CN112823795B

CN112823795B - Idiopathic pulmonary fibrosis drug composition and application thereof

Info

Publication number: CN112823795B
Application number: CN201911142214.1A
Authority: CN
Inventors: 冯靖; 曹洁; 刘娜娜; 魏路清; 宁文
Original assignee: Tianjin Medical University General Hospital
Current assignee: Tianjin Medical University General Hospital
Priority date: 2019-11-20
Filing date: 2019-11-20
Publication date: 2023-04-14
Anticipated expiration: 2039-11-20
Also published as: CN112823795A

Abstract

The invention discloses an idiopathic pulmonary fibrosis drug combination and application thereof, and the drug combination for resisting idiopathic pulmonary fibrosis comprises pirfenidone and dextromethorphan. 200-600mg of pirfenidone and 7.5mg of dextromethorphan. The anti-idiopathic pulmonary fibrosis drug combination is an oral drug. The administration mode of the anti-idiopathic pulmonary fibrosis drug combination is that the single dose of the pirfenidone is 200-600mg, 3 times a day; dextromethorphan is 7.5mg once daily. The dose of pirfenidone is increased by 200-400mg per week for a single dose. The pirfenidone dose is increased to 400-600mg per dose over a two week period. The invention can relieve acute exacerbation of pulmonary fibrosis, relieve pulmonary interstitial fibrosis earlier and improve the quality of life.

Description

Idiopathic pulmonary fibrosis drug composition and application thereof

Technical Field

The invention relates to the field of medicines, in particular to an idiopathic pulmonary fibrosis medicine composition and application thereof.

Background

Idiopathic Pulmonary Fibrosis (IPF) is a particular type of chronic progressive fibrotic interstitial pneumonia characterized by destruction of alveolar structures and abnormal deposition of extracellular matrix in the alveolar cavities and pulmonary interstitium, with imaging mainly manifested as bilateral subcorpleural symmetrical distribution, grid-like shadows dominated by the basal part of the lung, and the alveolar lung. The disease has a hidden onset and a very poor prognosis, clinically manifested by symptoms of progressive worsening dyspnea and dry cough, and in the late stage, clubbing fingers and double lower lung burst sounds may appear with the disease. In the early stage of the disease, alveolitis is mainly treated, a large amount of inflammatory cells such as monocytes and lymphocytes are infiltrated, and a plurality of fibrosis cytokines (such as TGF-beta, PDGF, IGF-1 and the like) are up-regulated to be expressed, so that epithelial cell necrosis and alveolar wall edema are caused. In the later stage, the repetition of necrosis and tissue repair results in the excessive proliferation of fibroblasts and the massive deposition of extracellular matrix, which finally form fibrous cords and pull surrounding lung tissues to form the honeycomb lung. This results in a decrease in lung compliance, a decrease in lung mass, and a major manifestation of lung function as restricted ventilation dysfunction and diffuse dysfunction. In the past, long-term chronic inflammation was considered to be a major cause of IPF, and glucocorticoids have been widely used in clinical practice due to their anti-inflammatory effects, but they have been found to have low efficacy in clinical studies and to be associated with serious side effects such as fungal infections, gastrointestinal bleeding, etc.

Cartin et al discovered in 1987 that the level of Myeloperoxidase (MPO) in alveolar lavage fluid (BALF) of IPF patients was increased, and later studies also discovered that inflammatory cells in alveoli of IPF patients had enhanced hydrogen peroxide (H2O 2) release capacity, increased lipid peroxides in lungs, increased apoptosis rate of lung epithelial cells compared with normal persons, and systemic oxidative stress level was positively correlated with pulmonary fibrosis degree. There is now increasing evidence that an oxidative/antioxidant imbalance plays a major role in the development of fibrosis, and oxidative stress can cause necrosis of epithelial cells, up-regulation of various pro-fibrotic cytokine expression, and imbalance of pulmonary cathepsins and antiproteases, ultimately leading to the deposition of large amounts of extracellular matrix, leading to the development of pulmonary fibrosis. Because early chest distress and short breath symptoms are easy to be ignored by patients, the diagnosis of most patients is delayed, the median survival time after the diagnosis is confirmed is only 2-3 years, the disease can be followed by pulmonary hypertension and right heart failure, deep venous thrombosis and even lung cancer risk, the life quality of the patients is seriously influenced, and the economic burden of the patients is increased. The disease cannot completely reverse the progress of the disease except for lung transplantation because of the progressive and irreversible nature of the disease. Therefore, the research on drugs capable of relieving acute exacerbation of pulmonary fibrosis is a problem to be solved by those skilled in the art.

