CN105343070A - Pharmaceutical composition containing chlorpheniramine maleate and its pharmaceutical application - Google Patents
Pharmaceutical composition containing chlorpheniramine maleate and its pharmaceutical application Download PDFInfo
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- CN105343070A CN105343070A CN201510774231.2A CN201510774231A CN105343070A CN 105343070 A CN105343070 A CN 105343070A CN 201510774231 A CN201510774231 A CN 201510774231A CN 105343070 A CN105343070 A CN 105343070A
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- pharmaceutical composition
- rheumatoid arthritis
- bulleyaconitine
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Abstract
The invention discloses a pharmaceutical composition containing chlorpheniramine maleate and its pharmaceutical application. An active ingredient of the pharmaceutical composition contains chlorpheniramine maleate or contains chlorpheniramine maleate and bulleyaconitine A. The pharmaceutical composition is synergistically effective in controlling rheumatoid arthritis, significantly reducing RA (rheumatoid arthritis) proinflammatory cytokines such as IL-1beta and TNF-alpha, reducing the swelling degree of a joint and thus controlling rheumatoid arthritis.
Description
Technical field
The invention belongs to medical art, in particular to a kind of pharmaceutical composition and the pharmaceutical applications thereof that contain chlorphenamine maleate.
Background technology
The autoimmune disease of rheumatoid arthritis (RA) to be a kind of with chronic joint inflammation be feature, its pathogenesis it be unclear that, and the cytokine of many immunocytes and generation thereof and cell-ECM interact and play a significant role in RA.Main clinical manifestation is the symptoms such as arthralgia, arthroncus, joint function disturbance, is one of major reason disabled.According to statistics, global arthritic reaches 3.55 hundred million, and China's arthritis is more than 100,000,000, and number is also in continuous increase.Arthritis has had a strong impact on life, working and learning, so there is the exploitation of the arthritis treatment medicine of good result to have great importance.
At present for the rheumatoid arthritis cure method that also neither one is satisfied, be generally all symptomatic treatment, namely alleviate arthralgia, improve range of motion, reduce joint function disturbance.Slight arthritis can take conservative treatment, and for most of patients with osteoarthritis, slightly can control by taking analgesic drug product to moderate pain, these drug mains will comprise the NSAID (non-steroidal anti-inflammatory drug) such as aspirin, diclofenac.The side effect of nonsteroidal antiinflammatory drug to gastrointestinal tract and kidney is comparatively obvious, and the importance of therefore basic pharmaceutical therapeutic alliance is appeared suddenly.The omeprazole of U.S. Xi Er large pharmaceutical factory development wets the compound recipe be made up of NSAID (non-steroidal anti-inflammatory drug) diclofenac and misoprostol, treatment of arthritis is evident in efficacy, misoprostol in compound recipe has stronger antiulcer action, but due to expensive, its application can not get popularizing.
Bulleyaconitine A (bulleyaconitineA, BLA) is the alkaloid extracted from aconitum plant the western regions of the Yunnan Province beep is drawn, and is a kind of novel plant medicine, has good anti-inflammatory and analgesic effect.There are some researches show that bulleyaconitine A all has analgesic activity to mice/rat chemical, hot plate, formaldehyde induced pain model, to mouse peritoneal capillary permeability, rat Ovum Gallus domesticus album causes pedal swelling and granuloma induced by implantation of cotton pellets propagation has inhibitory action.Clinical observation shows that bulleyaconitine A has anti-inflammatory and analgesic effect to chronic pain, can be used for treatment of arthritis, but the cost of its extraction and isolation is high, causes the price of formulation products higher.Chlorphenamine maleate (Chlorpheniraminemaleate) is as histamine H 1 receptor's antagonist, can to the telangiectasis caused by antianaphylaxis (histamine), as histamine H 1 receptor's antagonist, to the telangiectasis caused by antianaphylaxis (histamine), as histamine H 1 receptor's antagonist, can to the telangiectasis caused by antianaphylaxis (histamine), reduce the permeability of blood capillary, alleviate panting caused by bronchial smooth muscle contraction, antihistamine effect is more lasting, also there is obvious central inhibitory action, anesthetics can be increased, the effect of hypnotic and local anaesthetics, be applicable to skin allergy: urticaria, eczema, dermatitis, drug eruption, skin pruritus, neurodermatitis, insect bite disease, solar dermatitis, also can be used for allergic rhinitis, vasomotor rhinitis, medicine and food anaphylaxis.
