CA2516291A1 - Dosage form having a saccharide matrix - Google Patents
Dosage form having a saccharide matrix Download PDFInfo
- Publication number
- CA2516291A1 CA2516291A1 CA002516291A CA2516291A CA2516291A1 CA 2516291 A1 CA2516291 A1 CA 2516291A1 CA 002516291 A CA002516291 A CA 002516291A CA 2516291 A CA2516291 A CA 2516291A CA 2516291 A1 CA2516291 A1 CA 2516291A1
- Authority
- CA
- Canada
- Prior art keywords
- dosage form
- allergen
- form according
- solid dosage
- active substance
- 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.)
- Granted
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
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/35—Allergens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/35—Allergens
- A61K39/36—Allergens from pollen
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/542—Mucosal route oral/gastrointestinal
Abstract
The present invention provides a non-compressed fast-dispersing solid dosage form suitable for oromucosal administration of a pharmaceutically active substance comprising (a) a first matrix forming agent in the form of maltodextrin having a dextrose equivalent (DE) of between 1 and 20,(b) a second matrix forming agent in the form of sorbitol, and (c) the active substance.
Claims (42)
1. A non-compressed fast-dispersing solid dosage form suitable for oromucosal administration of a pharmaceutically active substance comprising (a) a first matrix forming agent in the form of maltodextrin having a dextrose equivalent (DE) of between 1 and 20, (b) a second matrix forming agent in the form of sorbitol, and (c) the active substance.
2. A dosage form according to claim 1 comprising one or more further matrix forming agents.
3. A dosage form according to claim 1 or 2, wherein the further matrix forming agent is a mono-, di- or tri-saccharide.
4. A dosage form according to any of claims 1-3, wherein the further matrix forming agent is mannitol.
5. A dosage form according to any of claims 1-4 further comprising polyethylene glycol (PEG).
6. A dosage form according to any of claims 1-5, wherein maltodextrin is present in an amount of 3-40 % (w/w), preferably 10-35 (w/w) and more preferably 15-25 % (w/w) of the dosing solution.
7. A dosage form according to any of claims 1-6, wherein sorbitol is present in an amount of 0.01-10 %(w/w), preferably 0.05-5 % (w/w) and more preferably 0.1-2 % (w/w) of the dosing solution.
8. A dosage form according to any of claims 4-6, wherein mannitol is present in an amount of 1-20 %(w/w), preferably 2-10 % (w/w) and more preferably 3-6 (w/w) of the dosing solution.
9. A dosage form according to any of claims 5-8, wherein PEG is present in an amount of 1-20 %(w/w), preferably 2-15 % (w/w) and more preferably 3-
10 % (w/w) of the dosing solution.
10. A dosage form according to any of claims 1-9 further comprising one or more additional excipients.
10. A dosage form according to any of claims 1-9 further comprising one or more additional excipients.
11. A dosage form according to claim 10, wherein the excipient is selected from the group consisting of adjuvants, antacids, diluents, enhancers, mucoadhesive agents, flavouring agents, taste masking agents, preservatives, antioxidants, surfactants, viscosity enhancers, coloring agents, pH modifiers and sweeteners.
12. A dosage form according to any of the preceding claims, wherein the active substance is an allergen.
13. A dosage form according to claim 12, wherein the allergen is selected from the group consisting of tree pollen allergens, grass pollen allergens, mite allergens, insect allergens, venom allergens, animal hair and dandruff allergens and food allergens.
14. A dosage form according to claim 12 or 13, wherein the allergen is in the form of an extract, a purified allergen, a modified allergen or a recombinant allergen or a mutant of a recombinant allergen or any combination thereof.
15. A dosage form according to any of claims 13-14, wherein the allergen is grass pollen.
16. A dosage form according to any of claims 13-14, wherein the allergen is dust mite.
17. A dosage form according to any of claims 1-14 comprising at least two different allergens.
18. A dosage form according to any of claims 1-17, wherein the potency is from 150 - 1000000 SQ-u/dosage form.
19. A dosage form according to any of claims 1-18, wherein the variation of content of allergen of units within a blister pack is ~10%, preferably ~7%, most preferable ~5 % compared to the dose set.
