JPH11130668A - Medicine for respiratory disease - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject medicine useful for treating/preventing pulmonary diseases typified by pneumonia by using ursolic acid and/or its derivative. SOLUTION: This medicine comprises ursolic acid and/or its derivative, pref. benzyl ursolate. An ursolic ester is prepared, pref. by treating ursolic acid with e.g. thionyl chloride to form the corresponding acid chloride which is then condensed with a relevant alcohol in the presence of an alkali. It is preferable that this medicine is orally administered at a daily dose of 1-10,000 mg/adult in one to several portions.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a drug for respiratory diseases and a pharmaceutical composition for respiratory diseases suitable for treatment and prevention of lung diseases.

[0002]

2. Description of the Related Art A respiratory disease such as pneumonia is a disease in which inflammation occurs in the lungs due to allergies or microbial infections, and at that time, enzymes released such as elastase destroy lung tissue and cause difficulty in breathing. . The lungs are the organs responsible for breathing, which are indispensable for the maintenance of life, and if such symptoms become severe, they can be life-threatening. Further, when symptoms such as pneumonia occur, it takes a long time until these tissues recover because the lung tissues are destroyed. For this reason, it is not unusual for a state in which the functions of the whole body are incomplete for a long period of time. Such a phenomenon that the lung function is inhibited for a long time is observed not only for pneumonia but also for all respiratory diseases such as pulmonary tuberculosis, and a means for promptly recovering the lung function has been desired.

[0003] On the other hand, ursolic acid and its derivatives such as esters are compounds known in the literature and are known to have a protective effect against photoaging, but they have an effect on respiratory diseases, in particular, are impaired. It has not been known that it has an effect of promptly restoring lung function or preventing lung tissue from being destroyed.

[0004]

DISCLOSURE OF THE INVENTION The present invention has been made in view of such circumstances, and it is an object of the present invention to provide a drug and a pharmaceutical composition useful for treating and preventing pulmonary diseases represented by pneumonia. Make it an issue.

[0005]

In view of such a situation, the present inventors
As a result of intensive studies in search of compounds useful for the treatment and prevention of pulmonary diseases represented by pneumonia, they have found such effects on ursolic acid and its derivatives such as esters, and have completed the invention. Hereinafter, the present invention will be described in detail focusing on embodiments.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION (1) Drug for Respiratory Disease of the Present Invention The drug for respiratory disease of the present invention comprises ursolic acid and / or a derivative thereof. Examples of ursolic acid derivatives include, for example, alkyl esters such as stearyl esters, alkenyl esters such as oleyl esters, aromatic esters such as aryl esters, alkyl amides such as stearyl amides, alkenyl amides such as oleyl amides, and aromatic amides such as aryl amides. Preferred examples include group amides and salts with bases. The carbon number of the side chain of these derivatives is preferably from 6 to 22. Further, as the salt, any physiologically acceptable salt can be used without any limitation, for example, alkali metal salts such as sodium and potassium, calcium,
Preferable examples include alkaline earth metal salts such as magnesium, ammonium salts, and organic amine salts. The most preferred of these derivatives is the benzyl ester.
These are all known compounds, which are commercially available, and their production methods are clear, so that they are easily available. For example, ursolic acid is commercially available, and its ester is obtained by treating ursolic acid with thionyl chloride or the like to form an acid chloride and condensing it with an alcohol in the presence of an alkali. May be condensed. The drug for respiratory diseases of the present invention acts on the lungs to quickly reconstruct destroyed tissue. For this reason, it is possible to quickly rebuild the lung tissue that has been destroyed due to severe symptoms and restore lung function, or to administer it during the mild period to suppress the destruction of lung tissue. it can. Therefore, it can be used for recovery of pulmonary function after pneumonia, and by using in this way, it is possible to recover from sequelae of pneumonia more quickly. Preferred dose of the respiratory drug of the present invention,
It depends on the disease type, symptoms, purpose of use, patient characteristics, etc.
It is preferable to administer 1 to 10,000 mg per adult per day in one to several divided doses. The administration route of the drug for respiratory diseases of the present invention can be used without particular limitation as long as it is a route usually used in medicine, for example, oral administration, intravenous administration, intraarterial administration, transtracheal administration (Inhalation), rectal administration and the like can be preferably exemplified. Intraoral administration, intravenous administration and inhalation are particularly preferred.

(2) Pharmaceutical composition for respiratory disease of the present invention The pharmaceutical composition for respiratory disease of the present invention contains one or more selected from the above ursolic acids and derivatives thereof. It is characterized by. The pharmaceutical composition of the present invention can contain, in addition to these substances, optional components usually used in pharmaceutical compositions. Such optional components include, for example, excipients, binders, coating agents, lubricants, sugar coatings, disintegrants, bulking agents, flavoring agents, emulsifying / solubilizing / dispersing agents, stabilizers, p
H regulators, isotonic agents and the like can be preferably exemplified. Furthermore, the pharmaceutical composition of the present invention can also contain a drug commonly used for respiratory diseases. Examples of such agents include infectious agents such as antibiotics, bronchodilators such as theophylline, and antiallergic agents. The dosage form of the pharmaceutical composition of the present invention can be used without any particular limitation as long as it is a dosage form usually used in pharmaceutical compositions. For example, injection preparations, oral administration preparations, inhalation preparations, suppositories Agents and the like can be exemplified as preferable preparations. The most preferred of these are inhalation preparations. These pharmaceutical compositions of the present invention can be used to treat diseases such as pneumonia, bronchitis, pulmonary tuberculosis, tracheal or lung damage due to asthma, emphysema, tracheal or lung damage due to epidemic cold, prevent symptom deterioration, and treat prognosis. Etc. can be used.

