A medicament for treating lung injury

Abstract

The present invention relates to a medicament for treating lung injury, in particular, the present invention provides the use of a Annexin for the manufacture of a composition or formulation for one or more uses selected from the group consisting of: (i) preventing and / or treating lung injury; (ii) reducing the number of neutrophils.

Description

Technical Field

[0001] This invention relates to the field of pharmaceuticals, and more specifically to a drug for treating lung injury. Background Technology

[0002] Acute lung injury and acute respiratory distress syndrome (ARDS) are lung injuries that seriously affect human health. ARDS is a clinical syndrome characterized primarily by alveolar-capillary damage, occurring after severe infections, trauma, shock, or other intrapulmonary or extrapulmonary attacks. It represents a severe stage or type of acute lung injury (ALI). Its clinical features include tachypnea and respiratory distress, progressive hypoxemia, and diffuse alveolar infiltration on X-ray. However, currently, there are still no effective drugs available for the treatment of acute lung injury and ARDS.

[0003] Therefore, there is a need in this field to develop a drug that can effectively treat lung injury diseases such as acute lung injury and acute respiratory distress syndrome (ARDS). Summary of the Invention

[0004] The purpose of this invention is to provide an application of annexin in the effective treatment of lung injury diseases such as acute lung injury and acute respiratory distress syndrome (ARDS).

[0005] In a first aspect, the present invention provides the use of annexin for preparing compositions or formulations for one or more uses selected from the group consisting of: (i) prevention and / or treatment of lung injury; and (ii) reduction of neutrophil count.

[0006] In another preferred embodiment, the annexin includes annexin A5.

[0007] In another preferred embodiment, the lung injury is selected from the group consisting of: acute lung injury, acute respiratory distress syndrome, or a combination thereof.

[0008] In another preferred embodiment, the respiratory distress syndrome includes acute respiratory distress syndrome.

[0009] In another preferred embodiment, the respiratory distress syndrome includes neonatal respiratory distress syndrome.

[0010] In another preferred embodiment, the lung injury includes lung injury caused by an increase in neutrophils.

[0011] In another preferred embodiment, the lung injury includes lung injury caused by a cytokine storm.

[0012] In another preferred embodiment, the prevention and / or treatment of lung injury includes preventing and / or treating lung injury by reducing the number of neutrophils.

[0013] In another preferred embodiment, the prevention and / or treatment of lung injury includes improving cytokine storm to prevent and / or treat lung injury.

[0014] In another preferred embodiment, the improvement of cytokine storm includes reducing, inhibiting, or eliminating it.

[0015] In another preferred embodiment, the prevention and / or treatment of lung injury includes preventing and / or treating lung injury by reducing the number of neutrophils and / or inhibiting the cytokine storm caused by an increase in the number of neutrophils.

[0016] In another preferred embodiment, the neutrophils include neutrophils in the lungs.

[0017] In another preferred embodiment, the cytokine storm includes a cytokine storm in the lungs.

[0018] In another preferred embodiment, the neutrophils include neutrophils in the alveoli.

[0019] In another preferred embodiment, the cytokine storm includes a cytokine storm in the alveoli.

[0020] In another preferred embodiment, "reducing the number of neutrophils" means that the number of neutrophils in a subject is reduced.

[0021] In another preferred embodiment, the object is a human or a non-human mammal (such as a rodent).

[0022] In another preferred embodiment, the subject is a person with an elevated neutrophil count.

[0023] In another preferred embodiment, the "elevated neutrophil count" refers to the subject's neutrophil count A1 being higher than A0 compared to the normal neutrophil count A0; preferably, A1 / A0 ≥ 1.1, more preferably ≥ 1.2, more preferably ≥ 1.3, more preferably ≥ 1.4, more preferably ≥ 1.5, more preferably ≥ 1.6, more preferably ≥ 1.8, more preferably ≥ 2, more preferably ≥ 3, more preferably ≥ 5, more preferably ≥ 8.

[0024] In another preferred embodiment, the object is a lung injury object.