20. A dosage form according to any of claims 1-19 wherein the dosage form is for sublingual administration.
21. A dosage form according to any of claims 1 to 20, wherein said solid dosage form disintegrates in less than about 90 seconds, preferably in less than 60 seconds, preferably in less than 30 seconds, more preferably in less than 20, even more preferably in less than 10 seconds in the oral cavity, even more preferably in less than 5 seconds, most preferably in less than about 2 seconds in the oral cavity.
22. A dosage form according to any of claims 1 to 21, wherein said dosage form is sufficiently strong to be removed form a blister pack without releasing residues to the surroundings.
23. A dosage form according to claim 22, wherein less than 500 SQ-U of allergen, more preferably less than 250 SQ-U of allergen, most preferably less than 150 SQ-U of allergen is released from each solid dosage during manual handling.
24. A dosage form according to any of claims 1-23 wherein the friability measured as the amount of allergen released is less than 500 SQ-U per solid dosage form, more preferably less than 250 SQ-U per solid dosage form, most preferably less than 150 SQ-U per solid dosage form in a suitable friability test.
25. A dosage form according to claim 24, wherein the friability is measured in an assay comprising the following steps:
a) placing single units of solid dosage form contained in sealed blisterpack unit in an equipment suitable for reproducible friability measurements, b) moving it for an appropriate time and at an appropriate velocity, c) removing the sealed solid dosage form unit, d) opening the sealed solid dosage form unit and emptying the unit in a container/ placing the fast dispersing dosage form unit in a container, e) removing the solid dosage form unit from the container leaving any loose residues in said container, f) performing an allergen specific assay on said residues and determining the allergen content in said residues, g) optionally calculating the percentage of allergen content in said residues in comparison to total allergen content of the solid dosage form unit.
a) placing single units of solid dosage form contained in sealed blisterpack unit in an equipment suitable for reproducible friability measurements, b) moving it for an appropriate time and at an appropriate velocity, c) removing the sealed solid dosage form unit, d) opening the sealed solid dosage form unit and emptying the unit in a container/ placing the fast dispersing dosage form unit in a container, e) removing the solid dosage form unit from the container leaving any loose residues in said container, f) performing an allergen specific assay on said residues and determining the allergen content in said residues, g) optionally calculating the percentage of allergen content in said residues in comparison to total allergen content of the solid dosage form unit.
26. A dosage form according to claim 1, wherein at least a part of the active substance is present in the form of microcapsules embedded in the matrix, the microcapsules comprising a first encapsulating agent and the active substance.
27. A dosage form according to claim 25, wherein the first encapsulating agent is poly(DL-lactide-co-glycolide).
28. A dosage form according to any of the proceeding claims, wherein the dosage form is in the form of a granular composition suitable for preparing a compressed tablet.
29. A blister pack containing a number of a solid dosage forms according to any one of claims 1 to 28.
30. A method of preventing or treating a disease comprising oromucosal administration of an effective amount of a dosage form according to any of claims 1 to 27.
31. A method for preventing or treating allergy or alleviating symptoms of allergy comprising oromucosal administration of an effective amount of an allergen vaccine dosage form according to any of claims 1 to 27.
32. Use of a pharmaceutically active substance for the manufacture of a fast dispersing non-compressed solid dosage form according to claim 1.
33. Use of an allergen for the manufacture of a fast dispersing non-compressed allergen vaccine solid dosage form according to claim 1.
34. A fast dispersing non-compressed solid dosage form according to claim 1 for oromucosal prevention or treatment of a disease.
35. A fast dispersing non-compressed allergen vaccine solid dosage form according to claim 1 for oromucosal prevention or treatment of allergy or alleviation of allergic symptoms.
