DE1900646A1 - Medicines for veterinary use - Google Patents

Description

Aziende Cliimiche Riunite Angelini Francesco, A.C.R.A. P. S.p.A » Via Amelia 70, Rome / Italy

Medicines for veterinary use

The present invention relates to a medicament for veterinary use Use, especially for the therapy of pathological disorders of the respiratory system such as catarrh of the throat, tracheitis, Tracheobronchitis, bronchopneumonia in dogs, cattle, horses, Pigs and poultry.

The medicament according to the invention contains the i-benzyl-J ^ T-dimethylamino-propox ^ -IH-indazole of the formula I as active ingredient:

CO-GH ₂ CH ₂ OH ₂ N

OH,

OH

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The compound in question can be derived from the corresponding 1-benzyl-3-oxyindazole from by treatment with j ^ -Chlorpropyl-dimethylamine can be obtained by the method described below.

All domestic animals (dogs, cattle, horses, pigs, and poultry) often show, especially when they are young, pathological affections of the respiratory system such as pharyngeal catarrh, tracheitis, traheobronchitis, bronchopneumonia. The affections are particularly common in the winter months, making the breeds very polluted and considerable economic Damage caused. Usually they are expressed by cough, slimy and purulent exudate from the nasal cavity, Depression and high fever.

As a result of the disease state, the animals no longer eat and sometimes wither considerably. In the thoracic area, remnants of lung atelectasis, hepatization zones, Pleura adhesionsj these are all damage that have a negative impact on the local and general condition and reduce animal production.

From an ethiological point of view, these affections are usually due to pneumotropic viruses, which cause changes to the detriment of the vessels and the lung parenchyma. On top of this, the original damage quickly forms Infections caused by pathogens secondary invasion affecting the anatomic-pathological Image change and worsen and to

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a specific point in time for clinical symptomatology are decisive.

Using the antibiotics alone can help eliminate the bacterial appearance. But you can do the elimination of the pathological material that is present inside the lung tissue, do not promote and lead to "restitutio ad integrum "of the damaged parts. This is the only way to get the organ itself back to its original state functional capacities and thus the disappearance of the above-mentioned disadvantages of an economic nature.

Therefore, the use of agents that aid antibacterial therapy is in some respects indispensable and decisive, since the organism is unable to restore the original functional conditions by itself.

It has now been found that 1-benzyl-3 ^ 3 "-dimethylaminopropoxyJ7-iH-indazole due to its special properties corresponds to the above. It actually exercises peripheral level an "anti-inflammatory" effect on the lung tissue and eliminates coughing irritations of the airways, without dampening the nerve centers, consequently the secretions easily removed, and lung ventilation becomes more efficient. It leads to regression in the tissues vascular congestion, edema, and exudation; the pain and the functional changes are thus eliminated

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without interfering with the processes of immune defense and without endocrine disorders. Furthermore, it has a protective and repairing effect on the tissue, and it accelerates the process Scarring processes.

The hydrochloride of the compound of the invention that extremely is water soluble can also be administered in the form of an aqueous solution, either alone or in association with an antibiotic with a broad spectrum of action. the the most suitable mode of administration is the buccal. This form of administration is particularly suitable for large cultivations, where there is a high concentration of animals that are difficult to administer parenterally leaves. In fact, buccal administration makes it possible to solve the problem of treating large numbers of specimens, for both therapeutic and prophylactic purposes. The administration of the substance to healthy specimens with The sick living together can prevent the spread of infection or at least reduce it.

Buccal administration is made easier by the possibility of combining the product with the feed or the food generally given to the animals on a daily basis. By finding the appropriate concentration of the Medicinal product in the feed itself can thus be administered to the animals gradually over the course of the day and thus constant and ensure permanent haematic sentences.

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For this purpose, the following manufacturing forms of the active ingredient have been prepared:

1) tablets;

2) suppositories;

3) capsules;

4) feed supplements;

5) Preparations for solutions in drinking water or in milk.

1) tablets of 50 mg each for small animals «

1 tablet per 10 kg live weight is administered daily » tablets of 500 mg each for large animals:

1 tablet per 100 kg live weight is administered daily.

2) Suppositories of 100 mg each for small animals:

1 suppository per 20 kg live weight is administered daily.

5) Capsules each containing 250 mg tetracycline and 50 mg 1-benzyl-3 ^ ¹ -dimethylamino-propoxv7 ^I -1H-indazole hydrochloride: one capsule is administered daily for every 10 kg of live weight.