[0025] In another preferred embodiment, the subject is a person who has received, is receiving, or will receive lung injury treatment.

[0026] In another preferred embodiment, "reducing the number of neutrophils" means reducing the number of neutrophils C1 in the lungs (e.g., alveoli) compared to the control number of neutrophils C0.

[0027] In another preferred embodiment, the neutrophil count C0 of the control is the neutrophil count Czs of the subject before treatment or administration with annexin; or the neutrophil count Cdz of the control group.

[0028] In another preferred embodiment, the control group comprises the number of neutrophils in a normal person.

[0029] In another preferred embodiment, “reducing the number of neutrophils” means C1 / Czs ≤ 0.9, preferably ≤ 0.8, more preferably ≤ 0.7, more preferably ≤ 0.6, more preferably ≤ 0.5, more preferably ≤ 0.4, more preferably ≤ 0.3, more preferably ≤ 0.2, and more preferably ≤ 0.1.

[0030] In another preferred embodiment, "reducing the number of neutrophils" means C1 / Cdz ≤ 0.9, more preferably ≤ 0.8, more preferably ≤ 0.7, more preferably ≤ 0.6, more preferably ≤ 0.5, more preferably ≤ 0.4, more preferably ≤ 0.3, more preferably ≤ 0.2, and more preferably ≤ 0.1.

[0031] In another preferred embodiment, the composition or formulation includes a pharmaceutical composition or formulation, a food composition or formulation, a health product composition or formulation, or a dietary supplement.

[0032] In another preferred embodiment, the composition or formulation further includes a pharmaceutically, food-, health-promoting, or dietary carrier.

[0033] In another preferred embodiment, the composition or formulation further includes other drugs for the prevention and / or treatment of lung injury;

[0034] Preferably, the other drugs for preventing and / or treating lung injury are selected from the group consisting of glucocorticoids, vitamins, or combinations thereof.

[0035] In another preferred embodiment, the vitamin is selected from the group consisting of vitamin C, vitamin E, or combinations thereof.

[0036] In another preferred embodiment, the dosage form of the composition or preparation is an oral preparation, a topical preparation, or an injectable preparation.

[0037] In another preferred embodiment, the dosage form of the composition or preparation is a solid dosage form, a liquid dosage form, or a semi-solid dosage form.

[0038] In another preferred embodiment, the dosage form of the composition or preparation is a powder, granules, capsules, injection, tincture, oral liquid, tablet, lozenge, powder inhaler, aerosol, or spray.

[0039] In another preferred embodiment, the dosage form of the composition or preparation is a respiratory administration preparation.

[0040] In another preferred embodiment, the injectable is an intravenous injection, an intramuscular injection, a subcutaneous preparation, or a respiratory administration preparation.

[0041] In another preferred embodiment, the respiratory administration preparation is an intratracheal nebulizer.

[0042] In another preferred embodiment, the annexin is present in the composition or formulation at a mass percentage of 5 wt%, preferably 1-20 wt%, based on the total weight of the composition or formulation.

[0043] The second aspect of the present invention provides a method for (i) preventing and / or treating lung injury and / or (ii) reducing the number of neutrophils, the method comprising: administering annexin to the desired target.

[0044] In another preferred embodiment, the non-human mammal includes pigs, cattle, sheep, rats, mice, or rabbits.

[0045] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Attached Figure Description

[0046] Figure 1 Neutrophil count in bronchoalveolar lavage fluid, *p<0.05, G2-G12 vs G1, using One-way ANOVA / Dunnett's.

[0047] Figure 2 Percentage of neutrophils in bronchoalveolar lavage fluid, *p<0.05,**p<0.01,***p<0.001, G2-G12VS G1, using One-way ANOVA / Dunnett's.

[0048] Figure 3 For lung pathology scoring.

[0049] Figure 4 Staining of lung tissue pathological sections. Detailed Implementation

[0050] Through extensive and in-depth research, the inventors have discovered for the first time that annexin can be used to prevent and / or treat lung injury and reduce neutrophil count. This invention was completed based on this discovery.

