CN106902119B - Application of tofacitinib citrate in medicine for treating multiple Takayasu arteritis - Google Patents
Application of tofacitinib citrate in medicine for treating multiple Takayasu arteritis Download PDFInfo
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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Abstract
The invention discloses a new application method of tofacitinib citrate in the medical field. The specific implementation method is oral administration for treating polyarteritis. Clinical trial research carried out by the invention shows that tofacitinib citrate given to patients with polyarteritis can obviously improve the symptoms of limb intermittent dyskinesia, aortic stenosis or occlusion of aorta and branches thereof or proximal aorta of limbs and the like, obviously reduce laboratory index C reactive protein, reduce the risk of disease recurrence and improve the life quality of the patients.
Description
Technical Field
The invention relates to an application of tofacitinib citrate in a medicine for treating multiple Takayasu arteritis.
Background
Takayasuartteritis (TA), also known as Kawasaki disease, is a chronic inflammatory disease with unknown etiology, mainly involving the aorta and its major branches, and also involving the pulmonary arteries. The disease is well developed in women of childbearing age, and can also be seen in men and other age groups. The clinical manifestations mainly include nonspecific general symptoms and characteristic ischemic symptoms. General symptoms mainly include fever, arthralgia, night sweat, weight loss and the like; the ischemic symptoms are related to the extent and severity of blood vessels, and specifically include intermittent claudication, weakened pulse, angina, weakened vision, stroke, and the like. The disease is a worldwide disease, and the incidence in east asia, south asia and latin america is higher than in other regions, with annual incidence in japan being about 1.2/10 million people. The disease not only affects the work and life of young women, but also brings heavy burden to families.
The cause of TA is currently unknown, and studies in the past have suggested that TA is an inflammation of the arteries directly caused by Mycobacterium tuberculosis or other bacteria. It is believed that after infection, antigenicity of the aorta wall and/or its main branch artery wall is induced, autoantibodies against the aorta wall are generated, and then antigen-antibody reaction occurs to trigger inflammatory reaction of the aorta and its main branch vessels. However, no pathogenic bacteria were found in the diseased arterial tissue and there was not sufficient evidence for each laboratory examination. In recent years, studies tend to consider aortic inflammation as an autoimmune disease. The immunoglobulin level is elevated in the laboratory index of the patient and the arterial antibody test in the blood is positive. Current research reports also suggest that the etiology of TA is associated with vascular endothelial injury, genetics, and endocrine secretion.
At present, no clear and effective drug treatment is available for TA, and the existing treatment means are only limited to controlling inflammatory reaction and relieving symptoms, and have no clear effect on preventing the progress of the disease. The current therapeutic approaches are mainly (1) adrenocortical hormones. The medicine has many adverse reactions when used in large dose, and the patient compliance is poor. (2) A cytotoxic drug. The selection of dosage of the medicine is difficult when the medicine is used, the incidence rate of adverse reactions is high, and the curative effect of the medicine needs to be further confirmed. (3) Tumor necrosis factor antagonists. The clinical reports of the use of the medicines are few, and the medicines have certain curative effect on patients with relapsing refractory type multiple Takayasu arteritis, but the application effect on patients with mild and moderate degrees is not clear. In addition, the method also has means such as interventional therapy and surgical therapy, but also has the defects of high cost, high risk, unsatisfactory long-term effect and the like.
In conclusion, a medicine treatment method with definite curative effect and less adverse reaction is still urgently needed for treating the polyarteritis, and the treatment effect of the medicine can definitely improve the treatment effect of the polyarteritis, reduce the recurrence rate and improve the life quality of patients.
Disclosure of Invention
The invention aims to provide a new medical application of tofacitinib citrate, namely an application in a medicine for treating polyarteritis.
The tofacitinib citrate also relates to a pharmaceutical composition containing tofacitinib citrate.
The tofacitinib citrate composition also relates to a pharmaceutically acceptable adjuvant containing tofacitinib citrate with effective treatment amount as an active ingredient, and the tofacitinib citrate composition is usually orally administered.
The invention also relates to a capsule or a coated tablet taking the quick-release pellets as contents.