Capsules or pills each containing 1 g of tetracycline and 200 mg of 1-benzyl ~ 3 ^ ~ dimethylamino «propoxv7- * 1 H-indazole: large animals are given one capsule or pill daily for every 50 kg of live weight.

4) Additives:

a) Supplement composed of 15 g of 1-Benzyl-3 ^ T— dimethylamino-propoxv7-1H-indazole hydrochloride and 985 g

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vegetable! carrier consisting of soy dust. It will be in administered at a dose of 1 kg per 100 kg of feed for pigs and chickens.

b) Supplements consisting of 15 g of i-Benzyl-3 / ^ J-dimethylamino-propoxyy-IH-indazole hydrochloride, 70 g tetracycline and 915 g vegetable carrier *, namely soy dust. It is administered at a dose of 1 kg per 100 kg of feed for pigs and chickens.

c) Supplements consisting of 15 g of 1-benzyl-3 ^ 3-dimethylamino ~ propoxy ^ -1H ^ indazole hydrochloride and 100 g of 1-chloramphenicol and 895 g of a vegetable carrier consisting of Soy dust. It is given in doses of 1 kg per 100 kg of pig and chicken feed.

5) Preparations for aqueous solutions

a) 1-Benzyl-J ^ -dimethylamino-propoxyT-iH-indazole-hydro

chloride 7.5 g

fine
Sucrose, powdered 92.5 g

They are dissolved in 100 liters of drinking water, for chickens or pigs, or in milk.

b) Tetracycline hydrochloride 35 g of 1-benzyl ^ / SVdimethylamino-propoxyJT "-! H-indazole hydrochloride 7.5 g finely powdered sucrose 57.5 g Dissolve it in 100 liters of drinking water, for chickens or Pigs, or in milk.

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The preparation of the active ingredient and the use of the invention Medicinal products are illustrated by the following examples.

example 1

The sodium salt of 1-Benzyl ~ 3-oxy-1H-indazole is produced by dissolving this substance (which in turn from the methyl N-benzylantranilate by HO bond on nitrogen and reduction with sodium hydrosulfite is obtained) in methanol containing an equivalent amount of sodium methylate, and by subsequent drying with the bridge lowered; 13g of this finely crushed salt are dissolved in 130 ml of xylene suspended. A solution of 7 g of chloropropyldimethylamine is then used in 10 ml of xylene added quickly. After 2 hours of heating, a further 2 g of Ohlorbase are added and finally after a further hour a third portion of 2 g. The heating continues for another 4 hours. One cools down washes with water, dries and evaporates the solvent. 15 g are obtained by distillation under reduced pressure a substance that boils at 160 ° at 0.05 torr. The hydrochloride of the substance melts at 160 ° C.

Example 2

A group of chickens afflicted with chronic respiratory disease was separated into two subgroups a) and b).

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^ ο * ■ *

Group a) was treated with tetracycline alone "; the Group b) was with tetracycline in association with 1-benzyl-3- ^ / J-dimethylamino-propoxy ^ -IH-indazole in the form of the hydrochloride treated. The drugs were in amounts of 70 g tetracycline and 15 g i-benzyl ^ / J-dimethylamino-rpropoxvJ-IH-indazole hydrochloride available per hundredweight of feed. The treatment lasted 7 days. It turned out that the chickens with the Antibiotic and 1-benzyl-3/5-dimethylajnino-propoxy_7-1H ~ indazole Hydrochloride treated responded much faster against the infection itself.

The anatomo-pathological examination carried out at a certain Number of specimens of the two subgroups carried out showed that one was using the combination of antibiotic and 1 -Benzyl-1-4 -dimethylamino-propoxyJT "-1 H-indazole * hydrochloride a rapid return of the pulmonary system to physiological states is achieved.

Example 3

Two groups of healthy chickens were brought together with chickens, who were afflicted with a chronic disease of the respiratory tract. One group of animals was fed with feed nourishes the 15 g of i-Benzyl ^ / J-dimethylamino-propoxyJT-iH-indazole hydrochloride contained per hundredweight. The other group, on the other hand, received normal feed.

The chronic respiratory disease has developed in both

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Groups spread. However, the treated group showed milder symptomatology of limited importance, without that More damage to the lung parenchyma, as well as a better response to antibiotics.

Example 4

From two groups of pigs affected by enzootic pneumonia was the one with feed containing 70 g tetracycline and 15 g 1-benzyl-3/3 ~ -dimethylamino-propox; ^ ~ iH-indazole hydrochloride and the other was treated with feed containing only 70 g tetracycline per hundredweight.

