DE2542225A1 - ANTIALLERGIC PHARMACEUTICAL PREPARATIONS - Google Patents

Description

DR. BERG DIPL.ING. STAPF DIPL.-ING. SCHWABE DR. DR. SANDMAIR

PATENT LAWYERS

8 MUNICH 86, POST BOX 860245

Dr. Berg Dipl.-Tng. Stapfund Partner, 8 Manchen 86, P. O. Box 860245

Your sign Your ref.

Our sign

Our ref. 26th

8 MUNICH 80 Mauerkircherstraße 45

2 2nd SEP. 1975

Lawyer file no .: 26

THE WELLCOME FOUNDATION LIMITED London, N, W. 1 / Great Britain

"Antiallergic Pharmaceutical Preparations"

The present invention relates to antiallergic pharmaceuticals Preparations containing certain acetyl-substituted compounds, the synthesis of these compounds and the Use of these compounds for the production of pharmaceutical preparations with antiallergic activity.

X / R

(089) 988272 987043 983310

Telegrams: BERGSTAPFPATENT Munich TELEX: 0524560 BERGtf

Banks: Bayerische Vereinsbank Munich 453100 Hypo-Bank Munich 3892623 Postscheck Munich 65343-808

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254222a

It has been found that acetyl-substituted compounds of the general formula I given below in mammals and in vitro mammalian preparations show activity as inhibitors of allergic reactions caused by the organism antibodies formed against invading infectious agents of the kind used for asthma in humans are responsible., and that this effect is the inhibition of the Release of anaphylactic mediators is attributable.

In the general formula I.

GH ₃ CO (/ \> OH (I)

the radical X is a carboxyl group, a carboxylate salt group, an alkyl carboxylate group in which the alkyl moiety has from 1 to 6, preferably from 1 to 4 carbon atoms, a carboxamide group, or one, through one or two alkyl groups, each of which has from 1 to 6, preferably from 1 to 4 carbon atoms, or with an acyl group 1 to 7 carbon atoms each, N-substituted carboxamide group.

The inhibitory activity of the compounds of the general

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Formula I was demonstrated by

(a) Experiments using the stimulus response of passive skin anaphylaxis (PCA test) in which the skin reaction is measured as a result of the interaction between an intravenously injected, specific antigen and a cell-fixed, reaginic antibody previously injected into the skin of a mammal (cf. for example Z. Ovary: Fedn. Proc. At the. Soc. exp. Biol., 24, 94 (1965));

(b) Measurement of made by dextran and phosphatidylserine peritoneal mast cells released amount of histamine (see. For example 1. Brit. J. Pharmac, j> 0, 137 (1974) and 2. Science, 173, 1034 (197D); and

(c) Measurement of comminuted human lung tissue passively sensitized in vitro with reagent antibody released histamine, after challenge with the homologous antigen (Br. Med. J., ^, 272 (1968)). Of the The anti-allergic effect is not related to an inhibiting effect on prostaglandin synthetase. the Activity of acids of the general formula I was, as described above, using solutions of the Carboxylate anion detected.

For the sake of convenience, links are general Formula I, in which the radical X is an alkyl carb

oxylate group, hereinafter referred to as "ester" of the general formula I. Similarly, the expression "Amides" of the general formula I are considered to refer to compounds of the general formula I, in which the radical X represents an optionally substituted carboxamide group, and "salts" of compounds are also intended of the general formula I denote those compounds of the general formula I in which the radical X is a carboxylate salt group is.

Pharmaceutically acceptable salts of compounds of general formula I include ammonium salts, alkali metal salts, such as sodium and potassium salts, alkaline earth metal salts such as magnesium and calcium salts, and Salts of organic bases, for example amine salts such as triethanolamine and diethylaminoethylamine salts, and Piperazine and morpholine salts. Particularly valuable are water-soluble salts of the compounds of the general Formula I, with those being particularly preferred which have a water solubility of at least 1 mg / ml.

The anti-allergic activity of the salts of compounds. of the general formula I is based on the anion and the nature of the cation contributes nothing to the activity, however the cation must of course be medicinal

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Pharmaceutically acceptable purposes.

Pharmaceutically acceptable cations in compounds of the general Formula I include hydrogen, ammonium, alkali metal cations such as sodium and potassium, Alkaline earth metal cations such as calcium and magnesium and organic base cations, for example Alkylammonium cations of such alkylamines as triethanolamine and diethylaminoethylamine, piperazinium and morpholinium Kat ions.

