CN102641269A - Application of bulleyaconitine to prepare medicament capable of suppressing pathological pain caused by paclitaxel chemotherapy medicament - Google Patents
Application of bulleyaconitine to prepare medicament capable of suppressing pathological pain caused by paclitaxel chemotherapy medicament Download PDFInfo
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- CN102641269A CN102641269A CN2012101431299A CN201210143129A CN102641269A CN 102641269 A CN102641269 A CN 102641269A CN 2012101431299 A CN2012101431299 A CN 2012101431299A CN 201210143129 A CN201210143129 A CN 201210143129A CN 102641269 A CN102641269 A CN 102641269A
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Abstract
The invention relates to application of bulleyaconitine to prepare a medicament capable of suppressing pathological pain caused by paclitaxel chemotherapy medicaments, which belongs to the technical field of medicaments, in particular to application of bulleyaconitine to analgesic medicaments. The bulleyaconitine provided by the invention has a prevention or treatment effect on the pathological pain caused by the paclitaxel chemotherapy medicaments, and the suppressing effects are different in different concentrations. When the suppressing effects are applied to chemotherapy, the pain of a patient can be reduced. The bulleyaconitine has a favorable application prospect.
Description
Technical field
The invention belongs to medical technical field, the application of especially a kind of bulleyaconitine A in analgesic.
Background technology
Ramulus et folium taxi cuspidatae class medicine is a kind of antitumor drug; It represents medicine is taxol, i.e. Taxol, this medicine use the widest medicine in the breast carcinoma chemotherapeutics of new generation; They all are through combining to disturb mitosis with tubulin, and then suppress tumor proliferation.This medicine has relied on the checking of multinomial clinical trial to curative effect and tolerability since being approved for the treatment metastatic breast cancer nineties in last century, be widely used in the NACT of breast carcinoma of early stage.Yet this medicine can produce the nerve injury toxic action; The inducing neural pathological pain, show as numbness of hands and feet, twinge, burn kind pain and touch bring out the pain, be one of most common complication in the chemotherapeutic antineoplaston; Bring very big misery to the patient; Influence the decision and the curative effect of chemotherapy of patients to a certain extent, but up to the present still had no medicine can be directed against this complication, played the effect of prevention and treatment.
Chemotherapeutics causes the mechanism of pathological pain complicated, and existing research shows that Copeptin causes the reason of numbness of hands and feet to be because nerve fiber minimizing in the epidermis of affected part especially conduct tactile Ab fiber and reduce, and the C fiber of the conduction pain sensation does not have significant change.And the reason that the Ab fiber reduces is after using Copeptin, and large neuron is impaired in the cell space Dorsal root ganglion of Ab fiber, and apoptosis takes place.Produce twinge, burn kind pain and touch the expression of bringing out the neuron generation different kinds of ions passage that the pain reason is to survive and change,, cause its irritability to raise, produce spontaneous discharge and the increased response of stimulation like the rise of sodium channel and calcium channel etc.
Bulleyaconitine A has analgesic activity extensively to be approved, its mechanism of action is to suppress the voltage-dependent sodium channel.Therefore, bulleyaconitine A is also relevant with blocking-up sodium channel or calcium channel with therapeutical effect to the prevention that causes pathological pain at the taxanes chemotherapeutics.
Summary of the invention
The purpose of this invention is to provide bulleyaconitine A and cause the application in the pathological pain medicine at preparation inhibition taxanes chemotherapeutics.
Bulleyaconitine A of the present invention suppresses the taxanes chemotherapeutics in preparation and causes the application in the pathological pain medicine, it is characterized in that the pathological pain that bulleyaconitine A causes the taxanes chemotherapeutics has prevention or therapeutical effect.
Described bulleyaconitine A is characterized in that causing pathological pain that inhibiting bulleyaconitine A solution concentration is arranged to the taxanes chemotherapeutics is 0.6mg/kg ~ 1.2mg/kg.
When the preventive effect of said bulleyaconitine A, content are 0.6mg/kg ~ 1.2mg/kg machinery is not had preventive effect bitterly, and burning pain is had preventive effect.
Described bulleyaconitine A does not have therapeutical effect to machinery pain, burning pain and cold type of pain when content is 0.6mg/kg.
Described bulleyaconitine A when content is 0.8mg/kg, in 2 hours, does not have therapeutical effect bitterly to machinery, and burning pain and cold type of pain is had therapeutical effect.
Described bulleyaconitine A when content is 1.2mg/kg, had therapeutical effect to machinery bitterly in 6 hours, in 4 hours burning pain is had therapeutical effect, in 2 hours cold type of pain was had therapeutical effect.