The invention also carries out further research on the possible mechanism of the tofacitinib citrate as a medicine for treating the polyarteritis: the JAK inhibitor tofacitinib citrate can effectively block the self-toxic immune reaction process of the polyarteritis, regulate and control the abnormal condition of cell metabolism mediated by a downstream signal channel mainly comprising STAT3, improve the condition of insufficient blood supply of tissues caused by vascular injury, and prevent the occurrence of complications such as weakened pulse, angina, weakened vision, stroke and the like.
Detailed Description
The following will describe embodiments of the present invention, but the contents of the present invention are not limited thereto at all.
Example 1 application of tofacitinib citrate in treating polyarteritis
1. Data and method
1.1 subjects and groups
26 cases of TA patients (diagnosis standard referring to American college of rheumatology: onset age is less than or equal to 40 years old, intermittent dyskinesia of limbs, pulsation of brachial artery, and double upper limb contraction pressure difference)>10 mmHg; subclavian artery or aorta vascular noise; sixthly, artery angiography shows that the aorta and the branch thereof or the proximal aorta of the limbs are narrow or blocked except for arteriosclerosis, fibroid dysplasia and other reasons. Note: digital subtraction angiography or angiography confirms the presence of stenosis or dilatation of the vessel as the final diagnostic criterion. ) Randomly divided into 16 treatment groups and 10 control groups, and the difference between the two groups has no significance in comparison of general clinical data such as sex, age, disease condition and the like (thep>0.05), comparable.
1.2 methods of treatment
The observation group was given conventional symptomatic treatment of TA: 1 time a day, 1mg a day, of a glucocorticoid betamethasone tablet is given; the vasodilator captopril tablet is taken 2 times a day, and 12.5mg a day; the anti-platelet aggregation medicine aspirin is 1 time daily, 300mg each time. The treatment group is administered with tofacitinib citrate tablet 2 times daily, 5mg each time. The treatment of both groups is performed for 3 weeks for 1 treatment course, and 2 treatment courses are observed and followed for half a year.
1.3 Observation indicators and methods
The effect is shown: clinical symptoms and signs disappear, and no recurrence occurs after half a year of observation. Improvement: the symptoms and signs disappear, and the patient has relapse after half a year observation. And (4) invalidation: and the symptoms and signs are reduced or not improved during the treatment period, and the patients relapse after stopping the medicine.
Effective rate = (number of effective people + number of improvement people)/total number of people in each group 100%
1.4 statistical methods
Statistical processing is carried out by adopting SPSS13.0, counting data is tested by adopting t,p<a difference of 0.05 is statistically significant.
2. Results
2.1 comparison of therapeutic effects of the two groups
After 2 treatment courses, the treatment groups of two groups of patients have 10 effective cases, 3 effective cases and 3 ineffective cases, and the total effective rate is 81%; the observation group has 2 cases of effectiveness, 4 cases of effectiveness and 4 cases of ineffectiveness, and the total effective rate is 60 percent; the total effective rate of the observation group is significantly higher than that of the control group (a)p<0.05), the detailed results are shown in table 1.
TABLE 1 comparison of the two groups of therapeutic effects
| Group of | Total number of people (n) | Show effect (n) | Effective (n) | Invalid (n) | Total effective rate (%) |
| Treatment group | 16 | 10 | 3 | 3 | 81% |
| Control group | 10 | 2 | 4 | 4 | 60% |
Note:p＜0.05
2.2 comparison of the therapeutic effects of C-reactive protein levels before and after treatment in two groups
After 2 treatment courses, the C-reactive protein levels of the patients in the treatment groups were significantly lower than those before the treatment, and had significant differences (p<0.01) without a significant decrease in control C-reactive protein. The specific results are shown in Table 2.