At present, in the treatment of rheumatoid arthritis, there is not yet using chlorphenamine maleate or by chlorphenamine maleate and the bulleyaconitine A coupling medicine as main active.
Summary of the invention
The present inventor finds under study for action, and chlorphenamine maleate has certain antiinflammatory action, and this medicine and bulleyaconitine A coupling can play the synergism for the treatment of rheumatoid arthritis.Based on this achievement in research, the object of the present invention is to provide a kind of pharmaceutical composition of the control rheumatoid arthritis containing chlorphenamine maleate.
The object of the present invention is achieved like this:
Prevent and treat a pharmaceutical composition for rheumatoid arthritis, in wherein said pharmaceutical composition, active component contains chlorphenamine maleate.
Do further preferably the pharmaceutical composition of above-mentioned control rheumatoid arthritis, in wherein said pharmaceutical composition, active component is except chlorphenamine maleate, also containing bulleyaconitine A.
Preferred as to consumption proportion, the pharmaceutical composition of above-mentioned control rheumatoid arthritis, wherein the weight ratio of chlorphenamine maleate and bulleyaconitine A is 50-200:1.
As to consumption proportion further preferably, the pharmaceutical composition of above-mentioned control rheumatoid arthritis, wherein the weight ratio of chlorphenamine maleate and bulleyaconitine A is 50-100:1.
As to consumption proportion more further preferably, the pharmaceutical composition of above-mentioned control rheumatoid arthritis, wherein the weight ratio of chlorphenamine maleate and bulleyaconitine A is 100:1.
The pharmaceutical composition of control rheumatoid arthritis of the present invention, it has carried out relevant animal test in gavage mode, and result medicine is remarkable through gastrointestinal absorption, and therefore described pharmaceutical composition can be oral formulations.Wherein said oral formulations comprises tablet, capsule, granule.
Rat assist agent arthritis is similar with human rheumatoid arthritis (RA) in clinical manifestation, pathology, immunology change etc., is the animal model that research RA is conventional.The main clinic symptoms of RA is arthroncus, arthralgia and distortion, and adjuvant arthritis model has good similarity as the animal model of RA and is widely adopted.This experiment adopts complete Freund's adjuvant to make inducing adjuvant rat model of arthritis, after 12d, model group rats occurs that inflammation secondary shows, and with reference to arthritis index standards of grading, assesses modelling effect, scoring reaches more than 6 points, successfully establishes adjuvant arthritis model.It is generally acknowledged, IL-1 β and TNF-α is the major pro-infalmmatory cytokines promoting RA, and both serve pivotal role in synovial cell proliferation, pannus formation and bone and cartilage destruction.Show the research of Rat Experimental arthritis model, TNF-α and IL-1 β is the Main Factors causing arthroncus and cartilage destruction respectively.In experiment of the present invention, modeling 12d adjuvant arthritis rats respectively organizes ankle joint obvious tumefaction, and arthritis score raises, and TNF-α and IL-1 β level significantly increase.After chlorphenamine maleate and bulleyaconitine A drug combination, swelling and the arthritis score index in adjuvant arthritis rats foot pawl joint obviously reduce, IL-1 β and TNF-alpha content significantly reduce, and prompting chlorphenamine maleate and bulleyaconitine A drug combination have good synergistic therapeutic action to RA.Based on this achievement in research, two of object of the present invention is to provide one or both active component for the preparation of the purposes in the medicine of hepatoprotective; That is: the compositions that chlorphenamine maleate and bulleyaconitine A form is preparing the purposes in the medicine preventing and treating rheumatoid arthritis as active component.
Compared with prior art, the pharmaceutical composition tool that the present invention relates to has the following advantages and progress significantly: (1) collaborative control rheumatoid arthritis, significantly can reduce the proinflammatory cytokine that IL-1 β and TNF-α etc. promote RA, reduce the swelling in joint simultaneously, thus reach the object of control rheumatoid arthritis.(2) when identical curative effect, drastically reduce the area the consumption that bulleyaconitine A is used alone, thus the expense of patient medication is reduced, add the safety of medication and the compliance of patient.
