CN109045299A - It is a kind of for alleviating and/or treating the pharmaceutical composition of inflammatory pain - Google Patents
It is a kind of for alleviating and/or treating the pharmaceutical composition of inflammatory pain Download PDFInfo
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Abstract
The present invention proposes a kind of for alleviating and/or treating the pharmaceutical composition of inflammatory pain, and described pharmaceutical composition is made of Radix Caulophylli extract and JAK2 inhibitor.The pharmaceutical composition that the present invention is mixed to prepare by the ground-breaking discovery Radix Caulophylli extract of a large number of experiments and JAK2 inhibitor according to preset blending ratio, it can be good at the alleviation and treatment for inflammatory pains such as pain caused by rheumatoid arthritis, oral cavity pain, myalgia, skeleton pain, headaches, not only extend the application range of Radix Caulophylli, and promote use of the JAK2 class inhibitor in Integrated TCM, and good Chinese and Western medicine synergistic effect is achieved, a kind of application prospect and the boundless pioneering innovation and creation of market prospects are belonged to.
Description
Technical field
The invention belongs to field of medicaments, and in particular to a kind of for alleviating and/or treating the pharmaceutical composition of inflammatory pain
And its alleviating and/or treating the application in inflammatory pain.
Background technique
With China's industrialization of Chinese medicine cause flourish, by Chinese and western drugs use in conjunction come the phenomenon that treating disease
It is more and more common, this to a certain extent for, can get twice the result with half the effort really, receive satisfactory therapeutic effect.Radix Caulophylli is
Tight celestial, the red hair Radix Notoginseng of the drying root and rhizome also known as Wei of Berberidaceae Radix Caulophylli category leontice robustumDiels, red capillary are pungent, are Qinling-dabashan Area In Shaanxis
The distinctive natural medicinal plant in area, is mainly used for rheumatism arthralgia and myalgia, traumatic injury, menoxenia easing stomach-QI civil
The disease treatments such as pain.The main component of Radix Caulophylli be triterpenoid saponin and alkaloid, discovered in recent years its have it is antibacterial, antiviral, anti-
Oxidation and antitumor isoreactivity.However in the prior art, this Radix Caulophylli is mostly used alone as a kind of Chinese medicine, not
It is used in mixed way with immunosuppressive western medicine composition is able to carry out, it is too many because of existing immunosuppressor type for tracing it to its cause,
And not yet discovery can be suitble to carry out the western medicine composition of inflammatory pain healing with Radix Caulophylli collocation in existing test.
JAK2 inhibitor (Janus kinase 2, JAK2) is a kind of nonreceptor tyrosine kinase, and it is thin to be distributed widely in body
In born of the same parents' endochylema, hematopoiesis and immune system are participated in, is played a significant role to the activation of RBC acceptor garland rate and immunocyte.JAK-
STAT signal path is a Cell signal propagation pathways closely related with inflammatory cytokine, tumour of discovered in recent years,
JAK family and STAT family member are various immune anti-in regulation rheumatoid arthritis (Rheumatoid arthritis, RA)
There is high degree of specificity in answering, and can be conditioned by number of mechanisms.Non-selective JAK inhibitor citric acid support method replaces cloth
(Tofacitinib citrate) obtained the treatment that FDA approval is used for RA in 2012, was used for psoriasis, inflammatory bowel disease
(IBD) research is in clinical investigation phase, since non-selective JAK inhibitor can inhibit JAK2, influence haemocyte and
The generation of lymphocyte has biggish toxic side effect.The inhibiting effect of JAK2 is such clinical drug trial process middle dosage
The principal element of limitation.In conclusion clinically still needing one kind can be improved JAK2 inhibitor for treating inflammatory disease, can also reduce
Dosage is to reduce the therapeutic modality of adverse reaction.
Applicant can be combined by the ground-breaking discovery JAK2 inhibitor of a large amount of live tests with Radix Caulophylli, control
Treating has remarkable result on inflammatory pain, the respective strong point of both performances that can be maximized favourable factors and minimized unfavourable ones, and realizes Chinese and Western medicine association well
With combination, the present patent application is proposed based on this.
