CN111494392A - Composition for treating acute lung injury and application thereof - Google Patents
Composition for treating acute lung injury and application thereof Download PDFInfo
- Publication number
- CN111494392A CN111494392A CN202010293140.8A CN202010293140A CN111494392A CN 111494392 A CN111494392 A CN 111494392A CN 202010293140 A CN202010293140 A CN 202010293140A CN 111494392 A CN111494392 A CN 111494392A
- Authority
- CN
- China
- Prior art keywords
- group
- dexamethasone
- lung
- lung injury
- acute lung
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a composition for treating acute lung injury and application thereof, wherein the composition comprises (a) dexamethasone and (b) WX-UK1 or WX-671. The research of the invention finds that the composition formed by dexamethasone and WX-UK1 or WX-671 has safe components, can effectively have synergistic treatment effect on acute lung injury, reduces the death rate caused by acute lung injury, recovers the normal lung function, and has important medical prospect and economic value.
Description
Technical Field
The invention belongs to the field of medicines, and relates to a composition for treating acute lung injury and application thereof.
Background
Whether acute lung injury is originated from lung or not can be divided into intrapulmonary factors (direct injury) and extrapulmonary factors (indirect injury), and the acute lung injury is represented by inflammatory factor release, so that pulmonary capillary injury is caused, and permeability of pulmonary alveoli and capillary vessels is increased, so that diffuse pulmonary interstitium and pulmonary alveolar edema are caused, oxygenation is further influenced, and breathing difficulty of a patient is caused. The lung volume reduction, the lung compliance reduction and the ventilation/blood flow ratio disorder are used as pathophysiological characteristics, and are clinically manifested as progressive hypoxemia and respiratory distress, and the lung imaging is manifested as non-uniform exudative lesion.
The etiology of acute lung injury is complex, the pathological mechanism of acute lung injury is not completely elucidated, and the mortality rate is high. At present, the treatment of acute lung injury mainly adopts large-dose hormone shock therapy, but lacks compelling experimental evidence, and a large number of clinical studies prove that glucocorticoid can not prevent the occurrence of acute lung injury and has no treatment effect on early acute lung injury. The existing medicine for treating acute lung injury has poor treatment effect, has the problem of treating symptoms but not treating root causes, and cannot treat acute lung injury fundamentally.
Disclosure of Invention
In view of the above problems, it is an object of the present invention to provide a composition effective for treating acute lung injury and use thereof.
In order to achieve the purpose, the invention adopts the technical scheme that: a composition comprising (a) dexamethasone and (b) WX-UK1 or WX-671; the structure of the WX-UK1 is shown as a formula (I), and the structure of the WX-671 is shown as a formula (II):
WX-UK1 is a uPA inhibitor, WX-671, also known as L H011, Upamostat, is a precursor of WX-UK1, WX-UK1 and WX-671 can be used for treating tumor metastasis and non-tumor diseases such as acute pancreatitis.
The invention also claims the application of the composition in preparing a medicament for treating acute lung injury.
The invention also provides a pharmaceutical preparation, which comprises the composition.
As a preferred embodiment of the present invention, the pharmaceutical preparation further comprises pharmaceutically acceptable adjuvants and/or carriers.
As a preferred embodiment of the present invention, the pharmaceutical preparation is an oral preparation.
The oral preparation contains WX-671 3mg/kg and dexamethasone 1 mg/kg.
As a preferred embodiment of the present invention, the solvent of the oral preparation is an aqueous solution containing 5% Tween-20 and 5% D-mannitol.
When WX-UK1 is used, WX-671 is replaced by an injection containing the same amount of WX-UK 1.
The research of the invention finds that the composition formed by dexamethasone and WX-UK1 or WX-671 has safe components, can effectively have synergistic treatment effect on acute lung injury, reduces the death rate caused by acute lung injury, recovers the normal lung function, and has important medical prospect and economic value.
Drawings
FIG. 1 shows body weight and mortality of rats in each group after 24 hours of treatment.
FIG. 2 shows the evaluation results of lung function of rats in each group after 24 hours of treatment.
FIG. 3 shows the effect of lung coefficient and lung permeability after 24 hours of treatment in rats in each group.
FIG. 4 shows the levels of blood inflammatory factors I L-1 β, TNF- α and I L-6 in rats of each group after 24 hours of treatment.
