EP0804242A1 - The use of dimeticone as a transport and carrier system and/or drug delivery system - Google Patents

The use of dimeticone as a transport and carrier system and/or drug delivery system

Info

Publication number
EP0804242A1
EP0804242A1 EP95913130A EP95913130A EP0804242A1 EP 0804242 A1 EP0804242 A1 EP 0804242A1 EP 95913130 A EP95913130 A EP 95913130A EP 95913130 A EP95913130 A EP 95913130A EP 0804242 A1 EP0804242 A1 EP 0804242A1
Authority
EP
European Patent Office
Prior art keywords
pharmaceutical composition
combination
composition containing
dimeticone
dimethylpoly
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.)
Withdrawn
Application number
EP95913130A
Other languages
German (de)
French (fr)
Inventor
Alfred Schmidt
Hans-Jürgen Upmeyer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of EP0804242A1 publication Critical patent/EP0804242A1/en
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/80—Polymers containing hetero atoms not provided for in groups A61K31/755 - A61K31/795
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • Dimeticone as a Transport and Carrier System and/or Drug Delivery System
  • the invention relates to dimethylpolysiloxane (dimeticone) to be used as a transport and carrier system and/or a drug delivery system for pharmaceutical drugs for instance for the treatment of gastro-intestinal diseases. Moreover, the invention relates to pharmaceutical compositions containing dimethylpolysiloxane as a transport and carrier system and/or as a drug delivery system in combination with an active ingredient and methods related thereto.
  • dimeticone-containing preparations are used to treat symptoms such as flatulence, sensation of repletion (bloating) and meteorism. Moreover, the use of dimeticone for treating inflammatory and ulcerous diseases of the esophagus, the stomach and the duodenum has been described.
  • the galenics of a pharmaceutical composition should be such that only the
  • the therapeutically active ingredient right at the site where it is to produce its effect or at the site where it is absorbed so as to increase the local bioavailability and/or general bioavailability of the active ingredient (for instance by averting a first pass effect in the liver) or so as to avoid systemic side effects as much as possible.
  • the continuous peristalsis, the variation of the chemical conditions over the length of the digestive tract, and the morphology of the surface of the GI tract are obstacles to a prolonged residence time in the different sections of the tract (such as the esophagus, stomach, duodenum, and colon) .
  • the present invention provides a carrier that lends itself for use in particular galenic pharmaceutical forms for oral, rectal and intraoperative applications which release and/or fix the active ingredient continuously at the very site where it is to produce its effect or is absorbed.
  • dimeticone because of its unique physico-chemical properties is ideally suited for such purposes.
  • Dimeticone has a very wide range of viscosities, depending on the degree of polymerization.
  • the viscosity of dimeticone to be used in accordance with the invention may vary, depending on the therapeutical purpose, the nature and location of the condition to be treated as well as the drug to be administered.
  • dimeticone having a kinematic viscosity in the range of 10 to 100,000 mm .S -1 is used.
  • dimeticone having a kinematic viscosity in the range of 300 to 1,500 mm .S "1 is particularly preferred. Dimeticone may also be supplemented with silicone dioxide as it is for example contained in the product Simeticone.
  • Dimeticone was found to show a particular association with or affinity to the surface structure of the GI tract. Because of an increased adhesion resulting from the adhesive properties of dimeticone, the residence time of an active ingredient in a region of the GI tract can be substantially prolonged if dimeticone is used as a transport or carrier system.
  • dimeticone because of the different chemical, morphological and physiological conditions along the GI tract, the affinity and association of dimeticone with the epithelial cells of the GI tract is not uniform. Thus, in order to optimize the effect of dimeticone as a transport and carrier system and/or drug delivery system for any particular drug at any particular site of the GI tract, dimeticone with the appropriate viscosity should be chosen, depending on the nature of the therapy and drug as well as the location in the GI tract. This may readily be determined' by experimentation.
  • dimeticone is not limited to the treatment of the GI tract. It may also be used in the treatment of the cardiovascular system the lungs, the brain and all hollow organs.
  • dimeticone was found to be particularly suitable as a transport and carrier system or a drug delivery system for cytostatic drugs, immunosup- pressants, immunomodulating and immunostimulative substances, biological response modifying (BRM) substances, radio-, chemo- and photosensitizers, anti-inflammatory substances, such as corticoids, antibiotics, analgesics, locally effective anestetics, antiphlogistics, non-steroidal antirheumatics, antiviral substances, bismuth preparations and motility inhibiting and motility enhancing substances.
  • BRM biological response modifying
  • dimeticone as a carrier for the photo- sensitizer ⁇ 5-amino levulinic acid (ALA) , the H-, antagonists (such as ranitidine and cimetidine) and the proton pump inhibitors (such as omeprazole and lansoprazole) is particularly preferred.
  • the pharmaceutical compositions which contain dimeticone in combination with one of the afore-mentioned substances therefore lend themselves particularly well for the treatment of inflammatory, infectious, ulcerous and neoplastic diseases of the GI tract.
  • the dimeticone-containing pharmaceutical composition may be formulated in an enteral form according to conventional methods in order to prevent dimeticone and the active ingredient from remaining in the upper zone of the GI tract.
  • the properties of the pharmaceutical composition should be so adjusted that it has an increased affinity for the lower part of the GI tract.
  • Direct application for instance via the bioptic channel of an endoscope, bronchoscope or proctoscope, intraoperative or by instillation, is particularly preferred.
  • the dimeticone-containing pharmaceutical composition should also contain highly dispersed silicon dioxide and/or a pharmaceutically acceptable surface-active agent.
  • the ratio of dimethylpolysiloxane to the surface-active agent is preferably 3 to 10 : 1, in particular 4 to 6 : 1, and the ratio of highly dispersed silicon dioxide to dimethylpolysiloxane is preferably 3 to 50% (wt/wt) .
  • a preferred range for the latter ratio is 30 to 40% (wt/wt) , the value of 35 to 36% being particularly preferred.
  • the concentration of the surface active agent is preferably at least 1.5 % (wt/wt).
  • a particularly preferred dimeticone formulation contains 8-10% (wt/wt) of the surface active agent.
  • Stearic salts or long chain alkanoic acids in particular C- j ⁇ -C- ⁇ g alkanoic acids, such as myristic acid, palmitic acid and stearic acid, and their salts, such as magnesium or calcium salts and mixtures thereof can be suitably used as pharmaceutically acceptable surface active agents.
  • ALA ⁇ -amino levulinic acid containing emulsion
  • colloidal magnesium aluminum silicate
  • the emulsion of the Example is intended for the photodynamic therapy of tumors of the GI tract, the emulsion being applied by means of an endoscope at the very site where the effect is to be elicited.