Suitable substituted carboxamide groups include N-alkyl and N, N-dialkyl substituted carboxamide wherein the alkyl portion is an alkyl group having 1 to 6 carbon atoms, preferably 1 to ¹ I carbon atoms.

Other substituted carboxamide groups include N-acyl carboxamide groups, wherein the acyl group has 1 to 7 carbon atoms and includes the benzoyl group.

The preparation of the compounds of the general formula I can be carried out according to any one skilled in the art for preparation of compounds of analogous structure are carried out, for example according to the methods described in Reports, 50, 1776 (1897) and ^ 7, 156 (1914). In general

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can the compounds of general formula I by treating acetylsalicylic acid with a Lewis acid, for example Aluminum chloride, or by acetylating a compound 2X-PhOH in which the radical X has the same meaning as shown in general formula I * Amides, esters or salts of the acid can be prepared directly by the acetylation process, or from the acid of general formula I with or without the preceding Isolation of the acid can be obtained.

Esters and amides of acids of general formula I can be prepared by any conventional method including the esterification of the acid or acid chloride with an alkyl or aryl alcohol under Formation of the corresponding alkyl or aryl ester, and reaction of the acid or the acid chloride with ammonia or a Amine to form the corresponding amide or substituted amide.

The compounds of general formula I are useful for the treatment or prophylaxis of allergic conditions Mammals useful, such as asthma or other allergic diseases of the breast, hay fever (allergic rhinitis), conjunctivitis, urticaria and eczema. In particular, they are of value in the reactive

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niche mediated type I hypersensitivity asthma ("Extrinsic Asthma"), and the so-called "Intrinsic Asthma", in which there is no sensitivity to one from the outside acting antigen can be shown.

The size of a prophylactic or therapeutic dose of a compound of general formula I will be understood with the nature of the degree of the allergic condition to be treated, and with the particular connection of the general one Formula I and the route of administration vary. Generally the dose will be between the 2 pg range up to 100 mg per kg of body weight of a mammal.

In the case of an allergic condition as defined above, for example in the case of allergic asthma, a suitable dosage in the range from 20 μg to 0.5 mg, for example from about 0.1 to 0.5 mg, of a compound of the general formula I is used , administered per kg of body weight of the patient to be treated when pulmonary administration as described below is used. In the case where a preparation for intravenous administration is used, a suitable dose range is from 0.2 to 10 mg (preferably 1 to 5 mg) of a compound of general formula I per kg of body weight of the patient, and in the case where one oral preparation is used, a suitable

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the dosage range of 1 to 50 mg of a compound of the general formula I per kg of body weight of a patient, preferably from 5 to 40 mg / kg, and particularly preferred about 10 mg / kg.

In the case where a preparation for nasal and ocular administration is used, for example for treatment of allergic rhinitis, a suitable dose of a compound of general formula I is in the range of 0.5 to 25 mg per patient.

The pharmaceutical preparations of the present invention comprise a compound of the general formula I as active ingredient, and can also include pharmaceutically acceptable carriers and, optionally, other therapeutic ones Ingredients included. The preparations include those suitable for oral, rectal, ophthalmic, pulmonary, nasal, dermal, topical or parenteral (including subcutaneous, intramuscular and intravenous) administration are suitable, although the most suitable route of administration in any given case depends on the nature and degree of conditions to be treated and the nature of the active ingredient. They can suitably be in unit dose form and prepared by any method known to the pharmacist.

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. Pharmaceutical compositions DER .vorliegenden · Erfindungj which are for oral administration, geeignet- _a can as discrete units ,,: such as capsules, tablets or Kaehets be presented, each containing a predetermined amount of the active ingredient, as a solution or a suspension.in. a watery one. Liquid * a non-aqueous. Liquid. ,, an oil-in-water emulsion, or on the one water-in-oil ~ liquid emulsion, such preparations can be prepared by, _s be prepared in any pharmaceutical methods, however sehließen the step of bringing into association the active ingredient with the carrier which all these methods , which contains one or more minor components. . . - ■

Desirably each discrete unit contains 50 mg up to 500 mg of active ingredient,

A valuable form of a pharmaceutical preparation of the present Ejrfindaangfür .a treatment front, allergic asthma is a s © lefae _y. dlie for pulmonary delivery is suitable on the oral cavity "Preferably, the preparation is designed so * that particles P with a diameter of 0.5 to JM ₁ more preferably from 1 to 6 _s that the active ingredient contained ^ into the lungs of a patient * Such preparations are to be introduced

