CN111714504A - Application of ITPP (International Teller Patent on Polypropylene) in preparation of medicine for preventing and/or treating ischemia/anoxia injury and lung injury - Google Patents

Abstract

The invention provides an application of ITPP in preparation of a medicine for preventing and/or treating ischemia-hypoxia injury and lung injury, and relates to the technical field of biological medicines. In the embodiment provided by the invention, mice and rats are taken as experimental materials, and the prevention or treatment effect of ITPP on ischemia, hypoxia and lung injury is explored by constructing a mouse ischemia and hypoxia model and a rat lung injury model. The test proves that: the ITPP can obviously prolong the survival time of a large dose of the isopropylene induced ischemia hypoxia mouse in a closed container; ITTP can obviously improve the lung function, lung coefficient, right lung wet-dry weight ratio, arterial oxygen content, serum inflammatory factor and lung tissue pathological change of LPS induced lung injury model rats, and has obvious improvement effect on lung injury tissues.

Description

Application of ITPP (International Teller Patent on Polypropylene) in preparation of medicine for preventing and/or treating ischemia/anoxia injury and lung injury

Technical Field

The invention belongs to the technical field of biological medicines, and particularly relates to application of ITPP (International Teller Polypropylene) in preparation of a medicine for preventing and/or treating ischemic and anoxic injuries and lung injuries.

Background

People live by oxygen, and the oxygen is sucked from the lung, enters the blood through the capillary vessels and is transmitted to organs or cells of various parts of the body by the blood. The higher the oxygen content in the blood, the better the human metabolism. Hypoxemia can cause insufficient oxygen supply to the body and further cause organ damage.

COVID-19 and its associated symptoms of pulmonary atrophy, fibrosis, etc., lead to dyspnea and, ultimately, death. The treatment of COVID-19 is still in the preliminary stage of research, and the medical problems caused by COVID-19 are very urgent.

Inositol Trispyrophosphate (ITPP) is a compound that has recently entered clinical vision and has the following structural formula:

it has been discovered that ITPP may be used to enhance immune responses and treat hyperproliferative disorders, or to treat obesity-related diseases such as arteriosclerosis, etc. There are no reports of the use of ITPP in COVID-19 therapy.

Disclosure of Invention

In view of the problems in the background art, the invention aims to provide an application of ITPP in preparing a medicament for preventing and/or treating ischemia-hypoxia injury and lung injury. The ITPP is used for increasing the cytoplasm oxygen supply of the milk-feeding animal cells so as to repair human tissues and organs. In particular, the lung function damage caused by the COVID-19 is recovered, thereby gaining the cure hope of patients with the COVID-19.

In order to achieve the above purpose, the invention provides the following technical scheme:

the invention provides application of ITPP in preparation of a medicament for preventing and/or treating lung injury.

Preferably, the lung injury comprises lung injury caused by ischemic hypoxia.

Preferably, the lung injury comprises one or more of viral pneumonia, bacterial pneumonia, mycoplasma pneumonia, chlamydia pneumonia, fungal pneumonia, pneumonia caused by chemical substances, and lung injury caused by pneumoconiosis.

The invention provides an application of ITPP in preparation of a medicine for preventing and/or treating ischemia-hypoxia injury.

Preferably, the ischemia-hypoxia injury comprises hypoxia-induced organ injury, the organ comprising one or more of a heart, a lung, a liver, and a kidney.

The invention provides a medicine for preventing and/or treating lung injury or ischemia and hypoxia injury, which comprises ITPP and auxiliary materials.

The invention provides an application of ITPP in preparing a medicament for treating COVID-19.

The invention provides a medicament for treating COVID-19, which comprises ITPP and auxiliary materials.

The invention provides an application of ITPP in preparing a medicament for preventing and/or treating organ ischemia and hypoxia injury and lung injury. In the embodiment provided by the invention, mice and rats are used as experimental materials, and the prevention or treatment effect of ITPP on related diseases is researched by constructing a mouse ischemia-hypoxia model and a rat lung injury model. The test proves that: the ITPP can obviously prolong the survival time of a large dose of the isopropylene induced ischemia hypoxia mouse in a closed container; ITTP can obviously improve the lung function, lung coefficient, right lung wet-dry weight ratio, arterial oxygen content, serum inflammatory factor and lung tissue pathological change of LPS induced lung injury model rats, and has obvious improvement effect on lung injury tissues.

