CN106333950B - A kind of drug for treating mirror-image pain caused by cancerous invasion - Google Patents
A kind of drug for treating mirror-image pain caused by cancerous invasion Download PDFInfo
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Abstract
The invention discloses a kind of drugs for treating mirror-image pain caused by cancerous invasion.The present invention provides a kind of drug for treating mirror-image pain, active constituent is CQ compound；The CQ compound is made of component first and component second；The component first is the salt of ligustrazine or ligustrazine；The component second is the salt of cucoline or cucoline；The mass ratio of the component first and the component second is 0.5-2.5:1.The present invention also provides the drug that second is treated mirror-image pain, active constituent is the CQ compound and amantadine hydrochloride.The present invention provides reference for the Mechanism Study and clinical treatment of cancerous invasion mirror-image pain, has great application value for the treatment of mirror-image pain.
Description
Technical field
The present invention relates to a kind of drugs for treating mirror-image pain caused by cancerous invasion.
Background technique
Cancer has become the first big foul disease and chronic disease for seriously endangering human health, leading to modern humans' death.Pain caused by cancer
It is one of most common clinical symptoms of cancer patient, any stage of cancer can be appeared in.Newly it is diagnosed as the trouble of malignant tumour
About 1/4 with pain in person, and about 1/3 with pain caused by cancer in therapeutic process, and progressive stage about 3/4 is with pain.Cancerous invasion pain (Cancer
Invasion Pain, CIP) it is due to pain caused by tumor-infiltrated, it is one of intractable pain caused by cancer that cancer patient, which takes place frequently,.
Also adverse effect is brought while the symmetry of body offers convenience to human action, as body side is damaged out
When existing pain or quick pain, also there is secondary pain in the opposite side antimere (mirror image position) of damage location and pain is quick, i.e. mirror
As pain (Mirror Image Pain, MIP).The phenomenon was found in earliest in American Civil War period, the soldier of limbs injury by
Also there is sensation of pain in the limbs for hurting opposite side.Clinically, some serious chronic aches (such as congenital facial joint myalgia,
Atypical facial pain, chronic migraine, tension-type headache etc.), Complex regional pain syndrome, amputation and apoplexy sequelae
There is secondary MIP, brings great pain to minimal invasive treatment.
Since the mechanism that MIP occurs, develops and maintains is not still fully aware of so far, therapeutic effect is also undesirable, generally controls
The drug for treating pain is uncertain to the therapeutic effect of MIP.
Summary of the invention
The object of the present invention is to provide a kind of drugs for treating mirror-image pain caused by cancerous invasion.
The present invention provides a kind of drug for treating mirror-image pain, active constituent is CQ compound.
The present invention also provides the drug that second is treated mirror-image pain, active constituent is the CQ compound and hydrochloric acid Buddha's warrior attendant
Alkanamine.Amantadine hydrochloride is used as the synergist of CQ compound, using the amount in dosage range human-acceptable.Institute
The mass ratio for stating CQ compound and the amantadine hydrochloride be can be 3:3-5, concretely 3:4.
The present invention also provides a kind of drug for treating mirror-image pain caused by cancerous invasion, active constituent is multiple for the CQ
Side.The cancerous invasion concretely cancerous invasion caused by S180 tumor strain cell.
The present invention also provides the drug that second is treated mirror-image pain caused by cancerous invasion, active constituent is multiple for the CQ
Side and amantadine hydrochloride.The cancerous invasion concretely cancerous invasion caused by S180 tumor strain cell.Amantadine hydrochloride conduct
The synergist of CQ compound uses, using the amount in dosage range human-acceptable.The CQ compound and hydrochloric acid gold
The mass ratio of rigid alkanamine be can be 3:3-5, concretely 3:4.
The present invention also protects application of the CQ compound in the drug of preparation treatment mirror-image pain.
The present invention also protects the application of the CQ compound and amantadine hydrochloride in the drug of preparation treatment mirror-image pain.Salt
Symmetrel is used as the synergist of CQ compound, using the amount in dosage range human-acceptable.The CQ is multiple
The mass ratio of the square and described amantadine hydrochloride be can be 3:3-5, concretely 3:4.
