NL8104929A - ANTICHOLINERGIC PREPARATIONS, PREPARATION AND USE THEREOF. - Google Patents

Description

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Anticholinergic preparations, as well as their preparation and application.

The present invention relates to anticholinergic preparations, the preparation and use of anticholinergic agents in the form of parent-age therapeutic systems which deliver these substances continuously, for the treatment of hyperacidity and ulcer diseases.

It is known that anticholinergic active substances can be administered orally for the treatment of hyperacidity and ulcer diseases.

According to the latest edition of the L.S. "The Pharmacological Basis of Therapeutics" textbook Goodman and A. Gilman (Mac Millan Publ. Co., 10 Inc. New York, 1980, 6th ed.) Affect atropine-type musearin-like cholinerg blocking agents and also scopolamine-type gastric acid secretion. However, it should be noted that only relatively high doses are effective. According to this current view, daily doses which reach the subtoxic limits are required for the inhibition of gastric acid secretion. For example, when using scopolamine, dosages of 1 mg and above are necessary to inhibit desired gastric acid secretion in humans. However, such high dosages almost always cause significant side effects, such as, for example, dryness of the mouth, visual disturbances, photo-phobia, acceleration of the wrist and urinary drainage disorders. K.3. Ivey, Gastroenterology 68, (1975) 154-166 comes to the same conclusion after reviewing about 400 publications on the use of anticholinergics in ulcer disease. The side effects that occur are so intolerable that many patients do not tolerate the treatment for quite a long time.

According to investigations by M. Feldman et al. (N. Engl. 3. Med. 297, (1977) 1427-1430) it is generally believed that inhibition of gastric acid secretion can only be achieved by very high doses of an administered parasympatholytic agent. , questioned 30. The authors noted above found that a low dose (15 mg) propantheline inhibits food uptake induced gastric acid secretion in patients with duodenal ulcer to the same degree as a sub-toxic dose of 48 mg. that this lower dose of propantheline in combination with a receptor antagonist, such as, for example, cimetidine, inhibited acid secretion more strongly than with the drugs alone.This concept, because of the uncertain 8104929 '-2 -2 activity, found no effect at all. widespread application.

Surprisingly, it has now been found that when anticholinergic agents in the form of parenterally applicable therapeutic systems which release these anticholinergic agents are used continuously, gastric acid secretion is effectively inhibited, with the undesirable side effects. be pushed back or totally supplanted. Therapeutic systems, which allow a continuous release of active substance, can be applied trans- or intradermally, subcutaneously or also intramuskularly.

The invention particularly relates to the use of anti-cholinergic substances in the form of transdermal therapeutic systems in the presence or absence of acid-inhibiting substances, such as, for example, antacids and / or H 2 receptor antagonists for the inhibition of gastric acid secretion.

The invention particularly relates to the use of anti-cholinergic substances of the atropine type in the form of transdermal therapeutic systems in the presence or absence of acid inhibitors, such as, for example, antacids and / or H 2 receptor antagonists for the inhibition of gastric acid secretion.

In particular, the invention relates to the use of scopol amine as an anticholinergic in the form of transdermal therapeutic systems in the presence or absence of antacids and / or also W 2 receptor antagonists for the inhibition of gastric acid secretion.

V

In particular, the invention relates to the use of scapolamine base as an anticholinergic in the form of transdermal therapeutic systems for inhibiting gastric acid secretion.

Anticholinergics, which are also called parasympatholytics, antimuscarinics or also cholinolytics, belong in the class of neutrope or atropine-like spasmolytics.

Anticholinergics, which are used, inter alia, for example for the inhibition of gastric acid secretion when a therapeutic system which continuously releases the active substance, are described by G. Erhardt and H. Ruschig, Arzneimittel, vol. 2, pages 75-79 (1972). However, as active substances, compounds of the atropine type, such as, for example, atropine, homatropine, scopolamine, benzotropin and etybenzatropine, and their therapeutically active salts for the inhibition of gastric acid secretion, which continuously produce the active substance, are particularly important. does not qualify. As other anticholinergics of particular significance, the oxyphenylene cyclimine, glycopyrrolate, poldine, propantheline, isopropamide and clidinium and their therapeutically active salts can also be used, for example.

