Use of diacerein for relaxing pre-contracted tracheal smooth muscle and treating asthma
阅读说明：本技术 双醋瑞因在用于舒张预收缩的气管平滑肌及治疗哮喘中的应用 (Use of diacerein for relaxing pre-contracted tracheal smooth muscle and treating asthma ) 是由 沈金花 时顺波 于 2019-11-27 设计创作，主要内容包括：本发明涉及双醋瑞因(Diacerein)在用于舒张预收缩的气管平滑肌及用于制备治疗哮喘的药物中的应用,属于医药领域。通过对实验小鼠离体气管环肌张力的检测,发现本发明的双醋瑞因具有高效的舒张气管平滑肌的作用,尤其是可舒张高钾诱导的气道平滑肌的预收缩以及乙酰胆碱诱导的气道平滑肌的预收缩,有望应用于缓解哮喘患者发作时气道阻塞的症状。(The invention relates to application of Diacerein (Diacerein) in relaxing pre-contracted tracheal smooth muscle and preparing a medicine for treating asthma, belonging to the field of medicines. Through the detection of the tension of isolated tracheal ring muscles of experimental mice, the diacerein disclosed by the invention is found to have a high-efficiency effect of relaxing tracheal smooth muscles, particularly can relax the pre-contraction of airway smooth muscles induced by high potassium and the pre-contraction of airway smooth muscles induced by acetylcholine, and is expected to be applied to relieving the symptoms of airway obstruction when asthma patients attack.)
1. Use of diacerein for the preparation of a medicament for the relaxation of pre-contracted tracheal smooth muscle.
2. Use of diacerein for the preparation of a medicament for the treatment of asthma.
3. A pharmaceutical composition for treating diastolic pre-systolic tracheal smooth muscle comprising diacerein and a pharmaceutically acceptable carrier.
4. The pharmaceutical composition according to claim 3, wherein the diacerein is present in an amount of 5.56% to 8.33% by weight of the pharmaceutical composition.
5. The pharmaceutical composition of claim 4, wherein the diacerein is present in an amount of 8.33% by weight of the pharmaceutical composition.
6. A pharmaceutical composition according to claim 4, further comprising sugar powder, preferably glucose powder.
7. A pharmaceutical composition for treating asthma comprising diacerein and a pharmaceutically acceptable carrier.
8. The pharmaceutical composition according to claim 7, wherein the diacerein is present in an amount of 5.56% to 8.33% by weight of the pharmaceutical composition.
9. The pharmaceutical composition of claim 8, wherein the diacerein is present in an amount of 8.33% by weight of the pharmaceutical composition.
10. Pharmaceutical composition according to claim 8, further comprising sugar powder, preferably glucose powder.
Technical Field
The invention belongs to the field of medicines, and particularly relates to application of Diacerein (Diacerein) in relaxing pre-contracted tracheal smooth muscle and treating asthma, which can be used for developing a new medicine for preventing or treating asthma.
Background
Asthma is a serious chronic respiratory disease and also an allergic disease with abnormal immune function, and is a worldwide problem. However, the disease has high incidence rate, long course of disease and easy recurrence, and is a serious public health problem. In recent years, with the intensive research on subjects such as genetics, immunology, cytology, biology, molecular biology and the like, the research on the pathogenesis of bronchial asthma has not progressed, and a new step is marked for the prevention and treatment of asthma. However, the pathogenesis of asthma is very complex, and some mechanisms are not clear, so that the disease cannot be completely cured clinically at present, and only proper medicines can be used for effectively controlling the disease and relieving symptoms.
Asthma attacks are generally characterized by several features: 1. airway Hyperresponsiveness (AHR), a condition that is extremely dangerous because it is closely linked to a decline in lung function. 2. Reversible airflow is limited, breathing is extremely difficult and wheezing, and severe cases are airway spasm, cough and the like. 3. Airway Remodeling (air remodelling), the occurrence of which is based on chronic inflammation of the airways. Airway remodeling is also an extremely dangerous condition, as long as the airway is slightly irritated, it is easily blocked, resulting in difficulty in breathing and, in severe cases, life threatening. Therefore, it is of great importance to develop new drugs for treating asthma by studying small molecule compounds that relax pre-contracted airway smooth muscle.