Drawings

FIG. 1-a is a pathological graph of HE staining in a normal group (. times.200) in the lung injury assay of LPS-induced pneumonia in rats treated with ITTP in example 2;

FIG. 1-b is a graph of the model group HE staining pathology (× 200) in the lung injury assay for LPS-induced pneumonia in rats treated with ITTP in example 2;

FIG. 1-c is a low dose HE staining pathogram (x 200) in the lung injury assay for LPS-induced pneumonia in rats treated with ITTP in example 2;

FIG. 1-d is a medium dose HE staining pathogram (x 200) in the lung injury assay for LPS-induced pneumonia in rats treated with ITTP in example 2;

FIG. 1-e is a pathological graph (X200) of HE staining in the high dose group in the lung injury assay of LPS-induced pneumonia in rats treated with ITTP in example 2.

Detailed Description

The invention provides an application of ITPP in preparing a medicament for preventing and/or treating ischemia and hypoxia injury and lung injury. In the invention, after the ITPP enters the body of a mammal, the oxygen supply of cytoplasm of mammal cells can be increased, and the function of preventing and/or treating ischemia and anoxia injury and lung injury is further realized. In the present invention, the ischemia-hypoxia injury preferably includes hypoxia-induced organ injury, and the organ preferably includes one or more of a heart, a lung, a liver, and a kidney, and more preferably includes a heart or a lung. In the present invention, the lung injury preferably includes lung injury caused by ischemic hypoxia. In the present invention, the lung injury preferably includes one or more of viral infection pneumonia, bacterial infection pneumonia, mycoplasma infection pneumonia, chlamydia infection pneumonia, fungal infection pneumonia, pneumonia caused by chemical substances, and lung injury caused by pneumoconiosis.

In a hypoxia-resistant test of a large-dose isoproterenol-induced ischemia-hypoxia model mouse, ITPP can increase oxygen supply to heart and lung, and can remarkably prolong the survival time of the model mouse in a closed container. In a lung injury model test of rat pneumonia induced by LPS, ITTP can obviously improve the lung function, lung coefficient, right lung wet-dry weight ratio, arterial oxygen content, serum inflammatory factors and lung tissue pathological changes of rats, and is better at a high dose (1 g/kg). The lung/body weight coefficient and the right lung wet to dry weight ratio also indicate that ITPP can repair lung edema caused by damaged lung tissue.

The invention provides a medicine for preventing and/or treating ischemia-hypoxia injury or lung injury, which comprises ITPP and auxiliary materials. The invention does not specially limit the types and the dosage of the auxiliary materials, and the auxiliary materials can be added according to the requirements of different formulations. In the present invention, the dosage form of the drug includes an injectable drug or an oral drug, more preferably an oral drug, and still more preferably an oral aqueous solution. In the present invention, the ITPP is preferably synthesized by a synthesis method described in "l.f. johnson, m.e. tate, CANADIAN jornal OF chemistry. vol.47, 1969", and the raw materials required for the synthesis preferably include: anhydrous calcium chloride (AR), w is not less than 96%, Limited corporation of Szelong scientific corporation; pyridine (AR), w is more than or equal to 99.5%, Guangzhou chemical reagent factory; sodium phytate (AR), w is more than or equal to 98%, Shanghai Yunye Biotech limited; na + exchange resin, 20-50mesh, SIGMA-ALORICH; h + exchange resin, 100-; DCC (AR), w is more than or equal to 99 percent, Innochem company; acetonitrile (AR), w is more than or equal to 99.0%, Guangzhou chemical reagent factory; methanol (AR), w is more than or equal to 99.5 percent, chemical reagents of national drug group, Inc.

The invention provides an application of ITPP in preparing a medicament for treating COVID-19. Respiratory difficulties are caused by pulmonary diseases such as COVID-19 and pneumonia caused by other various viruses, pneumonia caused by gram-negative bacilli, atrophy, pulmonary fibrosis and the like, and finally, the lung is damaged, so that the lung is dead. The invention utilizes ITPP to increase oxygen supply of cells, so that the severely damaged lung organ can recover the function, thereby having the treatment effect on patients with COVID-19.