Figure 5 shows the lung pathology score of rats 24 hours after treatment of each group of rats.
Detailed Description
To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to the accompanying drawings and specific embodiments.
Example 1 therapeutic Effect of 1L H011+ dexamethasone composition on acute Lung injury
(I) moulding and administration
60 SPF male SD rats, 220-250G, anesthetizing the rats, disinfecting the neck of the rat by iodine, making a longitudinal incision of about 1 cm at the central line position of 1/3 below the neck, exposing the lower edge of the thyroid gland, turning up, carefully separating and exposing the anterior muscle group of the trachea, exposing the trachea by longitudinally and sharply separating the muscle group, obliquely placing the animal at the head and foot bottom, inserting 1m L syringes (26G) into the trachea at about 2 trachea rings below the cricoid cartilage ring, pushing 2mg/kg lipopolysaccharide (L PS) solution, with the administration volume of 0.8m L/kg, observing that no air bubbles exist in the nose, vertically rotating the rat for 20s immediately after pushing, so as to ensure that the liquid medicine is uniformly distributed in lung tissues and fully enters the lung.
In addition, a sham-operated control group was set, and 12 rats were treated in total, and the trachea was filled with an equal volume of physiological saline, and the other operations were the same.
Rats successfully modelled were selected and randomly divided into 4 groups of 12 rats each, including a model control group, L H011 group, dexamethasone group, and L H011+ dexamethasone group, along with a sham-operated control group, for a total of 5 groups, based on body weight.
The respective test samples were administered to each group according to the schedule of table 1 3 times daily, 0h, 12h, 22h after molding, respectively.
Table 1 dosing regimen for treatment of acute lung injury in groups of rats
| Group of | Test article | Route of administration | Dosage to be administered | Frequency of administration |
| Sham control group | Physiological saline | Oral administration for gastric lavage | / | 3 times per day |
| Model control group | Physiological saline | Oral administration for gastric lavage | / | 3 times per day |
| L H011 group | LH011 | Oral administration for gastric lavage | 3mg/kg | 3 times per day |
| Dexamethasone group | Dexamethasone | Oral administration for gastric lavage | 1mg/kg | 3 times per day |
| L H011+ dexamethasone | L H011+ dexamethasone | Oral administration for gastric lavage | 3mg/kg+1mg/kg | 3 times per day |
Note that the solvent of group L H011 is an aqueous solution containing 5% Tween-20 and 5% D-mannitol.
(II) detection
Observing animal states (including activities, respiration, food intake and the like) before and after molding, weighing and recording the weight of the animal before molding and after 24h of molding treatment, detecting the lung function detection of the animal through a small animal lung function detection system after 24h of molding, after the detection is finished, anaesthetizing, taking a blood sample and collecting alveolar lavage fluid, wherein the preparation method of the alveolar lavage fluid comprises the steps of fixing the upper side of a rat after anaesthetizing, exposing a trachea, selecting a 5m L disposable syringe, slightly cutting a needle head into the trachea 1/2 by inclining for 30 degrees, horizontally inserting the needle head into the trachea immediately, taking care to prevent puncturing the trachea, ligating the trachea and the needle head at the tracheotomy position, pressing the joint of the needle head and the trachea by the left thumb of an operator and the index finger, extracting sterile physiological saline water to be slowly injected into a bronchus, withdrawing the sterile physiological saline after 1min, withdrawing the sterile physiological saline, performing the extraction 3 times in the way, collecting all lavage fluid, and measuring the protein content by adopting Coomassie brilliant blue, wherein the calculation method for measuring the lung permeability index:
lung permeability index ═ bronchoalveolar lavage fluid protein/serum protein.
Blood samples were tested by the kit for TNF- α, I L-6 and I L- β inflammatory factor content in blood.
After the detection and the material drawing, the animals are sacrificed, the chest is opened quickly by surgical operation, the complete lung tissue is dissociated, the gross observation is carried out by naked eyes and the weighing is carried out, even if the lung coefficient is obtained, the calculation method is as follows:
lung coefficient is lung weight/body weight 100%.