Summary of the invention
For the present invention by a large amount of experiments made on the living, ground-breaking discovery JAK2 inhibitor cooperates with combination in treatment class with Radix Caulophylli
Have in terms of the inflammatory pains such as pain caused by rheumatic arthritis, oral cavity pain, myalgia, skeleton pain, headache significant
Effect, and then the present invention proposes a kind of completely new pharmaceutical composition for being used to alleviate and/or treat inflammatory pain, not only extends
The application range of Radix Caulophylli, and promote application of the JAK2 inhibitor in terms of inflammation treatment, belong to a kind of application prospect and
The boundless pioneering innovation and creation of market prospects.
It is as follows that the present invention solves the technical solution that above-mentioned technical problem is taken:
It is a kind of for alleviating and/or treating the pharmaceutical composition of inflammatory pain, described pharmaceutical composition is extracted by Radix Caulophylli
Object and JAK2 inhibitor composition.
Further pharmaceutical composition according to the present invention, wherein the Radix Caulophylli extract and JAK2 inhibitor
Mass ratio range is 1000:1-25:1.
Further pharmaceutical composition according to the present invention, wherein the Radix Caulophylli extract and JAK2 inhibitor
Mass ratio is one of the following: 1000:1,900:1,800:1,700:1,600:1,500:1,400:1,300:1,200:1,
100:1,75:1,50:1 or 25:1.
Further pharmaceutical composition according to the present invention, wherein the Radix Caulophylli extract is by natural medicinal plant
The drying root and rhizome of Berberidaceae Radix Caulophylli category leontice robustumDiels is extracted by plant extraction method and is made.
Further pharmaceutical composition according to the present invention, wherein the main component of the Radix Caulophylli extract is three
Terpene saponin(e and alkaloid, wherein the alkaloid includes at least anagyrine and baptifoline, the triterpenoid saponin includes palm
Acid, hitodesterol, bessisterol-β-D-Glucose glycosides, beta -stigmasterol, 16 α, 23,28- trihydroxy-olive -12- alkene -
3-O- α-L- arabopyranose glycosides, 16 Alpha-hydroxies-olive -12- alkene -28- acid -3-O- α-L- arabopyranose glycosides, often
Spring rattan sapogenin -3-O- α-L- arabopyranose glycosides, leontin member -3-O- α-L- arabopyranose glycosides, ivy
At least one of sapogenin -3-O- β-D- glucopyanosyl-(1 → 2)-α-L- arabopyranose glycosides.
Further pharmaceutical composition according to the present invention, wherein the JAK2 inhibitor is as a kind of non-receptor junket
Histidine kinase, selected from least one of following inhibitor:
(1) BMS-911543, CAS No.:1271022-90-2, structural formula are as follows:
(2) Delgocitinib, CAS No.:1263774-59-9, structural formula are as follows:
(3) Cerdulatinib, Chinese are that match degree replaces Buddhist nun, CAS No.:1198300-79-6, structural formula are as follows:
(4) Gandotinib, CAS No.:1229236-86-5, structural formula are as follows:
(5) Pacritinib, CAS No.:937272-79-2, structural formula are as follows:
(6) Lestaurtinib, Chinese are lestaurtinib, CAS No.:111358-88-4, structural formula are as follows:
(7) Fedratinib, CAS No.:936091-26-8, structural formula are as follows:
(8) Baricitinib, CAS No.:1187594-09-7, structural formula are as follows:
(9) support method replaces cloth, CAS No.:540737-29-9, structural formula are as follows:
(10) officinal salt of Lestaurtinib；
(11) officinal salt of Fedratinib；
(12) officinal salt of Baricitinib；
(13) support method replaces the officinal salt of cloth, and preferably support method replaces cloth citrate.
Further pharmaceutical composition according to the present invention, wherein described pharmaceutical composition is made pharmaceutically acceptable
Following any dosage form: tablet, capsule, pill, granule, solution, suspension, syrup, injection, suppository, sucking
Agent or spray.