Application in the drug of mirror-image pain caused by the present invention also protects the CQ compound to treat cancerous invasion in preparation.It is described
Cancerous invasion concretely cancerous invasion caused by S180 tumor strain cell.
The medicine of mirror-image pain caused by the present invention also protects the CQ compound and amantadine hydrochloride to treat cancerous invasion in preparation
Application in object.The cancerous invasion concretely cancerous invasion caused by S180 tumor strain cell.Amantadine hydrochloride is as CQ compound
Synergist use, using the amount in dosage range human-acceptable.The CQ compound and the amantadine hydrochloride
Mass ratio be can be 3:3-5, concretely 3:4.
The CQ compound is made of component first and component second；The component first is the salt of ligustrazine or ligustrazine；Described group
Dividing second is the salt of cucoline or cucoline；The mass ratio of the component first and the component second is 0.5-2.5:1.The ligustrazine
Salt be Ligustrazine Hydrochloride or ligustrazine phosphat；The salt of the cucoline is Sinomenine or phosphoric acid cucoline.The component
The mass ratio of first and the component second is 0.8:1.
Any description above " treatment cancerous invasion caused by mirror-image pain " be presented as following (a) and/or (b) and/or (c) and/
Or (d) and/or (e): mechanical pain threshold (a) being promoted to increase；(b) RANTES content in myeloid tissue is promoted to reduce；(c) promote ridge
MCP-3 content reduces in myeloid tissue；(d) IL-6 content in serum is promoted to reduce；(e) MCP-1 content in serum is promoted to reduce.
The present invention provides reference for the Mechanism Study and clinical treatment of cancerous invasion mirror-image pain, has for the treatment of mirror-image pain
Great application value.
Detailed description of the invention
Fig. 1 is each group mouse cancerous invasion side (figure A) and image side (figure B) metapedes machinery pain threshold change ( N=
13)；*P < 0.05,**P < 0.01, compared with Native group；#P < 0.05,##P < 0.01, compared with Sham group.
Fig. 2 is the influence that amantadine hydrochloride acts on CQ compound pain (figure A is cancerous invasion side, and figure B is image side)；*P
<0.05,**P < 0.01, compared with CQ group.
Specific embodiment
Embodiment below facilitates a better understanding of the present invention, but does not limit the present invention.Experiment in following embodiments
Method is unless otherwise specified conventional method.Test material as used in the following examples is unless otherwise specified certainly
What routine biochemistry reagent shop was commercially available.Quantitative test in following embodiment, is respectively provided with and repeats three times, is as a result averaged
Value.
SPF grades of BALB/c male mices, weight 18-20g are purchased from National Institute for Food and Drugs Control, credit number:
SCXK (capital) 2014-0013.
S180 tumor strain cell (murine sarcoma cells strain): bibliography: Lee HJ, Lee JH, Lee EO, et
al.Substance P and beta-endorphin mediate electro-acupuncture induced
Analgesia in mouse cancer pain model [J] .AcupunctElectrother Res, 2009,34 (1-2):
27-40。
Muose Custom 8-plex kit: Beijing Quanto Biotechnology Co., Ltd.；Article No.:
T2C081217。Mouse Group 116-plex kit: Beijing Quanto Biotechnology Co., Ltd., article No.:
C261116。
The detection method of mechanical pain threshold (paw withdrawal threshold value): successively with standardized different stimulated dynamics (0.008g,
0.02g, 0.04g, 0.07g, 0.16g, 0.4g, 0.6g, 1g or 2g；Since 0.008g, with frequency of once per second) Von
Frey fiber filament, it is vertical to stimulate outside skin surface in mouse hind leg foot pawl bottom, observe the paw withdrawal reaction of mouse, long run test
5 times, the minimum fiber filament value of record appearance 3 times or 3 times or more paw withdrawal reactions, as mechanical pain threshold.
Animal Behavior Science data add and subtract standard error with meanIt indicates, is counted using 21.0 software of SPSS
Analysis.The variance analysis side of the Repeated Measurement Data of general linear model is used for the mechanical threshold group difference of duplicate measurements
Method detects group difference, the group difference specifically sometime put using the analysis of multifactor analysis of variance method.Cell factor inspection
Measured data is plus or minus standard deviation from the meanIt indicates, data analysis uses independent samples t test between two groups, is with P < 0.05
Difference is statistically significant.