The invention provides a medicament for treating COVID-19, which comprises ITPP and auxiliary materials. The invention does not specially limit the types and the dosage of the auxiliary materials, and the auxiliary materials are added according to the requirements of different formulations. In the present invention, the dosage form of the drug includes an injectable drug or an oral drug, more preferably an oral drug, and still more preferably an oral aqueous solution. In the present invention, the ITPP is preferably synthesized by the synthesis method described in the document "L.F.JOHNSON, M.E.TATE, CANADIAN JOURNAL OFCHEMISTRY. VOL.47, 1969", and the raw materials required for the synthesis preferably include: anhydrous calcium chloride (AR), w is not less than 96%, Szelong scientific corporation; pyridine (AR), w is more than or equal to 99.5%, Guangzhou chemical reagent factory; sodium phytate (AR), w is more than or equal to 98%, Shanghai Yunye Biotech limited; na + exchange resin, 20-50mesh, SIGMA-ALORICH; h + exchange resin, 100-; DCC (AR), w is more than or equal to 99 percent, Innochem company; acetonitrile (AR), w is not less than 99.0%, Guangzhou chemical reagent factory; methanol (AR), w is more than or equal to 99.5 percent, chemical reagents of national drug group, Inc.

The following examples are provided to illustrate the application of the ITPP of the present invention in the preparation of drugs for preventing and/or treating ischemia-hypoxia injury and lung injury, but they should not be construed as limiting the scope of the present invention.

Example 1

(1) Test animals and feeding conditions

(ii) test animals

Grade and species: SPF grade KM mice;

animal management: the animals are raised and managed by personnel approved by the management qualification of the experimental animals;

week age, number, sex at the time of purchase: 18 male SPF-grade KM mice (18-22 g);

breeding unit: guangdong province medical laboratory animal center;

the qualification number of the experimental animal is as follows: 44007200073676, respectively;

and (3) quarantine process: animal quarantine observation, observation of the indicators of animal appearance physical sign, behavior activity, fecal character, weight, diet, etc.;

the animal identification method comprises the following steps: marking with a tail marker;

the cage marking method is to hang the filled label card (indicating the name of the experiment, the species of the subject person, the animal, the sex, the number, the group, the feeding starting date, etc.) on the front of the squirrel cage.

② raising conditions

Raising a room: the experimental animal center of the university of Zhongshan SPF grade barrier environment animal house;

license number for experimental animals: SYXK (yue) 2010-;

temperature: 20-25 ℃;

humidity: the stability is 35 +/-1%;

and (3) ventilation frequency: more than 10 times/hour;

feeding density: 6/cage/group;

illumination time: 12 hours (light on at 7:00 am to light off at 7:00 pm).

Feed

The types are as follows: the production unit of the SPF level mouse sterilization feed: guangdong province medical laboratory animal center, address: the south China sea area Huangqi Poyang No. 119 in Foshan City, production license: SCXK (Yue) 2008-;

the feeding method comprises the following steps: free uptake;

the conventional nutritional ingredient indexes of the feed are as follows: the detection frequency is detected by the Guangdong province laboratory animal monitoring institute (refer to national standard GB14924.3-2010 of the people's republic of China): twice a year;

and (3) storage of the feed: stored in a special feed room and kept ventilated, clean and dry.

Fourthly, drinking water

Drinking water type: cleaning water;

the water supply method comprises the following steps: free uptake.

Fifthly, disposing the animal carcasses

Temporarily storing the animal carcasses in a special refrigerator at the temperature of-20 ℃ in an animal temporary storage room, and intensively delivering the animal carcasses to a Guangdong living environment harmless treatment center for harmless treatment.

(2) Main instrument and reagent

Main instrument

PL303 electronic balance: MettLerToLedo;

② main reagent

Sodium lime: shanghai Michelin Biochemical technology Ltd, product batch number: c10412480;

white vaseline: shanghai Michelin Biochemical technology Ltd, product batch number: c10567291;

isoproterenol hydrochloride: shanghai Michelin Biochemical technology Ltd, product batch number: c10636091;

(3) design of experiments

Grouping test animals

The groups were divided into 3 groups, i.e., a vehicle control group (6 animals), b model group (6 animals), and c.itpp intervention group (6 animals).

