CA2192110C - Active substance carrier for the controlled release of active substances in the gastrointestinal tract with delayed passage through the pylorus - Google Patents
Active substance carrier for the controlled release of active substances in the gastrointestinal tract with delayed passage through the pylorus Download PDFInfo
- Publication number
- CA2192110C CA2192110C CA002192110A CA2192110A CA2192110C CA 2192110 C CA2192110 C CA 2192110C CA 002192110 A CA002192110 A CA 002192110A CA 2192110 A CA2192110 A CA 2192110A CA 2192110 C CA2192110 C CA 2192110C
- Authority
- CA
- Canada
- Prior art keywords
- active substance
- substance carrier
- carrier according
- active
- poly
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Abstract
A web-shaped, sheet-like substrate provided with openings and charged with active substance is used as starting material for the manufacture of an active substance carrier for the controlled release of active substances in the gastrointestinal tract which has a delayed pylorus passage.
Description
c .~.
219211Q~
" I
Active substance carrier for the controlled release of active sub-stances in the gastrointestinal tract with a delayed pylorus pas-sage The present invention relates to the use of a web-shaped, sheet-like substrate provided with openings and loaded with active sub-stance.
Active substance carriers and administration forms having a pro-longed retention time in the stomach are used to make possible a local therapy of stomach diseases. In addition, they permit the re-lease of active substances over a period which altogether is longer than that of conventional peroral administration forms so that the frequency of intake can be reduced.
A prolonged residence time in the stomach is provided by admini-stration forms which either have a particularly low density and float on the gastric juice or cannot pass the pylorus owing to their size or bulkiness.
For example, floating administration forms are those having a large portion of lipophilic, low-density substances (DE 26 11 041 ). In addition, there are descriptions how a delayed-action tablet or capsule can be caused to float by means of a plurality of air inclu-sions (EP-A 0 297 978, DE-A 38 03 482). Finally, gas-producing substances or mixtures, for example, C03 producing effervescent mixtures, can be incorporated into an enclosed administration form; this at the same time results in an expansion of such a de-vice after application (US 4 996 058).
A great disadvantage of the floating administration forms is their unreliable gastro-retentivity. As long as their passage through the , 219~1~(~
219211Q~
" I
Active substance carrier for the controlled release of active sub-stances in the gastrointestinal tract with a delayed pylorus pas-sage The present invention relates to the use of a web-shaped, sheet-like substrate provided with openings and loaded with active sub-stance.
Active substance carriers and administration forms having a pro-longed retention time in the stomach are used to make possible a local therapy of stomach diseases. In addition, they permit the re-lease of active substances over a period which altogether is longer than that of conventional peroral administration forms so that the frequency of intake can be reduced.
A prolonged residence time in the stomach is provided by admini-stration forms which either have a particularly low density and float on the gastric juice or cannot pass the pylorus owing to their size or bulkiness.
For example, floating administration forms are those having a large portion of lipophilic, low-density substances (DE 26 11 041 ). In addition, there are descriptions how a delayed-action tablet or capsule can be caused to float by means of a plurality of air inclu-sions (EP-A 0 297 978, DE-A 38 03 482). Finally, gas-producing substances or mixtures, for example, C03 producing effervescent mixtures, can be incorporated into an enclosed administration form; this at the same time results in an expansion of such a de-vice after application (US 4 996 058).
A great disadvantage of the floating administration forms is their unreliable gastro-retentivity. As long as their passage through the , 219~1~(~
pylorus is not additionally impeded by their size (EP-A 0 308 9041, flotation takes place only in persons sitting or standing upright. In case of lying persons the pylorus is likely to come into contact with the surface of the gastric juice, with the floating administra-tion form being preferentially transported into the small intestine (A.J. Moes, Crit. Rev. Therap. Drug Carrier Syst. 10, 143, 1993).
Additionally, flotation of such devices requires the presence of a minimum amount of gastric juice; this, however, cannot always be supposed in patients.