The antacids and / or F 1 receptor antagonists can be administered orally or also the F 1 receptor antagonists together with the anticholinergics.

Substances which have a strong inhibitory effect on histamine-induced gastric juice secretion can be used as the F 1 receptor antagonists. Suitable F1 receptor antagonists are, for example, -10 ranitidine, metiamide, buriamide, tiotidine and in particular cimetidine and their therapeutically active salts.

As antacids, for example, those described by B. and H.F1. Flelwig (Modern Arzneimittel, 5th Edition, pp. 650-665, 1980) described compositions are administered. In particular, metal salts such as, for example, alkali metal, alkaline earth metal and also Group III metal salts can be used. Of particular importance are, for example, the sodium, calcium or magnesium carbonates, respectively.

-hydrogen carbonates or also aluminum silicates. It is also possible to use other hydrolysis, an aluminum hydroxide film-giving complex double silicates, for example sodium aluminum silicate.

Pepstatin or also cytoprotective substances, such as, for example, various prostaglandins, for example PGE2 or also 16,16-dimethyl-PGE2, can be used as other acid-inhibiting substances.

The aforementioned therapeutic systems, which are used, for example, trans- or intradermally, subcutaneously or also intramuscularly, enable a continuous release of the active substance at a defined rate and duration. According to the invention, the stated therapeutic systems can also be used for the continuous release of mixtures of active substances.

The transdermal therapeutic systems control the delivery of the active substance to the surface of the intact skin. The rate of delivery is substantially below the maximum absorption capacity of the skin. The active substance diffuses through the epidermis and enters the cycle through the capillaries.

Intradermal systems are used as implants immediately below the epidermis and subcutaneous systems under the dermis, for example, according to US Pat. No. 3,625,214, and continuously release the active substance, controlled by the biodegradation, to the cycle.

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Furthermore, systems using biodegradable polymers, which control the continuous release of the active compound, for example according to the Belgian patent specification 837-935, can also be used intramuscularly.

Preferably, however, the therapeutic systems are used, which can continuously deliver the active substance transdermally.

As transdermal therapeutic systems, depending on the use of the various suitable anticholinergic agents, for example, those in the. U.S. Pat. Nos. 3,598,122, 3,598,123, 3,797,494 and 4,060,084, preferably those described in German Offenlegungsschrift 2,604,718, respectively. transdermal therapeutic system described in U.S. Pat. Nos. 4,031,894 and 4,262,003, the use of the invention is not limited to that described in the patents or in the "Offenlegungsschrift" described transdermal therapeutic systems. The transdermal therapeutic system according to German Offenlegungsschrift 2,604,718 is a therapeutic preparation in the form of a plaster-like layer containing anticholinergic substances, such as, for example, scopolamine base in the presence or absence of a 20 H 2 receptor antagonist transdermally in an impact amount. - heid 2 of 10 to 200 µg / cm skin, thereby rapidly increasing the concentration of active substance in the plasma, inhibiting gastric acid secretion without the aforementioned unpleasant side effects and subsequently in an amount of 0.3 to 15 µg / h 25, so that the active substance content in the plasma is maintained almost constantly. In most cases, the initial impact is in the range of 50-150 µg of an anticholinergic agent, such as, for example, scopolamine, per cm of treated skin.

The concentration of scopolamine in the plasma can be related to the concentration of the free scopolamine in the urine. It appears that a moderate urinary excretion rate of about 0.5 µg free scopolamine per hour generally corresponds to a therapeutic level in the plasma. However, it has also been found that this rate is subject to an approximately 5-fold biological variation. Therefore, the speed is in the range - from about 0.1 to about 2.5 µg / h depending on the individual subject.