[0051] the term

[0052] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0053] As used herein, the terms “comprising,” “including,” and “containing” are used interchangeably and include not only open-ended definitions but also semi-closed and closed definitions. In other words, the terms include “consisting of” and “substantially consisting of”.

[0054] Annexin

[0055] Annexins are a widely distributed family of calcium-dependent phospholipid-binding proteins. Based on molecular phylogenetic and comparative genomics analysis, this protein family has been uniformly named annexins (abbreviated as Anx), followed by capital letters to represent different species: A, B, C, D, and E represent vertebrates, invertebrates, fungi and slime molds, plants, and protozoa, respectively. Currently, the Anx A family has 12 members: A1-A11 and A13 (A12 is unspecified).

[0056] Representatively, the annexins mentioned include annexin A5. Annexin A5 (AnxA5) is widely distributed in various tissues and cells of the body. In vitro studies have found that AnxA5 has multiple functions such as antiphospholipase, anticoagulation, and antikinase, but its specific in vivo functions are not very clear. Currently, it is mainly used as a reagent for detecting apoptosis.

[0057] The annexins used in this invention are not particularly limited and can be derived from any organism, preferably from mammals (such as primates), and more preferably from humans. Furthermore, it should be understood that "annexin" includes wild-type or mutant (including truncated) annexins, as long as the mutant annexin retains or maintains the detoxification activity of the wild-type annexin.

[0058] use

[0059] This invention provides a use of the annexin described herein for preparing compositions or formulations for one or more uses selected from the group consisting of: (i) prevention and / or treatment of lung injury; (ii) reduction of neutrophil count.

[0060] The lung injury described in this invention is not particularly limited. Preferably, the lung injury includes, but is not limited to, acute lung injury, respiratory distress syndrome, or a combination thereof.

[0061] Typically, the lung injury mentioned includes acute lung injury.

[0062] Typically, the lung injury mentioned includes acute respiratory distress syndrome.

[0063] The respiratory distress syndrome described in this invention is preferably acute respiratory distress syndrome.

[0064] Lung injury can be caused by a variety of factors, such as direct injury, shock, pancreatitis, inhalation of smoke and toxic gases, pneumonia, and reperfusion injury. This invention shows that "cytokine storm" is an important cause of lung injury. When the number of neutrophils in the lungs increases, they produce a large number of cytokines such as TNF-α, IL-1, and IL-6 (i.e., cytokine storm). These factors attack the body's own tissues, causing acute lung injury and organ failure. Lung injury can be prevented and / or treated by reducing the number of neutrophils in the lungs and improving the cytokine storm.

[0065] In a preferred embodiment of the invention, the lung injury includes lung injury caused by an increase in neutrophils.

[0066] In a preferred embodiment of the invention, the lung injury includes lung injury caused by a cytokine storm.

[0067] In a preferred embodiment of the invention, the prevention and / or treatment of lung injury includes preventing and / or treating lung injury by reducing the number of neutrophils.

[0068] In a preferred embodiment of the invention, the prevention and / or treatment of lung injury includes improving cytokine storm to prevent and / or treat lung injury.

[0069] In another preferred embodiment, the improvement of cytokine storm includes reducing, inhibiting, or eliminating it.

[0070] In a preferred embodiment of the invention, the prevention and / or treatment of lung injury includes preventing and / or treating lung injury by reducing the number of neutrophils and / or inhibiting the cytokine storm caused by an increase in the number of neutrophils.

[0071] In a preferred embodiment of the invention, the neutrophils include neutrophils in the lungs.

[0072] In another preferred embodiment, the neutrophils include neutrophils in the alveoli.

[0073] In a preferred embodiment of the invention, the cytokine storm includes a cytokine storm in the lungs.

[0074] In another preferred embodiment, the cytokine storm includes a cytokine storm in the alveoli.

[0075] In a preferred embodiment of the invention, "reducing the number of neutrophils" means that the number of neutrophils in a subject is reduced.

[0076] In another preferred embodiment, the object is a human or a non-human mammal (such as a rodent).

[0077] In a preferred embodiment of the invention, the subject is a person with an elevated neutrophil count.