Dextromethorphan (DM) is an antitussive drug acting on the central nervous system, and animal and clinical studies have found that it acts mainly by inhibiting the cough center of the medulla oblongata. DM is white crystal or crystalline powder, has a bitter and odorous taste and is slightly soluble in water, DM is artificially synthesized by Hoffman Roche company of Switzerland in the last century by modifying the structure of morphine, a levorotatory compound of the DM has an analgesic effect, and the DM has an obvious antitussive effect except the analgesic effect as a dextrorotatory morphinan derivative. In 1956, the food and drug administration of the United states of America lists it as a non-prescription drug and honors it as the most safe central antitussive in modern times. The prior study was the neuroprotective effect of DM: benfang et al demonstrated that DM can protect nerves by anti-inflammatory and anti-excitotoxic effects after acute brain injury, and that the reduction of the expression levels of TNF-alpha, IL-1 beta, and IL-6 proteins was somewhat lower than that of the group with acute brain injury, and that the expression levels of aspartate transporters and glutamate transporters-1 were higher. However, to date, there have been no reports of dextromethorphan in relation to the resistance of idiopathic pulmonary fibrosis.

Disclosure of Invention

The present invention is directed to solving, to some extent, one of the technical problems in the related art described above. Therefore, the invention aims to provide an anti-idiopathic pulmonary fibrosis pharmaceutical composition and application thereof, so that acute exacerbation of pulmonary fibrosis is relieved.

In order to solve the problems, the technical scheme adopted by the invention is as follows: a medicinal composition for resisting idiopathic pulmonary fibrosis comprises pirfenidone and dextromethorphan. 200-600mg of pirfenidone and 7.5mg of dextromethorphan. The anti-idiopathic pulmonary fibrosis drug combination is an oral drug.

The application of an idiopathic pulmonary fibrosis drug combination in preparing a drug for resisting idiopathic pulmonary fibrosis is characterized in that the drug combination for resisting idiopathic pulmonary fibrosis is administered in a mode that a single dose of pirfenidone is 200-600mg, and the dose is 3 times a day; dextromethorphan 7.5mg once daily.

The dose of pirfenidone administered is a single dose increase of 200-400mg per week.

Preferably, the pirfenidone increases the dosage to 400-600mg per time over a two week period.

Has the advantages that: acute exacerbation of pulmonary fibrosis is relieved, pulmonary interstitial fibrosis is relieved earlier, and life quality is improved.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the embodiments or the prior art descriptions will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.

FIG. 1 example 2 comparative image of chest CT double pulmonary interstitial fibrosis examination before and after application of the drug combination of the present invention.

FIG. 2 example 3 comparative image of CT double pulmonary interstitial fibrosis examination of breast before and after application of the drug combination of the present invention.

Detailed Description

Selecting the IPF diagnostic standard which meets the requirements of ATS/ERS/JRS/ALAT in 2018: HRCT is consistent with UIP type and likely UIP patients, divided into idiopathic pulmonary interstitial fibrosis IPF patients and idiopathic pulmonary interstitial fibrosis acute exacerbation AE-IPF patients. Monitoring the chest HRCT, the lung function, the improvement of symptoms and the occurrence of adverse reactions of the patient.

The present invention will be described in detail with reference to specific examples.

Example 1: the main clinical symptoms of the patient, male, are intermittent cough, expectoration and chest distress for 3 years and aggravation for 1 month. The patient is diagnosed as idiopathic acute pulmonary interstitial fibrosis (AE-IPF) and orally takes pirfenidone capsule from 200mg each time and 3 times a day, the dosage of each time is increased by 200mg each time every week, then the dosage is gradually increased by 600mg 3 times a day, and simultaneously, 7.5mg of dextromethorphan is added for 1 time a day. Patients were reviewed for breast CT idiopathic pulmonary fibrosis 1 month after drug treatment with no further progression. The symptoms of conscious cough, chest distress and the like of the patient are relieved before continuing to take the medicine orally for 3 months, and the double lungs are relieved by rechecking the chest CT to grind the glass shadow and the grid shadow before. Review of patient Lung function indicates that FEV1 increased from 1.62L to 2.05L, FEV1% pred by 16.3% and FVC% pred by 11.6%.

