CN112716923B

CN112716923B - Application of dioctadecyl alcohol in preparing medicine for treating pulmonary fibrosis

Info

Publication number: CN112716923B
Application number: CN202110041490.XA
Authority: CN
Inventors: 李金岭
Original assignee: Hebei Kangtai Pharmaceutical Co ltd
Current assignee: Hebei Kangtai Pharmaceutical Co ltd
Priority date: 2021-01-13
Filing date: 2021-01-13
Publication date: 2023-03-17
Anticipated expiration: 2041-01-13
Also published as: CN112716923A

Abstract

The invention provides the application of dioctadecyl alcohol in preparing the medicine for treating pulmonary fibrosis, and experiments prove that the dioctadecyl alcohol can improve the collagen deposition of the lung of a mouse with pulmonary fibrosis, has certain treatment effect on pulmonary fibrosis, and is expected to be developed into the medicine for treating pulmonary fibrosis.

Description

Application of dioctadecyl alcohol in preparation of medicine for treating pulmonary fibrosis

Technical Field

The invention belongs to the technical field of pharmacy, and particularly relates to application of octadecanol in preparation of a medicine for treating pulmonary fibrosis.

Background

Octacosanol (also known as n-octacosanol) is a naturally occurring higher aliphatic monohydric alcohol and is a worldwide recognized anti-fatigue functional substance. Since 1937 foreign scholars extracted wheat germ oil and found that it has therapeutic effect on reproductive disorders of human body, they are gradually known. Since 1949, university of illinois, t.k. Cureton, doctrine, et al, conducted over two decades of research demonstrating a series of unique physiological functions, studies on octacosanol have since been extensively conducted and have achieved a series of exciting results.

Pulmonary Fibrosis (PF) is a common outcome of interstitial diseases of the lung with various etiologies, and is a disease characterized by the repeated destruction and repair of lung tissues due to the continuous damage of alveoli, the proliferation of Fibroblasts (FB) and the deposition of a large amount of extracellular matrix (ECM), and finally the deposition of a large amount of collagen in the lung tissues.

Currently, no specific drugs exist for the treatment of pulmonary fibrosis, and the commonly used drugs include glucocorticosteroids, nitroimidazole thiopyrimidines, cyclosporine, mycophenolate mofetil, colchicine and penicillamine which can affect collagen formation, and the like. The glucocorticoid medicaments have been used for treating idiopathic pulmonary fibrosis for more than 50 years, and the result of various clinical studies summarizes and discovers that the glucocorticoid medicaments have the highest effect rate of not more than 16 percent on idiopathic pulmonary fibrosis patients. The effectiveness of azathioprine for the treatment of idiopathic pulmonary fibrosis has been in excess of 20 years and remains controversial. The clinical effectiveness of other drugs is also controversial to varying degrees. The pulmonary fibrosis diseases are seriously maintained, the fatality rate is high, and the clinical treatment measures are deficient, so that the development of a novel medicament for treating the pulmonary fibrosis is urgent on the basis of deeply understanding the pathogenesis of the pulmonary fibrosis.

Disclosure of Invention

In view of this, the present invention provides an application of dioctadecyl alcohol in the preparation of drugs for treating pulmonary fibrosis, aiming at overcoming the defects in the prior art.

In order to achieve the purpose, the technical scheme of the invention is realized as follows:

the use of dioctadecyl alcohol or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating pulmonary fibrosis, wherein the structural formula of the dioctadecyl alcohol is shown as formula I:

a pharmaceutical composition contains the aforementioned dioctadecyl alcohol or its pharmaceutically acceptable salt as active ingredient.

Preferably, the pharmaceutical composition is an inhaled pharmaceutical composition.

Preferably, the dosage form of the pharmaceutical composition is an aerosol inhalation, an aerosol or a powder spray.

Preferably, the dosage form of the pharmaceutical composition is an aerosol, and the pharmaceutical composition is prepared from the following raw materials in parts by weight: 10-50 parts of active ingredients, 5000-10000 parts of propellant and 500-1000 parts of solvent, wherein the propellant is selected from 1, 2-tetrafluoroethane and/or 1,1.2, 3-heptafluoropropane, and the solvent is selected from one or more of glycerol, propylene glycol, polyethylene glycol, ethanol and oleic acid.

Preferably, the propellant is 1, 2-tetrafluoroethane.

Preferably, the solvent is ethanol.

The dioctadecyl alcohol can improve the collagen deposition of the lung of a pulmonary fibrosis mouse, has certain curative effect on pulmonary fibrosis, and is expected to be developed into a medicament for treating pulmonary fibrosis.

Drawings

FIG. 1 is a lung tissue section (1-A) and a statistical result of the percentage of lung fibrosis of each group of mice in a paraquat-induced mouse pulmonary fibrosis model (1-B).

Detailed Description

Unless defined otherwise, technical terms used in the following examples have the same meanings as commonly understood by one of ordinary skill in the art to which the present invention belongs. The test reagents used in the following examples, unless otherwise specified, were all conventional biochemical reagents; the experimental methods are conventional methods unless otherwise specified.

The invention will be described in detail with reference to the following examples.

Pharmacological examples: treatment of paraquat-induced pulmonary fibrosis model in mice

1. Experimental methods

70 mice were randomly divided into 2 groups, 10 blank groups, 60 modeled groups, and males and females. The model building mice are fasted for 16h before modeling, the dosage of paraquat solution of 100mg/Kg is administered by gavage, the blank group is gavage by physiological saline with the same volume, and the day of modeling is recorded as day 1.