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suitable terweis-e in the form of; dry powders for administration from a Fulver inhalation device in the form of containers from which the powder is atomized, for example by means of a propellant gas; preferably ¹ 'the powders consist of particles which contain the active ingredient, with at least 9 & u & w. ~% of these particles having a diameter of more than Qy5 P and at least 95 % (by number) "a diameter of less than" 7 μ. It is particularly desirable that at least 95% by weight! of the particles have a diameter of greater than 1 μ and at least 90 % (based on the number) of the particles have a diameter of less than 6 ρ. »

The preparations in the form of dry powders are helpful preferably a diluent in the form of a solid fine powder and are suitably packaged in a steak capsule Example made of gelatine, presented,

Preparations according to the invention, which (for example by means of a propellant gas) themselves are only out of date, kSnrien either as powder-atomizing preparations or as Preparations containing the active ingredient in the form of Distribute droplets of solution or suspension. Contains self-atomizing powders — dispensing formulations a liquid propellant with a boiling point of low-ri-

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Less than 65 ° F (18.89 ° C) at atmospheric pressure. In general, the propellant can be 50 to 99.9 % w / w. of the preparation, whereas the active ingredient makes up 0.1 to 20 % w / w, for example about 2 % w / w, of the preparation. The carrier in such preparations may include other ingredients, particularly a liquid nonionic or solid anionic surfactant, or a solid diluent (preferably having a particle size of the same order of magnitude as the particles of the active ingredient), or both. The surfactant can be up to 20 % w / w. although it is preferably less than 1 % w / w. the preparation.

A self-atomizing preparation in which the active ingredient is present in solution contains an active ingredient, a propellant and a co-solvent, and advantageously an antioxidant stabilizer. The co-solvents can be 5 to 40 % w / w. make up the preparation, although they are preferably in an amount of less than 20 % w / w. are included in the preparation.

Preparations of the present invention can also be in the form of an aqueous or dilute alcoholic solution, optionally in the form of a sterile solution, the active one

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Constituent for. use in a nebulizer or an atomizer.

Preparations of the present invention that are suitable for parenteral Suitable for administration, suitably contain sterile aqueous solutions of the active ingredient, wherein these solutions are preferably isotonic with the blood of a patient to be treated and are desirably a preservative, such as thiomer salad.

Pharmaceutical compositions according to the invention which are suitable for topical application include compositions which are suitable for administration via the skin, eyes, nose and mouth. Preparations for application to the skin include lotions and creams containing liquid or semi-solid emulsions, either oil-in-water or water-in-oil, and ointments, preferably those having an active ingredient content of 0.2 up to 5 % w / v. Desirably, the creams and ointments should contain a preservative or protective agent such as methyl hydroxybenzoate.

Preparations for administration to the eye include eye drops which contain the active ingredient in aqueous or oily solution, and ointments, preferably with

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a content of 0.2 to 5 % w / v. ¹ active ingredient. The eye drops are desirably fungistatic and bacteriostatic and are preferably made sterile. '".- · _ ■■ · .'- ■ -

Formulations suitable for nasal administration include powder, propellant and spray formulations similar to those described as formulations suitable for pulmonary administration, but which, when dispersed, have a slightly larger particle size on the order "from 10 to 200 microns. Other preparations suitable for nasal administration include a coarser powder, having a particle size of 20 to 500 microns, which is administered in the same manner as snuff, that is, by rapid inhalation through the nasal passage from a container of powder held close to the nose Another preparation suitable for nasal administration are nasal drops which contain 0.2 to 5% w / v of the active ingredient in aqueous or oily solution.

Preparations suitable for topical administration in the mouth include lozenges containing 10 to 100 mg of active ingredient in a flavor base, usually Cane sugar and gum arabic or tragacanth, a,

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as well as lozenges containing from 10 to 100 mg of active ingredient in an inert base such as Gelatin and glycerin; or cane sugar and gum arabic.

Other therapeutic ingredients suitable for inclusion in the preparations described above, particularly in the case where these preparations are intended for use in the treatment of allergic asthma, include bronchodilators such as isoprenaline, adrenaline, orciprenaline, isoethanine and physiologically acceptable acid addition salts thereof, particularly isoprenaline sulfate. Suitably the bronchodilator is present in an amount of 0.1 to 50 % w / w of the weight of the active ingredient.