The basis for the next substantially constant release rate in the dosing program is to support, as necessary, the 8104929 * Μ -5- surge of the active substance, when sufficient scopolamine is added to provide the aforementioned therapeutic amount in the plasma. and maintain this level for as long as possible. It follows that the constant rate administration will last as long as the therapy requires. In this context, a total amount (including thrust) of 0.1-2.5 mg of scopolamine administered in accordance with the above dosing program gives a therapeutic effect of more than about 3 hours to 7 days. It also follows that the constant rate of administration may vary depending on the patient's body weight (plasma volume). In this connection, the rate is in most cases in the range of 1-15 µg / h for adults and 0.5-10 µg / h for children.

The layer may consist of a multilayer laminate composed from above of the following four layers: a) a protective backing; b) a gel-like mineral oil-polyiso-butene active substance reservoir containing the active substance, which represents the constant dosage source; c) a semipermeable membrane, which partly controls the constant release rate and d) a gel-like mineral oil-polyisobutene active adhesive layer, which serves as the source of the initial impact dose, as well as adhesives, which fix the layer to the skin .

Preferably, for the cover layer a), a laminate of polymer foil and a metal foil such as, for example, an aluminum foil is used.

Polymers that can be used for this layer are, for example, high and low density polyethylene, polypropylene, polyvinyl chloride and polyethylene terephthalate.

In the gel-like mineral oil-polyisobutene active substance reservoir b), the scopolamine base is partly dissolved and partly not dissolved homogeneously in the gel-shaped mixture of mineral oil with a viscosity of about 10-100 cP at 25 ° C and a polyisobutene dispersed. These mineral oil-polyisobutylene mixtures are excellent adhesives and also serve to hold the plaster-like layer together. For example, the mineral oil is used as a carrier for the scopolamine base, which has limited solubility in the mineral oil (about 2 mg / ml). The relative amounts in the reservoir layer are selected such that the mineral oil is saturated with the base substantially throughout the total release time of the patch-like layer.

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The next layer of the multilayer laminate is a semipermeable (microporous) layer c), the pores of which are filled with the mineral oil described above, and which controls the rate at which the scopolamine base is released to the skin. The flow-through of scopolamine through the semipermeable layer and the layer range of the membrane must be chosen such that the scopolamine from the reservoir layer is delivered to the skin at substantially constant speed in the range of 0.3-15 µg / h, after the transdermal therapeutic system has been applied to the skin. The semipermeable membrane is prepared from polymeric materials, allowing the active substance to pass through diffusion. Polymers that can be used for such membranes are, for example, polypropylene, polycarbonates, polyvinyl chloride, cellulose acetate, cellulose nitrate, polyacrylonitrate and organopolysiloxane rubber.

The layer d) of the laminate, which is designated as an adhesive layer, consists essentially of the same constituents as the layer b) described, and also contains the scopolamine base as active substance, which is responsible for the impact dosing at the start of the application of the system. With the aid of the strong adhesive layer d), the plaster-like layer is affixed to the skin after the peel-off protective layer has been removed immediately before application.

The therapeutic systems described according to the invention, which continuously release the anticholinergic active substances in the presence or absence of antacids and / or Hg receptor antagonists, can inhibit gastric acid secretion in acute gastritis or in ulcer diseases in the stomach or small intestine. (Duodenum) are applied without having to cause unpleasant parasympathological side effects, such as dryness of the mouth, disturbances in vision, photophobia, acceleration of the wrist and disturbances in the drainage of urine.

PGE2 as an acid-inhibiting agent is used in a dose of 0.1 to 0.3 mg, this dose being administered one to six times, so that the daily dose is 0> 1 to 9.0 mg.

H2 receptor antagonists are used in doses from 25 mg to 250 mg. In general, H2 receptor antagonists are administered orally one to six times a day, so that the daily dose is between 25 mg and 1500 mg.