On day 3 (mice model 7 days with pulmonary fibrosis symptoms according to the search results of the pre-experiment on the modeling time.) the 60 mice of the modeling group were randomly divided into 6 groups, which were: 10 model groups, 10 positive drug dexamethasone groups, 200mg/Kg twenty-eight alcohol groups, 300mg/Kg twenty-eight alcohol groups, 500mg/Kg twenty-eight alcohol groups (10 per group), and male and female halves. On day 8, mice are dosed with treatment (weighed before dosing), and dioctadecyl alcohol is dosed by intragastric administration; the positive dexamethasone is used for the treatment by intragastric administration at the dose of 0.45mg/Kg, and the mice in the blank group and the model group are used for the intragastric administration of normal saline with the corresponding volume according to the body weight. The general state of the mice was observed once daily in the morning and afternoon, and the mice were weighed and administered once daily for 28 days.

2. Results of the experiment

After the experiment is finished, the weight, the lung coefficient, the hydroxyproline content and the collagen content of each group of experimental mice are detected, and the experimental result is shown in the following table (means +/-s, n = 10)

Experiment grouping	Body weight (g)	Pulmonary factor (g/kg)	Hydroxyproline percentage (%)	Percentage of collagen (%)
					Blank group	24.2±1.38	5.99±0.85	0.35±0.10	2.61±0.34
Model set	19.9±1.48	7.46±1.27	0.46±0.02	3.43±0.31
					Dexamethasone group	22.6±1.16	6.43±1.16	0.42±0.06	3.13±0.27
Dioctadecyl alcohol 200mg/Kg	20.1±1.49	6.09±0.97	0.39±0.02	3.06±0.52
					300mg/Kg of dioctadecyl alcohol	22.4±1.29	6.01±1.47	0.38±0.01	2.92±0.41
500mg/Kg of dioctadecyl alcohol	21.6±1.07	6.11±1.02	0.41±0.03	3.11±0.43

2.1 weight monitoring results: after the administration, the body weight of the mice in the model group is obviously reduced compared with that in the blank group; the weight growth conditions of the dioctadecyl alcohol administration groups are better than those of the model group, which shows that the dioctadecyl alcohol can improve the weight conditions of mice, wherein the effects of 300mg/Kg and 500mg/Kg are more obvious.

2.2 pulmonary factor effects: compared with the blank group, the lung coefficient of the model group mouse is obviously improved to 124 percent of that of the blank group mouse, the lung coefficients of the dioctadecyl alcohol 300mg/Kg and the dioctadecyl alcohol 500mg/Kg are respectively 101 percent and 102 percent of that of the blank group mouse, and the lung coefficients of the model group mouse are obviously reduced compared with that of the model group mouse. The results show that the dioctadecyl alcohol can reduce the lung coefficient of mice with pulmonary fibrosis induced by paraquat under medium and high doses, can obviously improve the pulmonary fibrosis state, and can reduce the lung coefficient to a certain extent under low doses, and improve the pulmonary fibrosis state.

2.3 hydroxyproline and collagen content effects: compared with the blank group, the lung tissue hydroxyproline and collagen percentage of the model group mice is obviously increased, and the contents of hydroxyproline and collagen are 131% of those of the blank group mice. The lung tissue hydroxyproline and the collagen percentage of the dioctadecyl alcohol 300mg/Kg group of mice are 111% of that of the blank group, the lung tissue hydroxyproline and the collagen percentage of the compound 500mg/Kg group of mice are 108% of that of the blank group, and compared with the model group, the lung tissue hydroxyproline and the collagen percentage of each dosage group of the dioctadecyl alcohol are both obviously reduced. Experimental results show that the dioctadecyl alcohol can reduce the hydroxyproline and collagen percentage content of mice with pulmonary fibrosis induced by paraquat.

In conclusion: the dioctadecyl alcohol can improve the collagen deposition of the lung of the mouse with pulmonary fibrosis, has certain curative effect on pulmonary fibrosis, and is expected to be developed into a medicament for treating pulmonary fibrosis.

Formulation examples 1 to 3, formulations are given in the following table (parts by weight)

Numbering	Active ingredient	Solvent(s)	Propellant
				1	Dioctadecyl alcohol 10	Ethanol 500	HFA134a10000
2	Dioctadecyl alcohol 50	Ethanol 1000	HFA134a5000
				3	Dioctadecyl alcohol 100	Ethanol 1000	HFA134a5000

The preparation process comprises the following steps: adding ethanol into the active ingredients according to the prescription amount, stirring, filling in divided doses, sealing a dose valve system, and respectively injecting HFA134a under pressure to obtain the final product.

Claims

1. The use of dioctadecyl alcohol or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating pulmonary fibrosis, wherein the structural formula of the dioctadecyl alcohol is shown as formula I:

the pulmonary fibrosis is paraquat-induced pulmonary fibrosis.

2. Use according to claim 1, characterized in that: the active ingredient of the medicament is the dioctadecyl alcohol or the pharmaceutically acceptable salt thereof of claim 1.

3. Use according to claim 2, characterized in that: the medicament is an inhalation medicament.

4. Use according to claim 2, characterized in that: the medicament is in the form of aerosol, aerosol or powder spray.

5. Use according to claim 2, characterized in that: the medicament is in the form of aerosol and is prepared from the following raw materials in parts by weight: 10 to 50 parts of active ingredients, 5000 to 10000 parts of propellant and 500 to 1000 parts of solvent, wherein the propellant is selected from 1, 2-tetrafluoroethane and/or 1,2, 3-heptafluoropropane, wherein the solvent is one or more selected from glycerol, propylene glycol, polyethylene glycol, ethanol and oleic acid.

6. Use according to claim 5, characterized in that: the propellant is 1, 2-tetrafluoroethane.

7. Use according to claim 5, characterized in that: the solvent is ethanol.