A kind of purposes of pharmaceutical composition of the present invention, wherein described pharmaceutical composition is for alleviating and/or treating inflammation
Property pain, the inflammatory pain be selected from rheumatoid arthritis caused by pain, oral cavity pain, myalgia, skeleton pain, head
Bitterly.
Technical effect of the invention:
The present invention cooperates with combination with Radix Caulophylli with JAK2 inhibitor by a large amount of white mouse experiment made on the living, ground-breaking discovery
In terms for the treatment of the inflammatory pains such as pain, oral cavity pain, myalgia, skeleton pain, headache caused by rheumatoid arthritis
With remarkable result, this is a pioneering invention to Chinese and Western medicine connected applications, and not finding yet so far in the prior art can be with
The western medicine composition of inflammatory pain is cured in Radix Caulophylli collaboration, this is present invention innovation discovery the most great, the innovation of this discovery
Effect is effectively verified also by a large amount of white mouse live test, is prepared for carrying out the popularization and application for human body, can be with
Say that the following application prospect of the invention is boundless.
Specific embodiment
The exemplary tests side of inflammatory pain on the way is being alleviated and/or treated to drug combination of the invention presented below
Case, to show the favorable activity or advantageous effects of the present composition.It is understood that following testing programs are only
To the example of the content of present invention, rather than limiting the scope of the invention.Those skilled in the art under the introduction of this specification,
Modifications or changes appropriate can be carried out to technical solution of the present invention, without departing from the spirit and scope of the invention.
In the description and claims of this application, unless otherwise stated, science used herein and skill
Art noun has the normally understood meaning of those skilled in the art institute.
The present invention proposes a kind of for alleviating and/or treating the pharmaceutical composition of inflammatory pain, comprising: Radix Caulophylli extract
With JAK2 inhibitor, mass ratio between the two meets relationship 1000:1-25:1, further preferred Radix Caulophylli extract and
JAK2 inhibitor is according to following mass ratio mixed configuration: 1000:1,900:1,800:1,700:1,600:1,500:1,400:
1,300:1,200:1,100:1,75:1,50:1 or 25:1.More preferably according to 400:1,300:1,200:1,100:1,75:1
Or the mass ratio configuration of 50:1.Under the proportional region, the single taking dose of Radix Caulophylli extract should be excellent in 0.1-10g
It is selected as 0.5g, 1g, 1.5g, 2g, 2.5g, 3g, 4g, 5g, 6g, 7g, 8g, 9g, 10g, more preferable 1.5g, 9g, and the JAK2
The single taking dose of inhibitor should in 1-500mg, preferably 5mg, 10mg, 15mg, 20mg, 25mg, 30mg, 40mg,
50mg, more preferable 5mg, 10mg, 15mg, 20mg.
Wherein the Radix Caulophylli extract by natural medicinal plant Berberidaceae Radix Caulophylli category leontice robustumDiels dry root and
Rhizome is extracted by plant extraction method and is made, and existing method can be used in plant extraction method, and it is not described here in detail, can also directly adopt
The Radix Caulophylli extract sold as traditional Chinese medicine ingredients.Through pharmacology of Chinese materia medica the study found that the main component of Radix Caulophylli extract is
Triterpenoid saponin and alkaloid, content ratio are generally 0.8-2.5:1, wherein the alkaloid includes at least anagyrine and to wear leaf counterfeit
Indigo alkali, the triterpenoid saponin include palmitinic acid, hitodesterol, bessisterol-β-D-Glucose glycosides, beta -stigmasterol, 16 α, and 23,
28- trihydroxy-olive -12- alkene -3-O- α-L- arabopyranose glycosides, 16 Alpha-hydroxies-olive -12- alkene -28- acid -
3-O- α-L- arabopyranose glycosides, hederagenin -3-O- α-L- arabopyranose glycosides, leontin member -3-O-
α-L- arabopyranose glycosides, hederagenin -3-O- β-D- glucopyanosyl-(1 → 2)-α-L- arabopyranose glycosides
At least one of.