[0078] In another preferred embodiment, the "elevated neutrophil count" refers to the subject's neutrophil count A1 being higher than A0 compared to the normal neutrophil count A0; preferably, A1 / A0 ≥ 1.1, more preferably ≥ 1.2, more preferably ≥ 1.3, more preferably ≥ 1.4, more preferably ≥ 1.5, more preferably ≥ 1.6, more preferably ≥ 1.8, more preferably ≥ 2, more preferably ≥ 3, more preferably ≥ 5, more preferably ≥ 8.

[0079] In another preferred embodiment, the object is a lung injury object.

[0080] In another preferred embodiment, the subject is a person who has received, is receiving, or will receive lung injury treatment.

[0081] In a preferred embodiment of the invention, "reducing the number of neutrophils" means that the number of neutrophils C1 in the lungs (e.g., alveoli) is reduced compared to the control number of neutrophils C0.

[0082] In another preferred embodiment, the neutrophil count C0 of the control is the neutrophil count Czs of the subject before treatment or administration with annexin; or the neutrophil count Cdz of the control group.

[0083] In another preferred embodiment, the control group comprises the number of neutrophils in a normal person.

[0084] In another preferred embodiment, “reducing the number of neutrophils” means C1 / Czs ≤ 0.9, preferably ≤ 0.8, more preferably ≤ 0.7, more preferably ≤ 0.6, more preferably ≤ 0.5, more preferably ≤ 0.4, more preferably ≤ 0.3, more preferably ≤ 0.2, and more preferably ≤ 0.1.

[0085] In another preferred embodiment, "reducing the number of neutrophils" means C1 / Cdz ≤ 0.9, more preferably ≤ 0.8, more preferably ≤ 0.7, more preferably ≤ 0.6, more preferably ≤ 0.5, more preferably ≤ 0.4, more preferably ≤ 0.3, more preferably ≤ 0.2, and more preferably ≤ 0.1.

[0086] In another preferred embodiment, the composition or formulation includes a pharmaceutical composition or formulation, a food composition or formulation, a health product composition or formulation, or a dietary supplement.

[0087] In one preferred embodiment of the invention, and in another preferred embodiment, the composition or formulation further includes other medicaments for the prevention and / or treatment of lung injury.

[0088] In another preferred embodiment, the other drugs for preventing and / or treating lung injury are selected from the group consisting of glucocorticoids, vitamins, or combinations thereof.

[0089] In another preferred embodiment, the vitamin is selected from the group consisting of vitamin C, vitamin E, or combinations thereof.

[0090] Composition and application

[0091] The compositions described in this invention include (but are not limited to): pharmaceutical compositions, food compositions, health care compositions, dietary supplements, etc.

[0092] Typically, the cell-free fat extract of the present invention can be prepared into pharmaceutical compositions, such as tablets, capsules, powders, microparticles, solutions, lozenges, gels, creams, liniments, suspensions, tinctures, poultices, liniments, lotions, and aerosols. The pharmaceutical compositions can be prepared using commonly known preparation techniques, and suitable pharmaceutical additives can be added to the pharmaceutical composition.

[0093] The compositions of the present invention may further include pharmaceutically, food-, health product-, or dietaryally acceptable carriers. "Pharmaceutically, food-, health product-, or dietaryally acceptable carriers" refers to one or more compatible solid or liquid fillers or gelling substances suitable for human use and possessing sufficient purity and sufficiently low toxicity. "Compatibility" here refers to the ability of the components in the composition to interact with and be mixed with the compounds of the present invention without significantly reducing the efficacy of the compounds. Examples of acceptable carriers for pharmaceutically, food-, health product-, or dietary use include cellulose and its derivatives (such as sodium carboxymethyl cellulose, sodium ethyl cellulose, cellulose acetate, etc.), gelatin, talc, solid lubricants (such as stearic acid, magnesium stearate), calcium sulfate, vegetable oils (such as soybean oil, sesame oil, peanut oil, olive oil, etc.), polyols (such as propylene glycol, glycerin, mannitol, sorbitol, etc.), emulsifiers (such as... Wetting agents (such as sodium dodecyl sulfate), colorants, flavoring agents, stabilizers, antioxidants, preservatives, pyrogen-free water, etc.

