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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 promote lung water clearance, maintain connection homeostasis, reduce or avoid alveolar-capillary stress failure

Inactive Publication Date: 2010-09-08
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, rats were given exercise, and the alveolar-arterial oxygen partial pressure difference in the model group was established. significantly lower than the control group. In the alveolar washing fluid, the protein content and cell count of the model group were higher than those of the control group, but some pro-inflammatory factors were not statistically different. Similarly, the lung wet-dry specific gravity 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 pulmonary interstitium, smaller alveolar spaces, and fluid exudation and erythrocyte leakage in the ...

Embodiment 2

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

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

[0033] The rats with high altitude pulmonary edema were given normal saline, budesonide, salmeterol, KGF-2, KGF-2+salmeterol to observe the preventive effect of these drugs on HAPE.

[0034] Experimental group:

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

[0036] 2. In the hypobaric oxygen exercise group (HAPE model group), the animals were given continuous exercise under the simulated plateau hypoxia state;

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

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

[0039] 5. HAPE model + salmeterol inhalation of salmete...

Embodiment 3

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

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

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

[0047] The lung wet-dry ratio is used to reflect the overall severity of pulmonary edema. like figure 2 As shown, the lung w...

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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 preparing a medicine for preventing and treating lung injury, and belongs to the technical field of medicine for preventing and treating lung injury. Background technique [0002] Acute lung injury (ALI) / acute respiratory distress syndrome (ARDS) is a common critical illness in the respiratory system, with high morbidity and mortality, seriously threatening the lives of critically ill patients and affecting their quality of life. Epidemiological surveys show that ALI / ARDS is a common clinical critical illness. According to the diagnostic criteria of ALI / ARDS proposed by the European and American Joint Conference in 1994, the incidence of ALI is 18 / 100,000 per year, and ARDS is 13-23 / 100,000 per year. A 2005 study showed that the incidence of ALI / ARDS was 79 / 100,000 and 59 / 100,000 per year, respectively. The survey results of the Shanghai ARDS Collaborative Group showed that t...

Claims

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Application Information

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IPC IPC(8): A61K38/18A61P11/00
Inventor 白春学宋元林佘君
Owner SHANGHAI XINSHENGYUAN BIOLOGICAL MEDICAL
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