Wherein the JAK2 inhibitor is a kind of nonreceptor tyrosine kinase, is distributed widely in body cell endochylema, is joined
With hematopoiesis and immune system, play a significant role to the activation of RBC acceptor garland rate and immunocyte.JAK-STAT signal is logical
Road is a Cell signal propagation pathways closely related with inflammatory cytokine, tumour of discovered in recent years, JAK family and
STAT family member has height in regulation rheumatoid arthritis (Rheumatoid arthritis, RA) various immune responses
Specificity, and can be conditioned by number of mechanisms.In preferred embodiment of the invention scheme, JAK2 inhibitor is selected from BMS-
911543、CT-1578、 Delgocitinib、AC-410、Cerdulatinib、Jaktinib、Gandotinib、TD-1473、
TD-3504、Pacritinib、VR-588、SHR0302、Deuterated Ruxolitinib、KL130008、
Lestaurtinib or its officinal salt, Fedratinib or its officinal salt, Baricitinib or its officinal salt, support method
For the one or more of them in cloth or its officinal salt；It is preferred to be selected from following one of which:
(1) BMS-911543, CAS No.:1271022-90-2, structural formula are as follows:
(2) Delgocitinib, CAS No.:1263774-59-9, structural formula are as follows:
(3) Cerdulatinib, Chinese are that match degree replaces Buddhist nun, CAS No.:1198300-79-6, structural formula are as follows:
(4) Gandotinib, CAS No.:1229236-86-5, structural formula are as follows:
(5) Pacritinib, CAS No.:937272-79-2, structural formula are as follows:
(6) Lestaurtinib or its officinal salt, Chinese are lestaurtinib, CAS No.:111358-88-4, knot
Structure formula are as follows:
(7) Fedratinib or its officinal salt, CAS No.:936091-26-8, structural formula are as follows:
(8) Baricitinib or its officinal salt, CAS No.:1187594-09-7, structural formula are as follows:
(9) support method replaces cloth or its officinal salt, CAS No.:540737-29-9, structural formula are as follows:
For cooperateing with the JAK2 inhibitor used to select support with Radix Caulophylli in preferred pharmaceutical composition of the present invention
Method replaces cloth mesylate, support method for one of cloth sulfate for cloth citrate, support method for cloth hydrochloride, support method, most preferably
Support method replaces cloth citrate: being called citric acid support method for cloth, chemical name are as follows: (3R, 4R) -4- methyl -3- (methyl -7H- pyrroles
And [2,3-d] pyrimidine-4-yl amino)-β-oxo -1- piperidines propionitrile citrate, molecular formula: C16H20N6O·C6H8O7, molecule
Amount: 504.5, chemical structural formula are as follows:
Pharmaceutical composition of the present invention is made pharmaceutically acceptable following any dosage form: tablet, capsule, pill,
Granule, solution, suspension, syrup, injection (including injection, injection sterile powder and concentrated solution for injection),
Suppository, inhalant or spray.
The invention further relates to a kind of Radix Caulophylli extracts to combine with JAK2 inhibitor in preparation alleviation and/or treatment class
Use in the drug of the inflammatory pains such as pain caused by rheumatic arthritis, oral cavity pain, myalgia, skeleton pain, headache
On the way, wherein the dosage rate of Radix Caulophylli extract be once a day, two times a day, three times per day, weekly, two weeks once,
Once in three weeks, once a month, the dosage rate of JAK2 inhibitor be once a day, two times a day, three times per day, weekly,
Two weeks once, once in three weeks, once a month.
The test implementation process of pharmaceutical composition of the present invention is given below.
In the present invention, so-called " extract " refers to plant extracts or Chinese medical extract in the present invention, with plant or Chinese medicine
Material is raw material, according to the needs of the purposes of the final products to extraction, extracts separation process by physical chemistry, orientation obtain and
A certain kind or plurality of active ingredients in concentration plant, the product formed without changing its effective component structure.
