DE2006486A1 - New use of S carboxymethyl cysteine - Google Patents

Description

LAWYERS? ΠΠβ / οβ

DR. JUR. DIPL-CHEM. WALTER BEIl ^ UUO <f ÖD

ALFRED HOEPPENER _j7 c _p u 107Q

DR-JURDIPl-CHEM-HJ-WOLFF. ^{Ι £ ιΓΒϋι}

DR. JUR. HANS CHR. ROPE

623 FRANKFURTAM MAIN-HÖCHST

ADELONSTRASSE 58

Our Mio 16 141

HBGHERCHES PHAEMAGBTJTIQUES ET SCIEHTIFIQUES Paris, France

Today's use of S-carboxymethylcysteine

Medicines containing S-carboxymethylcysteine as an active ingredient are as isotonic or possibly hypertonic solutions in drip form for use in nasal sprays, nasal drops or aerosols. It has already been described that such Hedikaraente can be found in otorhinolaryngology and have it used in pulmonology,

It was surprisingly found that the S-garboxymethylcysteine when administered by the digestive tract exerts an effect that when administered by the respiratory tract could not determine, namely a favorable change in the viscosity of the trachea and bronchi (l'arbre respiratoire) secretions formed.

When the S-oxymethylcysteine in the form of an aqueous solution was administered by air to patients suffering from respiratory insufficiency, it increased the volume of secretion considerably, but did not change the viscosity of the secretion (measured after dismantling the tweezers and before the seroraucous thread breaks).

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On the other hand, in the investigation of 26 patients to whom S-carboxymethylcygteine was administered orally, it was found that the decrease in the viscosity of the secretions from the 2nd day on. statistically significant vmrde; the value ρ (viscosity), which was 0.005 on day 2, sank ^{to 0.001 on 3 rjL} 'ag and remained there for the entire duration of the treatment to be bound »

ils showed a specific cell localization of the Transferases, which are used for the synthesis of the sialglycosaminoglycans responsible at the level of the mucous cells of the bronchial tree are, as well as a localization of the sulfotransferase in the serous acini of the combined gusse and in the calf-shaped Cells,

One can therefore assume that this explanation is intended to be binding for the invention, that S-oxymethylcysteine acts selectively on the metabolism of the mucous elements. In bronchial diseases this agitation of the mucus is greatly increased, but generally only forms a mucin that is poor in sialic acid. UEAs S-öarboxymethylcystein Wi _r so kt to mucipare hyperplasia by an activation process of sialyltransferases, what would explain why this compound is effective only by the oral route and does not have the same effects in local administration.

On every i ¹ all the S-carboxymethylcysteine administered via the digestive system is absorbed more precisely and more regularly, since it does not need to penetrate a blocked and deformed bronchial tree from the outside; it is therefore much more constant and much safer both in terms of its tropic hell and its mucolytic effectiveness.

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According to the above remark, S-carboxymethylcysteine can be used for example as a syrup, in torrn of capsules, tablets or suppositories, optionally in combination with aiidez'en active ingredients, e.g. one or more representatives of the Class of antibiotics, antihistamias, oorticoids and bronchodilators, administered "-be."

The following examples serve to illustrate the preparation of the -Medication s. .. "-. .- -:

syrup

a) Syrup for children '. '

S-carboxymethylcysteiii '2 g

"",. Licked and perfumed losend.es

Medium ^:: ad (qsp) 100 ml

Solvent "consists of a sucrose syrup to which perfume, a preservative and a coloring agent are added is.

Example 1 "\

S-Garboxyme.thylcysteine - 2 g

Sucrose -. 70 g

Methyl parahydroxyl benzoate (preservative) 0.15 g

Perfume: blackberry concentrate ■ .. 1 ml

Cherry concentrate t -.- "■" 0.5 ml

Vanillin. 0.05 g

Red dye ■ '. 0.005 g

Sodium hydroxide until / reaching a

. '· - pH value of 6.2 -' .-. · - ..

Water ad ■ ■ -.... · - .100 ml

Given the insolubility of the

For the production of the syrup. first the S-Oarbox-vmethylcysteine with iiatrium hydroxide up to a pH value of 6.2:

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neutralized, then the other constituents were added, followed by stirring and filtering.

b) syrup for adults

S-carboxymethylcysteine 5 g

sugared and perfumed solvent

Medium to 100 ml

Example 2

S-carboxymethylcysteine 5 g

Sucrose. 40 g

Parahydroxymethyl benzoate 0.15 g

Color: caramel 0.10 g

Perfume: aromatic concentrate 2 ml

Cinnamon essence 0.002 g sodium hydroxide to pH 6 £

Water to 100 ml

Proceed as in Example 1

2. Capsules

For the production of capsules with 50, 100 or 250 mg S-carboxymethylcysteine became a simple mixture of S-carboxymethylcysteine and one in the - ^ egel lactose, a silica gel and dissolving agents containing magnesium stearate related and divided with the help of automatic machines.

example 1

S-carboxymethylcysteine 0.050 g

-Lactose 0.040 g

Silica gel 0.005 g

^ magnesium stearate 0.005 g

per capsule

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Example 2 "

S-carboxymethylcysteine, ■ x 0.250 g

Silica gel * 0.010g

Magnesium stearate. 0.015 g

Per capsule. _ '...