Administration forms retained in the stomach because of their size or bulkiness have also been known for a long time now. Since the administration form is to be swallowed and must~therefore not~ex-ceed a certain maximum dimension, different mechanisms used to enlarge the device in the stomach after application have been de-scribed. For example, this can be achieved by providing a gas phase in the device after contact with aqueous liquid (US 4 996 058), or by swelling of hydrophilic components in the gastric juice (EP 0 425 154, US 5 147 646, EP 0 310 326, US 4 207 890, US
4 434 153). The disadvantage of these administration forms pri- , marify lies in the fact that they either have an insufficient stability to resist the contractile forces produced by the musculature of the stomach wall or - in case they have this strength - involve the risk of resulting in an undesired and probably dangerous pylorus ob-struction which prevents the further transport of the remaining gastric contents.
Also, differently shaped, bulky active substance-carrying devices are known which, for application purposes, are present in a com-pressed or contracted form first. In this connection, the com-pressed or contracted state is generally fixed by means of enclo-sures, such as capsules, until these disintegrate in the gastric juice. After disintegration of the enclosure, recovery forces or the swelling pressure of hydrophilic components cause the bulky structures to revert to their original shape (US 4 735 804, EP 0 202 159, US 5 002 772, EPA 0 415 671 ~.
As long as their mechanical stability is sufficient to resist the gas-tric contraction, they might be best suitable as gastro-retentive administration forms because the pylorus passage is prevented reliably and emptying the remaining stomach contents is not im-peded.
In contrast to construction features'of various gastro-retentive systems, aspects with respect to.production.engineering are:only -scarcely described in the art. Owing to the complex shaping ofrthe knowngastro-retentive administration forms;~the industrial series production of such systems involves considerable effort and capi-tal cost. Continuous processes~have not been described as yet.
Gastro-retentive administration forms-frequently comprise different components serving either the conservation of the shape or the active substance release. Also, there are no pharmaceutical test methods ensuring the quality of these administration forms during production. Large and unwieldy structures having a high mechani-cal stability are difficult to manufacture; in addition, it is disadvan-tageous that they may cause stomach irritations.
It is the object of the present invention to provide an active sub-stance carrier for the controlled release of active substances in the gastrointestinal tract with a delayed pylorus passage, which avoids or even overcomes the above-mentioned disadvantages and difficulties, permits a considerably prolonged retention time in the stomach under release of active substances during a local therapy of the stomach or the gastric mucous membrane, facilitates the oral application to a very high degree, and is suitable for an eco-nomically efficient series production.
To solve this object, the present invention proposes the use of an active substance carrier in web form provided with openings and a - ' ' 2192110 substrate charged with active substance as starting material for the production of an active substance carrier for the controlled release of active substances in the gastrointestinal tract and which exhibits a delayed pylorus passage.
The material of the active substance carrier is very advantageous in many respects. It permits an economic production by using known, continuous processes for processing web-shaped, sheet-like material, such as winding up and off,~coating'and punching, as well as encasing with a material.promoting the coherence. The gastro-retentive embodiments which can be produced thereby have additional advantageous properties. Foninstance, owing to the sheet-like design of the active-substance carrier,-irritations~of ..
the gastric mucosa are not - or only to a very slight degree - to be expected; these occur when the known three-dimensional bulky structures are used which are retained in the stomach because of their size or bulkiness. In particular when the device which unfolds in the gastric juice after erosion of the casing has a sufficient me-chanical stability, a high reliability with respect to the gastro-re-tentivity is to be expected. At an obtainable minimum expansion of 5 cm', the active substance carrier is greater than the opening of the human pylorus, with the maximum expansion to up to 8 cm' providing an even greater certainty of preventing the pylorus passage. As compared with most of the previous systems, wherein the passage through the pylorus takes place as soon as the stomach musculature succeeds in reducing the device to a sufficient extent,' better adjustment.of the intended residence time of the active substance carrier in the stomach is achieved. Since the degree of stomach contractions depends on a great variety of factors which can hardly be controlled in practice, for example, the activity state of the autonomic nervous system, in particular that of the parasympathetic nervous system, the retention time of the administration forms proposed so far may well be subject to a high degree of individual variability when in use. In contrast to i this, the retention time of the active substance carrier according to the present invention can be adjusted with a considerably higher reliability by means of the galenic formulation: the composition determines the rate at which the device in the gastric juice -mainly by means of erosion - loses the properties causing its re-tention.