The pathological pain that bulleyaconitine A causes the taxanes chemotherapeutics has certain inhibitory action, and this application that acts in the chemotherapy can be lowered patient's misery, has a good application prospect.
Description of drawings
Fig. 1 is that bulleyaconitine A (BLA) is to machinery and thermally sensitized preventative effect change figure.Wherein A be mechanical changes of threshold time-dose-effect relationship figure, B is preclinical time of temperature-sensitive-dose-effect relationship figure.
Fig. 2 is that the bulleyaconitine A (BLA) of variable concentrations is irritated the therapeutical effect variation diagram of stomach to the machinery and the temperature pain sensation.Wherein, A is mechanical pain threshold variation diagram, and B is thermalgesia variation diagram incubation period, and C is crymodynia variation diagram incubation period.
The specific embodiment
Embodiment 1: the prophylactic effect of the pathological pain that chemotherapeutics is caused below in conjunction with bulleyaconitine A among 1 couple of the present invention of accompanying drawing is described in detail.
Laboratory animal: 200-220 restrains male Sprague-Dawley rat.
Behavioristics's method of testing: mechanical pain threshold test, temperature-sensitive test.
" taxol " is trade name (Taxol), its main component be " paclitaxel " (Paclitaxel).
Experiment is divided into groups: group one, Taxol paclitaxel+NaCl, 17;
Group two, Taxol paclitaxel+0.6mg/kg bulleyaconitine A, 16;
Group three, Taxol paclitaxel+1.2mg/kg bulleyaconitine A, 12.
Wherein, to be made into concentration respectively by 0.5% carboxymethyl cellulose be 0.6mg/kg and 1.2mg/kg suspension to bulleyaconitine A BLA.
Experimental project is implemented timetable:
Experimental result:
Adopt the mean standard error to represent, in the group relatively, the 2nd, 5,8 day respectively with the 0th day relatively, adopt Student t-test, * * P 0.01, * * * P < 0.001.Relatively, 0.6mg/>kg and 0.8mg/kg relatively and respectively compare with the normal saline group in the same time point, adopt Holm-Sidak method between group, and < 0.001, NS representes no significant difference to ###P.
Machinery threshold value test value (g) and statistical analysis (P value) are listed in the table below:
Temperature-sensitive test value incubation period (s) and statistical analysis (P value) are listed in the table below:
Can find out from test result, injected paclitaxel after:
For machinery pain, give normal saline, 0.6mg/kg or 1.2mg/kg bulleyaconitine A after, the still variant or significant difference of its P value.
For burning pain, give normal saline after, there were significant differences for its P value; But give its P value zero difference behind 0.6mg/kg and the 1.2mg/kg bulleyaconitine A.
Therefore, 0.6mg/kg and 1.2mg/kg bulleyaconitine A (BLA) do not have preventive effect to the machinery pain that paclitaxel causes, but burning pain is had preventive effect.
Embodiment 2: the treatment effect of the pathological pain that chemotherapeutics is caused below in conjunction with bulleyaconitine A among 2 couples of the present invention of accompanying drawing is described in detail.
Laboratory animal: 200-220 restrains male Sprague-Dawley rat.
Behavioristics's method of testing: mechanical pain threshold test, temperature-sensitive test, cold quick test.
Experiment is divided into groups: group one, Taxol paclitaxel+0.6mg/kg bulleyaconitine A;
Group two, Taxol paclitaxel+0.8mg/kg bulleyaconitine A;
Group three, Taxol paclitaxel+1.2mg/kg bulleyaconitine A.
Wherein, every group of rat behavior test quantity n is listed in the table below, and it is 0.6mg/kg, 0.8mg/kg and 1.2mg/kg suspension that bulleyaconitine A BLA is made into concentration respectively by 0.5% carboxymethyl cellulose.
| ? | The test of machinery pain threshold | The temperature-sensitive test | Cold quick test |
| Group one | 7 | 7 | 7 |
| Group two | 23 | 35 | 10 |
| Group three | 30 (during test in 6 hours is 19) | 12 | 10 |
Medication: paclitaxel at a distance from two days the injection once, accomplishes 3 times the injection after, disposable through the filling stomach give 0.6mg/kg, 0.8mg/kg and 1.2mg/kg bulleyaconitine A respectively.
Experimental result:
Adopt the mean standard error to represent, relatively, adopt Student t-test in the group, * P 0.01, * * * P < 0.001.Relatively, adopt Holm-Sidak between group, < 0.05, ###P < 0.001 for #P.NS representes no significant difference.