Diacerein, formula C19H12O8Are important inhibitors of osteoarthritis IL-1. Diacerein is also called diacetyl dihydro anthracene carboxylic acid, 1, 8-diacetyl-3-carboxyl anthraquinone, Daiselin, and ambudin, etc., is a new Interleukin (IL) -1 inhibitor, has a chemical name of diacetyl rhein, and belongs to anthraquinone compounds. The product can induce chondrogenesis, has effects of relieving pain, resisting inflammation and relieving fever, can also significantly improve joint function of osteoarthritis patients, delay disease course, relieve pain, improve life quality of patients, has good safety, and can be used for treating Osteoarthritis (OA) to exert antibacterial effect.
The research on the aspect of treating asthma by expanding airway smooth muscle with diacerein has no relevant report at home and abroad at present.
Disclosure of Invention
In view of the above, the present invention aims to provide the use of diacerein in relaxing pre-contracted smooth muscle of the pre-trachea and in preparing a medicament for treating asthma.
In order to achieve the above objects, the present invention provides, in one aspect, the use of diacerein for the preparation of a medicament for the relaxation of pre-contracted airway smooth muscle.
In one aspect, the diacerein is present in the patient in an amount of 0.7-1.4 mg/kg/d; preferably 1.4 mg/kg/d.
In one aspect, the diacerein is present in an amount of 5.56% to 8.33% by weight of the medicament; preferably 8.33 wt%.
In one aspect, the medicament further comprises sugar powder; preferably glucose powder.
In one aspect, the powdered sugar is present in the patient in an amount of 20-40 mg/kg/d; preferably 30 mg/kg/d.
In one aspect, the sugar powder is present in the medicament in an amount of 5.56% to 8.33% by weight; preferably 8.33 wt%.
In one aspect, in the medicine, the mass ratio of the diacerein to the powdered sugar is 1: 20-1: 30, preferably 1: 20, or the molar ratio of the two is 1: 20-1: 40, preferably 1: 30.
in one aspect, tracheal smooth muscle is relaxed after the patient receives the drug.
In one aspect, the patient is selected from a human or non-human animal; preferably a non-human animal; more preferably a mouse.
In order to achieve the above objects, another aspect of the present invention provides the use of diacerein for the preparation of a medicament for the treatment of asthma.
In another aspect, the diacerein is present in the patient in an amount of 0.7-1.4 mg/kg/d; preferably 1.4 mg/kg/d.
In another aspect, the diacerein is present in an amount of 5.56% to 8.33% by weight of the medicament; preferably 8.33 wt%.
In another aspect, the medicament further comprises powdered sugar; preferably glucose powder.
In another aspect, the powdered sugar is present in the patient in an amount of 20-40 mg/kg/d; preferably 30 mg/kg/d.
In another aspect, the powdered sugar is present in the medicament in an amount of 91.67% to 94.44% by weight; preferably 91.67 wt%.
In another aspect, in the medicament, the mass ratio of the diacerein to the glucose powder is 1: 20-1: 30, preferably 1: 20 or the molar ratio of the two is 1: 20-1: 40, preferably 1: 30.
in another aspect, asthma is inhibited after the patient receives the drug.
In another aspect, the patient is selected from a human or non-human animal; preferably a non-human animal; more preferably a mouse.
In yet another aspect, the present invention provides a pharmaceutical composition for relaxing pre-contracted tracheal smooth muscle comprising diacerein and a pharmaceutically acceptable carrier.
In yet another aspect, the diacerein is present in an amount of 5.56% to 8.33% by weight in the pharmaceutical composition; preferably 8.33 wt%.