The fact that the active substance ca«ier is provided with aper-tures counteracts the danger of an unintentional pylorus obstruc-tion. As a rule, the pylorus allows the passage of liquid material having a low to medium viscosity and of particulate material hav-ing a particle size of up to about 2 mm. If, for example, the active substahce carrier has openings of 3 mm or more in diameter, it is ensured that an undesired pylorus obstruction.cannot.take place:- .
Even in case the device should lie down over the pylorus opening, it would merely cause a screening effect.
According to one embodiment of the present invention, the active substance carrier comprises at least one active substance develop-ing a local effect in the stomach. This may be an active substance which is preferably absorbed by the gastric mucosa. However, it, may also be an active substance for which an absorption window exists in the upper portion of the small intestine. Thus, the subject matter of the present invention is also suitable for the administra-tion of active substances developing their effect in the upper por-tion of the small intestine. So far, conventional peroral depot forms have not been suitable for this purpose, since they release most of the dose not until having left the upper region of the small intestine. The active substance carrier according to the present invention can ensure that released active substance in dissolved form is supplied to the upper small intestine in an even manner over a prolonged period of time.
The present invention has several therapeutic advantages. On the one hand, it permits a considerably improved local treatment of stomach diseases, as compared with conventional administration forms. These particularly include the hyperacidity, microbial infec-tions, the gastritis, and the ulcer. Efficacious drugs are available for the treatment of these and other stomach diseases; their ef-fectiveness and therapeutic index, respectively, is increased by the fact that they are administered by means of the active substance carrier according to the present invention. Thereby a particularly large portion of the applied active substance dose is brought into immediate contact with the affected tissue: The period of local exposure to effective drug concentrations is increased. Examples of such active substances include mineral antacids, HZ receptor blockers, such as cimetidine, ranitidine, famotidine, nizatidine, roxatidine, and their salts; muscarine receptor.blockers; such as pirenzipine; so-called protowpumps, such as omeprazol and miso-prostol; drugs which are effective against heliobacter pylorii and other microbial noxae, such as proglumide and carbenoxolone.
According to an embodiment, the active substance carrier addi-tionally comprises gaseous substances, gas-producing substances and mixtures, or liquid and solid substances and/or their mixtures having a relative density of < 1. This supports the retention of the active substance carrier in the stomach by the fact that - in addi-tion to the size of its area - it becomes a floating device.
According to the present invention, the active substance carrier consists of or comprises a material which is erodable in biological liquids. The composition of the material that is used substantially determines the retention time of the gastro-retentive device in the stomach. It is preferred that it consist of one or several physio-logically acceptable polymers and further pharmaceutical adju-vants, for example, softening agents, wetting agents, hydrophiliz-_ ing agents, stabilizers, dyes, release agents, buffer salts, and the like. Examples of the polymers to be used include polysaccharides, such as gums, starch or cellulose derivatives; polyacrylates and i , 21921.0 polymethacrylates; polylactides, polyglycolides, poly(oxyethylenes) and polyoxypropylenes; proteins, polyvinyl alcohop, polyvinyl acetate), polyvinyl chloride), or polyvinyl pyrrolidone); silicone elastomers, and copolymers. By using suitable mixtures an erosion rate can be adjusted which achieves the intended retention time in the stomach. At the end of this period, a device manufactured ac-cording to the present invention has lost its mechanical stability to a degree that allows its size reduction by the gastric contraction and thus its passage through the pylorus. At the end of this pe-riod, an active substance carrier produced according to the pres-ent invention has lost its mechanical stability to a degree that al-lows its size reduction by gastric 'contractions and thus its passage through the pylorus.
The dimensions of active substance carriers that can be manufac-tured according to the present invention are changed by means of rolling or folding them in such a manner that they are rendered suitable for a peroral application. This implies that the sheet-like material be flexible and not brittle. After rolling up or folding, the devices are preferably provided with a suitable enclosure which , keeps them in this state until application. A hard gelatin capsule, for example, is such a casing; however, any other envelope is suitable which holds the device in its rolled or folded state, disin-tegrates in the gastric juice, and is pysiologically acceptable.