Taking partial lung tissues at the same position for paraformaldehyde fixation, taking pathological changes from inflammation degree, alveolar wall thickening degree, acidophilic substances and cell shedding degree respectively by HE staining, and evaluating lung injury according to the pathological change degree: according to the degree of lesion from light to heavy, the minimal amount or no lesion is changed into negative "-" and 0 is marked; mild or small amount of "+" note 1; medium or moderate amounts of "+" note 2; severe or major "+++" 3; very severe or large number of "++++" marks 4, and each index score is analyzed after being counted and summed.
Data processing: experimental data were statistically processed by GraphPad Prism 7.0 biometrics software: the metric data are expressed as Mean ± SD and analyzed using two-way ANOVA combined with Dunnett's multiple comparisons; analysis is carried out by combining variance analysis with Dunnett's multiple comparison method; the counting data is analyzed by Kruskal-Wallis rank sum test; one-way ANOVA was used in conjunction with Dunnett's multiple comparison method for analysis.
(III) results of the experiment
1) General status observations and mortality:
compared with a model control group, the weight average of bodies of L H011, dexamethasone and L H011+ dexamethasone after 24H treatment has no obvious statistical difference (P >0.05, see table 2 and figure 1A), after the model is made and treated for 24H, a sham operation control group, a model control group and each treatment group respectively have 0, 4, 2, 1 and 0 animals die, and the results show that the L H011+ dexamethasone combined treatment can obviously reduce the death rate of animals with acute lung injury (see table 2 and figure 1B).
Table 2 body weight and mortality for each group of rat models (N ═ 12, Mean ± SD)
2) Animal pulmonary function detection
Compared with a model control group, the L H011 group, the dexamethasone group and the L H011+ dexamethasone group can obviously reduce the indexes of airway stenosis index Penh, tidal volume TV, expiratory volume EV and end expiratory pause EEP (see table 3 and figure 2), have statistical significance (P is less than 0.05 or 0.01), and meanwhile, the L H011+ dexamethasone group has obviously better reduction effects on the indexes of airway stenosis index Penh, expiratory volume EV and end expiratory pause EEP than L H011 or dexamethasone singly, so that L H011 and dexamethasone have synergistic treatment effects.
Table 3 lung function test results of each group of rat models (N ═ 12, Mean ± SD)
| Group of | Penh airway stenosis index | TV tidal volume | EV expiratory volume | EEP end-expiratory pause |
| Sham control group | 0.51±0.32** | 1.29±0.27* | 1.29±0.27* | 20.90±5.03** |
| Model control group | 1.88±1.49 | 1.80±1.12 | 1.80±1.11 | 45.56±17.49 |
| L H011 group | 1.05±0.46** | 1.32±0.29* | 1.33±0.19* | 30.17±9.06* |
| Dexamethasone group | 0.68±0.15** | 1.11±0.42* | 1.11±0.42** | 20.54±8.15** |
| L H011+ dexamethasone | 0.55±0.36** | 1.18±0.17* | 1.03±0.19** | 18.17±9.06** |
Note: compared to the model control group,: p < 0.05; **: p < 0.01.
3) Lung coefficient and lung permeability index
Compared with a sham operation control group, the lung coefficient and the lung permeability index of the model control group are obviously reduced, the statistical difference is achieved (P is less than 0.01), the model control group shows that the model building is successful, compared with the model control group, the L H011 group, the dexamethasone group and the L H011+ dexamethasone group can obviously reduce the lung coefficient and the lung permeability index (see table 4 and figure 3), the statistical significance is achieved (P is less than 0.01), meanwhile, the effect of reducing the lung coefficient and the lung permeability index of the L H011+ dexamethasone group is obviously better than that of singly using L H011 or dexamethasone, and the synergistic treatment effect of L H011 and dexamethasone is shown.
Table 4 lung coefficients and lung permeability for each group of rat models (N ═ 6, Mean ± SD)
| Group of | Number of animals (only) | Lung permeability index (× 10)-3) | Lung coefficient (%) |
| Sham control group | 6 | 9.68±4.14** | 0.53±0.23** |
| Model control group | 6 | 28.28±8.14 | 0.67±0.06 |
| L H011 group | 6 | 11.83±2.45** | 0.61±0.05** |
| Dexamethasone group | 6 | 7.56±5.07** | 0.52±0.11** |
| L H011+ dexamethasone | 6 | 6.23±2.31** | 0.45±0.05** |
Note: compared to the model control group,: p < 0.05; **: p < 0.01.