In the present invention, so-called " joint or combination " is a kind of administration mode comprising two or more drug is successive,
Or the various situations being administered simultaneously, it is so-called herein to refer to that give Radix Caulophylli extract in same dosage period presses down with JAK2 " simultaneously "
Preparation or Radix Caulophylli extract and JAK2 inhibitor and any other third component drug, for example, in one day, in three days, one week
It is interior, in two weeks, in one month give two or more drug.So-called " successively or in succession " administration, then be included in difference to
Given respectively in the medicine period Radix Caulophylli extract and JAK2 inhibitor or Radix Caulophylli extract and JAK2 inhibitor with it is any other
The case where third component drug.These administration modes belong to administering drug combinations of the present invention.
" effective quantity " of the present invention includes to be enough to improve or prevent to cure the symptom of word illness or the amount of illness.Effective quantity
Still mean that the amount for being enough to allow or promoting diagnosis.It can be according to following factor for the effective quantity of particular patient or veterinary science subject
And change: as illness to be treated, the general health of patient, the method and approach of administration and dosage and side effect are serious
Property.Effective quantity can be the maximum dose or dosage regimen for avoiding significant side effect or toxic effect.
The Radix Caulophylli extract of the present invention of test example 1. and JAK2 inhibitor are combined to mouse ear swelling inflammatory model
Improvement result
One, test sample
Citric acid support method replace cloth (commercially available), Radix Caulophylli dry root and rhizome (picking up from Mount Taibai), aspirin (commercially available), two
Toluene (commercially available), sodium carboxymethylcellulose (CMC-Na, commercially available).
Two, experimental animal
Kunming mouse, male and female dual-purpose, 1.5 monthly ages, 18~22g of weight, by Xi'an Communications University medical board experimental animal
Center provides, Quality of Experimental Animals quality certification number: SCXK (Shan) 2012-003.Feeding environment: 22~26 DEG C of temperature, relative humidity
40%~70%.
Three, test apparatus and material
BS2202S electronic balance, Sai Duolisi Instrument Ltd.；DZ-18C vacuum oven, Tianjin Stettlen instrument
Co., Ltd；LABORTA4001 rotating thin film evaporimeter, German Heidoph；The electronic ear of YLS-25A is swollen to make ear device, and Jinan benefit is prolonged
Development in science and technology Co., Ltd.
Four, test solution is prepared
Radix Caulophylli extract is prepared: being taken Radix Caulophylli medicinal material 100g, is added 1000mL cold water, small fire decoction is changed to after being boiled by fire
3h filters out decoction, and slag is stayed to rejoin 1000mL cold water, and method ibid decocts 3h, filters out decoction, stay slag to add 1000mL cold
Water, method ibid decoct 2h, merge decocting liquid three times, filtering, and filtrate is condensed into medicinal extract in 60 DEG C with Rotary Evaporators, are dried in vacuo
It is dried, crushed into powder in case, obtains 17.4g Radix Caulophylli water extract, is ground well, is prepared into addition CMC-Na using preceding
0.5% CMC-Na suspension is stand-by.
Citric acid support method is prepared for cloth, aspirin: being ground well using preceding addition CMC-Na, is prepared into 0.5% CMC-Na
Suspension is stand-by.
Five, experimental method
Group technology and medication
Healthy Kunming mouse 50 is taken, half male and half female is randomly divided into 5 groups by weight, is divided into model control group group (n=
10), aspirin group (n=10), Radix Caulophylli group (n=10), support method replace cloth group (n=for cloth group (n=10), Radix Caulophylli+support method
10).Groups of animals is administered by weight, and 0.5%CMC-Na suspension is given in model control group stomach-filling；Aspirin group stomach-filling is given
Give 0.5g/kg aspirin 0.5%CMC-Na suspension；The Radix Caulophylli extract 0.5% of 1.5g/kg is given in Radix Caulophylli group stomach-filling
CMC-Na suspension (is equivalent to Radix Caulophylli crude drug 9g/kg)；Support method gives 0.02g/kg citric acid support method for the stomach-filling of cloth group for cloth
0.5%CMC-Na suspension；Radix Caulophylli+support method for cloth group simultaneously stomach-filling give 1.5g/kg Radix Caulophylli extract and
The citric acid support method of 0.02g/kg replaces the 0.5%CMC-Na suspension of cloth.Each group administered volume is 20 mL/kg, daily administration
It 1 time, is administered within continuous 7 days.