Antacids are administered orally one to six times in doses of 25 mg to 500 mg, so that the daily dose is between 25 mg and 3000 mg.

Due to the transdermal use of scopolamine, the values indicated above decrease in patients responding to scopolamine 8104929-7.

The transdermal doses of an anticholinergic, for example, scopolamine, are said to be effective in a range of 0.05 to 25 µg / h when used jointly or also parenterally with an aforementioned acid inhibitor.

The medicinal dressings required for transdermal use are prepared as follows: a) a solution of 29.2 parts of high molecular weight polyisobutene (Vistanex MML-100, average molecular weight 1,200,000 determined by viscosity measurement), 36.5 parts of polyisobutylene with low molecular weight 10 (Vistanex LM-MS determined by viscosity measurement, average molecular weight 35,000), 58.4 parts of mineral oil (10 cP at 25 ° C), 15.7 parts of scopolamine base and 860.2 parts of chloroform are added to about 65 .mu.m thick coating cast from an aluminum polyethylene terephthalate laminate (MEDPAR) to form a scopolamine base reservoir layer of about 50 .mu.m thickness. A combination of adhesive layer and peel-off layer is similarly prepared in that on a silicone-treated aluminum-polyethylene-polyethylene-terephthalate film having a thickness of 200 µm a solution of 31.8 parts of the high molecular weight polyisobutene, 39.8 parts of the low molecular weight polyiso-20 butene, 63.6 parts of the mineral oil, 4.6 parts of the scopolamine base and 860.2 parts of chloroform are poured. The resulting contact adhesive layer has a thickness of about 50 µm.

The combination of cover layer and reservoir layer prepared as described above is then saturated with mineral oil on one side of a microporous polypropylene membrane (25 µm thickness (Celgard 2400)) and the above described adhesive layer. and a peelable protective layer applied to the membrane on the other side.

2

Round, disc-shaped pieces with a size of 1 cm are formed from the resulting five-layer laminate. Each of these layers initially releases 2 130 to 150 µm / cm scopolamine and then releases 2 to 3 yum / cm / h at substantially constant rate, b) A solution of 22.3 parts of large molecule polyisobutene weight, as in a), 26 parts of low molecular weight polyisobutene, 35 as in a), 44.9 parts of mineral oil (66 cP at 25 ° C), 12.8 parts of scopolamine base, 8.8 parts of dimethyllaurylamide, and 835, 2 parts of chloroform was poured onto the coating described in a) to give a scopolamine base reservoir layer of about 50 µm thickness.

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A combination of adhesive layer and peel-off protective layer was similarly prepared by casting a solution of .23.5 parts of the high molecular weight isobutene, 29.5 parts of the low molecular weight isobutene, 47.6 parts of the mineral 5 oil ,. 7.8 parts of scopolamine base, 9.0 parts of dimethyllaurylamide and 882.6 parts of chloroform on the polyethylene terephthalate film treated with silicone described in a). The resulting contact layer had a thickness of about 50 µm.

The above-described coating-reservoir combination was then applied to one side of a 25 µm thick microporous polypropylene membrane (Celgard 2400) saturated with the mineral oil and the above-described adhesive-protective layer combination. was applied to the other side of the membrane. 2 round, disk-shaped pieces with a size of 4 cm were punched from the resulting five-layer laminate. Each layer is shaped such that it initially releases 125 µg / cm scopolamine and then releases 2 yug / cro / h scopolamine at a substantially constant rate.

c) Medicinal layers are prepared as described under a), however, the peelable adhesive layer consists of a silicone-treated polyethylene terephthalate film with a thickness of 127 µm 2 and the layer area is 2.5 cm. In vitro experiments show that these medicinal layers deliver 200 µg at the first burst within the first two hours and 10 µg / h in the following 72 hours.

The invention is further illustrated by the following non-limiting examples. Becoming part when nothing else. indicated, always means parts by weight. Temperatures are indicated in degrees Celsius.