Detailed description of the invention
Be below concrete test example of the present invention, the technique effect brought technical scheme of the present invention does and describes further, but protection scope of the present invention is not limited to this embodiment.Every do not deviate from the present invention's design change or equivalent substituting include within protection scope of the present invention.
Embodiment 1 chlorphenamine maleate coupling bulleyaconitine A is tested the impact of adjuvant arthritis model
Cleaning grade SD rat, male, body weight (150 ± 20) g.Random taking-up 8 rats are as Normal group, and all the other rats copy adjuvant arthritis model as follows: cause inflammation with complete Freund's adjuvant (being fully ground with autoclaved liquid paraffin the Emulsion being made into 10g/L after bacillus calmette-guerin vaccine 80 DEG C, deactivation in 1 hour) in the right back toes intradermal injection 0.1ml of Mus.The right back foot swelling peaking of 1d after injection, alleviates after 3d gradually.If there is secondary affection during 12d, sufficient pawl swelling, show as contralateral hind limb and the swelling of two forelimb foot pawl, Progressive symmetric erythrokeratodermia increases the weight of, and inflammatory tubercle and erythema appear in ear and afterbody, and prompting adjuvant arthritis model is induced successfully.After modeling success, rat model is divided at random: model control group, bulleyaconitine A group (100 μ g/kg, ig), chlorphenamine maleate group (10mg/kg, ig) and bulleyaconitine A associating chlorphenamine maleate group (50 μ g/kg+5mg/kg, ig), often organize 10, daily 1 time, gavage gives tested material 12d altogether; Normal group and model control group give equal-volume solvent (normal saline).
Administration the 0th, 5,9,13d observes and records general joint lesion degree.Whole body pathological changes, by Pyatyi scoring system in post-therapeutic evaluation, according to the lesion degree scores accumulated of all the other 3 limbs of non-injection adjuvant, calculates polyarthritis index.0 point: without red and swollen; 1 point: toe joint is red and swollen; 2 points: toe joint and pedal swelling; 3 points: the sufficient pawl swelling below ankle joint; 4 points: the whole sufficient pawl swelling comprising ankle joint; The scores accumulated in each joint are the arthritis score value of every rat.Last administration after 4 hours femoral artery get blood, centrifuging and taking supernatant, measure IL-1 β and TNF-α.
Cause scorching rear 13d to start, adjuvant arthritis rats polyarthritis is marked.From table 1, the sufficient pawl scoring of chlorphenamine maleate group to rat model reduces not obvious, bulleyaconitine A group and compared to model control group can obviously suppress adjuvant arthritis rats polyarthritis mark score value, bulleyaconitine A associating chlorphenamine maleate group is compared to individually dosed group, remarkable reduction adjuvant arthritis rats polyarthritis scoring, visible two medicine couplings have collaborative antiinflammatory action.
The comparison of rat foot claw scoring respectively organized by table 1
| Group | n | Administration 0d | Administration 5d |
| Model control group | 10 | 6.28±1.69 | 9.56±1.63 |
| Chlorphenamine maleate group | 10 | 6.25±2.10 | 9.35±2.01 |
| Bulleyaconitine A group | 10 | 6.30±3.28 | 8.51±1.46 # |
| Drug combination group | 10 | 6.37±2.97 | 7.13±1.85 #★● |
Continued 1 respectively organizes the comparison of rat foot claw scoring
| Group | n | Administration 9d | Administration 13d |
| Model control group | 10 | 12.02±0.91 | 10.25±1.51 |
| Chlorphenamine maleate group | 10 | 11.28±1.15 | 10.94±1.72 |
| Bulleyaconitine A group | 10 | 10.69±1.10 # | 7.72±1.47 ## |
| Drug combination group | 10 | 8.11±0.85 ##★★●● | 7.09±0.97 ##★★ |
Compare with model control group,
# p< 0.05,
## p< 0.01; Drug combination group compares with chlorphenamine maleate group,
★ p< 0.05,
★ ★ p< 0.01; Drug combination group compares with bulleyaconitine A group,
● p< 0.05,
● ● p< 0.01.
