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EP-4090340-B1 - COMPOSITIONS COMPRISING BISDEMETHOXYCURCUMIN FOR MANAGING CHRONIC OBSTRUCTIVE PULMONARY DISEASE

EP4090340B1EP 4090340 B1EP4090340 B1EP 4090340B1EP-4090340-B1

Inventors

  • MAJEED, MUHAMMED
  • NAGABHUSHANAM, KALYANAM
  • BANI, SARANG
  • PANDEY, ANJALI

Dates

Publication Date
20260506
Application Date
20210116

Claims (11)

  1. A composition for use in a method for regeneration of alveolar cells in a mammal with emphysema, said method comprising a step of administering said composition comprising not less than 20% w/w bisdemethoxycurcumin to said mammal to bring about a reduction in features of emphysema.
  2. The composition for use according to claim 1, wherein the features of emphysema are selected from the group consisting of hypoxia, decreased levels of lung surfactant proteins, increased permeability of the alveolar-capillary barrier, inflammation, increased accumulation and recruitment of neutrophils, elevated alveolar pressure, increased oxidative stress, elevated inflammatory cytokines and chemokines, increased numbers of activated T lymphocytes and muscle damage.
  3. The composition for use according to claim 1, wherein emphysema is induced by enzymes, viruses, bacteria, smoke and particulate irritants.
  4. A composition for use in a method of therapeutic management of chronic obstructive pulmonary disease in a mammal, said method comprising a step of administering said composition comprising not less than 20% w/w bisdemethoxycurcumin to said mammal to bring about a reduction in features and symptoms of chronic obstructive pulmonary disease.
  5. A composition for use in a method of preventing the progression of chronic obstructive pulmonary disease to acute respiratory distress syndrome in a mammal, said method comprising a step of administering said composition comprising not less than 20% w/w bisdemethoxycurcumin to said mammal to prevent onset acute respiratory syndrome by bringing about a reduction in features and symptoms of chronic obstructive pulmonary disease.
  6. The composition for use according to any one of claims 1, 4 or 5, wherein the composition further comprises 10-35% w/w demethoxycurcumin and 10-45% w/w curcumin.
  7. The composition for use according to claim 4 or 5, wherein the chronic obstructive pulmonary disease is emphysematous and non-emphysematous.
  8. The composition for use according to claim 4 or 5, wherein the features of chronic obstructive pulmonary disease are selected from the group consisting of hypoxia, decreased levels of lung surfactant proteins, increased permeability of the alveolar-capillary barrier, inflammation, increased accumulation and recruitment of neutrophils, elevated alveolar pressure, increased oxidative stress, elevated inflammatory cytokines and chemokines, increased numbers of activated T lymphocytes and muscle damage.
  9. The composition for use according to claim 4 or 5, wherein the symptoms of chronic obstructive pulmonary disease are selected from the group consisting of shortness of breath, especially during physical activities, wheezing, chest tightness, chronic cough that may produce mucus, respiratory infections, lack of energy, unintended weight loss, and swelling in ankles, feet or legs.
  10. The composition for use according to claim 4 or 5, wherein chronic obstructive pulmonary disease is induced by enzymes, viruses, bacteria, smoke and particulate irritants.
  11. The composition for use according to any one of claims 1, 4 or 5, wherein the mammal is human.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS This is a PCT filing claiming priority from U.S. Provisional application 62962343, filed on 17 January 2020, and U.S. Provisional application no. 63126920, filed on 17 December 2020. FIELD OF INVENTION The present invention relates to composition for the management of Chronic obstructive pulmonary disease. More specifically, the invention pertains to compositions comprising bisdemethoxycurcumin for regeneration of alveoli and for the management of Chronic obstructive pulmonary disease and Acute respiratory distress syndrome. BACKGROUND OF THE INVENTION Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes obstructed airflow from