EXAMPLE I

Unhealthy, healthy subjects are subjected to a physical examination to determine physical condition, hematology, blood chemistry and urinary status. The subject should not take any other medications one week before and during the trial duration to avoid falsifying the results of the study. The usual way of life should not be changed during the study and excesses of any type should be avoided.

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TABLE A

Effect of TTS scopolamine on basal gastric acid secretion.

Tj ^ Jd HCl (mval / 1) Trial versus ^ x + s value before TTS scopolamine 53 + 13 on the second day during 31 _ + 15 xx TTS scopolamine_ ~ _ 5 2 days after TTS scopolamine 22 + 20 x 1) linked t-test; n = 8 subjects x = p <0.05 xx - p <0.01 B # 8 voluntary healthy subjects are used for 4-8 hours 10 scopolamine base according to the described transdermal therapeutic system postauricular.

Before the start of the study, as well as on the second and fourth days of the ongoing study, the acid secretion (HCl and volume) becomes basic according to Lindenschmid et al., Zschr. Gastroenterology 17, 15 (1979) 820-826, determined.

The gastric acid secretion is collected by continuous suction at 10 minute intervals. The amount of hydrochloric acid separated off is determined by titration of a 5 ml sample against 0.1 n sodium hydroxide solution.

Adverse reactions of the subjects are recorded daily on a scale of 100 mm. Blood pressure, pulse and pupil size are recorded on days 0, 2 and 4.

From the attached Table A it can be shown that the acid secretion decreases considerably when TTS-scopolamine is used.

EXAMPLE II

Medicinal patches (bandages) are applied behind the ear (postauricular) of 5 adult male patients with Duodenal ulcer disease aged 21 to 40 years after removing the peel-off adhesive film. A study over a period of 48 hours using a placebo or scopolamine-containing patches in alternating nights is initiated.

At noon, before the start of the study, the skin surface behind the ear is cleaned and provided with a scopolamine or 8104929-10 r placebo containing patch. A standard meal is taken an hour later. Four hours later, the patient is fed a gavage tube and 1 hour afterwards, the patients again take a standard meal. From this time until the next morning, no further food, only water, is used.

The stomach contents are aspirated and removed five hours after the last meal. In the following nine hours, gastric acid secretion is collected per hour by means of a suction pump. 5 ml of the sample collected every hour is used for pH measurements and for the acid determination by titration with 0.1-n sodium hydroxide solution to pH 7 (neutral). The titration is carried out using an automatic titration device. executed. The electrodes used in the pH measurements are calibrated against standard buffer solutions after each determination.

The test results of the two consecutive nights are indicated by 15 'the hourly average mean acid excretion in millimoles / h and the hourly average hydrogen ion concentration in millimoles / l. The "Rank test" designated according to Wilcoxon is used for the statistical analysis. In addition, it is determined that the mean hourly acid excretion of 6.8 - + 1.8 mmol / h in overnight placebo use to the mean hourly acid excretion of 1.7 - + 0.4 - mmol / h when using reduces a scopolamine-containing patch. The results can be indicated as statistically significant (pO 0.001). The hydrogen ion concentration is unaffected (79.1 + 6.5 mmol / L in placebo use; 68.2 hh 3.5 mmol / 1) when using scopolamine-containing patches.

Four of the patients have a dry mouth when using scopolamine overnight and one of the patients suffers from a dry mouth shortly after the application of the scopolamine-containing patch. Other side effects cannot be reported.

EXAMPLE III

Scopolamine can be used, for example, as an anticholinergic active agent of the present invention in addition to conventional antacids, such as, for example, histamine receptor antagonists, cytoprotective agents and traditional neutralizing agents. Medicinal patches (dressings) according to the foregoing descriptions under a), b) and c) (described on pages 7 and 8) may be used in conjunction with other antacids, when these patches are on the mastodial area of ulcer diseases. suffering patients are introduced, who are also simultaneously subjected to conventional treatment according to the schedule indicated below.