It is operated continuously involved in embodiment 1 and embodiment 2, therefore continuous meter test number of days.
The structural formula of Ligustrazine Hydrochloride is as follows:
The structural formula of Sinomenine is as follows:
Ligustrazine can be extracted from Rhizoma Chuanxiong and be obtained, and can also be obtained by chemically synthesized method.Common extraction side
Method is as follows: Rhizoma Chuanxiong is extracted with EtOH Sonicate, extracting solution be concentrated and dried to get.Ligustrazine can also be replaced by the salt of ligustrazine, such as
Ligustrazine Hydrochloride, ligustrazine phosphat etc..
Cucoline can be extracted from caulis sinomenii and be obtained.Common extracting method is as follows: 1, sinomenium acutum alcohol extracting, and acid is molten, extraction,
Water recrystallization to get；2, sinomenium acutum is alkalized, and benzene mentions, and is crystallized, decoloration, water recrystallization to get.Due to the development of chemical synthesising technology,
Cucoline can also be obtained by synthetic method.Cucoline can also be replaced by the salt of cucoline, such as Sinomenine, phosphoric acid
Cucoline etc..
Amantadine hydrochloride: Northeast Pharmaceutical Group Shenyang First Pharmaceutical Co., Ltd., lot number: 5140102.
Embodiment 1, mouse cancerous invasion mirror-image pain (Cancer Invasion Induced Mirror Image Pain,
CIIMIP) the foundation of model
Pre-stimulation is carried out (once a day, every time with quantitative Von to SPF grades of BALB/c male mices for three days on end before test
The metapedes of Frey fiber filament stimulation mouse bilateral).Test the 1st day by bilateral metapedes machinery pain threshold >=mouse of 0.4g is random
It is divided into normal group (Native), operation control group (Sham), operation group (Surgery), every mouse of Surgery group is in right leg stock
Bone greater trochanter (be equivalent to sciatic nerve branch part above) injection 0.2mL S180 tumor strain cell liquid (viable cell concentrations are 1 ×
107A/mL), Sham group in same area injection same volume same concentrations inactivation S180 tumor strain cell liquid (ablation method:
15min is boiled in boiling water, then Trypan Blue is determined without living cells), Native group does not make any operation.
It tests the 4th day, Surgery group mouse activity is reduced, and hair color is partially dark, and the state of mind is bad.It tests the 4th day,
The most of neoplasm lines inoculation position enlargement of Surgery group is obvious, and art parapodum toe is unable to normal extension, turns up body in protectiveness
Position, and the tumor size of its leg and toes deformation extent gradually increase at any time.It tests the 11st day, is found after dissection
Sciatic nerve, mouse are progressively oppressed or invade to Surgery group mouse leg tumour in sciatic nerve bifurcation, tumour growth
The weight that tumor tissues are isolated in leg tissue is 1.493 ± 0.725g.It tests the 11st day, Sham group mouse leg has no swollen
Tumor tissue.
Test the 2-7 days continuous evaluation Native groups, Sham group and the mechanical threshold of pain of Surgery group mouse cancerous invasion side
Value finds that there were significant differences (P < 0.01) between three groups of cancerous invasion side machinery pain threshold groups, sees Figure 1A.Surgery group mouse cancer is invaded
It attacks side machinery pain threshold to begin to decline within the 2nd day in test, test the is stably maintained at (0.031 ± 0.006) g- for 4-7 days
(0.057 ± 0.029) g, hence it is evident that be lower than Sham group and Native group (P < 0.05 or P < 0.01).The cancerous invasion side of Sham group mouse
Mechanical pain threshold also reduces on the 2nd day in test, but then gradually gos up, and test reaches Native group after the 5th day horizontal.It is trying
The mechanical pain threshold for testing the 2-7 days continuous evaluation Native groups, Sham group and Surgery group mouse image side, finds three groups small
Also there were significant differences (P < 0.01) between mouse image side machinery pain threshold group, sees Figure 1B.The Surgery group mouse image side machinery threshold of pain
Value also declined at test the 2nd day, and test the is stably maintained at (0.044 ± 0.012) g- (0.101 ± 0.038) g for 4-7 days, bright
It is aobvious to be lower than Sham group and Native group (P < 0.05 or P < 0.01).Surgery group mouse left fore and abdomen were in test the 16th day
It inside has no apparent pain present, shows that the quick phenomenon of pain occurs over just the mirror image position of cancerous invasion side.
