal cord and some site tissue damage of above nervus centralis thereof and cause.According to the cause of disease, the nature and extent difference of nerve injury, be divided into the large class of the peripheral nerve pain two caused by nervus centralis pain and peripheral nerve injury clinically.Nervus centralis pain is called for short central pain, and infringement or dysfunction and the idiopathic pain that causes occur the pain transduction path for central nervous system, are common in wound or the cerebrovascular disease of spinal cord, multiple sclerosis and tumor etc.Caused by the factor such as peripheral nerve pain system wound, ischemia, compressing, infection, inflammation, metabolism damage peripheral nervous, as phantom pain, postherpetic neuralgia, polyneuritis, Diabetic Peripheral neuralgia etc.According to estimates, this disease is just tormenting the population of global 2.8%-4.7%, and the incidence rate of epidemiology display general population is 6%-7.7%.After diabetes nerve pain and herpes zoster, secondary pain is the bitterly the most general form of adult neural, and incidence rate is respectively 13%-37% and 10%-40%, and along with the aging incidence rate of population is higher, annual morbidity is 12/,100,000.The sickness rate of neuropathic pain syndrome in old people improves constantly: be on the one hand cancer, HIV, diabetes and other patient often causing the Disease long-term survival of neuropathic pain increase; On the other hand, also neuropathic pain can be produced when medicine and surgical operation therapy tumor and Other diseases.During morbidity patient usually have pain as calcination, tingle or just like electric shock pain, very acutely, as cutter cut out as severe pain.This pain is suddenly shown effect, and the position of pain and scope thereof, be limited to the domination field of this nerve.During outbreak, the neural position near epidermis of pressure, will feel violent pain.Neuropathic pain can produce great impact to the life of patient, the work that it has seized a lot of people, the ability of even wearing the clothes on foot.
Do not have a kind of medicine safely and effectively can alleviate the misery of this kind of patient in the market.Treat multiplex anticonvulsant, opioid drug and anti depressant medication, but most product is not specially for neuropathic pain, great majority are invalid or can only appropriate alleviating pain to most of patient, and can cause untoward reaction.Therefore, improve treatment and the prevention level of neuropathic pain, improve neuropathic pain quality of life of patients, the medicine of exploitation control neuropathic pain is significant.
Magnoflorine (magnoflorine): also known as thalictrine, magnoflorine, Magnoflorine etc.Its iodide (C20H40INO4) crystalline solid (by methanol+acetone), decomposition point 248 ~ 249 DEG C.Optical rotation+220.1 ° (methanol).Naturally to be present in the root street plant of ranunculaceae plant thick fruit Thalictrum aquilegifolium L. var. sibiricum Regel.Can chemosynthesis obtain.This product has the effects such as antiinflammatory, blood pressure lowering, antifertility.Formula containing this product has insecticidal action.The iodide of this product have antimicrobial and cytotoxicity.
Ranunculin (ranunculin): be a kind of special composition existed only in ranunculaceae plant, there is α, the undersaturated gamma lactone structure of β, is distributed in Ranunculus, Anemone and Radix clematidis floridae:
Summary of the invention
The object of the invention is the deficiency overcoming background technology, a kind of pharmaceutical composition of control neuropathic pain of evident in efficacy, safe without toxic side effect is provided.
The present invention adopts following technical scheme to realize: composition and the weight portion of making the crude drug of the pharmaceutical composition of this control neuropathic pain are:
Magnoflorine 1-10 weight portion Ranunculin 5-10 weight portion
Aforementioned pharmaceutical compositions can adopt the conventional method of galenic pharmacy to be prepared into various dosage form, as injection, tablet, capsule, granule, oral liquid, drop pill, micropill etc.
In side of the present invention, magnoflorine has good anti-inflammatory analgesic effect, and Ranunculin has and relaxes through dredging collateral effect, and Papillary, strengthens the efficacy of a drug mutually, pharmacodynamics is mutually promoted, complementary effect.The present composition has effect of wind-expelling pain-stopping, promoting blood circulation to remove obstruction in the collateral, to the various neuropathic pain for the treatment of, as evident in efficacy in diseases such as root neuropathic pain, sciatica, trigeminal neuralgia, postherpetic neuralgia, diabetic peripheral neuritiss.