② dosage of administration

ITPP intervention group: 2 g/kg;

③ frequency of administration: administered once each at 10:00 am and 2:00 pm;

and (4) administration route: intragastric administration;

dosage volume: 0.2mL/10 g;

medicine dispensing scheme

Dosage and preparation of the molding medicine:

molding medicine isoproterenol hydrochloride (20mg/kg, 100 times higher than normal dose), taking 10 mg of medicine powder and adding sterilized distilled water to prepare 10mL of solution; the administration volume is 0.2mL/10 g;

preparation of ITPP solution (2 g/kg): adding distilled water into 1.0g of ITPP powder to a constant volume of 10mL of solution; the administration volume is 0.2mL/10 g;

(4) test method and observation index

Grouping, administration and modeling

Selecting 18 SPF male KM mice with the age of 6-7 weeks and the weight of 18-22 g. The test pieces were divided into 3 groups, i.e., a vehicle control group, a model group, and a C.ITPP intervention group (2g/kg), 6 groups per group, according to body weight. The preparation method comprises the following steps of respectively administering the medicines once at 10:00 am and 2:00 pm, and 1h after the administration in the afternoon, carrying out intraperitoneal injection of isoproterenol (20mg/kg) to replicate an ischemia-hypoxia model for the model group and the test sample group, immediately placing a mouse into an hypoxia bottle with the capacity of 250mL after the model is made, wherein the hypoxia bottle contains 5g of soda lime, and sealing a bottle stopper coated with vaseline after the mouse is placed to cause airtight hypoxia. Immediately recording the time of sealing the bottle mouth, continuously observing the change of the heart beat, the breathing frequency, the depth, the skin and the color of the mouth and the lip of the mouse until the animal stops the heart beat, recording the death time, and taking the duration from the bottle stopper of the cover to the heart beat stop of the animal as the survival time of the mouse under the anoxic condition.

② survival time of mice

The duration from the closure to the cessation of the heartbeat of the animal was taken as the survival time of the mouse under hypoxic conditions.

(5) Data processing

Experimental data were statistically processed by GraphPad Prism 7.0 biometrics software: data are expressed as Mean ± SD and analyzed using analysis of variance in conjunction with Dunnett's multiple comparisons.

(6) Experimental records and reports are written

Except the data directly collected by computer or automatic instrument, all the data and data produced in experiment are recorded on the prepared form or paper by ink pen or sign pen, and the data is signed by the person who records the data. All data recorded is checked for signatures by another person (non-recorder). And (5) within 4 weeks after the experiment is finished, the thematic responsible person writes an experiment summary report according to the required format and content.

(7) Results of the experiment

General observation and weight

The general state of the animals before grouping is not abnormal. After administration, two of 6 animals in the c.itpp intervention group showed diarrhea, and none of the other animals had any significant abnormalities. No statistical difference in body weight after grouping (P > 0.05); specifically, as shown in table 1:

TABLE 1 ITPP hypoxia tolerance assessment post-experimental group body weights (g, Mean + -SD)

Group of	Number of animals	Body weight (g)
			A. Vehicle control group	6	19.48±0.57
B. Model set	6	19.65±0.51
			ITPP intervention group	6	19.38±0.89

Note: compared with the model group, the model group has no statistical difference;

② survival time of mice

The survival time of the animals in the model group was significantly shortened (P <0.01) compared to the vehicle control group a, indicating success of the model. The c.itpp intervention group extended mouse survival time compared to the b.model group. As shown in table 2 in detail, the following examples,

TABLE 2 ITPP hypoxia tolerance assessment Pre-experimental mouse survival time (min, Mean + -SD)

Group of	Number of animals	Survival time (min)
			A. Vehicle control group	6	48.53±3.44*
B. Model set	6	38.08±3.77
			ITPP intervention group	6	48.46±5.09**

Note: comparison with model group: p <0.05, x: p < 0.01;

(8) conclusion

The tested sample of the tri-pyrophosphate Inositol (ITPP) can obviously prolong the survival time of the isoproterenol-induced ischemia hypoxia and organ injury model mouse and recover to the normal level.

