CN106902120B - Application of tofacitinib citrate in auxiliary treatment medicine for senile degenerative heart valve disease - Google Patents
Application of tofacitinib citrate in auxiliary treatment medicine for senile degenerative heart valve disease Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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Abstract
The invention relates to a new application of a medicament, in particular to an auxiliary treatment effect of tofacitinib on senile degenerative valvular heart disease. Clinical trial research carried out by the invention shows that tofacitinib is given for auxiliary treatment while the conventional treatment is carried out on the senile degenerative heart valve disease patient, so that the symptoms of pulmonary congestion and pleural effusion of the senile degenerative heart valve disease patient can be remarkably treated, various arrhythmia such as atrial fibrillation and the like and atrial and ventricular hypertrophy can be effectively improved, the recurrence rate of the disease can be reduced, and the life quality of the patient can be improved.
Description
Technical Field
The invention relates to a new application of a medicament, in particular to an application of tofacitinib citrate in an adjuvant therapy medicament for senile degenerative valvular heart disease.
Background
Senile Degenerative Heart Valve Disease (SDHVD) is also known as senile calcific heart valve disease, senile calcification syndrome. The disease refers to the original normal valvular or slight valvular abnormality, the connective tissue of the valvular is degenerated, fibrosis, thickening and calcified with the age, thereby causing the abnormal function of the valvular and the support, mainly invading the aortic valve and the mitral valve ring, mainly having the calcified active valvular stenosis and insufficiency, the calcification of the mitral valve ring and the mitral valve, and the combined valve calcification existing in the two valves, and the like, and seriously causing the hemodynamic change, which becomes one of the main causes of the heart failure, arrhythmia, syncope and sudden death of the old. With the extended life of the population, the disease has become a heavy economic burden for individuals, families and society.
The pathology of SDHVD is mainly that colloidal fibers and elastic fibers of the valve are increased, and are gradually broken, decomposed and irregularly dyed by elastic fibers, and lipid stripes are visible on the surface of the ventricle of an adult heart valve such as a mitral valve anterior valve, and are increased with age. The pathogenesis of the disease is the theory of mechanical stress, abnormal deposition of calcium, atherosclerosis, apoptosis, reduction of the bioactivity of alkaline phosphatase, abnormal precipitation of lipid and the like.
There is no effective drug therapy for SDHVD, and the treatment for the disease varies according to the course and period of the disease. Patients with normal cardiac function and no clinical symptoms are followed up, and generally do not need to be treated; the medicine intervention is generally adopted for patients with high risk factors such as atherosclerosis or patients with related diseases such as hypertension, coronary heart disease and diabetes which are combined to induce the disease, such as statins and ACEI medicines; the clinical symptoms of patients are usually treated by medication for complications, and the serious patients are treated by surgical operation or intervention. Currently, in clinical use, percutaneous aortic valve balloon angioplasty replacing aortic valve replacement has low cost and low surgical risk, but has poor long-term effect, so that a medicament for treating SDHVD is urgently needed to effectively treat patients with clinical symptoms.
Disclosure of Invention
Aiming at the existing problems, the invention provides a new medical application of tofacitinib citrate, namely an application of tofacitinib citrate as an auxiliary treatment drug for senile degenerative valvular heart disease.
The tofacitinib citrate is a pharmaceutical composition containing tofacitinib citrate.
The tofacitinib citrate composition contains effective amount of tofacitinib citrate as active component and may be orally taken.
The tofacitinib citrate for oral administration is a capsule or a coated tablet taking a quick-release pellet as an inner content.
The invention further researches the possible mechanism of tofacitinib as an auxiliary treatment medicament for senile degenerative heart valvulopathy: tofacitinib citrate is a tyrosine kinase (JAK) inhibitor and can mediate the activation of downstream apoptosis and signal transducer and activator 3 (STAT 3) pathways. The JAK/STAT3 pathway is an intracellular signal conduction pathway and relates to various pathophysiological processes such as cell proliferation and differentiation, cell apoptosis, inflammation, tumor and the like. We speculate that tofacitinib citrate is involved in down-regulating angiogenic factors (VEGF) by inhibiting JAK pathways and mediating downstream STAT3, so that the generation of new blood vessels is reduced, the risk of the new blood vessels for promoting the bone formation and calcification of the valve chondromalacia of the valve is reduced, the degeneration, fibrosis, thickening and calcification of the connective tissue of the cardiac valve of a patient are obviously improved, the cardiac muscle cells are protected, the long-term effect of surgical treatment is maintained, and the risk of heart failure is reduced.
Detailed Description
The invention is further illustrated by the following specific examples.