[0094] There are no particular limitations on the method of administration of the composition of the present invention. Representative methods of administration include (but are not limited to): oral administration, parenteral administration (intravenous administration, intramuscular administration), and local administration. Preferred methods of administration are oral administration and injection administration.

[0095] The dosage forms of the compositions or preparations described in this invention are oral preparations, topical preparations, or injectable preparations. Representatively, solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In these solid dosage forms, the active compound is mixed with at least one conventional inert excipient (or carrier), such as sodium citrate or dicalcium phosphate, or with the following components: (a) fillers or compatibilizers, such as starch, lactose, sucrose, glucose, mannitol, and silica; (b) binders, such as hydroxymethyl cellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose, and gum arabic; (c) humectants, such as glycerin; (d) disintegrants, such as agar, calcium carbonate, potato starch or cassava starch, alginate, certain complex silicates, and sodium carbonate; (e) slowing agents, such as paraffin; (f) absorption accelerators, such as quaternary ammonium compounds; (g) wetting agents, such as cetyl alcohol and glyceryl monostearate; (h) adsorbents, such as kaolin; and (i) lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium dodecyl sulfate, or mixtures thereof. Buffers may also be included in capsules, tablets, and pills.

[0096] Solid dosage forms such as tablets, sugar pills, capsules, pellets, and granules can be prepared using coatings and shell materials, such as casings and other materials known in the art. They may contain opaque agents.

[0097] Liquid dosage forms intended for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, or tinctures. In addition to the active compound, liquid dosage forms may contain inert diluents conventionally used in the art, such as water or other solvents, solubilizers and emulsifiers, e.g., ethanol, isopropanol, ethyl carbonate, ethyl acetate, propylene glycol, 1,3-butanediol, dimethylformamide, and oils, particularly cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil, and sesame oil, or mixtures thereof.

[0098] In addition to these inert diluents, the composition may also contain auxiliaries such as wetting agents, emulsifiers and suspending agents, sweeteners, flavoring agents and fragrances.

[0099] In addition to the active ingredient, the suspension may contain suspending agents, such as ethoxylated isooctadecyl alcohol, polyoxyethylene sorbitol and dehydrated sorbitol esters, microcrystalline cellulose, aluminum methoxide and agar, or mixtures of these substances.

[0100] Compositions for parenteral injection may comprise physiologically acceptable sterile aqueous or anhydrous solutions, dispersions, suspensions, or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Suitable aqueous and non-aqueous carriers, diluents, solvents, or excipients include water, ethanol, polyols, and suitable mixtures thereof.

[0101] Dosage forms of the compounds of the present invention for topical application or administration include ointments, powders, patches, sprays, and inhalers. The active ingredient is mixed under sterile conditions with a physiologically acceptable carrier and any preservatives, buffers, or propellants as needed.

[0102] The cell-free fat extract of this invention can be applied or administered alone, or in combination with other drugs for the prevention and / or treatment of non-proliferative scars.

[0103] When administering the composition, a safe and effective amount of the cell-free lipid extract of the present invention is applied to humans or non-human animals (such as rats, mice, dogs, cats, cattle, sheep, chickens, ducks, etc.) requiring treatment, wherein the dosage administered is a pharmaceutically, food-, or health-product-acceptable effective dosage. As used herein, the term "safe and effective amount" refers to an amount that produces function or activity in humans and / or animals and is acceptable to humans and / or animals. Those skilled in the art will understand that the "safe and effective amount" can vary depending on the form of the pharmaceutical composition, the route of administration, the excipients used, the severity of the disease, and whether it is used in combination with other drugs. For example, for a person weighing 60 kg, the daily dosage is typically 0.1–1000 mg, preferably 1–600 mg, and more preferably 2–300 mg. Of course, the specific dosage should also consider factors such as the route of administration and the patient's health condition, which are within the scope of a skilled physician's expertise.