Example 2

(1) Test animals and feeding conditions

(ii) test animals

Basic information: SPF SD rats 220-250 g, 50 male;

breeding unit: the center of the animal for experiments of the college of medicine of Zhongshan university;

the qualification number of the experimental animal is as follows: 44007200074723, respectively;

② raising conditions

Raising a room: the experimental animal center of the university of Zhongshan SPF grade barrier environment animal house;

license number for experimental animals: SYXK (yue) 2010-;

temperature: 20-25 ℃;

humidity: 50% -70%;

and (3) ventilation frequency: more than 10 times/hour;

feeding density: 5/cage/group;

illumination time: 12 hours (light on at 7:00 am to light off at 7:00 pm).

(2) Main instrument and reagent

Main instrument

EMKA-WBP-4A small animal lung function detecting system: germany, EMKA company;

animal pulse oximeter: shanghai Yuyan scientific instruments, Inc.;

DVS612C oven: YAMATO, Japan;

② main reagent

Lipopolysaccharide: lot: 028M4094V, available from Sigma company.

(3) Design of experiments

Grouping: the groups were randomly divided into 5 groups of 12, i.e., a. normal control group, b. model group, c.ittp low dose (0.25g/kg) group, d.ittp medium dose (0.5g/kg) group, e.ittp high dose (1.0g/kg) group.

② administration: the preparation is administered by intragastric administration once a day with a volume of 20 mL/kg.

Mold making dosage: the dose of the lipopolysaccharide model is 2mg/kg, and the administration volume is 0.8mL/kg by adopting intratracheal injection;

fourthly, preparing the medicine: ITTP high dose (1.0g/kg) group: the volume of the drug is 10mL/kg, namely 5.0 g of ITTP is added with distilled water to be constant volume to 50mL of solution. 25mL of ITTP high-dose solution is taken and distilled water is added to be dissolved to 50mL of solution, namely the ITTP medium-dose (0.5g/kg) group. And adding distilled water into 25mL of ITTP medium dosage solution to reach a constant volume of 50mL of solution, thus obtaining the ITTP low dosage (0.25g/kg) group.

(4) Test method

50 SPF male SD rats (220-250 g) are randomly divided into an A. normal control group, a B. model group, a C.ITTP low dose (0.250g/kg) group, a D.ITTP medium dose (0.50g/kg) group and an E.ITTP high dose (1.0g/kg) group, and each group comprises 10 rats.

Each group of animals is anesthetized by injecting a pentobarbital sodium solution into the abdominal cavity, the neck of a rat is disinfected by iodine, a longitudinal incision of about 1 cm is made at the central line position of 1/3 below the middle neck, the lower edge of the thyroid is exposed and turned upwards, the anterior muscle group of the trachea is carefully separated and exposed, the trachea is exposed by a longitudinal sharp separation muscle group, the animal is obliquely placed at the high-foot bottom position of the head of the animal, 1mL of an injector (26G) is inserted into the trachea at about 2 tracheal rings below the annular cartilage ring, 2mg/kg of LPS solution is pushed in, the administration volume is 0.8mL/kg, no air bubbles are observed in the nose, the rat is vertically rotated for 20s immediately after being pushed in, so that the liquid medicine is uniformly distributed in the lung tissue, and the medicine is. Obliquely placing animals with high heads and low feet, suturing the incision layer by layer, obliquely placing for 10min, and returning to the mouse cage. The trachea of the normal control group is pushed with an equal volume of normal saline. Respectively carrying out administration intervention once a day before molding, 1h before molding, 5 h after molding and 22h after molding. Before material taking, the blood oxygen content of artery is detected by an oximeter, and then the respiratory physiological parameter index is detected and analyzed by a small animal lung function detection system. After the animal was sacrificed, the chest was opened by rapid surgical operation to free the intact lung tissue, the lungs were taken out and weighed, and the lung coefficient was calculated: lung coefficient 100% lung weight/body weight; then, the right lung is placed in an oven to be dried to constant weight, and the ratio of the wet dry weight of the right lung to the dry weight of the right lung is calculated.

(5) Test results

① pulmonary function, all appeared after LPS administration to rat tracheaBreathingAggravation, larger breath sound, and even difficult breathing of a few animals. ITTP administration improved respiratory status to varying degrees in each group. Compared with the normal group, the model group Penh (airway stenosis index), Ti (inspiration time), Te (expiration time), EEP (end-expiratory pause), Sr (specific airway resistance,%) are obviously increased, and f (respiratory rate) and EIP (end-inspiratory pause) are obviously reduced, which indicates thatSuccessfully make the mold. After the dry dosing prognosis, all parameters of each intervention group of ITTP are improved to different degrees compared with the model group, wherein the ITTP high dose group is most obvious.