36. Use of a pharmaceutically active substance for the manufacture of a fast dispersing or non-compressed solid dosage form according to claim 1 for oromucosal prevention or treatment of a disease.
37. Use of an allergen for the manufacture of a fast dispersing or non-compressed allergen vaccine solid dosage form according to claim 1 for oromucosal prevention or treatment of allergy or alleviation of allergic symptoms.
38. A method of producing a fast dispersing non-compressed solid dosage form according to claim 1, comprising the steps of:
preparing an aqueous dosing solution of the pharmaceutically active substance and maltodextrin and optionally one or more further matrix forming agents and suitable excipients, introducing the solution into depressions of a multilayer laminated blister sheet, and subjecting the loaded sheet to freezing and freeze-drying using standard conditions of shelf temperature and chamber pressure.
preparing an aqueous dosing solution of the pharmaceutically active substance and maltodextrin and optionally one or more further matrix forming agents and suitable excipients, introducing the solution into depressions of a multilayer laminated blister sheet, and subjecting the loaded sheet to freezing and freeze-drying using standard conditions of shelf temperature and chamber pressure.
39. A method of obtaining a fast dispersing non-compressed allergen vaccine solid dosage form suitable for oromucosal administration comprising 1) producing a fast dispersing, non-compressed solid allergen vaccine dosage form 2) measuring the friability of said dosage form in an assay comprising the steps of a) placing a solid dosage form contained in a sealed blister pack unit in an equipment suitable for friability measurements b) moving it for an appropriate time and at an appropriate velocity c) removing the sealed solid dosage form unit d) opening the sealed solid dosage form unit and emptying the unit in a container/ placing the fast dispersing dosage form unit in a container e) removing the solid dosage form unit from the container leaving any loose residues in said container f) performing an immunochemical allergen specific assay on said residues detecting the amount of allergen content in said residues g) calculating the percentage of allergen content in said residues in comparison to total allergen content of the solid dosage form unit h) detecting whether the dosage form fulfills the requirements for low friability.
3) repeating 1) and 2) until the requirements for the dosage form is fulfilled.
3) repeating 1) and 2) until the requirements for the dosage form is fulfilled.
40. A compressed tablet comprising the granular composition of claim 28.
41. An aqueous dosing solution for preparing a fast-dispersing solid composition suitable for oromucosal administration of a pharmaceutically active substance, the dosing solution comprising (a) a first matrix forming agent in the form of maltodextrin having a dextrose equivalent (DE) of between 1 and 20, and (b) microcapsules comprising a first encapsulating matrix forming agent and the active substance.
42. A method of preparing the dosage form according to claim 28 comprising the steps of:
preparing microcapsules comprising a first encapsulating matrix forming agent and a pharmaceutically active substance, preparing an aqueous dosing solution of the microcapsules and maltodextrin and optionally one or more further matrix forming agents and suitable excipients, spray-freeing the dosing solution to produce primary granules, and freeze-drying the primary granules to produce secondary granules.