Abstract

The invention relates to dimethylpolysiloxane (dimeticone) to be used as a transport and carrier system and/or a drug delivery system for pharmaceutical drugs. Moreover, the invention relates to pharmaceutical compositions containing dimethylpolysiloxane as a transport and carrier system and/or as a drug delivery system in conbination with an active ingredient.

Description

The Use of Dimeticone as a Transport and Carrier System and/or Drug Delivery System
TECHNICAL FIELD OF THE INVENTION
The invention relates to dimethylpolysiloxane (dimeticone) to be used as a transport and carrier system and/or a drug delivery system for pharmaceutical drugs for instance for the treatment of gastro-intestinal diseases. Moreover, the invention relates to pharmaceutical compositions containing dimethylpolysiloxane as a transport and carrier system and/or as a drug delivery system in combination with an active ingredient and methods related thereto.
Commercial dimeticone-containing preparations are used to treat symptoms such as flatulence, sensation of repletion (bloating) and meteorism. Moreover, the use of dimeticone for treating inflammatory and ulcerous diseases of the esophagus, the stomach and the duodenum has been described.
BACKGROUND OF THE INVENTION
In order to avoid dose-related side effects, the galenics of a pharmaceutical composition should be such that only the
dose of the active ingredient necessary to elicit the desired therapeutic effect needs to be administered.
Hence, it is desirable to apply the therapeutically active ingredient right at the site where it is to produce its effect or at the site where it is absorbed so as to increase the local bioavailability and/or general bioavailability of the active ingredient (for instance by averting a first pass effect in the liver) or so as to avoid systemic side effects as much as possible.
In view of the different physiological properties of the different sections of the gastro-intestinal tract (GI tract) , local therapy is particularly difficult in this case.
The continuous peristalsis, the variation of the chemical conditions over the length of the digestive tract, and the morphology of the surface of the GI tract are obstacles to a prolonged residence time in the different sections of the tract (such as the esophagus, stomach, duodenum, and colon) .
Especially in the case of chronic diseases, such as inflammatory, infectious, ulcerous or neoplastic changes of the GI tract, direct local therapy capable of being continued over a prolonged period of time is desirable.
Furthermore, local treatment is also desirable in the case of disorders in the cardiovascular system, the lungs, the brain, and all hollow organs.
Local treatment requires a suitable transport and carrier system and/or drug delivery system. SUMMARY OF THE INVENTION
The present invention provides a carrier that lends itself for use in particular galenic pharmaceutical forms for oral, rectal and intraoperative applications which release and/or fix the active ingredient continuously at the very site where it is to produce its effect or is absorbed.
It was surprisingly found that dimeticone, because of its unique physico-chemical properties is ideally suited for such purposes. Dimeticone has a very wide range of viscosities, depending on the degree of polymerization. The viscosity of dimeticone to be used in accordance with the invention may vary, depending on the therapeutical purpose, the nature and location of the condition to be treated as well as the drug to be administered. Preferably, dimeticone having a kinematic viscosity in the range of 10 to 100,000 mm .S-1 is used.
The use of dimeticone having a kinematic viscosity in the range of 300 to 1,500 mm .S"1 is particularly preferred. Dimeticone may also be supplemented with silicone dioxide as it is for example contained in the product Simeticone.
Dimeticone was found to show a particular association with or affinity to the surface structure of the GI tract. Because of an increased adhesion resulting from the adhesive properties of dimeticone, the residence time of an active ingredient in a region of the GI tract can be substantially prolonged if dimeticone is used as a transport or carrier system.