Detailed description of the invention
Embodiment 1: the pharmaceutical composition of control neuropathic pain
Composition and the weight portion of the crude drug of the pharmaceutical composition of control neuropathic pain are:
Magnoflorine 1 weight portion Ranunculin 5 weight portion.
Embodiment 2: the pharmaceutical composition of control neuropathic pain
Composition and the weight portion of the crude drug of the pharmaceutical composition of control neuropathic pain are:
Magnoflorine 10 weight portion Ranunculin 10 weight portion.
Embodiment 3: the pharmaceutical composition of control neuropathic pain
Composition and the weight portion of the crude drug of the pharmaceutical composition of control neuropathic pain are:
Magnoflorine 4 weight portion Ranunculin 5 weight portion.
Embodiment 4: the pharmaceutical composition of control neuropathic pain
Composition and the weight portion of the crude drug of the pharmaceutical composition of control neuropathic pain are:
Magnoflorine 6 weight portion Ranunculin 7 weight portion.
Embodiment 5: the drug combination preparation of control neuropathic pain
Composition and the weight portion of the crude drug of the pharmaceutical composition of control neuropathic pain are:
Magnoflorine 1-10 weight portion Ranunculin 5-10 weight portion.
Aforementioned pharmaceutical compositions can adopt the conventional method of galenic pharmacy to be prepared into various dosage form, as injection, tablet, capsule, granule, oral liquid, drop pill, micropill etc.
Pharmacological test results of the present invention is as follows
Experimental example 1, glutamic acid caused to PC12 cell injury affect experimental study
1. test material
1.1 medicines and reagent
Sample: embodiment 1-4 compositions.
Cell line: PC12 cell line ((source: Ratt μ s norvegic μ s Adrenal Pheochromocytoma, Nanjing KaiJi Biology Science Development Co., Ltd provides.）。
Reagent: H-DMEM cell culture medium (Hyclone, Sai Mo fly generation that biochemistry goods Beijing company limited); Hyclone (Israel Bioind); Pancreatin cell dissociation buffer (the green skies), penicillin streptomycin mixed liquor is dual anti-, cisplatin for inj (Qilu Pharmaceutical Co., Ltd.), citrate buffer (Beijing Bioisystech Co., Ltd of Zhong Shan Golden Bridge), paraformaldehyde (solarbio), Pidolidone (Klonetech, Japan).
1.2 test apparatus
Vertical pressure steam sterilization pan (LDZX-50FBS, Shen, Shanghai is pacified); Double one side clean work station (SW-CJ-1C, Suzhou purifies); CO2 gas incubator (BB16 μ V/BB5060 μ V, HERAE μ S); Desk centrifuge (H3, Sigma); Microplate reader (M μ ltiskan MK3, Thermo Scientific); Electric heating constant-temperature blowing drying box (101, Shanghai roc is along scientific instrument company limited); Inverted microscope (XDS-1B, Chongqing optical instrument factory); Water-bath constant temperature oscillator (SHZ-82, Medical Instruments factory of Jintan City); Pipettor (Gilson, Eppendorf); Culture bottle (Corning); 96 orifice plates (Costar, μ SA).
2. test method
Prepare PC12 cytochemistry damage model with glutamic acid, adopt tetrazolium bromide (MTT) method to measure absorption value in 570nm place, observe drug candidate to the repair of PC12 cell injury.Use SOD, NO, LDH, MDA test kit to detect each index content, illustrate the mechanism of action of each medicine.
The glutamic acid (this is application of sample final concentration, is dissolved in incomplete culture medium) of modeling: 30mmol/l acts on PC12 cell 24h.
Grouping: blank group, chemical damage model group, chemical damage+medicine group
3. content of the test.
3.1 cell culture
Frozen PC12 cell recovery is got in culture bottle, with the H-DMEM culture medium culturing containing 10% hyclone from ultra cold storage freezer.When PC12 Growth of Cells to 80% merges, digest, be inoculated in 96 orifice plates with 1 × 104 cell per well with the pancreatin cell dissociation buffer (containing 0.02%EDTA) of 0.25%, zeroing hole does not add cell.
3.2 cell injury
After the cell in 96 orifice plates covers with monolayer, discard culture medium, aseptic PBS liquid cleans 2 times, except zeroing group, blank group, every hole adds the glutamic acid (being dissolved in incomplete culture medium) that final concentration is 30mmol/l and cultivate 24h in incubator, namely causes PC12 cell injury model.