The data of lung function indexes of the rat with lung injury induced by LPS induced by ITTP are detailed in tables 3 and 4.

Table 3. effects of ITTP on LPS-induced lung injury in lung function index 1 in rats (n ═ 10, Mean ± SD)

Note: compared to model group, a: p < 0.05; **: p < 0.01.

Table 4. effects of ITTP on LPS-induced lung injury in pneumonia lung injury rat lung function index 2 (n ═ 10, Mean ± SD)

Note: compared to model group, a: p < 0.05; **: p < 0.01.

As can be seen from tables 3 and 4, in the lung function index of rat, the model groups Penh, Ti, Te, EEP, and, Sr (%) increased significantly; the EIP is obviously reduced, which indicates that the molding is successful (P)<0.05 or<0.01). Each intervention group compared to the model group Has effects in improving lung function to different degrees, wherein the lung function is improved by ITTP high dose groupIt is best known (P)<0.05 or<0.01)。

Weight of lung: compared with the normal group, the lung/weight coefficient and the wet-dry weight ratio of the right lung are obviously increased in the model group. The ITTP was reduced to a different extent in each intervention group compared to the model group, with the improvement being most evident in the high dose group of ITTP.

③ oxygen content of artery: the model group was significantly reduced compared to the normal group. Compared with the model group, the ITTP intervention groups have different effects of increasing the arterial oxygen content, wherein the improvement is most obvious in the ITTP high-dose group.

ITTP treatment LPS induced lung injury in rats the lung/body weight coefficient, the wet-dry weight ratio of the right lung and the blood oxygen content of the rats are detailed in table 5.

TABLE 5 effects of LPS treatment on ITTP treatment on Lung injury in rats the Lung injury the Lung/weight factor, the Wet-to-Dry weight ratio of the Right Lung, and the blood oxygen content in rats (n ═ 10, Mean. + -. SD)

Note: compared to model group, a: p < 0.05; **: p < 0.01.

As can be seen from Table 5, the lung coefficient and the wet-dry weight ratio of the right lung of the model group are significantly increased compared with the normal group, indicating that the modeling is successful (P < 0.01). The effect of reducing lung coefficient, the wet-dry-weight ratio of the right lung, was different in each intervention group compared to the model group, with the improvement being most pronounced in the ITTP high dose group (P <0.05 or < 0.01). The arterial oxygen content was significantly reduced in the model group compared to the normal group, indicating successful modeling (P < 0.01). Compared with the model group, each intervention group has different effects of increasing the arterial oxygen content, wherein the improvement is most obvious in the ITTP high dose group (P <0.05 or <0.01)

ITTP treatment LPS induces pneumonia lung injury of rat serum inflammatory factor index data of rat are detailed in Table 6.

Table 6 biochemical indices of serum from ITTP-treated LPS-induced pneumococcal injury rats (n 10, Mean ± SD)

Note: compared to model group, a: p < 0.05; **: p < 0.01.

As can be seen from Table 6, the serum IL-1. beta., TNF-. alpha., IL-6 levels in the model group were significantly increased as compared with the normal group, indicating successful modeling (P < 0.01). Compared with the model group, each intervention group has the function of reducing the content of IL-1 beta, TNF-alpha and IL-6 in serum in different degrees; in the ITTP dose group, the ITTP high dose group has better effect of reducing the content of IL-1 beta, TNF-alpha and IL-6 in serum.

Sixthly, the pathological scoring condition of the lung injury of the rat induced by LPS treated by ITTP is shown in the table 7.

Table 7 ITTP treatment LPS induced pneumoconiosis pathology score in rats (n ═ 10, Mean ± SD)

Note: compared to model group, a: p < 0.05; **: p < 0.01.

As can be seen from table 7, in the model group, compared with the normal group, the lung tissue pathology has an increased inflammation score, a significant alveolar wall thickening, a significant increase of eosinophilic substances in alveoli, and a significant increase of total score (P <0.05 or <0.01), each intervention group has an effect of alleviating lung pathology damage to a different extent, and in the ITTP dose group, the ITTP high dose group is superior in improvement of lung tissue pathology.