[0008]

The present invention will be described in more detail with reference to the following examples, but it goes without saying that the present invention is not limited to these examples.

Example 1 Therapeutic Action of the Respiratory Disease Drug of the Present Invention on Pneumonia A group of three Chinese hamsters (male, 90 to 120 g) were administered elastase at 5 mg / Kg via the respiratory tract to prepare a pneumonia model. From 24 hours after elastase administration,
Once a day, 5 times a day, 5 times a day
mg / Kg / day. The control group received no elastase or drug. In the untreated group, elastase was administered and no drug was administered. Four days after the last drug administration, the animals were sacrificed, the lungs were taken out, cut out as frozen sections, dehydrated, and stained with hematoxylen-eosin, and the degree of tissue damage was observed under a microscope and scored. As for the score, the average degree of damage in the untreated group was 5, and the average degree of damage in the control group was 0. The results are shown in Table 1 as average scores. From these results, it can be seen that the drug for respiratory diseases of the present invention has an action of rapidly recovering respiratory damage caused by respiratory diseases such as pneumonia.

[0010]

[Table 1]

<Example 2> Preventive action of the drug for respiratory disease of the present invention on pneumonia Three groups of Chinese hamsters (male, 90 to 120 g) were administered 1 mg / Kg of the drug for respiratory disease of the present invention via the respiratory tract. 4 hours after the administration, elastase was administered into the respiratory tract by 5 mg / Kg to prepare a pneumonia model. The control group received no elastase or drug. In the untreated group, elastase was administered and no drug was administered. Four days after the administration of elastase, the animals were sacrificed, the lungs were taken out, cut out as frozen sections, dehydrated and stained with hematoxylen-eosin, and the degree of damage to the tissues was observed under a microscope and scored. As for the score, the average degree of damage in the untreated group was 5, and the average degree of damage in the control group was 0. The results are shown in Table 2 as average scores. From these results, it can be seen that the drug for respiratory diseases of the present invention has an action of preventing respiratory damage from being caused by respiratory diseases such as pneumonia.

[0012]

[Table 2]

Example 3 Formulation Example The following ingredients were mixed, packed in an aerosol can, and filled with Freon gas to prepare an inhalation agent. Ursolic acid 10 parts by weight Propylene glycol 5 parts by weight Polyoxyethylene hydrogenated castor oil 0.1 part by weight

Example 4 Formulation Example The following ingredients were mixed, packed in an aerosol can, and filled with Freon gas to prepare an inhalation agent. Benzyl ursoleate 10 parts by weight Propylene glycol 5 parts by weight Polyoxyethylene hydrogenated castor oil 0.1 part by weight

Example 5 Formulation Example The following formulation components were mixed, packed in an aerosol can, and filled with Freon gas to prepare an inhalation agent. Stearyl ursoleate 10 parts by weight Propylene glycol 5 parts by weight Polyoxyethylene hydrogenated castor oil 0.1 part by weight

Example 6 Formulation Example The following formulation components were mixed, packed in an aerosol can, and filled with Freon gas to prepare an inhalation agent. Ursolic acid stearylamide 10 parts by weight Propylene glycol 5 parts by weight Polyoxyethylene hydrogenated castor oil 0.1 part by weight

Example 7 Formulation Example The following formulation components were mixed, packed in an aerosol can, and filled with Freon gas to prepare an inhalation agent. Benzyl ursoleate 10 parts by weight Propylene glycol 5 parts by weight Polyoxyethylene hydrogenated castor oil 0.1 part by weight Beclomethasone propionate 10 parts by weight

Example 8 Formulation Example The following formulation components were mixed, packed in an aerosol can, and filled with Freon gas to prepare an inhalation agent. Benzyl ursoleate 10 parts by weight Propylene glycol 5 parts by weight Polyoxyethylene hydrogenated castor oil 0.1 part by weight Theophylline 10 parts by weight

Example 9 Formulation Example The following formulation components were mixed, packed in an aerosol can, and filled with Freon gas to prepare an inhalation agent. Benzyl ursolic acid 10 parts by weight Propylene glycol 5 parts by weight Polyoxyethylene hydrogenated castor oil 0.1 part by weight Fosfomycin 10 parts by weight

Example 10 Formulation Example The following formulation components were granulated with a 50% ethanol aqueous solution of 50 parts by weight using a Glad granulator, and then tableted with a tableting machine to obtain an oral administration preparation. Benzyl ursoleate 10 parts by weight Lactose 40 parts by weight Microcrystalline cellulose 35 parts by weight Hydroxypropyl methylcellulose 14 parts by weight Zinc stearate 1 part by weight

[0021]

According to the present invention, it is possible to provide a drug or a pharmaceutical composition useful for treating or preventing a pulmonary disease represented by pneumonia.

Claims (4)

[Claims] 1. A respiratory disease drug comprising ursolic acid and / or a derivative thereof. 2. The respiratory disease drug according to claim 1, wherein the ursolic acid derivative is ursolic acid benzyl ester. 3. The remedy for respiratory disease according to claim 1, wherein the respiratory disease is pneumonia. 4. A pharmaceutical composition for treating or preventing lung disease, comprising the drug for respiratory disease according to any one of claims 1 to 3.