Excluded from the scope of the present invention are non-sterile mixtures which only contain solutions and Suspensions of the known compounds of the general formula I described above in solvents and liquids are those in the literature for use in the synthesis and isolation of the compounds according to those described therein Procedures are known. Such known solutions are within the scope of the present invention and suspensions which are pharmaceutically acceptable and which are also pharmaceutically acceptable to the host carrying the infection to be treated

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at least one other pharmaceutically acceptable substance contain.

Included in the present invention, but by no means limited to this are the following specific designs:

1. A compound of the general formula I defined above, provided it is new.

2. The synthesis of compounds of the general formula I defined in more detail above according to any one known to the person skilled in the art Process for the production of the same and of compounds with an analogous chemical structure.

3. Pharmaceutical preparations containing a compound of the general formula I defined in more detail above together with a pharmaceutically acceptable carrier therefor, wherein however, known aqueous solutions of sodium 5-acetylsalicylate, which do not contain any other pharmaceutically acceptable ingredient are excluded.

4. Sterile injection preparations containing a compound of the general formula I defined in more detail above with a pharmaceutically acceptable carrier therefor and preferably a preservative or protective agent.

5. Oral preparations consisting of discrete units, each unit containing a predetermined amount of a compound of the general formula I defined in more detail above, together

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men with a pharmaceutically acceptable carrier therefor.

6. Pharmaceutical preparation containing 5-acetylsalicylic acid in admixture with a pharmaceutically acceptable carrier therefor.

7. Pharmaceutical preparation containing sodium 5-acetylsalicylate in admixture with a pharmaceutically acceptable carrier therefor, except for aqueous solutions, which does not contain any other pharmaceutically acceptable ingredient.

8. Production of pharmaceutical preparations as defined above, containing a compound of those defined above general formula I as the active ingredient, by any conventional method including one Mixture of ingredients.

9. A method for the treatment or prophylaxis of allergic conditions in mammals which the administration a therapeutic or prophylactic dose of a compound of the general formula I defined in more detail above.

10. Essentially solid or semi-solid pharmaceutical preparations, containing a compound of the general formula I in the form of a finely divided solid together with a solid or semi-solid, pharmaceutically acceptable carrier therefor.

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11. Tablet containing a compound; the general Formula I in intimate admixture with a pharmaceutically acceptable carrier therefor.

The following examples serve to illustrate the invention.

Example 1 syrup

5-acetylsalicylic acid sodium salt 5.0 g

Cane sugar 5O ₃ O g

I-ethyl hydroxybenzoate O ₃ I g

Glycerin 1O ₃ O g

Sufficient flavor

Purified water to 10O ₃ O ml

The methyl hydroxybenzoate was dissolved in purified water (50 ml) dissolved at 80 ° C. The cane sugar was added and dissolved and the resulting solution was allowed to stand to cool. Glycerin ^ the sodium salt of 5-acetylsalicylic acid and the flavoring agent was then added along with purified water. The syrup obtained contained in each case 5 ml 250 mg 5-acetylsalicylic acid.

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Example 2 Syrup suspension

5-acetylsalicylic acid in finely powdered form 5 ₃ 0 g

Cane sugar 5O ₃ O g

Glycerin 10.0 g

Saceharin sodium. 0.1 g

Tragacanth powder 0.3 g

Gum arabic powder 0.3 g

Methyl hydroxybenzoate O ₅ I g

Sufficient flavoring agent

Purified water ad 100.0 ml

The tragacanth powder and the gum arabic powder were made dispersed in the glycerol and the mixture obtained to a solution of the methyl hydroxybenzoate, the saccharin sodium and most of the cane sugar was added to the water. Then 5-acetylsalicylic acid was added and dispersed. Finally the flavoring agent was added and the resulting mixture diluted to volume.

Example 3 Nasal Drops

Sodium salt of acetylsalicylic acid 0.5 g

Chlorobutol ...... ,,, ...., 0.5 g

Sodium chloride 0.5 g

Distilled water ..,., ... ad 100.0 ml

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The ingredients were dissolved together in 90 % of the available amount of distilled water, diluted to final volume, and the solution filtered.