preparing microcapsules comprising a first encapsulating matrix forming agent and a pharmaceutically active substance, preparing an aqueous dosing solution of the microcapsules and maltodextrin and optionally one or more further matrix forming agents and suitable excipients, spray-freeing the dosing solution to produce primary granules, and freeze-drying the primary granules to produce secondary granules.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DKPA200300318 | 2003-02-28 | ||
DKPA200300318 | 2003-02-28 | ||
US46538303P | 2003-04-25 | 2003-04-25 | |
US60/465,383 | 2003-04-25 | ||
PCT/DK2004/000119 WO2004075875A1 (en) | 2003-02-28 | 2004-02-24 | Dosage form having a saccharide matrix |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2516291A1 true CA2516291A1 (en) | 2004-09-10 |
CA2516291C CA2516291C (en) | 2012-02-14 |
Family
ID=32929063
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2516291A Expired - Fee Related CA2516291C (en) | 2003-02-28 | 2004-02-24 | Dosage form having a saccharide matrix |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP1599185A1 (en) |
JP (1) | JP4688787B2 (en) |
KR (1) | KR101136573B1 (en) |
AU (1) | AU2004216559B2 (en) |
CA (1) | CA2516291C (en) |
HK (1) | HK1089083A1 (en) |
MX (1) | MXPA05009079A (en) |
PL (1) | PL210707B1 (en) |
WO (1) | WO2004075875A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9731018B2 (en) | 2011-09-16 | 2017-08-15 | Ferring B.V. | Fast dissolving pharmaceutical composition |
US10023335B2 (en) | 2010-03-29 | 2018-07-17 | Ferring B.V. | Fast dissolving pharmaceutical composition |
US10086078B2 (en) | 2010-03-29 | 2018-10-02 | Ferring B.V. | Fast dissolving pharmaceutical composition |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060210590A1 (en) | 2005-02-03 | 2006-09-21 | Alk-Abello A/S | Minor allergen control to increase safety of immunotherapy |
US20090155351A1 (en) | 2005-10-04 | 2009-06-18 | Alk-Abello A/S | Solid Vaccine Formulation |
MY150626A (en) | 2009-10-30 | 2014-02-07 | Ix Biopharma Ltd | Fast dissolving solid dosage form |
JP5800527B2 (en) * | 2010-03-30 | 2015-10-28 | 日東電工株式会社 | Stabilized pharmaceutical composition, stabilized pharmaceutical composition solution preparation, film-form preparation and method for producing film-form preparation |
EA024566B1 (en) * | 2010-11-04 | 2016-09-30 | Норджин Бв | Solid formulation for oral administration (embodiments), method of therapeutically or non-therapeutically preventing gastrointestinal disorders or of maintaining gastrointestinal health using the same (embodiments) and pack comprising the same |
JP2012240978A (en) * | 2011-05-20 | 2012-12-10 | Nitto Denko Corp | Pharmaceutical composition and gelatinous preparation |
JP2012240975A (en) * | 2011-05-20 | 2012-12-10 | Nitto Denko Corp | Pharmaceutical composition and jerry-form preparation |
EP3998080A1 (en) * | 2013-03-14 | 2022-05-18 | Société des Produits Nestlé S.A. | Manufacture of peanut formulations for oral desensitization |
EP2952200A1 (en) | 2014-06-04 | 2015-12-09 | Alk-Abelló A/S | Allergen for prophylactic treatment of allergy |
GB2545880A (en) | 2015-10-20 | 2017-07-05 | Glide Pharmaceutical Tech Ltd | Solid formulation |
WO2019101832A1 (en) * | 2017-11-27 | 2019-05-31 | Dsm Ip Assets B.V. | Freeze-dried multiparticulate solid dosage form |
JP6592791B1 (en) * | 2018-01-29 | 2019-10-23 | 株式会社リタファーマ | Pharmaceutical preparation and method for producing the same |
CA3137295A1 (en) | 2019-05-10 | 2020-11-19 | Aimmune Therapeutics, Inc. | Methods for improving the quality of life of a patient with a peanut allergy |
CN116891827B (en) * | 2023-09-08 | 2024-01-30 | 山东康华生物医疗科技股份有限公司 | NK cell activity activation system |
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IE45770B1 (en) * | 1976-10-06 | 1982-11-17 | Wyeth John & Brother Ltd | Pharmaceutical dosage forms |