Test the 5-7 days, the mechanical pain threshold of cancerous invasion side and image side≤the Surgery group mouse of 0.07g, as
Model mice.
Embodiment 2, CQ compound are to the function and effect of cancerous invasion mirror-image pain
One, CQ compound is prepared
CQ compound is made of Ligustrazine Hydrochloride and Sinomenine, and the mass ratio of Ligustrazine Hydrochloride and Sinomenine is
0.8:1.CQ compound is taken, is dissolved with ultrapure water, the storing liquid of 40mg/mL is obtained, normal saline dilution is then used, obtains CQ compound
Solution.
Two, grouping administration
Model group (Model, n=12): object is the model mice that embodiment 1 obtains, and is tested the 8th day, the 9th day and the 10th
Respectively physiological saline of intraperitoneal injection, bolus doses are 0.4mL physiological saline/20g mouse for it；
CQ compound high dose group (H-CQ, 200mg/kg, n=12): object is the model mice that embodiment 1 obtains, test
8th day, the 9th day and the 10th day respectively intraperitoneal injection CQ compound solution, bolus doses be 0.4mL CQ compound solution/
20g mouse, the concentration of CQ compound is 10mg/mL in 0.4mL CQ compound solution；
CQ compound middle dose group (M-CQ, 150mg/kg, n=11): object is the model mice that embodiment 1 obtains, test
8th day, the 9th day and the 10th day respectively intraperitoneal injection CQ compound solution, bolus doses be 0.4mL CQ compound solution/
20g mouse, the concentration of CQ compound is 7.5mg/mL in 0.4mL CQ compound solution；
CQ compound low dose group (L-CQ, 100mg/kg, n=11): object is the model mice that embodiment 1 obtains, test
8th day, the 9th day and the 10th day respectively intraperitoneal injection CQ compound solution, bolus doses be 0.4mL CQ compound solution/
20g mouse, the concentration of CQ compound is 5mg/mL in 0.4mL CQ compound solution；
Sham group (Sham, n=11): object is the Sham group mouse in embodiment 1, is tested the 8th day, the 9th day and the 10th
Respectively physiological saline of intraperitoneal injection, bolus doses are 0.4mL physiological saline/20g mouse for it；
Native group (Native, n=13): object is the Native group mouse in embodiment 1, is tested the 8th day, the 9th day
Respectively physiological saline of intraperitoneal injection, bolus doses were 0.4mL physiological saline/20g mouse with the 10th day.
Three, the mechanical pain threshold of mouse after CQ compound is administered
It tests the 10th day, the mouse cancerous invasion side machinery pain threshold evaluating result before administration and after administration in 240min is shown in Table
1 and table 2.
Table 1 is tested the 10th day, each group mouse administration front and back cancerous invasion side machinery pain threshold
| Before administration | 30min after administration | 60min after administration | 90min after administration | 120min after administration | 180min after administration | 240min after administration | |
| Native | 0.37±0.07 | 0.38±0.07 | 0.34±0.05 | 0.37±0.05 | 0.35±0.05 | 0.40±0.06 | 0.37±0.05 |
| Sham | 0.24±0.05 | 0.22±0.05 | 0.22±0.05 | 0.26±0.05 | 0.27±0.04 | 0.25±0.04 | 0.26±0.04 |
| Model | 0.02±0.00**## | 0.03±0.01**## | 0.03±0.01**## | 0.03±0.01**## | 0.02±0.01**## | 0.02±0.01**## | 0.02±0.01**## |
| L-CQ | 0.01±0.00 | 0.22±0.18 | 0.22±0.18 | 0.32±0.18 | 0.32±0.19 | 0.15±0.06 | 0.07±0.03 |
| M-CQ | 0.02±0.01 | 0.73±0.27△ | 0.72±0.27△ | 0.76±0.27△ | 0.59±0.22△ | 0.33±0.10△ | 0.28±0.13 |
| H-CQ | 0.03±0.01 | 1.33±0.25△△ | 1.31±0.22△△ | 1.22±0.21△△ | 0.86±0.17△△ | 0.47±0.15△ | 0.30±0.16 |
**P < 0.01, compared with Native group；##P < 0.01, compared with Sham group；△P < 0.05,△△P < 0.01, with Model
Group is compared.