Example 4 eye drops

Sodium salt of 5-acetylsalicylic acid 0.5 g

Sodium chloride 0.6 g

Methyl hydroxybenzoate 0.1 g

Phenylethyl alcohol 0.5 ml

Distilled water ad 100.0 ml

The methyl hydroxybenzoate was dissolved in 90 ml of water at 80 ° C solved. The solution was allowed to cool and then the remaining ingredients were added. The solution was diluted to their final volume and sterilized by filtration.

Example 5 Injection

Sodium salt of 5 ~ acetylsalicylic acid 10.0 g

Water for injections to 100.0 ml

Chlorocresol 0.1 g

The sodium salt of 5-acetylsalicylic acid was dissolved in water for

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Injections dissolved and diluted to final volume. the Solution was sterilized by filtration and aseptically dispensed into vials. The vials were each filled with a closed and sealed with suitable rubber stoppers.

Example 6 ointment

5-acetylsalicylic acid (in finely powdered form) .... 5 _s 0 g White soft paraffin 95.0 g

The 5-acetylsalicylic acid was mixed with a small amount of the paraffin and rubbed into a smooth paste. This was gradually incorporated into the bulk of the paraffin. The ointment obtained was squeezable on appropriately Metal tubes distributed.

Example 7

Tablet acid

5-acetylsalicylic acid 250 mg

Lactose 100 mg

Strength 60 mg

Polyvinylpyrrolidone 10 mg

Magnesium stearate x 5 mg

425 mg

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The 5-AeefeylsaÜeyisäure was mixed with d & f lactose and starch and granulated with a solution of PoiyvinylpyrPölidöns in water ", the granules were dried mixed in the Magnesiuffistearat and Hersteilung of tablet ^ th with a weight of 425 mg compressed" Each tablet contained 250 mg of 5-acetylsalicylic acid.

JL.e__i ... A. & .. Ä A A Capsules

Lactose ..... * <«<<» .. «... 100 mg

The powders were intimately mixed with one another and filled into Hartge latine capsules. Each capsule contained 250 mg S ^ -acetylsalicylic acid,

Example 9

Antiallergic activity

A. Peritoneal cell suspensions containing mast cells were obtained from Wistar rats and treated with a mixture of dextran and phosphatidylserine and the compound to be tested 5-acetylsalicic acid using the method of Garland, LG & Mongar, JL, Brit.J. Pharmac, 50, 137 to 143 (197 ¹ O (cf. also

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Goth et al | Sciences 1 | 3 ₃ 1034 to 1035 (1971)) included »
The released and the remaining histamine would be made using an atropinized guinea pig rule
your ability to fully Böüfä, A »L, A. ₄ ^: Möngär, JL * &"Schild * H.Ö. Brit« J. ^ häfrnäö * Ghemöther * ₃ £, 24 to 3Ö (I95 ^) s fair valued *

ResultJMi

The released amine was given as a percentage of the original total histatidyl present (released + remaining) and corrected for spontaneous release in the absence of dextran and phosphatidylserine.
Using a 10 molar concentration of B ^ acetylsaiicylic acid, a 77% inhibition of histemia was obtained *

example 9

A. 5-Acetylsalicylic acid was essentially determined for its antiallergic activity by oral administration to rats
according to the method of Goose ₃ J., et al., Immunology, 1β_, 7 ^ 9 (1969) »but modified to use dilute
high titer of reactive antibody, prepared according to
Orr TSC, et al., Immunology, 2 £, I85 (1971).

The following results were obtained:

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Dosage: mg of drug per kg of body weight

Percent inhibition

300 orally

100 orally

30 orally

10 orally

60 57 35 28

Example 10

5-N-diacety! Salicylamide

5-Acetylsalicylamide (1.0 g) was made with acetic anhydride (10 ml) refluxed for 2 hours. The solution was evaporated to a smaller volume at 60 ° C and ethanol (20 ml) added. On cooling, white needles of 5,0-diacetylsalicylamide precipitated, which after drying gave a Had a melting point of 117 to 119 ° C.

5,0-diacetylsalicylamide was dissolved in 2N aqueous ammonium hydroxide dissolved and concentrated hydrochloric acid added. 5-N-diacetylsalicylamide was precipitated, filtered off and recrystallized from ethanol; Melting point 198 to 200 ° C,

example

11

5-acetylsalicylic acid

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This was made by hydrolysis of the ethyl ester with potassium hydroxide carried out in ethanol over the course of 5 hours. Acidification with concentrated hydrochloric acid gave this Title compound which, after recrystallization from ethanol, had a melting point of 218 to 219 ° C.