As a whole the active substance carrier is superior to the state of the art by a great variety of advantages. These include the fact that the active substance carrier makes it possible in a long-term therapy to reduce the frequency of taking to an extent by far ex-ceeding that of conventional sustained-release forms. In general, depot drugs are useful in the long-term therapy if the active sub-stance is eliminated from the body very quickly, i.e., at an elimination half-life of less than about 10-20 h. In case the intake frequency can be reduced by means of sustained-release forms, 21921iQ
-extreme variations of the blood level and with that undesired side effects can be avoided and the patient compliance be improved.
When the active substance carrier according to the present inven-tion is used, the intake frequency of many active substances can be reduced to a once-a-day dose which represents another prog-ress in the therapeutic safety.
Additionally, flotation of such devices requires the presence of a minimum amount of gastric juice; this, however, cannot always be supposed in patients.
Administration forms retained in the stomach because of their size or bulkiness have also been known for a long time now. Since the administration form is to be swallowed and must~therefore not~ex-ceed a certain maximum dimension, different mechanisms used to enlarge the device in the stomach after application have been de-scribed. For example, this can be achieved by providing a gas phase in the device after contact with aqueous liquid (US 4 996 058), or by swelling of hydrophilic components in the gastric juice (EP 0 425 154, US 5 147 646, EP 0 310 326, US 4 207 890, US
4 434 153). The disadvantage of these administration forms pri- , marify lies in the fact that they either have an insufficient stability to resist the contractile forces produced by the musculature of the stomach wall or - in case they have this strength - involve the risk of resulting in an undesired and probably dangerous pylorus ob-struction which prevents the further transport of the remaining gastric contents.
Also, differently shaped, bulky active substance-carrying devices are known which, for application purposes, are present in a com-pressed or contracted form first. In this connection, the com-pressed or contracted state is generally fixed by means of enclo-sures, such as capsules, until these disintegrate in the gastric juice. After disintegration of the enclosure, recovery forces or the swelling pressure of hydrophilic components cause the bulky structures to revert to their original shape (US 4 735 804, EP 0 202 159, US 5 002 772, EPA 0 415 671 ~.
As long as their mechanical stability is sufficient to resist the gas-tric contraction, they might be best suitable as gastro-retentive administration forms because the pylorus passage is prevented reliably and emptying the remaining stomach contents is not im-peded.
In contrast to construction features'of various gastro-retentive systems, aspects with respect to.production.engineering are:only -scarcely described in the art. Owing to the complex shaping ofrthe knowngastro-retentive administration forms;~the industrial series production of such systems involves considerable effort and capi-tal cost. Continuous processes~have not been described as yet.
Gastro-retentive administration forms-frequently comprise different components serving either the conservation of the shape or the active substance release. Also, there are no pharmaceutical test methods ensuring the quality of these administration forms during production. Large and unwieldy structures having a high mechani-cal stability are difficult to manufacture; in addition, it is disadvan-tageous that they may cause stomach irritations.
It is the object of the present invention to provide an active sub-stance carrier for the controlled release of active substances in the gastrointestinal tract with a delayed pylorus passage, which avoids or even overcomes the above-mentioned disadvantages and difficulties, permits a considerably prolonged retention time in the stomach under release of active substances during a local therapy of the stomach or the gastric mucous membrane, facilitates the oral application to a very high degree, and is suitable for an eco-nomically efficient series production.
To solve this object, the present invention proposes the use of an active substance carrier in web form provided with openings and a - ' ' 2192110 substrate charged with active substance as starting material for the production of an active substance carrier for the controlled release of active substances in the gastrointestinal tract and which exhibits a delayed pylorus passage.
The material of the active substance carrier is very advantageous in many respects. It permits an economic production by using known, continuous processes for processing web-shaped, sheet-like material, such as winding up and off,~coating'and punching, as well as encasing with a material.promoting the coherence. The gastro-retentive embodiments which can be produced thereby have additional advantageous properties. Foninstance, owing to the sheet-like design of the active-substance carrier,-irritations~of ..