Machinery threshold value test value (g) and statistical analysis (P value) are listed in the table below:
Because when 0.6mg/kg and 0.8mg/kg dosage, 4 hours with 0 hour zero difference, so do not test 6 hours value.
Temperature-sensitive test value incubation period (s) and statistical analysis (P value) are listed in the table below:
Cold quick test value incubation period (s) and statistical analysis (P value):
Can find out paclitaxel end course of treatment back from test result:
For machinery pain, give the 0.6mg/kg bulleyaconitine A after, its P value zero difference; After giving the 0.8mg/kg bulleyaconitine A, its P value zero difference; After giving the 1.2mg/kg bulleyaconitine A, its P value is all variant or significant difference in 6 hours.
For burning pain, give the 0.6mg/kg bulleyaconitine A after, its P value zero difference; After giving 0.8mg/kg and 1.2mg/kg bulleyaconitine A, in 2 hours, there were significant differences for its P value, has only its P value of 1.2mg/kg bulleyaconitine A variant in 4 hours.
For cold type of pain, give the 0.6mg/kg bulleyaconitine A after, its P value zero difference; After giving 0.8mg/kg and 1.2mg/kg bulleyaconitine A, in 2 hours, there were significant differences for its P value.
Therefore, the 0.6mg/kg bulleyaconitine A does not have therapeutical effect to machinery pain, burning pain and cold type of pain; In 2 hours, the bulleyaconitine A of 0.8mg/kg does not have therapeutical effect bitterly to machinery, and burning pain and cold type of pain are had therapeutical effect.And the bulleyaconitine A of 1.2mg/kg has therapeutical effect to machinery in 6 hours bitterly, in 4 hours burning pain is had therapeutical effect, in 2 hours cold type of pain is had therapeutical effect.
Claims (6)
1. bulleyaconitine A suppresses the taxanes chemotherapeutics in preparation and causes the application in the pathological pain medicine, it is characterized in that the pathological pain that bulleyaconitine A causes the taxanes chemotherapeutics has prevention or therapeutical effect.
2. bulleyaconitine A as claimed in claim 1 suppresses the taxanes chemotherapeutics in preparation and causes the application in the pathological pain medicine, it is characterized in that causing pathological pain that inhibiting bulleyaconitine A solution concentration is arranged to the taxanes chemotherapeutics is 0.6mg/kg ~ 1.2mg/kg.
3. bulleyaconitine A as claimed in claim 1 suppresses the taxanes chemotherapeutics in preparation and causes the application in the pathological pain medicine; The preventive effect that it is characterized in that said bulleyaconitine A; When content is 0.6mg/kg ~ 1.2mg/kg; Machinery is not had preventive effect bitterly, and burning pain is had preventive effect.
4. bulleyaconitine A as claimed in claim 1 suppresses the taxanes chemotherapeutics in preparation and causes the application in the pathological pain medicine, it is characterized in that described bulleyaconitine A, when content is 0.6mg/kg, machinery pain, burning pain and cold type of pain is not had therapeutical effect.
5. bulleyaconitine A as claimed in claim 1 suppresses the taxanes chemotherapeutics in preparation and causes the application in the pathological pain medicine; It is characterized in that described bulleyaconitine A, when content is 0.8mg/kg, in 2 hours; Machinery is not had therapeutical effect bitterly, and burning pain and cold type of pain are had therapeutical effect.
6. bulleyaconitine A as claimed in claim 1 suppresses the taxanes chemotherapeutics in preparation and causes the application in the pathological pain medicine; It is characterized in that described bulleyaconitine A; When content is 1.2mg/kg; In 6 hours, machinery there is therapeutical effect bitterly, in 4 hours burning pain is had therapeutical effect, in 2 hours cold type of pain is had therapeutical effect.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104326981A (en) * | 2014-10-16 | 2015-02-04 | 云南大围山生物制药有限公司 | Bulleyaconitine A efficient extraction and separation method |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101480392A (en) * | 2008-01-07 | 2009-07-15 | 云南昊邦制药有限公司 | Application of bulleyaconitine A in preparing medicament for treating ache related to sodium channel |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101480392A (en) * | 2008-01-07 | 2009-07-15 | 云南昊邦制药有限公司 | Application of bulleyaconitine A in preparing medicament for treating ache related to sodium channel |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104326981A (en) * | 2014-10-16 | 2015-02-04 | 云南大围山生物制药有限公司 | Bulleyaconitine A efficient extraction and separation method |
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Application publication date: 20120822 |