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CN-122005591-A - Pharmaceutical composition for treating chronic obstructive pulmonary disease and preparation method thereof

CN122005591ACN 122005591 ACN122005591 ACN 122005591ACN-122005591-A

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition for treating chronic obstructive pulmonary disease and a preparation method thereof. The pharmaceutical composition comprises, by weight, 1-1.5 parts of guava glycoside derivative, 1.5-2 parts of resveratrol and 0.5-0.8 part of aureobasil. The components are matched for use, so that the expression level of inflammatory factors IL-6 and TNF-alpha in alveolar lavage fluid can be obviously reduced at a lower dosage, and further the lung function of mice is improved.

Inventors

  • ZHANG NALI
  • LI XINRUI
  • ZHANG XINYI

Assignees

  • 洛阳市中心医院（郑州大学附属洛阳中心医院）

Dates

Publication Date
20260512
Application Date
20260202

Claims (9)

  1. 1. The pharmaceutical composition for treating the chronic obstructive pulmonary disease is characterized by comprising, by weight, 1-1.5 parts of guava glycoside derivatives, 1.5-2 parts of resveratrol and 0.5-0.8 part of aureobasil, wherein the structural formula of the guava glycoside derivatives is as follows: 。
  2. 2. The pharmaceutical composition for treating chronic obstructive pulmonary disease according to claim 1, wherein the preparation process of guava glycoside derivative comprises the steps of: (1) Adding guava glycoside into acetone, adding anhydrous potassium carbonate, stirring uniformly, and adding 2, 3-dibromo-3-phenylpropionic acid for heating reaction; The structural formula of the intermediate 1 is as follows: (2) Adding ethyl acetoacetate, 7-hydroxy coumarone-3-formaldehyde, p-toluenesulfonic acid and urea into ethanol, uniformly stirring, and reacting at 60-70 ℃; the structural formula of the intermediate 2 is as follows: (3) Adding the intermediate 1, the intermediate 2 and 1H-benzotriazole-1-yl oxygen tripyrrolidine hexafluorophosphate into anhydrous N, N-dimethylformamide, uniformly stirring, adding triethylamine for reaction, and purifying after the reaction is finished to obtain the guava glycoside derivative.
  3. 3. The pharmaceutical composition for treating chronic obstructive pulmonary disease according to claim 2, wherein the molar ratio of guava glycoside, anhydrous potassium carbonate and 2, 3-dibromo-3-phenylpropionic acid in step (1) is 1 (1.5-1.8): 1-1.2.
  4. 4. The pharmaceutical composition for treating chronic obstructive pulmonary disease according to claim 2, wherein the heating reaction in step (1) is performed at a temperature of 50 to 60 ℃ for a period of 12 to 16 hours.
  5. 5. The pharmaceutical composition for treating chronic obstructive pulmonary disease according to claim 2, wherein the molar ratio of 7-hydroxy coumarone-3-formaldehyde, ethyl acetoacetate, p-toluenesulfonic acid and urea in step (2) is 1 (1.2-1.5): 0.3-0.5): 1.2-1.5.
  6. 6. The pharmaceutical composition for treating chronic obstructive pulmonary disease according to claim 2, wherein the reaction time in step (2) is 3-5 h.
  7. 7. The pharmaceutical composition for treating chronic obstructive pulmonary disease according to claim 2, wherein the molar ratio of the intermediate 1, the intermediate 2, the 1H-benzotriazole-1-yl oxy tripyrrolidinyl hexafluorophosphate and triethylamine in the step (3) is 1 (1.2-1.5): 1.5-2: (2.5-3.2).
  8. 8. The pharmaceutical composition for treating chronic obstructive pulmonary disease according to claim 2, wherein the reaction time in step (3) is 4 to 8 hours.
  9. 9. A method for preparing a pharmaceutical composition for treating chronic obstructive pulmonary disease according to any one of claims 1 to 8, comprising the steps of: Weighing resveratrol, aureobasidin and guava glycoside derivatives according to the weight parts, and uniformly mixing to obtain the pharmaceutical composition.