The treatment lasted 6 days. The animals which received the antibiotic + 1-benzyl-3 _/ / T-dimethylamino-propoxyJ7'-1H-indazole showed a more rapid regression of the symptomatology, a more rapid return of appetite and a better feed conversion index.

Example 5

From two groups of artificial milk fed calves weighing an average of 100 kg infected by the flu were afflicted with complications by pathogen secondary intrusion, the one was with milk in which 7.5 g of 1-benzyl-3 ^ 3-dimethylamino-propoxy ^ -iH-indazole hydrochloride and 35 g of tetracycline was dissolved per 100 liters, and the other was treated with milk in which only 35 g of tetracycline was dissolved. The treatment lasted 6 days.

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The clinical symptomatology, the return of appetite and the return to normal growth states were with the Animals treated with iindazole hydrochloride +! Tetracycline, faster and more remarkable.

The examples show how the use of 1-benzyldimethylamino-propoxy_7-iH-indazole hydrochloride alone for prophylactic purposes or in association with antibiotics for therapeutic purposes is able to repair the damage that caused by pathogenic agents with pneumotropic effects. Administration of the drug "per os" does not cause any secondary disturbances. The drug is well tolerated and none remain Sensitivities or reactions of a general or local nature.

The medicine has also been tested in dogs with muscle inflammation and arthritis. The Medicine was administered buccally or rectally in doses of 5 mg per kg live weight. The clinical symptomatology and the painful sensations quickly subsided. The return to normal was very quick.

Patent claims:

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Claims (10)

Patent claims: 1. Medicines for veterinary use, especially for the therapy of pathological disorders of the respiratory system, such as pharyngeal catarrh, tracheitis, iracheobronchitis, Bronchopneumonia in dogs, cattle, horses, pigs and G-eflügel, characterized that the active ingredient is 1-benzyl-3 ^ -dimethylamino ~ propoxv7-1H-indazole of formula I: CO-CH ₂ CH ₂ GH ₂ Ii CH in the form of hydrochloride or another non-toxic salt, possibly in association with drugs that already found for the veterinary use mentioned contains. 2. Medicament according to claim 1, characterized in that it is for administration "per os" in the form of tablets, capsules, aqueous solutions or as a feed supplement. -12- 909835/149 5 5. Medicament according to claim. 2, characterized in that it is in lOrm of tablets containing 50-500 mg of 1-benzyl-3 ^ -dimethylamino-pröp oxy ^ -i H-indazol-Hydr ο contain chloride, is present. 4. Medicament according to claim 2, characterized in that it is in the form of capsules containing 50-250 mg of 1-benzyl-3 ^ 3 "-dimethyl · ajaino-propoxv7-1H-indazole ~ hydrochloride and 250-1,000 mg Containing tetracycline is present. 5. Medicament according to claim 2, characterized in that it is in the form of pills containing 50-250 mg of 1-benzyl-3 / 5'-dimethylamino-propoxyJ-iH-indazole hydrochloride and contain 250-1,000 mg tetracycline. 6. Medicament according to claim 2, characterized in that it consists of an aqueous solution containing 5-15 g of 1-benzyl-3 ^ T— dimethylaminowpropoxyj ^ -iH-indazole hydrochloride pro Contains 100 l of water. 7. Medicament according to claim 2, characterized in that it consists of a feed supplement containing 5-25 g of 1-benzyl-3/5 "-dimethylamino-propoxy_7 ^r -1 H-indazole hydrochloride per 1,000 g of mixture, the Difference to 1,000 consists of a vegetable carrier. -13- 9098 35 / U95 _ ₁₅ - 190öb46 8. Medicament according to claims 1, 2 and / or 7, characterized characterized in that it continues to contain 50-100 g or tetracycline Contains chloramphenicol. 9 · Medicament according to claim 1, characterized in that it in the form of suppositories containing 50-200 mg of 1-benzyl-3 / ^ - contain dimethylamino-propox ^ -IH-indazole hydrochloride, is present. 10. Method for the therapy of pathological affections of the respiratory system such as pharyngeal catarrh, tracheitis, tracheobronchitis, bronchopneumonia in dogs, cattle, horses, Pigs and poultry, characterized in that i-benzyl-J / T-dimethylamino-propoxvT'-IH-indazole in Form of hydrochloride or another non-toxic salt, possibly in association with a drug, that is already being used for this veterinary use. 909835/1495