3.3 dosing reparations
Discard culture medium, clean 2 times with aseptic PBS liquid, the every hole of administration group adds the DMEM culture medium 100 μ l being followed successively by 100 μ g/ml, 10 μ g/ml, 1 μ g/ml containing screening of medicaments final concentration respectively, and the medicine of each concentration adds 6 holes.With the DMEM culture medium of not drug containing for blank group.Then cell inserted 37 DEG C, continue in 5%CO2 incubator to cultivate 24h.
3.4 index determining
3.4.1 mtt assay measures cell survival rate
After discarding culture medium, every hole adds 100 μ l plasma-free DMEM medium, then adds 5mg/mlMTT solution 20 μ l lucifuge in incubator in every hole and react 4 h.Discard culture medium and add 100 μ lDMSO microplate reader in 570nm mensuration OD value, calculate cell survival rate;
3.4.2 SOD, LDH assay
Within after administration 24 hours, centrifugal 20 minutes (2000r/min), carefully collects supernatant, by test kit description time-and-motion study LDH content with sterile tube collecting cell supernatant;
After administration, 24 hours supernatant discarded, add 2%Trion-100X, and mix cell suspension after leaving standstill 12 hours in 4 DEG C, centrifugal 20 minutes (2000r/min), carefully collects supernatant, by test kit description time-and-motion study SOD content.
4. result of the test
All data represent with X ± SD, and one factor analysis of variance and LSD many groups mean compare the significance of group difference between two, and P<0.05 is significant difference.
4.1 impacts of PC12 cell survival rate on damage
The each embodiment of table 1 is to the result (n=10) of PC12 cell survival rate
| Group | OD value | Cell survival rate % |
| Model group | 0.6512±0.0813 | 78.37±6.33 |
| Embodiment 1 compositions | 0.803±0.0822 | 90.15±8.026 ** |
| Embodiment 2 compositions | 1.202±0.0679 | 147.30±20.38 ** |
| Embodiment 3 compositions | 1.100±0.0653 | 138.90±28.051** |
| Embodiment 4 compositions | 1.108±0.0572 | 141.50±23.20 ** |
Note: compared with model group, * * P<0.01; Compared with model group, * P<0.05
Table 1 result shows, and embodiment 1-4 compositions has good repair function to neural cell injury.
The each embodiment of table 2 is to the result (n=10) of PC12 cell SOD and LDH
| Group | SOD concentration (U/L) | LDH concentration (IU/L) |
| Blank group | 10.310±2.2360 | 1.684±0.1254 |
| Model group | 5.920±1.2340 | 2.284±0.1504 |
| Embodiment 1 compositions | 45.420±5.6771** | 1.595±0.1570 ** |
| Embodiment 2 compositions | 26.297±4.5470** | 1.829±0.1561 ** |
| Embodiment 3 compositions | 25.208±2.8990** | 1.635±0.1530** |
| Embodiment 4 compositions | 24.871±5.3820** | 1.803±0.1472 ** |
Note: compared with model group, * * P<0.01; Compared with model group, * P<0.05;
Table 2 result shows, and compared with model group, embodiment 1-4 compositions makes cell SOD vigor significantly increase, and LDH concentration significantly reduces.
Test example 2: clinical observation is tested.
1 data and method
1.1 physical data: neuropathic pain patients 304 example, according to medical history, symptom, make diagnosis in conjunction with clinical examination analysis.Trigeminal neuralgia 45 example, sciatica 55 example, scorching 58 examples of radicular pain 65 example, postherpetic neuralgia 81 example, diabetic nerve tip.
1.2 therapeutic schemes: oral present composition every day 2 times, take l5 days 1 course for the treatment of continuously, period in a medicine is stopped using the medicine of other sacred disease.Often take medicine 1 course for the treatment of, do clinical analysis and clinical symptoms is added up.
1.3 Pain Grading standards: main suit's Pain Grading method (VRS) that Pain Grading is formulated according to WHO.0 grade: painless; I level (mild pain): though there is pain, can stand, and sleep is interference-free; H level (severe pain): sharp ache is impatient at, and needs analgesic, and sleep is disturbed, with autonomic nervous dysfunction performance or positive position.
1.4 curative effect determinate standards: after 4 courses for the treatment of of medication, judge effect.Cure: subjective symptoms disappears completely, follows up a case by regular visits to and does not recur for 2 years; Effective: cardinal symptom is improved or substantially disappeared; Effective: cardinal symptom disappears substantially; Invalid: cardinal symptom is all without improvement.