However, because of the different chemical, morphological and physiological conditions along the GI tract, the affinity and association of dimeticone with the epithelial cells of the GI tract is not uniform. Thus, in order to optimize the effect of dimeticone as a transport and carrier system and/or drug delivery system for any particular drug at any particular site of the GI tract, dimeticone with the appropriate viscosity should be chosen, depending on the nature of the therapy and drug as well as the location in the GI tract. This may readily be determined' by experimentation.
The use of dimeticone is not limited to the treatment of the GI tract. It may also be used in the treatment of the cardiovascular system the lungs, the brain and all hollow organs.
According to the invention, dimeticone was found to be particularly suitable as a transport and carrier system or a drug delivery system for cytostatic drugs, immunosup- pressants, immunomodulating and immunostimulative substances, biological response modifying (BRM) substances, radio-, chemo- and photosensitizers, anti-inflammatory substances, such as corticoids, antibiotics, analgesics, locally effective anestetics, antiphlogistics, non-steroidal antirheumatics, antiviral substances, bismuth preparations and motility inhibiting and motility enhancing substances.
The function of dimeticone as a carrier for the photo- sensitizer <5-amino levulinic acid (ALA) , the H-, antagonists (such as ranitidine and cimetidine) and the proton pump inhibitors (such as omeprazole and lansoprazole) is particularly preferred.
The pharmaceutical compositions which contain dimeticone in combination with one of the afore-mentioned substances therefore lend themselves particularly well for the treatment of inflammatory, infectious, ulcerous and neoplastic diseases of the GI tract. In the treatment of disorders in the lower area of the GI tract, the dimeticone-containing pharmaceutical composition may be formulated in an enteral form according to conventional methods in order to prevent dimeticone and the active ingredient from remaining in the upper zone of the GI tract. Alternatively, the properties of the pharmaceutical composition should be so adjusted that it has an increased affinity for the lower part of the GI tract.
Direct application, for instance via the bioptic channel of an endoscope, bronchoscope or proctoscope, intraoperative or by instillation, is particularly preferred.
The dimeticone-containing pharmaceutical composition should also contain highly dispersed silicon dioxide and/or a pharmaceutically acceptable surface-active agent.
The ratio of dimethylpolysiloxane to the surface-active agent is preferably 3 to 10 : 1, in particular 4 to 6 : 1, and the ratio of highly dispersed silicon dioxide to dimethylpolysiloxane is preferably 3 to 50% (wt/wt) . A preferred range for the latter ratio is 30 to 40% (wt/wt) , the value of 35 to 36% being particularly preferred.
The concentration of the surface active agent is preferably at least 1.5 % (wt/wt). A particularly preferred dimeticone formulation contains 8-10% (wt/wt) of the surface active agent.
Stearic salts or long chain alkanoic acids, in particular C-j^-C-^g alkanoic acids, such as myristic acid, palmitic acid and stearic acid, and their salts, such as magnesium or calcium salts and mixtures thereof can be suitably used as pharmaceutically acceptable surface active agents.
The invention is illustrated by the following example. Example
δ-amino levulinic acid containing emulsion (ALA)
amount/dose g / 250 ml
ALA 5,000.0000 simeticone
(dimeticone 1000 - Si02 94:6) 2,000.0000
Aerosil 200 125.0000
Kollidon CL M1 2,500.0000 hydroxyethylcellulose 20,000.0000
Veegum K2 2,500.0000 cinnamon oil DA B 10 0.1228
85% indigotin 0.0250 water, purified ad 250 ml
1 = polyvinylpyrrolidone (INN: providone)
2 = colloidal magnesium = aluminum silicate
The emulsion of the Example is intended for the photodynamic therapy of tumors of the GI tract, the emulsion being applied by means of an endoscope at the very site where the effect is to be elicited.
While we have described an embodiment of this invention, it is apparent that our embodiment may be altered to provide other embodiments which utilize the method of this invention. Therefore, it will be appreciated that the scope of this invention is to be defined by the appended claims, rather than by the specific embodiment which has been presented by way of example.