the lungs. It is typically caused by long-term exposure to irritating gases like cigarette smoke, fuel combustion, viral infections or particulate matter. Emphysema and chronic bronchitis are the two most common conditions that contribute to COPD. Emphysema is a condition in which the alveoli at the end of the smallest air passages (bronchioles) of the lungs are destroyed. Emphysema is defined by the American Thoracic Society as follows: "Emphysema is a condition of the lung characterized by abnormal, permanent enlargement of the air spaces distal to the terminal bronchiole, accompanied by destruction of their walls." It is a major component of COPD and is characterized by alveolar extracellular matrix destruction, reduction in the alveolar capillary exchange area, which leads to partially reversible airflow obstruction. This causes destruction of the fragile walls and elastic fibers of the alveoli causing collapse in the small airways collapse impairing airflow out of lungs. The signs and symptoms include Shortness of breath, especially during physical activities, Wheezing, Chest tightness, A chronic cough that may produce mucus, Frequent respiratory infections, Lack of energy, Unintended weight loss (in later stages), Swelling in ankles, feet or legs (Thurlbeck et al., Emphysema: Definition, Imaging, and Quantification, Benjamin Felson lecture, AJR 1994;163:1017-1025), Evidence indicated marked difference in the pathological features of normal and COPD lungs. In a healthy individual, cells respond to mild damage through exogenous ROS by activating repair mechanisms such as antioxidant, DNA-repair and autophagy. If the damage is too great, cells will undergo senescence thus preventing oncogenic changes. Stem cell renewal plays an important role in tissue regeneration and healing. However, in a person affected with COPD, excessive ROS results in increased damage to lung cells aggravated by a defective repair mechanism. Increased senescent cells further stimulate inflammation, alveolar destruction, endothelial dysfunction increasing the risk of oncogenic changes. ROS also results in loss of stem cells renewal by induced loss of quiescence and stem cell senescence. This leads to loss in tissue regeneration (Mercado et al., Accelerated ageing of the lung in COPD: new concepts, Thorax 2015;70:482-489. doi:10.1136/thoraxjnl-2014-206084). In addition to emphysematous COPD, non-emphysematous COPD is also prevalent (Occhipinti et al., Emphysematous and Nonemphysematous Gas Trapping in Chronic Obstructive Pulmonary Disease: Quantitative CT Findings and Pulmonary Function, Radiology: 2018, Volume 287: Number 2-683-692). Acute respiratory distress syndrome (ARDS) is also observed in the late stages of COPD. It is characterized by dyspnea, severe hypoxemia, decreased lung compliance, and diffuse bilateral pulmonary infiltrates. There are typically three phases in the pathology of ARDS: exudative, proliferative, and fibrotic. Type I alveolar cells are irreversibly damaged and there is deposition of proteins, fibrin, and cellular debris, producing hyaline membranes in the denuded space. Injury to the surfactant-producing type II cells also contributes to alveolar collapse. The type II cells proliferate with some epithelial cell regeneration, fibroblastic reaction, and remodelling in the proliferative phase (Udobi et al., Acute Respiratory Distress Syndrome, Am Fam Physician. 2003 Jan 15;67(2):315-322). Thus, there is alveolar degeneration in both COPD and ARDS. JP2016204264 discloses curcumin or an analog thereof for use in for suppressing the onset of ischemic heart disease in COPD patients. Tang F et al. (Journal of International Medical Research, 2019, 47(10):4764-4774) teaches that curcumin ameliorates COPD. It shows that curcumin decreased the inflammatory cell infiltration and reduced the lung emphysema and fibrosis in a dose-dependent manner. Lelli D et al. (Pharmacological Research, 2017, 115:133-148) mentions that curcumin is effective in the treatment of pulmonary diseases, including COPD and acute respiratory distress syndrome (ARDS). Recently, it was observed that COPD may be a risk factor for more severe COVID-19 disease (Alqahtani et al. Prevalence, severity and mortality associated with COPD an