Example 1 adjuvant treatment of tofacitinib citrate for patients with senile degenerative cardiac valves
1. Data and method
1.1 subjects and groups
69 cases of SDHVD patients (diagnosis standard is thickening, calcification and reflection enhancement of aortic valve and mitral valve or valve ring, edge regulation and mobility reduction, x-ray examination finds that the aortic valve or mitral valve has calcification shadow, more than two levels of systolic noise or diastolic noise are heard in the aortic valve region, or noise is heard in both the aortic valve region and mitral valve region) are randomly divided into an observation group 39 and a control group 30, and the two groups of gender and illness condition are statistically treated without significant difference (the diagnosis standard is that the aortic valve and mitral valve or valve ring have calcification shadow, the two groups of gender and illness condition are statistically treatedp>0.05), comparable.
1.2 methods of treatment
The observation group and the control group both actively treat the complications, firstly, patients accompanied with heart failure and arrhythmia are actively administered with digitoxin tablets (orally, 0.05-0.1 mg every 6-8 hours, the maintenance dose is 0.05-0.1 mg daily), diuretic furosemide tablets (1 time daily and 40mg each time), cardiotonic digoxin tablets (1 time daily and 0.25mg each time), beta-receptor blocker propranolol tablets (3 times daily and 30mg each time), and the like for symptomatic treatment; in addition, all the patients in the observation group and the control group take the sulfuric acid ointment A orally, 3 times a day, 0.3g each time, so as to block the deposition of calcium on the blood vessel wall, and 3 months is a treatment course. The observation group received the above treatment and given tofacitinib citrate tablet 2 times daily at 5mg each time. A treatment course is 3 months.
1.3 Observation indicators and methods
The effect is shown: the symptoms of heart failure, arrhythmia, dyspnea and the like are obviously fewer or disappear, and are reduced by about 75 percent compared with the symptoms before treatment. Review of the echocardiogram showed that the atrioventricular radial line of the heart was significantly reduced compared to that before treatment, and the heart was substantially normal in size. The method has the following advantages: the symptoms of heart failure, arrhythmia, dyspnea and the like are relieved and reduced by about 50 percent compared with the symptoms before treatment. Echocardiography shows a decrease in atrioventricular radial lines and a recovery in heart size, but to a lesser extent. And (4) invalidation: no improvement in symptoms or an exacerbation or death during treatment. The total effective rate is the number of effective people, and the sum of the effective people accounts for the percentage of the total number of the effective people.
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 therapeutic effects
After a treatment course, 19 cases of obvious effect, 15 cases of effect and 5 cases of no effect are observed in an observation group, and the total effective rate is 87%; the observation groups have 10 effective cases, 11 effective cases and 9 ineffective cases, and the total effective rate is 70 percent; the total effective rate of the observation group is obviously higher than that of the control group,p＜0.05。
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 (%) |
| Observation group | 39 | 19 | 15 | 5 | 87% |
| Control group | 30 | 10 | 11 | 9 | 70% |
Note:p＜0.05
2.2 prognosis
27 patients in an observation group are treated and improved to be discharged from a hospital, 15 patients in a control group are treated and improved to be discharged from the hospital, follow-up visits are carried out on two groups of discharged patients in one year, 2 patients in a treatment group are subjected to compound hospitalization treatment again, and the recurrence rate is 7.4%; the control group has 6 patients who are hospitalized again, the recurrence rate is 40%, and the recurrence rate of the control group is obviously higher than that of the control group.
3. Conclusion
When the conventional medicament treatment is carried out on a patient suffering from SDHVD, the Tofacitinib citrate is given for adjuvant therapy, so that the symptoms of heart failure or arrhythmia, dyspnea and the like can be obviously improved, the occurrence of the heart failure and arrhythmia is reduced, the recurrence rate of the SDHVD is effectively reduced, and the life quality of the patient is improved.
Claims (4)
1. The application of tofacitinib citrate in preparing the medicine for the adjuvant treatment of the senile degenerative heart valve disease; 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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| Application Number | Priority Date | Filing Date | Title |
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| CN201510968845.4A CN106902120B (en) | 2015-12-22 | 2015-12-22 | Application of tofacitinib citrate in auxiliary treatment medicine for senile degenerative heart valve disease |
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| CN201510968845.4A CN106902120B (en) | 2015-12-22 | 2015-12-22 | Application of tofacitinib citrate in auxiliary treatment medicine for senile degenerative heart valve disease |
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| CN110327346A (en) * | 2019-06-27 | 2019-10-15 | 慧生医学科技(徐州)有限公司 | Ba Ruike is preparing the application in the drug for treating characteristics of calcific valvular heart disease for Buddhist nun |
| CN112957362A (en) * | 2021-04-30 | 2021-06-15 | 复旦大学附属中山医院 | Application of tofacitinib citrate in preparation of medicine for treating myocarditis related to immune checkpoint inhibitor |
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Non-Patent Citations (2)
| Title |
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| "JAK/STAT信号通路与组织器官纤维化的相关性研究进展";余雄伟，等;《新医学》;20141130;第45卷(第11期);710-713页 * |
| 心血管疾病中JAK-STAT通路研究进展;李婉秋;《昆明医学院学报》;20121231;第33卷;11-13页 * |
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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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