[0104] The main advantages of this invention include

[0105] The inventors have discovered for the first time that annexin can be used to prevent and / or treat lung injury and reduce the number of neutrophils.

[0106] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Percentages and parts are by weight unless otherwise stated.

[0107] Example

[0108] Annexin A5: Extracted and purified from human adipose tissue, Accession number: P08758.

[0109] Example 1

[0110] 1. Test Content

[0111] 1.1 Model Preparation

[0112] Normal adult male SD rats were randomly divided into groups of 5. Animals were administered lipopolysaccharide (LPS) via intraperitoneal injection combined with nebulized airway administration as a modeling agent, as detailed in the table below:

[0113] Table 1. Model Construction Conditions

[0114]

[0115] Modeling method:

[0116] Groups G1-G2 were administered lipopolysaccharide (LPS) intraperitoneally (0.8 mg / kg body weight) according to animal body weight. Sixteen hours after the intraperitoneal injection, the animals were anesthetized with isoflurane inhalation, and then received LPS via nebulization (5 mg / kg body weight). Group G0 served as the normal control group, receiving no LPS treatment and a normal diet. Rats in groups G1-G2, after LPS treatment, exhibited clinical symptoms of acute respiratory distress syndrome.

[0117] Intraperitoneal injection of lipopolysaccharide (LPS): Based on the weighed animal, the amount of LPS administered to each animal is drawn using a disposable microsyringe and injected intraperitoneally.

[0118] Intratracheal nebulization of lipopolysaccharide (LPS): Animals were anesthetized with isoflurane inhalation and then fixed to a rat restraint at a 45° angle. Using a small animal anesthesia laryngoscope, the base of the animal's tongue was pressed down to expose the glottis. A blunt needle of a micro-liquid nebulizer containing a measured amount of lipopolysaccharide (LPS) solution was gently inserted into the trachea. The piston was then quickly pushed to nebulize the LPS solution into the lungs. The needle was quickly withdrawn, and the animal was removed from the restraint with its head facing upward. The animal was rotated left and right to distribute the LPS as evenly as possible in each lung lobe.

[0119] 1.2 Grouping and Dosing

[0120] The first administration of the modeling reagent (LPS) was given to the animals via nebulization in the airway, and the second administration was given 24 hours later; please see Table 2 below for the specific administration groups and administration regimens.

[0121] Table 2. Dosage groups and dosing regimens

[0122]

[0123] Note: Annexin A5 is administered in annexin A5 PBS buffer, and the dosage is based on the amount of annexin A5.

[0124] 1.3 Sampling and End Time of In Vivo Experiments

[0125] The day after the second administration (48 hours after the modeling reagent was administered via nebulization in the airway).

[0126] 1.4 Detection Indicators

[0127] 1.4.1 General Clinical Observation

[0128] During the animal quarantine period and medication administration, observe twice daily (once in the morning and once in the afternoon), or increase the frequency as needed. Observation content: mental status, behavior, death, respiration, secretions, fecal characteristics, and other abnormalities.

[0129] 1.4.2 Weight

[0130] Before grouping, animals were weighed on the day of modeling and on the day of administration of the test sample; animals were also weighed when they were found to be dead or near death and were euthanized.

[0131] 1.4.3 Collection and Detection of Bronchoalveolar Lavage Fluid (BALF)

[0132] Sample Collection: The day after the second administration, all animals in all groups were euthanized with CO2 and their abdominal cavities were opened. The middle abdominal artery was cut to release blood. The trachea in the neck was exposed with small scissors, a small incision was made, a syringe tube was inserted, and the incision was tied tightly with suture. 5 ml of PBS (containing 1% FBS) was injected into the lungs, and the aspiration was repeated three times to collect the pulmonary lavage fluid. The lavage fluid (BALF) was centrifuged at 1200 rpm for 10 min at 4°C, and the supernatant was stored at -70°C for later use. The cells in the precipitate were resuspended in 1 mL of PBS, and the total number of cells in the BALF was counted using a hemocytometer and trypan blue staining.