Table 2 is tested the 10th day, and front and rear mirror image side machinery pain threshold is administered in each group mouse
| Before administration | 30min after administration | 60min after administration | 90min after administration | 120min after administration | 180min after administration | 240mi after administration | |
| Native | 0.47±0.10 | 0.47±0.19 | 0.45±0.10 | 0.47±0.09 | 0.42±0.09 | 0.42±0.09 | 0.48±0.14 |
| Sham | 0.26±0.05 | 0.22±0.06 | 0.28±0.05 | 0.26±0.05 | 0.26±0.05 | 0.30±0.06 | 0.28±0.05 |
| Model | 0.03±0.01**## | 0.03±0.02**## | 0.03±0.01**## | 0.03±0.01**## | 0.03±0.01**## | 0.03±0.01**## | 0.03±0.01**## |
| L-CQ | 0.02±0.00 | 0.11±0.05 | 0.41±0.24 | 0.30±0.18 | 0.15±0.07 | 0.16±0.06 | 0.05±0.01 |
| M-CQ | 0.04±0.01 | 0.09±0.04 | 0.68±0.24△ | 0.84±0.26△ | 0.58±0.20△ | 0.22±0.06△ | 0.21±0.06△ |
| H-CQ | 0.06±0.03 | 0.98±0.42△△ | 1.23±0.21△△ | 1.27±0.19△△ | 0.85±0.15△△ | 0.37±0.09△△ | 0.32±0.11△ |
**P < 0.01, compared with Native group；##P < 0.01, compared with Sham group；△P < 0.05,△△P < 0.01, with Model
Group is compared.
The result shows that the CIP of model mice primary is substantially reduced after using CQ compound, secondary MIP also obtains bright
Aobvious to alleviate, upon administration 30min starts to play apparent analgesic activity, and drug effect height is generally reached in 30min or 60min
Peak, 240min still have preferable analgesic effect, and are in apparent dose-effect dependence between dosage group.
Four, after the administration of CQ compound in mouse spinal cord tissue RANTES and MCP-3 content
RANTES, MCP-3 belong to chemotactic factor (CF) in spinal cord.
The 11st day execution mouse is tested, L3-L5 sections of myeloid tissues is taken, through homogenate, deproteinized, particle is gone to obtain spinal cord homogenate
Treatment fluid, using RANTES and MCP-3 in AimPlex streaming high throughput multiple-factor detection technique detection mouse spinal cord tissue
Content.
It the results are shown in Table 3.Compared with Sham group, RANTES, MCP-3 content in Model group significantly increase (P < 0.01, P
< 0.05), L-CQ and H-CQ can significantly reduce the content (P < 0.05) of RANTES, MCP-3 in model mice myeloid tissue.
RANTES, MCP-3 content in myeloid tissue after the administration of table 3CQ compound
#P < 0.05,##P < 0.01, compared with Sham group；△P < 0.05, compared with Model group.
Five, the content of inflammatory factor IL-6 and chemotactic factor (CF) MCP-1 in mice serum after CQ compound is administered
It tests eye socket before the 11st day mouse is put to death and takes blood, collect serum, detected using AimPlex streaming high throughput multiple-factor
Technology detects the content of inflammatory factor IL-6 and chemotactic factor (CF) MCP-1 in mice serum.
It the results are shown in Table 4.Compared with Native group, IL-6, MCP-1 content in Model group model mice serum are significant
It increases (P < 0.05), CQ compound can significantly reduce the content (P < 0.01) of IL-6, MCP-1 in model mice serum.
The content of inflammatory factor IL-6 and chemotactic factor (CF) MCP-1 in mice serum after the administration of table 4CQ compound
*P < 0.05, compared with Native group；△△P < 0.01, compared with Model group.