In yet another aspect, the pharmaceutical composition further comprises a sugar powder; preferably glucose powder.
In yet another aspect, the sugar powder is present in the medicament in an amount of 91.67% to 94.44% by weight; preferably 91.67 wt%.
In still another aspect, in the pharmaceutical composition, the mass ratio of the diacerein to the powdered sugar is 1: 20-1: 30, preferably 1: 20 or the molar ratio of the two is 1: 20-1: 40, preferably 1: 30.
in yet another aspect, the pharmaceutical composition may be formulated into a pharmaceutical formulation according to conventional methods. In the formulation process, it is preferable to mix the diacerein with a pharmaceutically acceptable carrier or dilute the diacerein with a carrier. When the carrier serves as a diluent, it may be solid, semi-solid or liquid. The preparation is selected from tablet, pill, powder, capsule, suspension, emulsion, solution, aerosol, injectable solution, etc.
In yet another aspect, the present invention provides a pharmaceutical composition for treating asthma comprising diacerein and a pharmaceutically acceptable carrier.
In yet another aspect, the diacerein is present in an amount of 0.7 to 1.4 mg/kg/d; preferably 1.4 mg/kg/d.
In yet another aspect, the pharmaceutical composition further comprises a sugar powder; glucose powder is preferred.
In still another aspect, in the pharmaceutical composition, the mass ratio of the diacerein to the glucose powder is 1: 20-1: 30, preferably 1: 20 or the molar ratio of the two is 1: 20-1: 40, preferably 1: 30.
in yet another aspect, the pharmaceutical composition may be formulated into a pharmaceutical formulation according to conventional methods. In the formulation process, it is preferable to mix the diacerein with a pharmaceutically acceptable carrier or dilute the diacerein with a carrier. When the carrier serves as a diluent, it may be solid, semi-solid or liquid. The preparation is selected from tablet, pill, powder, capsule, suspension, emulsion, solution, aerosol, injectable solution, etc.
The invention has the beneficial effects that: through the detection of the tension of isolated tracheal ring muscles of experimental mice, the diacerein disclosed by the invention is found to have a high-efficiency effect of relaxing tracheal smooth muscles, particularly can relax the pre-contraction of airway smooth muscles induced by high potassium and the pre-contraction of airway smooth muscles induced by acetylcholine, and is expected to be applied to relieving the symptoms of airway obstruction when asthma patients attack. The diacerein can relax the pre-contraction of the tracheal smooth muscle caused by high potassium, and the relaxation percentage reaches 81.02 +/-1.947%; for the pre-contraction of the tracheal smooth muscle caused by ACh, the relaxation percentage reaches 98 +/-2.185%, and the mechanism that the diacerein can relax the pre-contracted tracheal smooth muscle is utilized, so that the diacerein is expected to be developed into a medicine for treating asthma.
Drawings
FIG. 1 is a graph of the pre-contraction of airway smooth muscle induced by the relaxation of high potassium by diacerein;
FIG. 2 is a graph showing the control group's inability to relax high potassium induced airway smooth muscle under the same experimental conditions as in FIG. 1;
FIG. 3 is a graph of the pre-contraction of the airway smooth muscle induced by diacerein relaxation of acetylcholine;
FIG. 4 is a graph showing the failure of the control group to relax acetylcholine-induced airway smooth muscle under the same experimental conditions as in FIG. 3.
Detailed Description
The present invention is explained below with reference to examples, which are merely illustrative of the present invention. Unless otherwise specified, the technical means used in the present invention are well known to those skilled in the art. In addition, the embodiments should be considered illustrative, and not restrictive, of the scope of the invention, which is defined solely by the claims. It will be apparent to those skilled in the art that various changes or modifications in the components and amounts of the materials used in these embodiments can be made without departing from the spirit and scope of the invention.
The test materials used in the following test methods are readily available from commercial companies unless otherwise specified.