Pathological pattern of HE staining (× 200) of LPS-induced lung injury in rats treated with ITTP is shown in the figure. Wherein FIG. 1-a is the normal group; FIG. 1-b is a model set; FIG. 1-c is the low dose group; FIG. 1-d is the medium dose group; fig. 1-e is the high dose group.

As can be seen in fig. 1-a: normal group bronchial epithelium was intact, lumen was clear, local alveolar walls were light to moderately thickened with a small amount of inflammatory cell infiltration (black arrows), eosinophilic filaments were seen in a small amount of alveoli (red arrows), a small amount of perivascular edema, gap widening, loose connective tissue with a small amount of inflammatory cell exudation (yellow arrows), and a small amount of arterial wall hypertrophy (green arrows).

As can be seen from fig. 1-b: in the model group, a small amount of bronchial epithelial cells are exfoliated (black arrows), neutrophil exudation is observed in part of bronchial lumens (red arrows), a large amount of inflammatory cells on alveolar walls are infiltrated, so that the alveolar walls are thickened to different degrees (yellow arrows), alveoli are not uniform in size, eosinophilic filaments are observed in a small amount of alveoli (green arrows), and the arterial walls are thickened.

As can be seen from fig. 1-c: in the low dose group, neutrophil infiltration (black arrow) was observed in the bronchial lumen, and a large amount of inflammatory cells were infiltrated into the alveolar wall, resulting in a different thickening of alveolar wall (red arrow), uneven alveolar size, infiltration of a large amount of inflammatory cells such as neutrophils, macrophages and the like in the large range of alveoli (yellow arrow), and also infiltration of a small amount of eosinophilic filaments (green arrow), infiltration of inflammatory cells around a large amount of blood vessels (blue arrow), and a small amount of arterial wall hypertrophy.

As can be seen in FIGS. 1-d: in the medium dose group, the bronchial epithelium was intact, neutrophil exudation was observed in some of the lumens (black arrows), and a large amount of inflammatory cells were infiltrated into the alveolar wall, resulting in a different thickening of alveolar wall (red arrows), uneven alveolar size, a small amount of eosinophilic filaments (yellow arrows) in alveolar wall, and a small amount of hypertrophy of arterial wall (green arrows).

As can be seen in fig. 1-e: the bronchial epithelium of the high-dose group is intact, inflammatory cell exudation mainly comprising neutrophils is seen in part of the cavities (black arrows), and a large amount of inflammatory cells infiltrate on the alveolar wall, so that the alveolar wall is thickened to different degrees (red arrows), the alveolar size is not uniform, and a small amount of acidophilic filaments are seen in the alveoli (yellow arrows); edema around part of the vessels, widening of the space, loosening of connective tissue with a small amount of inflammatory cells exuding (green arrows).

(3) Conclusion

The tested drug ITTP obviously improves the lung function, lung coefficient, right lung wet-dry weight ratio, arterial oxygen content, serum inflammatory factors and lung tissue pathological changes of a rat pneumonia lung injury model induced by LPS, and is better at a high dose (1 g/kg).

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims (8)

1. The application of ITPP in preparing a medicament for preventing and/or treating lung injury.
2. 2. The use of claim 1, wherein the lung injury comprises ischemia-hypoxia induced lung injury.
3. 3. The use of claim 1, wherein the lung injury comprises one or more of viral-infected pneumonia, bacterial-infected pneumonia, mycoplasma-infected pneumonia, chlamydia-infected pneumonia, fungal-infected pneumonia, pneumonia caused by chemicals, lung injury caused by pneumoconiosis.
4. The application of ITPP in preparing the medicine for preventing and/or treating ischemia-hypoxia injury.
5. 5. The use of claim 4, wherein the ischemia-hypoxia injury comprises hypoxia-induced organ injury comprising one or more of a heart, a lung, a liver, and a kidney.
6. 6. A medicament for the prevention and/or treatment of lung injury according to claim 1 or ischemic-hypoxic injury according to claim 4, wherein the medicament comprises ITPP and an excipient.
7. Application of ITPP in preparing medicament for treating COVID-19.
8. 8. The medicament for treating COVID-19 is characterized by comprising ITPP and auxiliary materials.

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