Embodiment 3, amantadine hydrochloride enhance CQ compound for the analgesic activity of MIP
One, model mice is prepared
Pre-stimulation is carried out (once a day, every time with quantitative Von to SPF grades of BALB/c male mices for three days on end before test
The metapedes of Frey fiber filament stimulation mouse bilateral).Test take within the 1st day bilateral metapedes machinery pain threshold >=mouse of 0.4g, often
It is (living that mouse in right leg greater trochanter of femur (being equivalent to above sciatic nerve branch part) injects 0.2mL S180 tumor strain cell liquid
Cell concentration is 1 × 107A/ml).Test the 5-7 days, the mechanical pain threshold of cancerous invasion side and image side≤0.07g
Surgery group mouse, as model mice.
Two, CQ compound is prepared
CQ compound is made of Ligustrazine Hydrochloride and Sinomenine, and the mass ratio of Ligustrazine Hydrochloride and Sinomenine is
0.8:1.CQ compound is taken, is dissolved with ultrapure water, the storing liquid of 40mg/mL is obtained, normal saline dilution is then used, obtains CQ compound
Solution.
Three, grouping administration
Amantadine hydrochloride solution: amantadine hydrochloride (Ama) is taken to obtain 10mg/mL's with physiological saline ultrasonic dissolution
Amantadine hydrochloride solution.
Ama+CQ group (n=12): object is the model mice that step 1 obtains, and is tested the 8th day, and it is multiple that a CQ is injected intraperitoneally
(150mg/kg, injection dosage are 0.4mL CQ compound solution/20g mouse to square solution, CQ compound in 0.4mL CQ compound solution
Concentration is 7.5mg/mL), the amantadine hydrochloride solution of 10mg/mL is given in stomach-filling before CQ compound solution 30min is injected intraperitoneally
(200mg/kg, dosage are 0.4mL/20g mouse).
CQ group (n=11): object is the model mice that step 1 obtains, and the test CQ compound of intraperitoneal injection in the 8th day is molten
(injection dosage is 0.4mLCQ compound solution/20g mouse to liquid, and the concentration of CQ compound is 7.5mg/ in 0.4mLCQ compound solution
mL)；
In -30min (before giving Ama), 0min (intraperitoneal injection CQ compound before) and give 30 after CQ compound, 60,90,
120,180, the mechanical pain threshold of 240min equi-time point assessment bilateral metapedes.
Before CQ compound 30min is given in CIIMIP model mice abdominal cavity, Ama is given in stomach-filling, and to enhance CQ compound small to model
The raising of mouse cancerous invasion side and image side machinery pain threshold acts on.6 time points can significantly increase in 30-240min upon administration
Strong CQ compound is shown in Fig. 2A for the analgesic activity (P < 0.01 or P < 0.05) of CIP.5 times of 30-180min are equal upon administration
CQ compound can be significantly increased for the analgesic activity (P < 0.01 or P < 0.05) of MIP, see Fig. 2 B.
Claims (12)
1. a kind of drug for treating mirror-image pain, active constituent is CQ compound and amantadine hydrochloride；
The mass ratio of the CQ compound and the amantadine hydrochloride is 3:3-5；
The CQ compound is made of component first and component second；The component first is the salt of ligustrazine or ligustrazine；The component second
For cucoline or the salt of cucoline；The mass ratio of the component first and the component second is 0.5-2.5:1.
2. drug as described in claim 1, it is characterised in that: the salt of the ligustrazine is Ligustrazine Hydrochloride or phosphoric acid Rhizoma Chuanxiong
Piperazine；The salt of the cucoline is Sinomenine or phosphoric acid cucoline；The mass ratio of the component first and the component second is
0.8:1。
3. a kind of drug for treating mirror-image pain caused by cancerous invasion, active constituent is CQ compound and amantadine hydrochloride；
The mass ratio of the CQ compound and the amantadine hydrochloride is 3:3-5；
The CQ compound is made of component first and component second；The component first is the salt of ligustrazine or ligustrazine；The component second
For cucoline or the salt of cucoline；The mass ratio of the component first and the component second is 0.5-2.5:1.