Can be found out by the test statistics result of table 2, compare with normal group, in model group rats serum, IL-1 β and TNF-α significantly raises.Chlorphenamine maleate group and bulleyaconitine A group compared to model control group, IL-1 β and the decrease to some degree of TNF-alpha levels.Chlorphenamine maleate associating bulleyaconitine A group is compared to individually dosed group, and IL-1 β and TNF-alpha levels significantly reduce, and two medicine couplings demonstrate obvious synergism further.
Table 1 respectively group rat blood serum IL-1 β, TNF-alpha levels compares (pg/mL)
| Group | n | IL-1β | TNF-α |
| Normal group | 8 | 51.29±9.42 | 202.44±20.15 |
| Model control group | 10 | 173.06±25.53 * | 431.19±47.60 * |
| Chlorphenamine maleate group | 10 | 158.33±18.49 # | 395.05±50.71 |
| Bulleyaconitine A group | 10 | 135.17±20.62 # | 375.96±42.39 # |
| Drug combination group | 10 | 84.52±18.38 ##★★● | 262.48±48.16 ##★★●● |
Model control group compares with Normal group,
* p< 0.01; Compare with model control group,
# p< 0.05,
## p< 0.01; Drug combination group compares with chlorphenamine maleate group,
★ p< 0.05,
★ ★ p< 0.01; Drug combination group compares with bulleyaconitine A group,
● p< 0.05,
● ● p< 0.01.
Claims (8)
1. prevent and treat a pharmaceutical composition for rheumatoid arthritis, it is characterized in that, described pharmaceutical composition contains chlorphenamine maleate.
2. the pharmaceutical composition of control rheumatoid arthritis according to claim 1, is characterized in that, described pharmaceutical composition is also containing bulleyaconitine A.
3. the pharmaceutical composition of control rheumatoid arthritis according to claim 2, is characterized in that, the weight ratio of chlorphenamine maleate and bulleyaconitine A is 50-200:1.
4. prevent and treat the pharmaceutical composition of rheumatoid arthritis according to claim 3, it is characterized in that, the weight ratio of chlorphenamine maleate and bulleyaconitine A is 50-100:1.
5. prevent and treat the pharmaceutical composition of rheumatoid arthritis according to claim 4, it is characterized in that, the weight ratio of chlorphenamine maleate and bulleyaconitine A is 100:1.
6. according to any one of claim 1-5, prevent and treat the pharmaceutical composition of rheumatoid arthritis, it is characterized in that, described pharmaceutical composition is oral formulations.
7. prevent and treat the pharmaceutical composition of rheumatoid arthritis according to claim 6, it is characterized in that, described oral formulations comprises tablet, capsule, granule.
8. the compositions that chlorphenamine maleate and bulleyaconitine A form is preparing the purposes in the medicine preventing and treating rheumatoid arthritis as active component.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022507646A (en) * | 2018-11-19 | 2022-01-18 | ユンナン ハオピィ ファーマシューティカルズ エルティーディー | Uses of braiaconitine A |
-
2015
- 2015-11-13 CN CN201510774231.2A patent/CN105343070A/en active Pending
Non-Patent Citations (4)
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| 张源潮 等: "草乌甲素治疗骨关节炎及类风湿关节炎临床观察", 《中药药理与临床》 * |
| 沈凌汛 等: "正清风痛宁治疗类风湿关节炎27例", 《医药导报》 * |
| 温博 等: "类风湿关节炎的研究进展", 《世界中西医结合杂志》 * |
| 王国华: "风湿关节炎免疫发病机制研究进展", 《中国组织化学与细胞化学杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022507646A (en) * | 2018-11-19 | 2022-01-18 | ユンナン ハオピィ ファーマシューティカルズ エルティーディー | Uses of braiaconitine A |
| EP3884942A4 (en) * | 2018-11-19 | 2022-05-04 | Yunnan Haopy Pharmaceuticals Ltd | Use of bulleyaconitine a |
| JP7190571B2 (en) | 2018-11-19 | 2022-12-15 | ユンナン ハオピィ ファーマシューティカルズ エルティーディー | Uses of Bray Aconitine A |
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