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Application of keratinocyte growth factor-2 in preparation of medicines for preventing and curing lung injury

A technology of growth factors and keratinocytes, applied in drug combinations, pharmaceutical formulations, peptide/protein components, etc., to reduce or avoid alveolar-capillary stress failure, maintain connection homeostasis, and promote lung water clearance

Inactive Publication Date: 2013-01-23
SHANGHAI XINSHENGYUAN BIOLOGICAL MEDICAL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no in vivo study of KGF-2 for lung injury, and the present invention fills this gap

Method used

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  • Application of keratinocyte growth factor-2 in preparation of medicines for preventing and curing lung injury
  • Application of keratinocyte growth factor-2 in preparation of medicines for preventing and curing lung injury
  • Application of keratinocyte growth factor-2 in preparation of medicines for preventing and curing lung injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Establishment of high altitude pulmonary edema model:

[0028] Based on the method published in the European Journal of Respiratory Diseases, an animal model of high altitude pulmonary edema was established (Eur Respir J 2010, doi: 10.1183 / 09031936.00001709). At a simulated altitude of 4700 meters, the rats were given exercise, and the alveolar-arterial oxygen partial pressure difference in the model group significantly lower than that of the control group. In the alveolar lavage fluid, the protein content and cell count in the model group were higher than those in the control group, but there were no statistical differences in some pro-inflammatory factors. Similarly, the lung wet-dry ratio of the model group was also significantly higher than that of the control group. The morphological changes of the lung tissue in the model group included thickening of the interstitium, smaller alveolar spaces, fluid exudation in the alveoli and leakage of red blood cells. Studies...

Embodiment 2

[0031] KGF-2 increases survival in animals with high altitude pulmonary edema:

[0032] The human recombinant KGF-2 freeze-dried powder provided by Shanghai Xinxinyuan Pharmaceutical Research Co., Ltd. was added with normal saline to make a dosage of 5 mg / kg, and instilled in the airway.

[0033] The rat model of high altitude pulmonary edema was given normal saline, budesonide, salmeterol, KGF-2, KGF-2+salmeterol in advance, and the preventive effect of these drugs on HAPE was observed.

[0034] Experimental group:

[0035] 1. Normal air pressure group (control group)

[0036] 2. The hypobaric oxygen exercise group (HAPE model group) was given continuous exercise to animals under simulated plateau hypoxic state;

[0037] 3. HAPE model + normal saline were given sterile saline before modeling;

[0038] 4. HAPE model + budesonide nebulized budesonide before modeling, and once every 12 hours thereafter;

[0039] 5. HAPE model + salmeterol atomized inhalation of salmeterol be...

Embodiment 3

[0044] The role of KGF-2 in reducing pulmonary edema formation in high altitude pulmonary edema:

[0045] The human recombinant KGF-2 freeze-dried powder provided by Shanghai Xinxinyuan Pharmaceutical Research Co., Ltd. was added with normal saline to make a dosage of 5 mg / kg, and instilled in the airway.

[0046] Methods: Animal tissues were obtained after exposure for 48 hours in a hypobaric hypoxic environment at a simulated altitude of 4700 meters. The chest cavity was opened, and the lungs were taken out and placed in aluminum platinum paper that had been weighed in advance, and weighed again to calculate the wet weight of the lungs. Then fully baked in an oven at 60°C for 72 hours to constant weight and weighed to calculate the dry weight of the lungs. Lung wet-to-dry weight ratio (lung wet-to-dry weight ratio) is the ratio of lung wet weight to lung dry weight.

[0047] The lung wet-to-dry ratio was used to reflect the severity of overall pulmonary edema. Such as f...

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Abstract

The invention relates to an application of keratinocyte growth factor-2 in the preparation of medicines for preventing and curing lung injury. The invention has the advantages that single-medicine or medicine combination scheme is used to recombine human keratinocyte growth factor-2 (KGF-2) to cure and prevent lung injury / respiratory distress syndrome caused by any factor; and the lung injury / respiratory distress syndrome is in an important position of the special medicine such as the treatment of high altitude lung injury, the military medicine, the sports medicine and the treatment of lung injury / respiratory distress syndrome caused by other diseases. The above diseases can be subclinical, mild, moderate, severe or life-threatening lung injury. Researches show that KGF-2 can maintain the dynamic equilibrium of alveolar surfactants to promote hyperplasia, migrate cells and repair lung injury; and the KGF-2 plays an important role in protecting air-blood barrier to be intact, maintaining the cytoskeletal and intercellular splicing homeostasis, promoting the lung water to be removed and reducing or avoiding alveolus-capillary stress failure.

Description

technical field [0001] The invention relates to the application of keratinocyte growth factor-2 in the preparation of medicines for preventing and treating lung injuries, and belongs to the technical field of medicines for preventing and treating lung injuries. Background technique [0002] Acute lung injury (ALI) / acute respiratory distress syndrome (ARDS) is a common critical illness of the respiratory system, with high morbidity and mortality, which seriously threatens the life of critically ill patients and affects their quality of life. Epidemiological surveys show that ALI / ARDS is a common clinical critical illness. According to the ALI / ARDS diagnostic criteria proposed by the European-American Joint Conference in 1994, the incidence rate of ALI is 18 / 100,000 per year, and that of ARDS is 13-23 / 100,000 per year. Research in 2005 showed that the incidence rates of ALI / ARDS were 79 / 100,000 and 59 / 100,000 per year, respectively. The investigation results of the Shanghai ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/18A61P11/00
Inventor 白春学宋元林佘君
Owner SHANGHAI XINSHENGYUAN BIOLOGICAL MEDICAL
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