the gastric mucosa are not - or only to a very slight degree - to be expected; these occur when the known three-dimensional bulky structures are used which are retained in the stomach because of their size or bulkiness. In particular when the device which unfolds in the gastric juice after erosion of the casing has a sufficient me-chanical stability, a high reliability with respect to the gastro-re-tentivity is to be expected. At an obtainable minimum expansion of 5 cm', the active substance carrier is greater than the opening of the human pylorus, with the maximum expansion to up to 8 cm' providing an even greater certainty of preventing the pylorus passage. As compared with most of the previous systems, wherein the passage through the pylorus takes place as soon as the stomach musculature succeeds in reducing the device to a sufficient extent,' better adjustment.of the intended residence time of the active substance carrier in the stomach is achieved. Since the degree of stomach contractions depends on a great variety of factors which can hardly be controlled in practice, for example, the activity state of the autonomic nervous system, in particular that of the parasympathetic nervous system, the retention time of the administration forms proposed so far may well be subject to a high degree of individual variability when in use. In contrast to i this, the retention time of the active substance carrier according to the present invention can be adjusted with a considerably higher reliability by means of the galenic formulation: the composition determines the rate at which the device in the gastric juice -mainly by means of erosion - loses the properties causing its re-tention.
The fact that the active substance ca«ier is provided with aper-tures counteracts the danger of an unintentional pylorus obstruc-tion. As a rule, the pylorus allows the passage of liquid material having a low to medium viscosity and of particulate material hav-ing a particle size of up to about 2 mm. If, for example, the active substahce carrier has openings of 3 mm or more in diameter, it is ensured that an undesired pylorus obstruction.cannot.take place:- .
Even in case the device should lie down over the pylorus opening, it would merely cause a screening effect.
According to one embodiment of the present invention, the active substance carrier comprises at least one active substance develop-ing a local effect in the stomach. This may be an active substance which is preferably absorbed by the gastric mucosa. However, it, may also be an active substance for which an absorption window exists in the upper portion of the small intestine. Thus, the subject matter of the present invention is also suitable for the administra-tion of active substances developing their effect in the upper por-tion of the small intestine. So far, conventional peroral depot forms have not been suitable for this purpose, since they release most of the dose not until having left the upper region of the small intestine. The active substance carrier according to the present invention can ensure that released active substance in dissolved form is supplied to the upper small intestine in an even manner over a prolonged period of time.
The present invention has several therapeutic advantages. On the one hand, it permits a considerably improved local treatment of stomach diseases, as compared with conventional administration forms. These particularly include the hyperacidity, microbial infec-tions, the gastritis, and the ulcer. Efficacious drugs are available for the treatment of these and other stomach diseases; their ef-fectiveness and therapeutic index, respectively, is increased by the fact that they are administered by means of the active substance carrier according to the present invention. Thereby a particularly large portion of the applied active substance dose is brought into immediate contact with the affected tissue: The period of local exposure to effective drug concentrations is increased. Examples of such active substances include mineral antacids, HZ receptor blockers, such as cimetidine, ranitidine, famotidine, nizatidine, roxatidine, and their salts; muscarine receptor.blockers; such as pirenzipine; so-called protowpumps, such as omeprazol and miso-prostol; drugs which are effective against heliobacter pylorii and other microbial noxae, such as proglumide and carbenoxolone.
According to an embodiment, the active substance carrier addi-tionally comprises gaseous substances, gas-producing substances and mixtures, or liquid and solid substances and/or their mixtures having a relative density of < 1. This supports the retention of the active substance carrier in the stomach by the fact that - in addi-tion to the size of its area - it becomes a floating device.
According to the present invention, the active substance carrier consists of or comprises a material which is erodable in biological liquids. The composition of the material that is used substantially determines the retention time of the gastro-retentive device in the stomach. It is preferred that it consist of one or several physio-logically acceptable polymers and further pharmaceutical adju-vants, for example, softening agents, wetting agents, hydrophiliz-_ ing agents, stabilizers, dyes, release agents, buffer salts, and the like. Examples of the polymers to be used include polysaccharides, such as gums, starch or cellulose derivatives; polyacrylates and i , 21921.0 polymethacrylates; polylactides, polyglycolides, poly(oxyethylenes) and polyoxypropylenes; proteins, polyvinyl alcohop, polyvinyl acetate), polyvinyl chloride), or polyvinyl pyrrolidone); silicone elastomers, and copolymers. By using suitable mixtures an erosion rate can be adjusted which achieves the intended retention time in the stomach. At the end of this period, a device manufactured ac-cording to the present invention has lost its mechanical stability to a degree that allows its size reduction by the gastric contraction and thus its passage through the pylorus. At the end of this pe-riod, an active substance carrier produced according to the pres-ent invention has lost its mechanical stability to a degree that al-lows its size reduction by gastric 'contractions and thus its passage through the pylorus.