Description

Pharmaceutical composition for treating chronic obstructive pulmonary disease and preparation method thereof Technical Field The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition for treating chronic obstructive pulmonary disease and a preparation method thereof. Background Chronic obstructive pulmonary disease (Chronic Obstructive PulmonaryDisease, COPD) is a type of respiratory chronic disease, which has a long disease period and involves a large number of disease-causing factors, and the pathogenesis of COPD is not completely clear, and is mostly a hypothesis. COPD pathogenesis hypothesis includes protease imbalance hypothesis, oxidative stress hypothesis, inflammatory hypothesis and Chlamydia infection hypothesis. Although the four pathogenesis hypotheses are not completely defined, the four pathogenesis hypotheses together outline the pathological outlines of multiple targets and multiple links of COPD, and provide theoretical engagement for subsequent drug classification and intervention strategies. The drug treatment scheme of COPD is mainly divided into beta 2 receptor agonist, M receptor blocker, glucocorticoid and traditional Chinese medicine. Beta 2 receptor agonists (terbutaline, salmeterol, formoterol, indacaterol and the like) can rapidly relieve symptoms by dilating bronchial smooth muscle, but the effect is maintained for only 4-24 hours, palpitation, hypokalemia and rapid tolerance are easy to occur, M receptor blockers (tiotropium bromide, aclidinium bromide, glycopyrrolate and the like) have longer action time, but are often accompanied with dry mouth, urinary retention, glaucoma exacerbation and arrhythmia risks, and inhaled glucocorticoids (beclomethasone, budesonide, triamcinolone and the like) can rapidly relieve inflammation in the acute exacerbation stage, but can not prevent progressive decline of pulmonary function after long-term use, but increase incidence rate of oral candidiasis, pneumonia and osteoporosis, and traditional Chinese medicines (Yupingfeng particles, bai capsules, liujunzi decoction and the like) emphasize the symptoms of 'spleen and kidney tonifying', have certain improvement on cough and asthma in the stable stage, easy cold and the defects of formulation quality and potential hepatorenal toxicity and the like. Thus, there is a need for a pharmaceutical composition for the treatment of chronic obstructive pulmonary disease that overcomes the existing drawbacks. Disclosure of Invention In order to overcome the defects of the prior art, one of the purposes of the invention is to provide a pharmaceutical composition for treating chronic obstructive pulmonary disease, and the expression level of inflammatory factors IL-6 and TNF-alpha in alveolar lavage fluid can be obviously reduced by collocating and using all the components, so that the lung function of mice is improved. One of the purposes of the invention is realized by adopting the following technical scheme: the pharmaceutical composition for treating the chronic obstructive pulmonary disease comprises, by weight, 1-1.5 parts of guava glycoside derivatives, 1.5-2 parts of resveratrol and 0.5-0.8 part of golden grass, wherein the structural formula of the guava glycoside derivatives is as follows: 。 Preferably, the preparation process of the guava glycoside derivative comprises the following steps: (1) Adding guava glycoside into acetone, adding anhydrous potassium carbonate, stirring uniformly, and adding 2, 3-dibromo-3-phenylpropionic acid for heating reaction; The structural formula of the intermediate 1 is as follows: (2) Adding ethyl acetoacetate, 7-hydroxy coumarone-3-formaldehyde, p-toluenesulfonic acid and urea into ethanol, uniformly stirring, and reacting at 60-70 ℃; the structural formula of the intermediate 2 is as follows: (3) Adding the intermediate 1, the intermediate 2 and 1H-benzotriazole-1-yl oxygen tripyrrolidine hexafluorophosphate into anhydrous N, N-dimethylformamide, uniformly stirring, adding triethylamine for reaction, and purifying after the reaction is finished to obtain the guava glycoside derivative. Preferably, in the step (1), the molar ratio of guava glycoside, anhydrous potassium carbonate and 2, 3-dibromo-3-phenylpropionic acid is 1 (1.5-1.8): 1-1.2. Preferably, the temperature of the heating reaction in the step (1) is 50-60 ℃ and the time is 12-16 h. Preferably, in the step (2), the molar ratio of the 7-hydroxy coumarone-3-formaldehyde, the ethyl acetoacetate, the p-toluenesulfonic acid and the urea is 1 (1.2-1.5): 0.3-0.5): 1.2-1.5. Preferably, the reaction time in the step (2) is 3-5 h. Preferably, in the step (3), the molar ratio of the intermediate 1 to the intermediate 2 to the 1H-benzotriazole-1-yl oxy-tripyrrolidinyl hexafluorophosphate to the triethylamine is 1 (1.2-1.5): 1.5-2): 2.5-3.2. Preferably, the reaction time in the step (3) is 4-8 hours. The second object of the present invention is to provide a