TABLE B

Drug Dosage 5 Histamine HU receptor antagonist

Cimetidine 1 g daily with meals for 6 weeks, reducing the dose to 400 mg with continued treatment thereafter.

10 CGEOPROTECTIVE SUBSTANCES PGE2 3 mg PGE2 three times daily with meals, reducing the dose to 2 mg three times daily after one week of treatment.

25 Antacids

Aluminum resp. magnesium salts 250 mg three times a day with meals, followed by 100 mg three times a day after one week administration.

example IV. 2q A transdermal therapeutic system based patch (TTS bandage), calculated at a constant release rate of 2 µg / cm / h, which releases 0.5 mg of constant rate scopolamine over a period of 3 days is administered at the subjects placed behind the ear (postauricular).

Nocturnal acid secretion is determined on two consecutive nights in 6 male ulcer patients under special supervision for 48 hours. (The average age is indicated with 31.2 years). In the afternoon, before each trial, the skin surface is cleaned behind the ear and a placebo (first 30 trial) or scopolamine-coated TTS patch (second trial) is applied to the skin. At 17:00 (i.e., 5 hours thereafter), a gastric tube (10 G-Salem gastric tube) (Argyle Medical) is inserted into the subjects. Standard meals are used by the subjects on both days at 1 pm and 6 pm. After that, only the use of water is permitted. The stomach contents are aspirated and removed at 11 pm and the gastric secretion is collected per hour by aspiration until 8 am and * if necessary, assisted by aspiration. 5 ml of the secretion samples collected every hour are then necessary for measuring the pH value and for titration with 1-n sodium hydroxide solution, to obtain the pH value 7 (neutral), 8104929 Ί & * «• 12-. automatic titration device (radiometer, copenhagen) is used.

The pH electrodes are calibrated against a standard buffer-5 solution after each determination.

All subjects are asked in the morning for any side effects that occur.

The results are indicated by the hourly mean mean acid discharges in mmol / h and the hourly mean hydrogen ion concentration TH + J in mmol / l. For the statistical analysis, the "Rank test" designated according to Wilcoxon is used. Valuation of results.

In one of the 6 selected subjects, when using a TTS placebo patch, the stomach cry was aspirated of technically unsatisfactory quality, so that this participant was excluded from the further trial.

The other 5 subjects found that the mean acid excretion per hour (23:00 - 08:00) of 6.8 + _ 1.8 mmol / h with placebo application at night to the mean acid excretion per 20 hours of 1.7 + 0.4mmol / h when using a scopolamine-containing patch. This 75% reduction in gastric acid secretion can be identified as significant (p 0.001). The hydrogen ion concentration is unaffected (79.1 + 6.4 mmole / l with placebo, 68.2 + 3.5 mmole / l with scopolamine-containing patch).

It is known that some subjects do not respond to H 2 receptor antagonists. In this case, a subject did not respond to the administration of cimetidine. In this subject, gastric acid secretion was reduced by 88% overnight using TTS scopolamine. However, care should be taken that acid secretion is reduced, but the pH value (hydrogen ion concentration) is not affected, so that the bacterial flora remains unchanged.

The gastric juice is distinguished by the absence of mucus, which appears when using H2 receptor antagonists, for example, cimetidine.

The results of this study have shown that TTS scopolamine at a release rate of 5 µg / h (i.e., with transdermal supply of scopolamine) significantly reduces nocturnal acid secretion in patients suffering from Duodenal ulcer. The transdermal therapeutic system (TTS) indicates the anticholinergic active substance, such as, for example, scopolamine, in a continuous flow over a period of 72 hours.