The dimensions of active substance carriers that can be manufac-tured according to the present invention are changed by means of rolling or folding them in such a manner that they are rendered suitable for a peroral application. This implies that the sheet-like material be flexible and not brittle. After rolling up or folding, the devices are preferably provided with a suitable enclosure which , keeps them in this state until application. A hard gelatin capsule, for example, is such a casing; however, any other envelope is suitable which holds the device in its rolled or folded state, disin-tegrates in the gastric juice, and is pysiologically acceptable.
As a whole the active substance carrier is superior to the state of the art by a great variety of advantages. These include the fact that the active substance carrier makes it possible in a long-term therapy to reduce the frequency of taking to an extent by far ex-ceeding that of conventional sustained-release forms. In general, depot drugs are useful in the long-term therapy if the active sub-stance is eliminated from the body very quickly, i.e., at an elimination half-life of less than about 10-20 h. In case the intake frequency can be reduced by means of sustained-release forms, 21921iQ
-extreme variations of the blood level and with that undesired side effects can be avoided and the patient compliance be improved.
When the active substance carrier according to the present inven-tion is used, the intake frequency of many active substances can be reduced to a once-a-day dose which represents another prog-ress in the therapeutic safety.
Claims (11)
1. A sheet-like active substance carrier, provided with openings, for the controlled release of active substances in the gastrointestinal tract with a delayed pylorus passage, characterized in that it is produced using a web-shaped, sheet-like substrate provided with openings and charged with active substance as starting material, wherein said active substance carrier consists of or comprises said material that consists of one or several physiologically acceptable polymers and further pharmaceutical adjuvants, said polymers being selected from the group consisting of polysaccharides, polyacrylates and polymethacrylates, polylactides, polyglycolides, poly (oxyethylenes) and polyoxypropylenes, proteins, poly (vinyl alcohol), poly (vinyl acetate), poly (vinyl chloride), or poly (vinyl pyrrolldone) silicone elastomers and copolymers or mixtures thereof, and said adjuvants being selected from the group consisting of softening agents, wetting agents, hydrophilizing agents, stabilizers, dyes, release agents, and buffer salts.
2. The active substance carrier according to claim 1, characterized in that it comprises at least one active substance developing a local action in the stomach.
3. The active substance carrier according to claim 1 or 2, characterized in that it comprises at least one active substance which is primarily absorbed by the gastric mucosa.
4. An active substance carrier according to claim 1 characterized in that it comprises at least one active substance absorbable in the upper small intestine.
5. The active substance carrier according to any one of claims 1 to 4 characterized in that it additionally comprises gaseous substances, gas-producing substances or substance mixtures, or liquid and solid substances or mixtures thereof, which have a relative density of <1.
6. The active substance carrier according to any one of claims 1 to 5 characterized in that it consists of or comprises a material which is erodable in biological liquids.
7. The active substance carrier according to any one of claims 1 to 6 characterized in that it is formed with an orally applicable compacted form as a roll or folded compressed article.
8. The active substance carrier according to any one of claims 1 to 7 characterized in that in a compact form it is surrounded by a casing which disintegrates in the gastric juice.
9. The active substance carrier according to any one of claims 1 to 8 characterized in that it has an area of at least 5 cm2 in an unrolled or unfolded state.
