CS238046B1 - Oral liquid allergen preparation - Google Patents

Abstract

Oral liquid allergen preparation containing an allergen extract with the addition of glycerol as a stabilizer, which may optionally be combined with some other known stabilizer, for example sorbitol, aldopentoses or aldohexoses.

Description

The invention relates to an oral liquid allergen preparation obtained by extracting one or more allergens formulated into an oral dosage form with the addition of a stabilizer.

Atopic allergy type I allergy / is the basis of the whole group of allergic diseases. A characteristic feature is the disposition factor, which, together with the non-psychological change and harmful effects of the environment and stabilizing antigens, explains the steady increase in the number of allergens, especially in the youngest generation.

The need for the active substance and treatment with simple application is increasing. Oral application of desensitizing allergens is particularly suitable for pediatric allergy sufferers. Unlike adults, the enteric antigen barrier in children is readily permeable to relatively large antigen molecules, such as pollen, yeast, bacteria and the like, which therefore enter the lymphatic system and result in the desired immunological stimulation.

V čsl. No. 203552 discloses a liquid allergen composition adapted for oral administration by the addition of at least one stabilizer selected from the group consisting of sorbitol, aldopentoses, and aldohexoses.

The formulation according to AO 203552 has still been proven in practice in particular for particularly sensitive children. However, its disadvantage is the relative cost of the stabilizers of this class of substances, in particular sorbitol, therefore the present inventors have investigated the possibility of using other stabilizers that are less expensive and commercially available.

Glycerol has proven to be a suitable stabilizer, which also has a sweet taste, which is particularly well tolerated by pediatric patients. Long-term experience has also shown that glycerol is harmless even for very young children under 1 year of age.

Accordingly, it is an object of the present invention to provide an oral liquid allergen composition obtained by extracting allergens formulated into an oral dosage form by the addition of a stabilizer which comprises glycerol as stabilizer in an amount of from 5%, preferably 50%.

The preparation according to the invention may of course also contain glycerol in combination with another stabilizer, in particular the stabilizer known from AO 203552, for example sorbitol, aldopentosaml and aldohexoses.

For practical production purposes, it is expedient that the composition according to the invention also contains a flavoring agent, possibly a fragrance and an additive of 0.1 to 4, as well as a preservative-free substance. Such a substance is in particular a paraben (e.g. methylparaben and propylparaben, or a mixture thereof). The purpose of the preservative additive is to protect the preparation according to the invention against deterioration by microorganisms, in particular by bacteria and fungi. However, the preservative must be chosen so that it is free of unpleasant taste and odor and is particularly non-irritating for pediatric patients.

If desired, the preparation can also be produced in such a form that the taste or aroma flavorant is added either by the manufacturing plant or by the consumer according to his own taste. The invention will be further elucidated by means of exemplary embodiments in which some suitable formulations are given, without however exhausting the scope of further combinations within the definition of the subject invention and without limiting the scope of the legal protection of the invention.

He did

7,5 g mixed pollen from plants:

Agrostis alba

Alopecurus pratensis

Anthoxanthum odoratum

Apera spica venti / Chundelka broom /

Arrhenatherum elatius

Avenastrum pratense / Meadow Oat /

Dactylis glomerata

Festuca rubra / Red fescue /

Holcus lanatus

Lolium sp. /Rye grass/

Phleum pratense / Timothy /

Poa pratensis

Secale cereale / Rye sown /

Plantago lanceolata is extracted in a 100 ml solution of the following composition:

sodium chloride 5 g sodium bicarbonate 2.75 g phenol 4.0 g distilled water to 1000 ml

The pH of the solution is adjusted to pH 8.2-8.4 by bubbling CO ₂ solution. clock shake.

The first dose of extractant is 40 to 50 ml, the next 2 to 3 doses of 25 or 20 ml each.

After centrifugation and filtration, the individual extracts are combined, stabilized, for example by adding 1: 20,000 nonionic surfactant to 1 ml per 100 ml of stabilized solution, and the pH is adjusted to 6.4 to 7.4. The resulting solution is sterilized by filtration through a 0.22 µm bacteriological filter, such as the Millipore brand.

The sterile allergen solution is diluted 1: 1 with glycerol, after previously determining the protein nitrogen (PN) content of the allergen solution and diluting to the appropriate concentration. extraction liquid with parabens.

The following applies to the definition of an international entity:

PNU = 0.00001 in 1 ml solution.

Example 2 g of housing dust, ie dust collected from at least 40 bytes of allergy sufferers and mixed, biologically active, delivered by allergy centers, collected and sieved to No. VII nets according to CsL 3, is extracted in a 100 ml solution of the following composition:

sodium chloride 5 g primary potassium phosphate 0.36 g secondary sodium phosphate 1.43 g phenol 0.4 g distilled water to 100 ml

Extract for 48 to 72 hours at +2 to +10 ° C by shaking the mixture every 2 hours. The first dose of extraction fluid is 40 to 50 ml, the next 2 to 3 doses of 25 or 20 ml each.

The pH is adjusted to 6.4 to 7.4 after extraction. After sterile filtration as described in the previous example, the dust allergen is sterile enriched by the addition of 1% allergen from a mixture of mites and 1% of a mixture of allergens from fungi, alfaria, Aspergillus, Botrytis, Cladosporium /. The obtained dust-enriched dust allergen with a mixture of mites and molds is diluted with extraction fluid, where the phenol is replaced with parabens (0.67 g methylparaben and 0.33 g propylparaben per 1000 ml) for appropriate dilution according to the determined protein nitrogen content (International PNU) Dilute 40% with a mixture of glyceol and sorbitol.

Example 3. The procedure is as in Example 1 or 2, except that a mixture of glycerol, glucose and ribose mixed with 1% sodium salicylate is used instead of a mixture of glycerol and sorbitol with parabens.

Example 4

The procedure is as in Example 1 or 2, except that a mixture of glycerol and mannose with a 1% mixture of methylparaben and propylparaben is used.

Example 5

A combination of sterile allergen solutions is used according to the individual prescription of the physician-allergologist, for example, an allergen from house dust, pollen, mold and pollen + bacterial allergens, dust allergen + mites and the like. A mixture of the allergens listed in Examples 1 and 2 may be used in a ratio determined by the physician.

Example 6

The procedure is as in Example 1 or 2, and the obtained allergens are diluted with an extraction liquid, where the phenol is replaced with a 1: 1 mixture of methylparaben and propylparaben with the desired concentration with glycerin and raspberry syrup 20 g per 100 ml is added.

Claims (3)

SUBJECT OF THE INVENTION An oral liquid allergen preparation obtained by extracting allergens formulated into an oral dosage form with a stabilizer additive, characterized in that it contains glycerol in an amount of from 5%, preferably 50%, as a stabilizer. 2. An oral liquid allergen composition according to claim 1, comprising glycerol in combination with another stabilizer, for example sorbitol. 3. An oral liquid allergen composition according to any one of claims 1 or 2, characterized by an additive of flavoring or odor and an alimentary harmless preservative, for example a paraben or a mixture thereof, of from 0.1 to 4%.