1.5 observation indexs: safety is observed: general health check-up project, the inspection of blood, urine, feces routine
Look into, the heart, Liver and kidney function inspection; Health giving quality is observed: the observation of Tibetan medicine's syndrome manifestations, neural
The observation of systemic symptom sign, blood examination.
2 results
2.1 comparitive study: 304 routine patients cure 167 examples, effective and effective 119 examples, invalid 18 examples.Total effective rate is 94.1% (see table 3)
Table 3 present composition treatment neuropathic pain result
| Sick kind (example) | Cure (%) | Effective and effective (%) | Invalid (%) | Total effective rate (%) |
| Trigeminal neuralgia (45) | 22（48.9） | 21（46.7） | 2（4.4） | 95.6 |
| Sciatica (55) | 32（58.2） | 20（36.4） | 3（5.5） | 94.5 |
| Radicular pain (65) | 35（53.8） | 30（46.2） | 4（6.2） | 93.8 |
| Postherpetic neuralgia (81) | 53（65.4） | 24（29.6） | 4（4.9） | 95.1 |
| Diabetic peripheral neuritis (58) | 25（43.1） | 28（48.3） | 5（8.6） | 91.4 |
Untoward reaction situation: 304 routine patients, all do not find any toxic and side effects and untoward reaction in clinical observation process.
Claims (6)
1. prevent and treat a pharmaceutical composition for neuropathic pain, it is characterized in that: composition and the weight portion of making the crude drug of this pharmaceutical composition be,
Magnoflorine 1-10 weight portion Ranunculin 5-10 weight portion.
2. the pharmaceutical composition of control neuropathic pain as claimed in claim 1, is characterized in that: composition and the weight portion of making the crude drug of this pharmaceutical composition be, magnoflorine 10 weight portion Ranunculin 10 weight portion.
3. the pharmaceutical composition of control neuropathic pain as claimed in claim 1, is characterized in that: composition and the weight portion of making the crude drug of this pharmaceutical composition be,
Magnoflorine 4 weight portion Ranunculin 5 weight portion.
4. the pharmaceutical composition of control neuropathic pain as claimed in claim 1, is characterized in that: composition and the weight portion of making the crude drug of this pharmaceutical composition be,
Magnoflorine 6 weight portion Ranunculin 7 weight portion.
5. the pharmaceutical composition of control neuropathic pain as claimed in claim 1, is characterized in that: the conventional method of galenic pharmacy can be adopted to be prepared into injection, tablet, capsule, granule, oral liquid, drop pill, micropill.
6. the pharmaceutical composition of control neuropathic pain as claimed in claim 1, is characterized in that: be used for the treatment of trigeminal neuralgia, sciatica, radicular pain, postherpetic neuralgia, diabetic nerve tip inflammation.
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| CN1260982A (en) * | 1999-01-19 | 2000-07-26 | 曾永山 | Exterior-applied antalgesic Chinese medicine 'Rudijinniu' |
| CN1406591A (en) * | 2001-08-24 | 2003-04-02 | 胡世卿 | Medicine against aseptic inflammation by ranunculaceae plant and use thereof |
| CN102464616A (en) * | 2010-11-12 | 2012-05-23 | 江苏康缘药业股份有限公司 | Method for preparing magnoflorine from Chinese medicinal Chelidonium majus L. |
| CN102626448A (en) * | 2012-04-26 | 2012-08-08 | 南京泽朗医药科技有限公司 | Method for extracting total alkaloids from thalictrum plants |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1260982A (en) * | 1999-01-19 | 2000-07-26 | 曾永山 | Exterior-applied antalgesic Chinese medicine 'Rudijinniu' |
| CN1406591A (en) * | 2001-08-24 | 2003-04-02 | 胡世卿 | Medicine against aseptic inflammation by ranunculaceae plant and use thereof |
| CN102464616A (en) * | 2010-11-12 | 2012-05-23 | 江苏康缘药业股份有限公司 | Method for preparing magnoflorine from Chinese medicinal Chelidonium majus L. |
| CN102626448A (en) * | 2012-04-26 | 2012-08-08 | 南京泽朗医药科技有限公司 | Method for extracting total alkaloids from thalictrum plants |
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