10. The active substance carrier according to claim 8 wherein the casing is a capsule.
11. The active substance carrier according to claim 1 wherein the polysaccharide is selected from the group consisting of gums, starch, and cellulose derivatives.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4419818A DE4419818C2 (en) | 1994-06-07 | 1994-06-07 | Drug carrier for the controlled release of active substances in the gastrointestinal tract with delayed pyloric passage and method for producing the same |
| DEP4419818.3 | 1994-06-07 | ||
| PCT/EP1995/002121 WO1995033449A1 (en) | 1994-06-07 | 1995-06-03 | Active substance carrier for the controlled release of active substances in the gastro-intestinal tract with delayed passage through the pylorus |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2192110A1 CA2192110A1 (en) | 1995-12-14 |
| CA2192110C true CA2192110C (en) | 2006-05-02 |
Family
ID=6519958
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002192110A Expired - Fee Related CA2192110C (en) | 1994-06-07 | 1995-06-03 | Active substance carrier for the controlled release of active substances in the gastrointestinal tract with delayed passage through the pylorus |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP0765158B1 (en) |
| JP (1) | JP3801200B2 (en) |
| KR (1) | KR100499898B1 (en) |
| CN (1) | CN1204878C (en) |
| AT (1) | ATE172875T1 (en) |
| AU (1) | AU702676B2 (en) |
| CA (1) | CA2192110C (en) |
| CZ (1) | CZ356696A3 (en) |
| DE (2) | DE4419818C2 (en) |
| DK (1) | DK0765158T3 (en) |
| ES (1) | ES2126287T3 (en) |
| FI (1) | FI118952B (en) |
| HU (1) | HU221675B1 (en) |
| IL (1) | IL113930A (en) |
| MY (1) | MY130546A (en) |
| NO (1) | NO965236L (en) |
| NZ (1) | NZ287884A (en) |
| PL (1) | PL317378A1 (en) |
| SK (1) | SK281043B6 (en) |
| WO (1) | WO1995033449A1 (en) |
| ZA (1) | ZA954650B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0936903B1 (en) | 1996-09-07 | 2003-10-08 | Günther Beisel | Product with extender effect |
| DE19745208A1 (en) * | 1997-10-13 | 1999-04-15 | Labtec Gmbh | Pharmaceutical film that dissolves in mouth |
| DE19757298A1 (en) | 1997-12-22 | 1999-06-24 | Basf Ag | Process for the preparation of polymer powders |
| DE19822278A1 (en) * | 1998-05-18 | 1999-12-02 | Lohmann Therapie Syst Lts | Device for the controlled release of active substance in the gastrointestinal tract with delayed pyloric passage |
| DE19849848A1 (en) * | 1998-10-29 | 2000-05-04 | Lohmann Therapie Syst Lts | Oral application, spontaneous disintegration with liquid and dosage form and process for its preparation |
| FR2840221B1 (en) * | 2002-06-04 | 2006-01-13 | Backert Marie Elisabeth Cuine | POLYMERIC FILM CONTAINING "ACTIVE" TO BE RELEASED IN A LIQUID |
| DE102007026037A1 (en) | 2007-06-04 | 2008-12-11 | Lts Lohmann Therapie-Systeme Ag | Gastroretentive system with alginate body |
| DE102011006844A1 (en) | 2011-04-06 | 2012-10-11 | Siemens Aktiengesellschaft | Electric machine |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH624846A5 (en) * | 1975-12-15 | 1981-08-31 | Hoffmann La Roche | Solid pharmaceutical unit dose form and process and apparatus for producing it |
| DE2746414A1 (en) * | 1977-10-15 | 1979-04-26 | Gerlach Eduard Chem Fab | Foil-like tape for dispensing measured amts. of substance - consisting of the substance, binding agent and adjuvants, tape length being proportional to weight of substance |
| CA1273872A (en) * | 1985-05-10 | 1990-09-11 | Larry J. Caldwell | Drug delivery device which can be retained in the stomach for a controlled period of time |
| JPS63501794A (en) * | 1985-10-09 | 1988-07-21 | デジテイン アルツナイミツテル ゲ−エムベ−ハ− | Methods for providing pharmaceutically active substances, reagents, and other active substances or for producing dosage forms |
| DE3630603A1 (en) * | 1986-09-09 | 1988-03-10 | Desitin Arzneimittel Gmbh | PHARMACEUTICAL AND DOSAGE FORM FOR MEDICINAL ACTIVE SUBSTANCES, REAGENTS OR THE LIKE, AND METHOD FOR THE PRODUCTION THEREOF |