[0133] Leukocyte differential diagnosis: The remaining cells were resuspended for smear preparation and stained with Wright-Giemsa staining solution to distinguish neutrophils.

[0134] 1.4.4 Histopathological examination

[0135] After collecting bronchoalveolar lavage fluid from all animals, the right lung was harvested from the thoracic cavity. Formalin was then injected into the lung tissue using an injection needle. The tissue was fixed in 10% neutral buffered formalin solution, embedded in paraffin, sectioned, prepared, and stained with hematoxylin and eosin (HE) for pathological morphological observation. Pathological examination of the lung tissue was performed by a professional pathologist. The histopathological evaluation indicators are shown in Table 3 below.

[0136] Table 3. Evaluation Indicators for Lung Pathology

[0137]

[0138] 2. Statistical Analysis

[0139] Experimental data are expressed as mean ± standard error (Mean ± SEM). Data were analyzed using Graphpad Prism or SPSS with appropriate statistical methods. P < 0.05 was considered statistically significant.

[0140] 3. Results

[0141] 3.1 Weight

[0142] After LPS modeling, the body weight of animals in all groups decreased significantly compared with that before modeling, with no significant difference between groups. The body weight of animals in each group is shown in Table 4.

[0143] Table 4 Weight Changes

[0144]

[0145] 3.2 Cell count in bronchoalveolar lavage fluid

[0146] Bronchoalveolar lavage fluid (BALF) cytometer data showed that, compared with the normal control group G0 rats, the number of neutrophils in the model control group G1 was significantly increased. Compared with the model control group G1, the drug-treated group G2 significantly inhibited the neutrophil (Neu cell) count in BLF. BLF cell typing percentage data also showed the inhibitory effect of G2 (drug-treated group) on the percentage of neutrophils. The Neu cell count results in BLF are shown in Table 5. Figure 1 As shown in Table 6, the percentage of Neu cells in the bronchoalveolar lavage fluid is as follows. Figure 2 As shown:

[0147] Table 5 Neu cell count in bronchoalveolar lavage fluid (*10) 6 )

[0148]

[0149] Table 6. Percentage of Neu cells in bronchoalveolar lavage fluid (%)

[0150]

[0151] 3.3 Pathological Analysis

[0152] The results showed that the drug-treated group G2 exhibited a more significant improvement in LPS-induced acute respiratory distress syndrome compared to the model control group G1. The lung pathology scores of the model control group G1 and the drug-treated group G2 are shown in Table 6. Figure 3 As shown, the typical lung tissue pathological sections of the normal control group G0, the model control group G1, and the drug-treated group G2 are stained as follows. Figure 4 As shown.

[0153] Table 6 Lung Pathology Scores

[0154]

[0155] from Figure 4 It can be seen that, compared with the model control group G1, the lung injury in the treatment group G2 was significantly improved, thus indicating that annexin A5 has excellent therapeutic effect on respiratory distress syndrome.

[0156] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A use of annexin A5, characterized in that, This is used to prepare a composition or formulation for preventing and / or treating lung injury caused by elevated neutrophils by reducing the number of neutrophils, wherein the neutrophils are neutrophils in the lungs; and the lung injury is acute respiratory distress syndrome. The term "reducing neutrophil count" refers to decreasing the number of neutrophils in a subject, where the subject is a person with an elevated neutrophil count. The term "elevated neutrophil count" refers to a neutrophil count A1 / A0 = 1.2 compared to the normal neutrophil count A0 in a person.

2. The use as described in claim 1, characterized in that, The composition or formulation also includes other drugs for the prevention and / or treatment of lung injury.

3. The use as described in claim 2, characterized in that, Other drugs for the prevention and / or treatment of lung injury are selected from the group consisting of glucocorticoids, vitamins, or combinations thereof.

4. The use as described in claim 1, characterized in that, The dosage form of the composition or preparation is a respiratory administration preparation.

5. The use as described in claim 1, characterized in that, The dosage form of the composition or preparation includes an injection, which is an intravenous injection, intramuscular injection, or subcutaneous injection.

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