4. drug as claimed in claim 3, it is characterised in that: the salt of the ligustrazine is Ligustrazine Hydrochloride or phosphoric acid Rhizoma Chuanxiong
Piperazine；The salt of the cucoline is Sinomenine or phosphoric acid cucoline；The mass ratio of the component first and the component second is
0.8:1。
Application of the 5.CQ compound in the drug of preparation treatment mirror-image pain；The CQ compound is made of component first and component second；Institute
State the salt that component first is ligustrazine or ligustrazine；The component second is the salt of cucoline or cucoline；The component first and described
The mass ratio of component second is 0.5-2.5:1.
6. application as claimed in claim 5, it is characterised in that: the salt of the ligustrazine is Ligustrazine Hydrochloride or phosphoric acid Rhizoma Chuanxiong
Piperazine；The salt of the cucoline is Sinomenine or phosphoric acid cucoline；The mass ratio of the component first and the component second is
0.8:1。
The application of 7.CQ compound and amantadine hydrochloride in the drug of preparation treatment mirror-image pain；
The mass ratio of the CQ compound and the amantadine hydrochloride is 3:3-5；
The CQ compound is made of component first and component second；The component first is the salt of ligustrazine or ligustrazine；The component second
For cucoline or the salt of cucoline；The mass ratio of the component first and the component second is 0.5-2.5:1.
8. the use as claimed in claim 7, it is characterised in that: the salt of the ligustrazine is Ligustrazine Hydrochloride or phosphoric acid Rhizoma Chuanxiong
Piperazine；The salt of the cucoline is Sinomenine or phosphoric acid cucoline；The mass ratio of the component first and the component second is
0.8:1。
Application in the drug of mirror-image pain caused by 9.CQ compound treats cancerous invasion in preparation；The CQ compound is by component first and group
Divide second composition；The component first is the salt of ligustrazine or ligustrazine；The component second is the salt of cucoline or cucoline；Described group
Dividing the mass ratio of first and the component second is 0.5-2.5:1.
10. application as claimed in claim 9, it is characterised in that: the salt of the ligustrazine is Ligustrazine Hydrochloride or phosphoric acid Rhizoma Chuanxiong
Piperazine；The salt of the cucoline is Sinomenine or phosphoric acid cucoline；The mass ratio of the component first and the component second is
0.8:1。
Application in the drug of mirror-image pain caused by 11.CQ compound and amantadine hydrochloride treat cancerous invasion in preparation；
The mass ratio of the CQ compound and the amantadine hydrochloride is 3:3-5；
The CQ compound is made of component first and component second；The component first is the salt of ligustrazine or ligustrazine；The component second
For cucoline or the salt of cucoline；The mass ratio of the component first and the component second is 0.5-2.5:1.
12. application as claimed in claim 11, it is characterised in that: the salt of the ligustrazine is Ligustrazine Hydrochloride or phosphoric acid Rhizoma Chuanxiong
Piperazine；The salt of the cucoline is Sinomenine or phosphoric acid cucoline；The mass ratio of the component first and the component second is
0.8:1。
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| CN1634057A (en) * | 2004-12-13 | 2005-07-06 | 北京正大绿洲医药科技有限公司 | Dripping pills for reducing swelling and easing pain and its preparing method |
| CN101411707A (en) * | 2008-10-10 | 2009-04-22 | 西南大学 | Pharmaceutical composition for treating rheumatoid arthritis |
| CN103083401A (en) * | 2012-12-31 | 2013-05-08 | 中国中医科学院医学实验中心 | Compound pharmaceutical composition comprising szechwan lovage rhizome extract and caulis sinomenii extract |
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| CN1634057A (en) * | 2004-12-13 | 2005-07-06 | 北京正大绿洲医药科技有限公司 | Dripping pills for reducing swelling and easing pain and its preparing method |
| CN101411707A (en) * | 2008-10-10 | 2009-04-22 | 西南大学 | Pharmaceutical composition for treating rheumatoid arthritis |
| CN103083401A (en) * | 2012-12-31 | 2013-05-08 | 中国中医科学院医学实验中心 | Compound pharmaceutical composition comprising szechwan lovage rhizome extract and caulis sinomenii extract |
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