TABLE 2 Effect on C-reactive protein before and after treatment of two groups: (x±s`mg·L-1）
| Group of | Total number of people (n) | Before treatment | The treatment lasts for 2 weeks | The treatment lasts for 4 weeks | The treatment lasts for 6 weeks |
| Treatment group | 16 | 93.77±4.16 | 63.12±10.09 | 40.58±13.54* | 12.72±4.53** |
| Control group | 10 | 97.21±6.34 | 74.53±9.28 | 63.45±14.67 | 41.58±7.33 |
Note:* p<0.05；** p<0.01
2.3 prognosis
The patients in the treatment group are discharged from the hospital after treatment in 15 cases, the patients in the control group are discharged from the hospital after treatment in 8 cases, the follow-up visit of half a year is carried out on the patients discharged from the hospital in two groups, the patients in the treatment group are treated in a compound mode again, and the recurrence rate is 12.5%; the control group had 3 patients who were hospitalized again, the recurrence rate was 30%, and the recurrence rate was significantly higher in the control group than in the treatment group.
3. Conclusion
The Tofacitinib citrate is used for treating patients with polyarteritis, so that the condition of aortic stenosis or aortic occlusion of main arteries and branches or proximal main arteries of limbs of the patients with TA can be remarkably treated, the general symptoms of fever, arthralgia, night sweat and weight loss are improved, the recurrence rate is reduced, and the life quality of the patients is definitely improved.
Claims (4)
1. The application of tofacitinib citrate in preparing the medicine for treating the polyarteritis; the medicine is a medicine composition containing tofacitinib citrate.
2. The use of claim 1, wherein the tofacitinib citrate pharmaceutical composition comprises a therapeutically effective amount of tofacitinib citrate as an active ingredient and pharmaceutically acceptable excipients.
3. Use according to claim 1, characterized in that its route of administration is oral.
4. The use of claim 3, wherein tofacitinib citrate is formulated as a capsule or coated tablet comprising immediate release pellets as the main content.
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| CN201510968787.5A CN106902119B (en) | 2015-12-22 | 2015-12-22 | Application of tofacitinib citrate in medicine for treating multiple Takayasu arteritis |
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| CN201510968787.5A CN106902119B (en) | 2015-12-22 | 2015-12-22 | Application of tofacitinib citrate in medicine for treating multiple Takayasu arteritis |
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| CN113440614A (en) * | 2020-03-26 | 2021-09-28 | 长沙晶易医药科技有限公司 | Composition for treating rheumatoid arthritis and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2008144011A1 (en) * | 2007-05-16 | 2008-11-27 | Avalon Pharmaceuticals | Compounds and methods for treating or preventing autoimmune diseases |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2008144011A1 (en) * | 2007-05-16 | 2008-11-27 | Avalon Pharmaceuticals | Compounds and methods for treating or preventing autoimmune diseases |
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| Title |
|---|
| 急性期川崎病信号转导和转录激活因子3的表达及意义;李永钦，等;《中国免疫学杂志》;20111231;第27卷(第8期);743-747 * |
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Address after: 221004 No. 6, Yang Shan Road, Jinshan Economic Development Zone, Jiangsu, Xuzhou Co-patentee after: SHANGHAI FOSUN PHARMACEUTICAL(GROUP)CO., Ltd. Patentee after: JIANGSU WANBANG BIOPHARMACEUTICAL GROUP CO.,LTD. Address before: 221004 No. 6, Yang Shan Road, Jinshan Economic Development Zone, Jiangsu, Xuzhou Co-patentee before: SHANGHAI FOSUN PHARMACEUTICAL(GROUP)CO., Ltd. Patentee before: Jiangsu Wan Bang Biochemical Medicine Co.,Ltd. Address after: 221004 No. 6, Yang Shan Road, Jinshan Economic Development Zone, Jiangsu, Xuzhou Co-patentee after: SHANGHAI FOSUN PHARMACEUTICAL(GROUP)CO., Ltd. Patentee after: Jiangsu Wan Bang Biochemical Medicine Co.,Ltd. Address before: 221004 No. 6, Yang Shan Road, Jinshan Economic Development Zone, Jiangsu, Xuzhou Co-patentee before: SHANGHAI FOSUN PHARMACEUTICAL(GROUP)CO., Ltd. Patentee before: JIANGSU WANBANG BIOPHARMACEUTICALS Co.,Ltd. |
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