Mouse ear swelling method
20 μ L/ of proinflammatory agent dimethylbenzene is uniformly smeared only in the left auricle two sides of mouse after last dose 1h, and auris dextra does not do any place
Reason is normal ear.Mouse cervical dislocation is put to death after 1h, and it is same in ears respectively to cut ears 7mm diameter punch along auricle base line
Position lays round auricle and claims quality, calculates ear swelling and ear swelling inhibiting rate.
Ear swelling=left auricle quality (mg)-auris dextra tablet quality (mg)；
Ear swelling inhibiting rate (%)=(model control group ear swelling-administration group ear swelling)/model control group ear is swollen
Expansibility × 100%.
Data representation and statistical procedures
Data analysis, measurement data data mean ± standard deviation are carried out using 19.0 statistics software of SPSS It indicates, more comparison among groups use the one-way analysis of variance of completely randomized design, compare two-by-two between group and are examined using LSD-t
It tests, wherein * indicates corresponding administration group P < 0.05 compared with model control group, has statistical significance；* indicates corresponding administration group
The P < 0.01 compared with model control group has statistical significance；# indicates Radix Caulophylli+support method for cloth group and aspirin group, red
Seven groups of hair, support method compare P < 0.05 for cloth group, have statistical significance.
Experimental result
1 Radix Caulophylli water extract of table and citric acid support method be combined for cloth to mouse ear swelling influence (N=10)
| Group | Dosage (g/kg) | Number of elements | Ear swelling (mg) | Ear swelling inhibiting rate (%) |
| Model control group | / | 10 | 12.99±1.66 | / |
| Aspirin group | 0.5 | 10 | 9.85±1.13* | 24.1 |
| Radix Caulophylli group | 1.5 | 10 | 10.19±1.228* | 21.6 |
| Support methodFor cloth group | 0.02 | 10 | 8.57±0.95* | 34.0 |
| Radix Caulophylli+support methodFor cloth group | 1.5+0.02 | 10 | 6.36±132**# | 51.0 |
Experiment conclusion:
The experimental result of table 1 shows that Radix Caulophylli+support method replaces cloth group, Radix Caulophylli group phase for cloth group and aspirin group, support method
Than significantly improving the antiphlogistic effects that support method replaces cloth and Radix Caulophylli extract to be administered alone, Radix Caulophylli extract being prompted to replace with support method
Cloth combination has drug effect synergistic effect in terms of improving inflammatory reaction early stage inflammatory edema.
The Radix Caulophylli extract of the present invention of test example 2. changes mouse hot-plate pain model with the combination of JAK2 inhibitor
Kind effect
One, test sample
Citric acid support method replaces cloth (commercially available), Radix Caulophylli dry root and rhizome (picking up from Mount Taibai), Indomethacin (commercially available), carboxylic
Sodium carboxymethylcellulose pyce (CMC-Na, commercially available).
Two, experimental animal
With embodiment 1.
Three, test apparatus and material
ZH-YLS intelligence hot-plate instrument, Anhui Zhenghua Biology Instrument Equipment Co., Ltd.；BS2202S electronic balance, Sai Duoli
This Instrument Ltd.
Four, test solution is prepared
Radix Caulophylli extract is prepared with test example 1.
Citric acid support method is prepared for cloth, Indomethacin: being ground well using preceding addition CMC-Na, is prepared into 0.5% CMC-Na
Suspension is stand-by.