Analogously, TTS scopolamine, alone or in combination with another predefined acid-inhibiting agent, such as, for example, 5 in the case of an α 1-receptor antagonist, for example, cimetidine, may be used therefor to reduce the rate of cure patients previously suffering from Duodenal ulcer.

k «8104929

Claims (15)

1. Pharmaceutical composition, in particular for the inhibition of gastric acid secretion, characterized by the presence of anticholinergic substances in the form of parenterally applicable therapeutic systems, which continuously release these active substances. 2. A process for the preparation of pharmaceutical preparations, in particular for the inhibition of gastric acid secretion, characterized in that anticholinergic substances are introduced in the form of parenterally applicable therapeutic systems, which release these active substances continuously. 3. Use of anticholinergic substances in the form of parenterally applicable therapeutic systems, which continuously release these active substances, for the inhibition of gastric acid secretion. 4. Use according to claim 3, characterized in that anticholinergic substances in the form of trans- or intradermal, subcutaneous or also intramuscularly applicable therapeutic systems, which deliver these active substances continuously, in the presence. or use absence of antacids or also H 2 receptor antagonists for inhibition of gastric acid secretion. Use according to claim 3, characterized in that anticholinergic substances in the form of transdermal therapeutic systems, which release these active substances continuously, in the presence or absence of antacids and / or also receptor antagonist and for the inhibition of apply gastric acid secretion. 6. Use according to claim 3, characterized in that anticholinergic substances of the atropine type in the form of transdermal therapeutic systems, which release the active substances continuously, in the presence or absence of antacids and / or also 1 - - - receptor antagonists to inhibit gastric acid secretion. Use according to claim 3, characterized in that scopolamine is used as an anticholinergic in the form of transdermal therapeutic systems which release the scopolamine continuously, in the presence or absence of antacids and / or also H2 receptor antagonists for the inhibition of apply gastric acid secretion. 8. Use according to claim 3, characterized in that scopolamine base is used as an anticholinergic in the form of transdermal therapeutic systems, which continuously release the scopolamine, for the inhibition of gastric acid secretion. 810 4 92 9 -15- ..... "......................," Use according to claim 3, characterized in that scopolamine base is used as an anticholinergic in the form of transdermal therapeutic systems, which release the scopolamine continuously in an amount of 0.3 to 15 µg / g, for the inhibition of gastric acid. 5 uses secretion. Use according to claim 3, characterized in that scopolamine base is used as an anticholinergic in the form of transdermal therapeutic systems, which inject the scopolamine in an incremental amount at the beginning of 10-200 yug / cm skin and then 10. continuously. at a rate of 0.3-15 µg / h, for inhibiting gastric acid secretion. 11. Use for the treatment of hyperacidity and ulcer diseases by inhibiting gastric acid secretion, characterized in that anticholinergic active substances in the form of trans- or intradermal, subcutaneous or also intramuskularly applicable therapeutic systems, which deliver these active substances continuously, in the presence or absence of antacids and / or also administer receptor antagonists. 12. Method according to claim 11, for the treatment of hyperacidity and ulcer diseases by inhibiting gastric acid secretion, characterized in that anticholinergic active substances in the form of transdermal therapeutic systems, which deliver these active substances continuously, in the presence or absence of administer antacids and / or receptor antagonists. Method according to claims 11 and 12 for the treatment of hyperacidity and ulcer diseases by inhibiting gastric acid secretion, characterized in that scopolamine is used as an anticholinergic in the form of transdermal therapeutic systems, which continuously release the scopolamine, in the presence or also absence of antacids and / or also administer H 2 receptor antagonists. 14>. A method according to claims 11-13 for the treatment of hyperacidity and ulcer diseases by inhibiting gastric acid secretion, characterized in that scopolamine base is administered as an anticholinergic in the form of transdermal therapeutic systems which continuously release the scopolamine. A method according to claims 11-14 for the treatment of hyperacidity and ulcer diseases by inhibiting gastric acid secretion, characterized in that scopolamine base is used as an anticholinergic in the form of transdermal therapeutic systems, containing scopolamine in an amount of 0.3 to Continuously deliver 15 µg / h. 8104929