GB1548022A (en) * | 1976-10-06 | 1979-07-04 | Wyeth John & Brother Ltd | Pharmaceutial dosage forms |
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US5558880A (en) | 1989-12-22 | 1996-09-24 | Janssen Pharmaceutica Inc. | Pharmaceutical and other dosage forms |
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US5343672A (en) * | 1992-12-01 | 1994-09-06 | Scherer Ltd R P | Method for manufacturing freeze dried dosages in a multilaminate blister pack |
CN1120310A (en) * | 1993-03-11 | 1996-04-10 | 塞科雷泰克公司 | Polymeric mucoadhesives in the delivery of immunogens at mucosal surfaces |
US6010719A (en) * | 1997-09-16 | 2000-01-04 | Universiteit Gent | Freeze-dried disintegrating tablets |
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US20020197321A1 (en) * | 1997-10-27 | 2002-12-26 | Harry Seager | Solid dispersing vaccine composition for oral delivery |
EP1062341B1 (en) | 1998-03-16 | 2008-09-17 | ALK-Abelló A/S | Mutant recombinant allergens |
GB9901819D0 (en) | 1999-01-27 | 1999-03-17 | Scherer Corp R P | Pharmaceutical compositions |
FR2790387B1 (en) | 1999-03-01 | 2001-05-18 | Prographarm Laboratoires | ORODISPERSIBLE TABLET HAVING LOW FRIABILITY AND PROCESS FOR THE PREPARATION THEREOF |
US20060073188A1 (en) * | 1999-03-31 | 2006-04-06 | Pierre Fabre Medicament | Fast-dissolving isotropic expanded microporous composition or structure for pharmaceutical, veterinary, dietetic, food or cosmetic use and method for obtaining same |
FR2791569B1 (en) | 1999-03-31 | 2003-05-09 | Pf Medicament | ISOTROPIC FAST DISSOLVING ISOTROPIC MICROPOROUS COMPOSITION OR STRUCTURE FOR PHARMACEUTICAL, VETERINARY, DIETETIC, FOOD OR COSMETIC USE AND PROCESS FOR OBTAINING THE SAME |
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DE19951970A1 (en) * | 1999-10-28 | 2001-05-03 | Bionetworks Gmbh | Medicines for tolerance induction |
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ITMI20010571A1 (en) * | 2001-03-19 | 2002-09-19 | Grisotech S A | TRANS-MUCOSAL ABSORBABLE VACCINES |
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-
2004
- 2004-02-24 AU AU2004216559A patent/AU2004216559B2/en not_active Ceased
- 2004-02-24 KR KR1020057015834A patent/KR101136573B1/en not_active IP Right Cessation
- 2004-02-24 CA CA2516291A patent/CA2516291C/en not_active Expired - Fee Related
- 2004-02-24 PL PL378543A patent/PL210707B1/en unknown
- 2004-02-24 EP EP04713847A patent/EP1599185A1/en not_active Withdrawn
- 2004-02-24 JP JP2006501528A patent/JP4688787B2/en not_active Expired - Fee Related
- 2004-02-24 WO PCT/DK2004/000119 patent/WO2004075875A1/en active Search and Examination
- 2004-02-24 MX MXPA05009079A patent/MXPA05009079A/en active IP Right Grant
-
2006
- 2006-08-25 HK HK06109448.3A patent/HK1089083A1/en not_active IP Right Cessation
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10023335B2 (en) | 2010-03-29 | 2018-07-17 | Ferring B.V. | Fast dissolving pharmaceutical composition |
US10086078B2 (en) | 2010-03-29 | 2018-10-02 | Ferring B.V. | Fast dissolving pharmaceutical composition |
US9731018B2 (en) | 2011-09-16 | 2017-08-15 | Ferring B.V. | Fast dissolving pharmaceutical composition |
Also Published As
Publication number | Publication date |
---|---|
JP4688787B2 (en) | 2011-05-25 |
MXPA05009079A (en) | 2006-05-19 |
PL378543A1 (en) | 2006-05-02 |
WO2004075875A8 (en) | 2004-12-29 |
HK1089083A1 (en) | 2006-11-24 |
KR20050105491A (en) | 2005-11-04 |
KR101136573B1 (en) | 2012-04-23 |
AU2004216559A1 (en) | 2004-09-10 |
CA2516291C (en) | 2012-02-14 |
AU2004216559B2 (en) | 2010-05-27 |
WO2004075875A1 (en) | 2004-09-10 |
EP1599185A1 (en) | 2005-11-30 |
PL210707B1 (en) | 2012-02-29 |
JP2006519187A (en) | 2006-08-24 |
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