EP1001747A1 - Compositions for nasal administration - Google Patents
Compositions for nasal administrationInfo
- Publication number
- EP1001747A1 EP1001747A1 EP98940262A EP98940262A EP1001747A1 EP 1001747 A1 EP1001747 A1 EP 1001747A1 EP 98940262 A EP98940262 A EP 98940262A EP 98940262 A EP98940262 A EP 98940262A EP 1001747 A1 EP1001747 A1 EP 1001747A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- composition according
- oil
- fatty acid
- mono
- amphiphilic agent
- 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- Withdrawn
Links
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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
-
- 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
- A61K9/0043—Nose
Definitions
- the present invention relates to a novel composition for nasal administration of medicaments.
- the nasal passages may be used as a route of administration, for instance an ointment such as Bactroban Nasal may be applied to the anterior nares of the nose for a local topical effect.
- Spray formulations may applied to the nostrils.
- medicaments may administered to the lungs via the nostrils, using an aerosol or nebuliser.
- the nasal passages comprise mucosal tissues which might be used as means of systemically delivering a medicament. Such local topical or systemic delivery would be enhanced if the formulation was to have a prolonged residence time in the nasal passages.
- the present invention provides a sprayable composition adapted for prolonged residence in the nasal passage, in particular the nasal pharynx, which comprises:
- Amphiphilic agents are substances containing both hydrophilic and lipophilic groups. In liquid form, these agents are generally capable of spontaneous self-association in the presence of water, with a consequent increase in viscosity. This self-association results in a change in properties ranging from the formation of viscous liquids to semi-rigid gels. This behaviour has been characterised as due to the formation of long range order in the liquid system giving several distinct phases which have been called "liquid crystalline phases”.
- Materials known to exhibit such properties and which are suitable for use in a medicament formulation include mono-glycerides such as mono-olein and mono-linolein, phospholipids such as phosphatidyl cholines, and galactolipids such as galactoyl- diglycerides.
- the monoglycerides are long-chain fatty acid monoglycerides, optionally comprising up to 10% (w/w) of a long-chain fatty acid diglyceride and/or a small amount by weight of a free long-chain fatty acid.
- the mono- and di-glycerides may each include blends of different long-chain fatty acid mono- and di-glycerides.
- Suitable long-chain fatty acid monoglycerides include glycerol monooleate, glycerol monopalmitate and glycerol monostearate.
- MYVEROL such as MYVEROL 18-99, MYVATEX, MYVAPLEX, and GMORPHIC 80 respectively, from Eastman Kodak Chemicals, Rochester, New York.
- a further useful long-chain fatty acid monoglyceride- containing product is ARLACEL 186 (available from ICI Americas Inc.) which includes, in addition to glycerol monooleate, propylene glycol (10%).
- the main fatty acids of MYVEROL 18-99 are oleic acid (61%), linoleic acid (21%), linolenic acid (9%) and palmitic acid (4%).
- the major fatty acid component is a Ci g-saturated, monounsaturated or polyunsaturated fatty acid, preferably a C i g-monounsaturated or polyunsaturated fatty acid.
- the monoglyceride will have an HLB value in the range of about 2.5 to 6.
- the HLB value of the product MYVEROL 18-99 is 3.7.
- the amphiphilic substance is preferably glyceryl mono-oleate (mono-olein).
- glyceryl monooleate is a material which is predominantly glyceryl mono-oleate but also contains minor amounts of related mono and di-glycerides. Accordingly, the amount that is effective in a particular spray formulation will vary dependent on the level of glyceryl mono-oleate in the commercial material used.
- a diluent is selected on the basis of compatibility e.g. producing a stable blend with the amphiphilic agent, and the ability to achieve a sprayable blend without excessive dilution that will reduce the self-association on contact with water and detract from the desired viscosity increase.
- a diluent is a pharmaceutically acceptable oil, most preferably a fatty acid triglyceride, typically vegetable (i.e. plant derived) oil, since mineral oils such as paraffin oil have been implicated in undesirable side effects when inhaled. Suitable vegetable oils include coconut oil, sesame oil and soya bean oil.
- the preferred diluent is a vegetable oil, most preferably coconut oil, that has been fractionated so that it is predominantly medium chain length triglycerides.
- the proportion of amphiphilic agent to oil is from 2:1 to 1 :4, preferably 1 :1 to 1 :2.
- the amount of diluent is adjusted so that the formulation is of a viscosity that is suitable for spray delivery at 20°C or above.
- Suitable medium-chain fatty acid triglycerides for use in the present invention may be of natural, semi-synthetic or synthetic origin and may include blends of different medium chain fatty acid triglycerides.
- the term "medium-chain fatty acid” as used herein refers to a fatty acid having from 6 to 12, preferably 8 to 10 carbon atoms which may be branched or unbranched, preferably unbranched and which may be optionally substituted.
- Certain neutral plant oils, such as fractionated coconut oils provide convenient sources of medium-chain fatty acid triglycerides.
- the triglyceride suitably comprises from 50 to 100%> (w/w) of caprylic (Cg) acid and from 0 to 50% (w/w) of capric (Ci Q) acid triglycerides.