Claims

We Claim:
1. The use of dimethylpolysiloxane as a transport or carrier system for active ingredients for the preparation of a pharmaceutical composition.
2. A pharmaceutical composition containing dimethyl¬ polysiloxane in combination with a photosensitizer.
3. The pharmaceutical composition according to claim 2 wherein the photosensitizer is <S-amino levulinic acid ALA.
4. A pharmaceutical composition containing dimethyl¬ polysiloxane in combination with an H2-antagonist and/or a proton pump inhibitor.
5. A pharmaceutical composition containing dimethyl¬ polysiloxane in combination with one or more anti¬ biotics.
6. A pharmaceutical composition containing dimethyl¬ polysiloxane in combination with an immunomodulating substance or an immunostimulating substance.
7. A pharmaceutical composition containing dimethylpoly¬ siloxane in combination with an analgesic or locally effective anesthetic.
8. A pharmaceutical composition containing dimethylpoly¬ siloxane in combination with an antiphlogistic or non- steroidal antirheumatic.
9. A pharmaceutical composition containing dimethylpoly¬ siloxane in combination with an anti-viral substance.
10. The use according to claim 1, wherein the active ingredient is a corticoid.
11. A pharmaceutical composition containing dimethylpoly¬ siloxane in combination with a bismuth preparation.
12. A pharmaceutical composition containing dimethylpoly¬ siloxane in combination with a motility-inhibiting or motility-enhancing substance.
13. A pharmaceutical composition containing dimethylpoly¬ siloxane in combination with BRM (biological response modifying) substances.
EP95913130A 1994-03-18 1995-03-15 The use of dimeticone as a transport and carrier system and/or drug delivery system Withdrawn EP0804242A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE4409357 1994-03-18
DE4409357A DE4409357C2 (en) 1994-03-18 1994-03-18 Use of Dimeticon to eradicate Heliobacter pylori
PCT/EP1995/000973 WO1995025545A1 (en) 1994-03-18 1995-03-15 The use of dimeticone as a transport and carrier system and/or drug delivery system