Example 2: the patient, male, is 82 years old, and the main clinical symptoms of the patient are intermittent cough, expectoration for more than 10 years, and exacerbation with asthma for 1 week. The patient is examined that CT is idiopathic pulmonary fibrosis IPF 10 years ago, the patient is not specially treated, the patient has subjective cough aggravation with asthma in nearly 1 week, the patient is examined that the lung is double and diffuse interstitial change is shown, the fibrosis of the lung is aggravated earlier, and the patient is considered to be AE-IPF. The oral pirfenidone capsule is orally administered from 200mg every time and 3 times a day, the dosage of each time is increased by 200mg every week, then 400mg is gradually increased for 3 times a day of anti-fibrosis treatment, and 7.5mg of dextromethorphan is added for 1 time a day. There was no obvious progress in the one month reexamination of breast CT double-lung interstitial fibrosis. The patient insists on oral administration for 4 months to recheck the chest CT that the pulmonary interstitial fibrosis is reduced earlier, and the result is shown in figure 1, and the patient is old and has intolerance to the pulmonary function, so the pulmonary function is not checked.

Example 3: the patient, male, 70 years old, had 2 years of intermittent breathing with 1 week of exacerbation. The patient reexamines chest CT in 2019 in 5 months that diffuse double-lung frosted glass shadow, grid shadow and honeycomb shadow are increased, and the lung interstitial fibrosis is advanced earlier. Lung function examination showed FEV1% pred 57.8%, FVC% pred 44.6%. The patient is administered oral pirfenidone capsule from 200mg every time and 3 times a day, the dosage of each time is increased by 200mg every week, then 400mg is gradually increased for 3 times a day of anti-fibrosis treatment, and 7.5mg of dextromethorphan is added for 1 time a day. After the oral administration for 4 months, the CT of the reexamination chest of a patient shows that the fibrosis of the double lung interstitium is reduced earlier, the vitreous opacities of the double lungs are reduced earlier, the result is shown in figure 2, the reexamination lung function shows that the FEV is 1 percent pred 77.0 percent, the FVC percent pred 59.6 percent, and the subjective symptoms of the patient are also obviously improved.

Example 4: patient, male, 61 years old, patient history of idiopathic pulmonary interstitial fibrosis 2 years. The patient has stable state of illness and is not specially treated. The patient takes oral pirfenidone capsule from 200mg every time and 3 times a day, dose increases 200mg every time every week, then gradually increases 400mg 3 times a day for anti-fibrosis treatment, and simultaneously adds dextromethorphan 7.5mg 1 time a day. The CT of the breast of the patient is that the grid image and the honeycomb image of the double lungs are reduced compared with the former, and the fibrosis of the lung interstitial is reduced compared with the former.

Example 5: the patient, female, 65 years old, had the main clinical symptoms of intermittent chest distress and suffocation for 3 years, and aggravation for 2 months. The CT of the patient chest is the diffuse grinding glass shadow and grid shadow of the two lungs, and the interstitial fibrosis of the lungs is considered. The patient takes oral pirfenidone capsule from 200mg every time and 3 times a day, dose increases 200mg every time every week, then gradually increases 400mg 3 times a day for anti-fibrosis treatment, and simultaneously adds dextromethorphan 7.5mg 1 time a day. After the oral administration for 3 months, the CT of the breast of a patient reexamines the reduction of the double pulmonary interstitial fibrosis, the reduction of the ground glass shadow and the grid shadow and the reduction of the pulmonary interstitial fibrosis.

The present invention has been described in detail above. The principles and embodiments of the present invention have been described herein using specific examples, which are presented only to assist in understanding the method and its core concepts of the present invention. It should be noted that various changes and modifications can be made by those skilled in the art without departing from the principle of the present invention, and these changes and modifications also fall into the protection scope of the appended claims.

Claims

1. The anti-idiopathic pulmonary fibrosis pharmaceutical composition is characterized by comprising pirfenidone 200-600mg and dextromethorphan of 7.5mg, and the administration mode of the anti-idiopathic pulmonary fibrosis pharmaceutical composition is oral medication.

2. The anti-idiopathic pulmonary fibrosis pharmaceutical composition of claim 1, for use in preparing an anti-idiopathic pulmonary fibrosis medicament.