4) Detection of indicators in blood
Compared with a sham operation control group, the levels of I L-1 β, TNF- β 3 and I β 0-6 of the model control group are obviously increased and have statistical difference (P is less than 0.01), compared with the model control group, the levels of I β 5-1 β 2, TNF- α and I β 6-6 of the β 1H011 group, the dexamethasone group and the β 4H011+ dexamethasone group can be obviously reduced (the P is less than 0.01), and meanwhile, the reduction effect of the L H011+ dexamethasone group on I L-1 β, TNF- α and I L-6 is obviously better than that of single L H011 or dexamethasone, so that the L H011 and dexamethasone have synergistic treatment effect.
TABLE 5 Biochemical indices of the rat models of each group (N12, Mean + -SD)
Note: compared to the model control group,: p < 0.05; **: p < 0.01.
5) Morphological observation of lung tissue pathology
Compared with a sham operation control group, the lung pathology scores of the model control group are obviously increased, the statistical difference is obvious (P is less than 0.01), the modeling success is shown, compared with the model control group, the lung pathology scores of the L H011 group, the dexamethasone group and the L H011+ dexamethasone group are all obviously reduced (table 6 and figure 5), the statistical significance is realized (P is less than 0.01), the pathology improvement of the L H011+ dexamethasone group is obviously better than that of the single use of L H011 or dexamethasone, and the combination of L H011 and dexamethasone is shown to have the synergistic treatment effect.
Table 6 lung pathology scores for each group of rat models (N ═ 6, Mean ± SD)
| Group of | Number of animals (only) | Lung pathology scoring |
| Sham control group | 6 | 5.08±1.29** |
| Model control group | 6 | 12.25±3.57 |
| L H011 group | 6 | 8.12±2.36* |
| Dexamethasone group | 6 | 6.89±2.78** |
| L H011+ dexamethasone | 6 | 5.16±2.09** |
Note: compared to the model control group,: p < 0.05; **: p < 0.01.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention, and not for limiting the protection scope of the present invention, although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (6)
1. A composition comprising (a) dexamethasone and (b) WX-UK1 or WX-671; the structure of the WX-UK1 is shown as a formula (I), and the structure of the WX-671 is shown as a formula (II):
2. use of a composition according to claim 1 for the preparation of a medicament for the treatment of acute lung injury.
3. A pharmaceutical formulation comprising the composition of claim 1.
4. The pharmaceutical formulation of claim 3, further comprising a pharmaceutically acceptable adjuvant and/or carrier.
5. The pharmaceutical formulation of claim 3, wherein the pharmaceutical formulation is an oral dosage form.
6. The pharmaceutical formulation of claim 5, wherein the solvent of the oral formulation is an aqueous solution comprising 5% tween-20 and 5% D-mannitol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010293140.8A CN111494392A (en) | 2020-04-14 | 2020-04-14 | Composition for treating acute lung injury and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010293140.8A CN111494392A (en) | 2020-04-14 | 2020-04-14 | Composition for treating acute lung injury and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111494392A true CN111494392A (en) | 2020-08-07 |
Family
ID=71866272
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010293140.8A Withdrawn CN111494392A (en) | 2020-04-14 | 2020-04-14 | Composition for treating acute lung injury and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111494392A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113559100A (en) * | 2021-08-30 | 2021-10-29 | 广州领晟医疗科技有限公司 | Composition for treating lung injury and application thereof |
| CN114191424A (en) * | 2021-11-17 | 2022-03-18 | 广州领晟医疗科技有限公司 | Pharmaceutical composition and application thereof in preparation of medicine for treating acute lung injury |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080226624A1 (en) * | 2007-03-07 | 2008-09-18 | Wolfgang Schmalix | Combined treatment of cancer by urokinase inhibition and a cytostatic anti-cancer agent for enhancing the anti-metastatic effect |
| CN110475567A (en) * | 2017-03-31 | 2019-11-19 | 勃林格殷格翰国际有限公司 | Anticancer combination therapy |