Five, experimental method
Group technology and medication
Healthy Kunming kind female mice is taken, is placed in (55 ± 0.5) DEG C hot plate pain threshold detector, to lick metapedes as pain reaction
Index, from pain threshold detector is put into there is (pain threshold) the time required to pain reaction,<5 s or>30s or leaper abandon record mouse
It goes not having to.The mouse of primary dcreening operation qualification is respectively surveyed into 2 pain thresholds, every minor tick 10 minutes takes its average value as normal before administration
Pain threshold.Female mice 50 that screening is qualified are taken, 5 groups is randomly divided by weight, is divided into model control group group (n=10), Yin
Pungent group of U.S. of diindyl (n=10), Radix Caulophylli group (n=10), support method replace cloth group (n=10) for cloth group (n=10), Radix Caulophylli+support method.Mould
0.5%CMC-Na suspension is given in type control group stomach-filling；0.02g/kg Indomethacin 0.5%CMC- is given in Indomethacin group stomach-filling
Na suspension；The Radix Caulophylli extract 0.5%CMC-Na suspension that 1.5g/kg is given in Radix Caulophylli group stomach-filling (is equivalent to Radix Caulophylli
Crude drug 9g/kg)；Support method gives 0.02g/kg citric acid support method for the stomach-filling of cloth group for cloth 0.5%CMC-Na suspension；Radix Caulophylli+
Support method replaces the 0.5% of cloth for the citric acid support method of Radix Caulophylli extract and 0.02g/kg that 1.5g/kg is given in the stomach-filling simultaneously of cloth group
CMC-Na suspension.Each group administered volume is 20mL/kg, is administered once daily, and is administered within continuous 7 days.
Hot plate method in mice
Mouse pain threshold is measured respectively at after the last administration 30,60,90,120min, if without pain is reacted in 60s, immediately
Mouse is taken out, pain threshold is based on 60s.
Data representation and statistical procedures
Data analysis, measurement data data mean ± standard deviation are carried out using 19.0 statistics software of SPSS It indicates, more comparison among groups use the one-way analysis of variance of completely randomized design, compare two-by-two between group and are examined using LSD-t
It tests, wherein * indicates corresponding administration group P < 0.05 compared with model control group, has statistical significance；* indicate corresponding medicine group with
Model control group compares P < 0.01, has statistical significance；# indicates support method for cloth+Radix Caulophylli group and Indomethacin group, Radix Caulophylli
Water group, support method compare P < 0.05 for cloth group, have statistical significance.
Experimental result
2 Radix Caulophylli water extract of table and citric acid support method be combined for cloth to hot plate method mouse pain threshold influence (N=
10)
Experiment conclusion:
The hot plate genealogy of law, to generate pain reaction, is started using the warm stimulation a certain position of animal body of some strength with stimulation
It is to survey pain index to the incubation period for occurring reacting, is a kind of reaction that high-order maincenter participates in.The experimental result of table 2 shows, red hair
Seven+support method compared with Indomethacin group, support method are for cloth group, Radix Caulophylli group, significantly improve support method and mentions for cloth and Radix Caulophylli for cloth group
The effect for the anti-inflammatory pain for taking object to be administered alone prompts Radix Caulophylli extract and support method to be combined on improving inflammatory pain for cloth
It acts synergistically with drug effect.
Can be good at announcement citric acid support method by test example is improving inflammation for cloth and the combination of Radix Caulophylli extract
Property pain on there is drug effect synergistic effect, further research and development discovery by citric acid support method for cloth replace with BMS-911543,
CT-1578、Delgocitinib、AC-410、Cerdulatinib、Jaktinib、 Gandotinib、TD-1473、TD-
3504, Pacritinib, VR-588, SHR0302, Deuterated Ruxolitinib, KL130008, Lestaurtinib or
Any one in its officinal salt, Fedratinib or its officinal salt, Baricitinib or its officinal salt also can reach
Similar effect has absolutely proved that Radix Caulophylli extract on improving inflammatory pain there is drug effect to cooperate with the combination of JAK2 inhibitor
Effect, it is desirable to the protection of independent IP of first time can be obtained by present patent application.
Claims (8)
1. a kind of for alleviating and/or treating the pharmaceutical composition of inflammatory pain, which is characterized in that described pharmaceutical composition is by red
Seven extracts of hair and JAK2 inhibitor composition.