Publications (1)

Publication Number Publication Date
EP0804242A1 true EP0804242A1 (en) 1997-11-05

Family

ID=6513210

Family Applications (1)

Application Number Title Priority Date Filing Date
EP95913130A Withdrawn EP0804242A1 (en) 1994-03-18 1995-03-15 The use of dimeticone as a transport and carrier system and/or drug delivery system

Country Status (14)

Country Link
EP (1) EP0804242A1 (en)
JP (1) JPH09510466A (en)
CN (1) CN1244129A (en)
AU (1) AU699199B2 (en)
CA (1) CA2185882A1 (en)
CZ (1) CZ300796A3 (en)
DE (1) DE4409357C2 (en)
FI (1) FI963682A (en)
HU (1) HU215595B (en)
NO (1) NO963893L (en)
NZ (1) NZ282805A (en)
PL (1) PL316307A1 (en)
SK (1) SK132496A3 (en)
WO (1) WO1995025545A1 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6100245A (en) * 1999-09-07 2000-08-08 Mcneil-Ppc, Inc. Use of simethicone to treat ulcerative colitis
MXPA05012791A (en) * 2003-05-25 2006-02-22 Wang Yuwan Dimeticone-containing sustained formulation.

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR3848M (en) * 1964-05-04 1966-01-17 Robert Schapiro Therapeutic associations for the treatment of numerous organic or functional digestive disorders.
GB1357737A (en) * 1970-10-09 1974-06-26 Arpic Sa Sustained release pharmaceutical compositions
NZ217844A (en) * 1985-10-11 1989-10-27 Sumitomo Pharma A sustained release pharmaceutical composition containing silicone elastomer and an albumin
US4837029A (en) * 1987-04-06 1989-06-06 Carolina Medical Products, Inc. Low foaming, aqueously homogenizable rifampin composition
US5446070A (en) * 1991-02-27 1995-08-29 Nover Pharmaceuticals, Inc. Compositions and methods for topical administration of pharmaceutically active agents
EP0406248B1 (en) * 1989-01-19 1994-06-08 Alfred Schmidt Use of dimethylpolysiloxane for treating disorders of the gastrointestinal tract
IE903302A1 (en) * 1989-09-15 1991-04-10 Pehrom Pharmaceutical Corp Topical preparation for treatment of aphthous ulcers and¹other lesions
IN171919B (en) * 1989-11-01 1993-02-06 Mcneil Ppc Inc
US5229137A (en) * 1992-05-06 1993-07-20 Brigham And Women's Hospital, Inc. Methods and pharmaceutical compositions for treating episodic heartburn
AU4682193A (en) * 1992-07-29 1994-03-03 Merck & Co., Inc. Dexibuprofen/antacid/simethicone combinations

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9525545A1 *

Also Published As

Publication number Publication date
NZ282805A (en) 1998-02-26
FI963682A0 (en) 1996-09-17
NO963893D0 (en) 1996-09-17
FI963682A (en) 1996-11-13
HUT75711A (en) 1997-05-28
HU215595B (en) 1999-01-28
AU699199B2 (en) 1998-11-26
PL316307A1 (en) 1997-01-06
SK132496A3 (en) 1997-06-04
AU2071395A (en) 1995-10-09
DE4409357A1 (en) 1995-09-21
JPH09510466A (en) 1997-10-21
CN1244129A (en) 2000-02-09
WO1995025545A1 (en) 1995-09-28
CZ300796A3 (en) 1997-09-17
DE4409357C2 (en) 1996-10-17
CA2185882A1 (en) 1995-09-28
HU9602839D0 (en) 1996-12-30
NO963893L (en) 1996-11-04

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