| JPH03163011A (en) * | 1989-08-31 | 1991-07-15 | Yamanouchi Pharmaceut Co Ltd | Device stayed in stomach |
| GB9203474D0 (en) * | 1992-02-19 | 1992-04-08 | Smithkline Beecham Plc | Novel composition |
-
1994
- 1994-06-07 DE DE4419818A patent/DE4419818C2/en not_active Expired - Fee Related
-
1995
- 1995-05-31 IL IL11393095A patent/IL113930A/en not_active IP Right Cessation
- 1995-06-03 CA CA002192110A patent/CA2192110C/en not_active Expired - Fee Related
- 1995-06-03 SK SK1573-96A patent/SK281043B6/en unknown
- 1995-06-03 JP JP50035396A patent/JP3801200B2/en not_active Expired - Fee Related
- 1995-06-03 NZ NZ287884A patent/NZ287884A/en unknown
- 1995-06-03 ES ES95921828T patent/ES2126287T3/en not_active Expired - Lifetime
- 1995-06-03 AT AT95921828T patent/ATE172875T1/en active
- 1995-06-03 CZ CZ963566A patent/CZ356696A3/en unknown
- 1995-06-03 KR KR1019960706983A patent/KR100499898B1/en not_active IP Right Cessation
- 1995-06-03 EP EP95921828A patent/EP0765158B1/en not_active Expired - Lifetime
- 1995-06-03 WO PCT/EP1995/002121 patent/WO1995033449A1/en not_active Application Discontinuation
- 1995-06-03 AU AU26743/95A patent/AU702676B2/en not_active Ceased
- 1995-06-03 HU HU9603326A patent/HU221675B1/en not_active IP Right Cessation
- 1995-06-03 DE DE59504159T patent/DE59504159D1/en not_active Expired - Lifetime
- 1995-06-03 PL PL95317378A patent/PL317378A1/en unknown
- 1995-06-03 CN CNB951934333A patent/CN1204878C/en not_active Expired - Fee Related
- 1995-06-03 DK DK95921828T patent/DK0765158T3/en active
- 1995-06-06 MY MYPI95001477A patent/MY130546A/en unknown
- 1995-06-06 ZA ZA954650A patent/ZA954650B/en unknown
-
1996
- 1996-12-05 FI FI964885A patent/FI118952B/en not_active IP Right Cessation
- 1996-12-06 NO NO965236A patent/NO965236L/en not_active Application Discontinuation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU758324B2 (en) | Orally administered controlled drug delivery system providing temporal and spatial control | |
| ES2219709T3 (en) | A CHARACTERIZED PHARMACEUTICAL TABLET BECAUSE IT PRESENTS A GREAT INCREASE IN VOLUME WHEN IT COMES IN CONTACT WITH BIOLOGICAL FLUIDS. | |
| KR100890180B1 (en) | Oral preparations and supports for oral preparations | |
| US6960356B1 (en) | Orally administered drug delivery system providing temporal and spatial control | |
| US20090047330A1 (en) | Oral fast dissolving films for erectile dysfunction bioactive agents | |
| Garg et al. | Gastroretentive drug delivery systems for therapeutic management of peptic ulcer | |
| CA2192110C (en) | Active substance carrier for the controlled release of active substances in the gastrointestinal tract with delayed passage through the pylorus | |
| US20090202597A1 (en) | Ache-Nmda Combination Wafer | |
| US20030064101A1 (en) | Floating osmotic device for controlled release drug delivery | |
| MXPA02008568A (en) | Orally administered controlled delivery system for once daily administration of ciprofloxacin. | |
| Rathod et al. | A review on stomach specific floating in situ gel | |
| Patel et al. | A review: Gastroretentive drug delivery systems and its rational in peptic ulcer treatment | |
| Bhowmik et al. | Gastro Retentive Drug Delivery Systems-a Novel Approaches of Controlled Drug Delivery Systems | |
| MXPA96006146A (en) | Carrier of active substance for the controlled release of active substances in the gastrointestinal tract with a step delayed by the pil | |
| Gouda et al. | An Overview on Various Approaches for Gastroretentive Drug Delivery systems | |
| Prakash et al. | Floating Drug Delivery System: Applications based on in situ gel | |
| Shinde et al. | A novel approach of gastroretentive drug delivery: in situ gel | |
| Principal | Oral In-Situ Gel: A Review | |
| WO2003026555A2 (en) | Floating osmotic device for controlled release drug delivery | |
| Gangadharappa et al. | APTI ijper | |
| ZA200506028B (en) | Composition comprising a mixture of active principles, and method of preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20130604 |