3. tablets -; ■ -

To He position of different "doses of S-carboxymethylcysteine are tablets containing the usual Herstellungsme-.thoden applied (Preparation of a granulate, addition of a lubricant and pressing on conventional machines) ₀

Example . . '- ■' "

S-carboxymethylcysteine 0.100 g

Sucrose '. 0., 100 g

Strength ... . -: ■ '0.045 g

Magnesium stearate 0.005 g

per tablet

The ■ tablets can be uncoated, provided with a sugar layer or any other coating commonly used in the production of dragees. . "

4. Suppository

The S-carboxy _me -} - j _; jyi _C y _S t _e ^ _n with a conventional suppository, dissolving agents, for example, cocoa butter or _e mixed with the product prepared according to Imhausen dissolving agent,

Example 1 " "

S- ^ arboxymethylcysteine 0.100 g or 0.200 g or 0.500 g

solvent ad 2g

Balsam essences such as eucalyptol,

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Camphor and the like are added,
Example 2

3-carboxymethylcysteine 0.500 g

Camphor 0.060 g

Eucalyptol 0.100 g

dissolving smock ad 2g

The galenic forms mentioned above can be used with various Active ingredients that enhance the effect of S-carboxymetlrylcysteine complete, e.g. antibiotics, antihistamines, cortocoids and bronchodilators.

The following examples serve to explain these possible combinations.

1 · S-carboxymethylcysteine + antibiotics

a) capsules

a) S-carboxymethylcysteine 0.100 g tetracycline 0.250 g

Addition of the solvent in one
amount required for one capsule

b) S-carboxymethylcysteine 0.200 g chloramphenicol 0.200 g

Addition of the solvent in one

amount required for one capsule, i.e. 0.450 g

c) S-carboxymethylcysteine 0.100 g synthetic penicillin 0.250 g

Addition of the solvent in one

amount required for one capsule, i.e. 0.375 g

b) syrups

The combination of S-carboxymethylcysteine + antibiotic can be administered in the form of syrup, which is

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Twist by adding a-certain. To produce amount of water are. One then makes a powder composition or made a granulate that is filled into! bagsi

example

2 G 2.31 G .0 / 10 G 2 G 0.15 G 67.6 G 0.15 G

S-carboxymethylcysteine
Tetracycline (base)
Sodium metabisulfite. ■ "-....
Has riumhexameta.pho sphat
Ifetrium ethyl parahydroxybenzoate
Sa.ccha.rQse
Carboxymethyl cellulose;

When using, enough water is added that 100 ml Syrup can be obtained. -, -. .- "■ '-

2. S-Carboxymethylcysteine + Antihistamines Example 1 ^. - - ^: -.

S-carboxymethylcysteine + promethazine syrup.

S-Garboxymethylcysteine ■ 2g or 5 g

Promethazine. . 0.05 g "0.10 g

zipped and perfumed. '. ';. solvent ad "100 ml

Bas solvent can be colored and perfumed Zuclcer syrup consist, for example, of: '

Sucrose: - 50 to 70 g

Diethyl parahydroxy alsoate 0.10 g

Cocoa perfume. . 0.5 ml -

Vanillin 0.025 g

dye (tartrazine) 0.0005 g

v / ater ad 100 ml

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Example 2

Tablets made from S-carboxymethylcysteine + diphenhydramine

S-Oarboxymethylcysteine 0.200 g to 0.500 g

Diphenhydramine hydrochloride 0.025 g to 0.050 g

Adding the solvent in
such a !! close that the

Tablet weighing 0.300 g to 0.650 g having,

3, S-carboxymethylcysteine + gorticoids

S-carboxymethylcysteine can be used with various corticoids, such as hydrocortisone or prednisone, are combined in the form of tablets,

example

S-carboxymethyl-cysteine 0.200 g to 0.500 g

Prednisone 0.001 g to 0.005 g

Addition of the solvent,

until the tablet weighs 0.275 g to 0.600 g

having.

The releasing agent such as stearic acid or IIA £ nesiumstearat contains eil · 'from a übliciien mixture oo.er lactose sucrose, starch al ^ disintegrating and a lubricant: en, -The l'role kill \; earth /. n ... ch he.vi:öi!u.ilic ^; .ien l-lethoi-cr.

4 ο S-Cur] joxymeth; / lcysteine + Eronchodil .-: torcn

The i.oi.-ibinaticn lcaiai in the form of suppositories, iahletton odc: Capsules e ^ ici .er ..

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20Q6486

example

Suppository:. . -. - '

S-carboxymethylcysteine 0.500 g

Theophylline 0.300 g

Solvent for suppositories ad 2 g

Tablets or capsules:.

S-Cfi.r "bo> iymethylcysteine 0.400 g

Theophylline. ■. 0.050 g

Addition of the solvent, "until the

Tablet weighing ·. 0.600 g

having,-

or addition of the solvent in one
'Excessive amount for one capsule, cLlr'. 475 g.

The tablets can be "uncoated" or according to the usual Methods have been brought into Dragee-i'orm "

Double-core tables in which the theophylline with a counter ttagenic acid-resistant coating is provided can also be produced. With such a formulation a small theophylline tablet is produced, which is coated with a coating of e.g. rubber lacquer or cellulose aceto- phtnalat provided wix-d; The tablet thus obtained is the Core for a larger, from S-Garbox ^ nnethylcysteine and one solvent formed tablet,

The daily dose can average 1.3 to 3 g of S-carboxymethylcysteine amount

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Claims (1)

P A T E I T A Ii S P R ίί C H E: 1 _β Use of S-carboxymethylcysteine as an active ingredient for the production of drugs that can be administered via the digestive tract in pneumology and otorhinolaryngology. 2ο Use according to claim 1, characterized in that the S-carboxymethylcysteine in syrups, capsules, tablets or suppositories, optionally in combination with others Active ingredients such as antibiotics and / or antihistamines, gorticoids and bronchodilators incorporated. For RIiCHJRCHES EHATCiACETJl ¹ IQUES Ει SCIEHTIPIQTJES Paris, France L Lawyer 109817/2017