2. pharmaceutical composition according to claim 1, which is characterized in that wherein the Radix Caulophylli extract and JAK2 inhibit
The mass ratio range of agent is 1000:1-25:1.
3. pharmaceutical composition according to claim 2, which is characterized in that wherein the Radix Caulophylli extract and JAK2 inhibit
The mass ratio of agent is one of the following: 1000:1,900:1,800:1,700:1,600:1,500:1,400:1,300:1,200:
1,100:1,75:1,50:1 or 25:1.
4. pharmaceutical composition according to claim 1-3, which is characterized in that wherein the Radix Caulophylli extract by
The drying root and rhizome of natural medicinal plant Berberidaceae Radix Caulophylli category leontice robustumDiels is extracted by plant extraction method and is made.
5. pharmaceutical composition according to claim 4, which is characterized in that the wherein main component of the Radix Caulophylli extract
For triterpenoid saponin and alkaloid, wherein the alkaloid includes at least anagyrine and baptifoline, the triterpenoid saponin includes
Palmitinic acid, hitodesterol, bessisterol-β-D-Glucose glycosides, beta -stigmasterol, 16 α, 23,28- trihydroxy-olive -12-
Alkene -3-O- α-L- arabopyranose glycosides, 16 Alpha-hydroxies-olive -12- alkene -28- acid -3-O- α-L- arabopyranose glycosides,
Hederagenin -3-O- α-L- arabopyranose glycosides, leontin member -3-O- α-L- arabopyranose glycosides, Chang Chun
At least one of rattan sapogenin -3-O- β-D- glucopyanosyl-(1 → 2)-α-L- arabopyranose glycosides.
6. pharmaceutical composition according to claim 1-5, which is characterized in that the wherein JAK2 inhibitor conduct
A kind of nonreceptor tyrosine kinase, selected from least one of following inhibitor:
(1) BMS-911543, CAS No.:1271022-90-2, structural formula are as follows:
(2) Delgocitinib, CAS No.:1263774-59-9, structural formula are as follows:
(3) Cerdulatinib, Chinese are that match degree replaces Buddhist nun, CAS No.:1198300-79-6, structural formula are as follows:
(4) Gandotinib, CAS No.:1229236-86-5, structural formula are as follows:
(5) Pacritinib, CAS No.:937272-79-2, structural formula are as follows:
(6) Lestaurtinib, Chinese are lestaurtinib, CAS No.:111358-88-4, structural formula are as follows:
(7) Fedratinib, CAS No.:936091-26-8, structural formula are as follows:
(8) Baricitinib, CAS No.:1187594-09-7, structural formula are as follows:
(9) support method replaces cloth, CAS No.:540737-29-9, structural formula are as follows:
(10) officinal salt of Lestaurtinib；
(11) officinal salt of Fedratinib；
(12) officinal salt of Baricitinib；
(13) support method replaces the officinal salt of cloth, and preferably support method replaces cloth citrate.
7. pharmaceutical composition according to claim 1-6, which is characterized in that pharmacy is made in described pharmaceutical composition
Upper acceptable following any dosage form: tablet, capsule, pill, granule, solution, suspension, syrup, injection, bolt
Agent, inhalant or spray.
8. a kind of purposes of any one of claim 1-7 described pharmaceutical composition, which is characterized in that described pharmaceutical composition is used for
Alleviate and/or treatment inflammatory pain, the inflammatory pain are selected from pain, oral cavity pain, muscle caused by rheumatoid arthritis
Pain, skeleton pain, headache.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112748203A (en) * | 2020-12-30 | 2021-05-04 | 苏州海科医药技术有限公司 | Biological analysis method for Jactinib and ZG0244 concentrations in plasma sample in clinical research of Jettitinib cream serving as innovative medicine |
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2018
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112748203A (en) * | 2020-12-30 | 2021-05-04 | 苏州海科医药技术有限公司 | Biological analysis method for Jactinib and ZG0244 concentrations in plasma sample in clinical research of Jettitinib cream serving as innovative medicine |
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