Example 12 5-Acetylsalicylamide

Methyl 5-acetyl salicylate was treated with ammonia, filtered and acidifying the piltrate with concentrated hydrochloric acid to produce the title compound; after Recrystallizing from ethanol, the compound had a melting point of 228 to 230 ° C.

Example 13 Ethyl 5-acetyl salicylate

Ethyl salicylate was slowly added to a stirred mixture of acetyl chloride in carbon disulfide, including aluminum chloride had already been added quickly. After refluxing and removing the carbon disulfide ice water acidified with hydrochloric acid was added by distillation. The obtained oil was washed with ether extracted, washed with water and dried. The ether was evaporated and the solid residue from ethanol to Title compound recrystallized; Melting point 62 to 64 ° C.

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Example l4 Sodium 5-acetyl salicylate

5-acetylsalicylic acid was dissolved in water containing one equivalent of sodium hydroxide and the filtered solution evaporated to dryness. The sodium 5-acetylsalicylate obtained crystallized from ethanol on addition of ether and had a melting point of 270 to 275 ° (decomp.). Its infrared spectrum showed strong absorption at 1359, 1392, 1450, 1497, 1587, 1629 and 1670 cm " ¹ .

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Claims (16)

Patent claims (ΐ) Antiallergic pharmaceutical preparation containing a compound of the general formula I. CH ₃ CO (/ Y) OH (I) wherein the radical X is a carboxyl group, a carboxylate salt group, an alkyl carboxylate group in which the alkyl moiety Has 1 to 6 carbon atoms, a carboxamide group, or one, through one or two alkyl groups, each of which has 1 to 6 carbon atoms, or through an acyl group each has 1 to 7 carbon atoms, N-substituted carboxamide group together with a pharmaceutically acceptable carrier therefor. 2. Preparation according to claim 1, characterized j that the radical X is a carboxyl group, a carboxylate salt group, an alkyl carboxylate group, or represents a carboxamide group optionally substituted by one or two alkyl groups, each of which has 1 to 6 carbon atoms is N-substituted. - 27 - 609815/1324 3. Preparation according to claim 1, characterized in that the compound of the general Formula I 5 is acetylsalicylic acid or a pharmaceutically acceptable salt thereof. 4. Preparation according to one of claims 1 to 3, characterized in that the salt is a sodium, potassium, ammonium or calcium salt. 5. Preparation according to one of claims 1 to 3 »characterized in that it contains an antiallergic prophylactically effective amount of a compound of the general formula I contains. 6. Preparation according to one of claims 1 to 5 »characterized in that the compound of the general formula I is present in an amount that is suitable for administration to a patient in a Dose not exceeding 10 mg per kg body weight of the recipient is appropriate. 7. Preparation according to claim 6, characterized in that g e label. It means that the available amount for a Dose of 2 to 5 mg per kg of body weight is suitable. - 28 - 609815/132 * 8. Preparation according to one of claims 1 to J _3, characterized in that the preparation is in the form of a discrete unit dose which contains no more than 600 mg of a compound of the general formula I. 9. Preparation according to claim 8, characterized in that the amount of a compound of the general formula I does not exceed 300 mg. 10. Preparation according to one of claims 1 to S _3, characterized in that it is in the form of a tablet, a capsule or a cachet. 11. Preparation according to one of claims 1 to S _3, characterized in that it is in the form of a sterile, injectable preparation. 12. Preparation according to one of claims 1 to S _3, characterized in that it is in the form of a form suitable for intra-pulmonary administration
is present, in which the compound of the general formula I is present in the form of particles with a diameter νοη · 0.5 to J U. 609815/1324 13 · preparation according to claim 12, characterized in ₃ that it is in the form of a selbstzerstäubenden preparation. 14. ' Tablet, characterized by a content of one antiallergic effective amount of 5-acetylsalicylic acid or a pharmaceutically acceptable salt thereof. 15. "Process for the manufacture of a pharmaceutical preparation according to one of claims 1 to 14, characterized characterized in that it is the mixing of a compound of general formula I with a pharmaceutical acceptable carrier therefor. 16. Use of a compound of the general formula I or a pharmaceutically acceptable salt thereof for Manufacture of a pharmacological preparation against antiallergic conditions. 609815/1324