| CN110785172A (en) * | 2017-07-21 | 2020-02-11 | 红山生物医药有限公司 | WX-UK1 and use of WX-671 product thereof for treating non-cancerous medical conditions |
-
2020
- 2020-04-14 CN CN202010293140.8A patent/CN111494392A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080226624A1 (en) * | 2007-03-07 | 2008-09-18 | Wolfgang Schmalix | Combined treatment of cancer by urokinase inhibition and a cytostatic anti-cancer agent for enhancing the anti-metastatic effect |
| CN110475567A (en) * | 2017-03-31 | 2019-11-19 | 勃林格殷格翰国际有限公司 | Anticancer combination therapy |
| CN110785172A (en) * | 2017-07-21 | 2020-02-11 | 红山生物医药有限公司 | WX-UK1 and use of WX-671 product thereof for treating non-cancerous medical conditions |
Non-Patent Citations (4)
| Title |
|---|
| YAN CHEN ET AL: "Mucoactive effects of naringin inlipopolysaccharide-induced acute lung injury miceand beagle dogs", 《ENVIRON TOXICOL PHARMACOL》 * |
| 丁国生主编: "《呼吸内科诊疗进展》", 30 June 2017, 吉林科学技术出版社 * |
| 李永东等: "尿激酶(uPA) 化学合成抑制剂", 《化学进展》 * |
| 陈曦等: "特发性肺纤维化的机制与治疗", 《生命的化学》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113559100A (en) * | 2021-08-30 | 2021-10-29 | 广州领晟医疗科技有限公司 | Composition for treating lung injury and application thereof |
| CN113559100B (en) * | 2021-08-30 | 2023-01-17 | 广州领晟医疗科技有限公司 | Composition for treating lung injury and application thereof |
| CN114191424A (en) * | 2021-11-17 | 2022-03-18 | 广州领晟医疗科技有限公司 | Pharmaceutical composition and application thereof in preparation of medicine for treating acute lung injury |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111514137A (en) | Application of compound in preparation of medicine for treating acute lung injury | |
| CN110604098B (en) | Method for constructing animal model of rheumatoid arthritis combined with interstitial lung disease | |
| Hatch | Prolonged nasotracheal intubation in infants and children | |
| CN111494392A (en) | Composition for treating acute lung injury and application thereof | |
| CN105726572A (en) | Application of donkey-hide gelatins to preparation of medicament or healthcare product for treating respiratory injury caused by fine air particulate matters | |
| CN114794015A (en) | Construction method and application of lung injury animal model | |
| CN114432421B (en) | KdPT polypeptide for treating acute lung injury and application thereof | |
| CN114191424B (en) | Pharmaceutical composition and application thereof in preparation of medicines for treating acute lung injury | |
| CN116076438B (en) | Animal model for rheumatoid arthritis combined with interstitial lung disease, construction method and application thereof | |
| Eisenberg et al. | Nebulization of amphotericin B | |
| CN111714504A (en) | Application of ITPP (International Teller Patent on Polypropylene) in preparation of medicine for preventing and/or treating ischemia/anoxia injury and lung injury | |
| CN114344343B (en) | Application of lactobacillus plantarum in preparation of acute lung injury resistant medicines | |
| WO2022236585A1 (en) | Use of hyaluronic acid in preparation of medication for treating pulmonary fibrosis | |
| CN116829157A (en) | Application of polyanionic fiber diglycoside compound | |
| CN113908149A (en) | Application of formononetin in preparation of medicine for preventing and treating acute lung injury | |
| CN113559100B (en) | Composition for treating lung injury and application thereof | |
| Heard | Pentothal: a new intravenous anaesthetic | |
| AU2020104218A4 (en) | Application of interleukin-37 in treating idiopathic pulmonary fibrosis | |
| Smart et al. | Intra-thoracic lipomata | |
| Kinch | Pure Nitrous Oxide at Labour: An Experimental and Clinical Investigation of The Blood Gases in Conjunction with Intermittent Administration of Pure Nitrous Oxide as Pain Relieving Agent during Delivery Labour | |
| CN108096240B (en) | Traditional Chinese medicine composition for treating pulmonary fibrosis | |
| CN113875699A (en) | Method for establishing pulmonary fibrosis rhesus monkey model | |
| CN105769914A (en) | Application of donkey-hide gelatin in preparing haze-prevention medicine or health-care products | |
| CN116965377A (en) | Preparation method of nanometer-level coal dust-exposed rheumatoid arthritis rat model | |
| CN117981712A (en) | Method for establishing adenovirus-induced pulmonary fibrosis acute exacerbation animal model |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20200807 |