- Suitable examples include those available under the trade names MYRITOL; CAPTEX (Karlshams Lipid Specialties, Columbus OH), for instance CAPTEX 355, CAPTEX 300, CAPTEX 350, CAPTEX 850 and CAPTEX 8000; MIGLYOL (BASF), for instance the grades MIGLYOL 810, MIGLYOL 812 AND MIGLYOL 818 (which also comprises a linoleic acid triglyceride) and MAZOL 1400 (Mazer Chemical, Guernee, II).
- the fatty acid content of representative products is: CAPTEX 355TM - CAPROIC ACID (2%), CAPRYLIC ACID (55%) and capric acid (42%); CAPTEX 8000 - at least 98% caprylic acid, MYGOL 810 - caproic acid (2%), caprylic acid (65-75%), capric acid (25-35%) and MIGLYOL 812 - caproic acid (3%), caprylic acid (50-65%), capric acid (30-45%) and lauric acid (5%) (manufacturer's data).
- the sprayable formulations of this invention are especially suitable for nasal delivery, because in the humid environment of the nasal passages they increase in viscosity by contact with water, and so are better able to resist wash-out when in contact with nasal surfaces.
- the prolonged residence time of formulations of the present invention in the nasal passages, especially the nasal pharynx, makes them particularly suitbable for topical treatment with local action or, since it provides prolonged contact of the formulation with an absorptive region, systemic delivery of a medicament.
- Suitable medicaments include antibiotics, for instance mupirocin or a pharmaceutically acceptable salt or ester thereof
- An antibiotic such as mupirocin may be used in the prophylactic treatment of recurrent sinusitis, and otitis media.
- Suitable pharmaceutically acceptable salts of mupirocin are well known in the art and include alkali metal salts such as sodium and lithium and alkaline earth metal salts such as calcium, of which the calcium salt is preferred, in particular the crystalline dihydrate from thereof described in EP 0 167 856-A (Beecham Group).
- alkali metal salts such as sodium and lithium
- alkaline earth metal salts such as calcium
- Other suitable salts include silver and aluminium salts and ammonium and substituted- ammonium salts.
- the salts may be anhydrous or may be in the form of pharmaceutically acceptable solvates, for instance alcoholates and, especially, hydrates.
- Preferred salts include the calcium, silver and lithium salts, in particular the calcium salt.
- the crystalline salt is preferably used, especially the crystalline hydrated calcium salt, more preferably the crystalline dihydrate salt.
- esters of mupirocin are well known in the art and include lower alkyl esters, especially the methyl and ethyl esters.
- the medicament is suspended in a non-aqueous carrier, it is preferably present as a finely divided powder. This may be achieved by milling, and most suitably by micronising (fluid energy milling) so that the medicament has a particle size less than 100 ⁇ m, preferably less than 10 ⁇ m.
- an antibiotic will be used at between 0.1 and 10%, preferably 2 and 8%, typically about 4-6%, by weight of the formulation. It is preferred to use a relatively high dosage level, to reduce the risk of the development of bacterial resistance. Also, to avoid excessive spray volumes which will be uncomfortable in nasal administration, the medicament is preferably present at a relatively high loading compared to other topical administration formulations.
- mupirocin may be added at a level of 4% w/w to a carrier based on coconut oil and glycerylmono-oleate, so that a sprayed dose of 125 ⁇ l will deliver approximately 5 mg approximately 5 mg of mupirocin.
- Formulations of the present invention may be administered by a conventional pump dispenser suitable for nasal administration.
- a conventional pump dispenser suitable for nasal administration.
- the formulation is preferably sprayed into the nasal passages where natural processes carry the medicament through the nasal passages to reach deep seated sites of infection.
- the viscosity increase on contact with moisture prolongs the residence of the medicament and prevents early wash-out.
- amphiphilic agent and non-aqueous diluent are typically in the preferred forms described above.
- composition of this invention may be produced by conventional pharmaceutical techniques.
- amphiphilic substance and diluent may be blended by mixing together at an elevated temperature.
- the mixture may then be cooled to room temperature, and, after the addition of any further optional ingredients, stirred to ensure adequate dispersion.
- the medicament may be added during hot preparation of the base, or may be added with additional ingredients after cooling of the base. If necessary, the composition may be provided in sterile condition.
- Optional ingredients that may be added if desired include colourings and flavourings.
- the invention is illustrated by the following Example.
- Example A carrier for a nasal spray formulation was prepared by forming a blend of 67% w/w fractionated coconut oil (medium chain length)* and 33% w/w of glyceryl mono-oleate **. To this blend was added 0.2% w/w of powdered lemon juice flavour, followed by 4% w/w of micronized calcium Mupirocin.
- the resultant formulation has a viscosity which is sprayable at 20°C or above.
- the liquid When sprayed into the nose of a patient, the liquid coats the nasal passages and contact with moisture inside the nose (from the mucous membranes, and the humid environment generally) causes the carrier to thicken. This prolongs the residence time of the sprayed formulation on the nasal surfaces.
- a spray volume of about 125 ⁇ l contains approximately 5 mg Mupirocin.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Otolaryngology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
New compositions adapted for nasal administration of medicaments are described.
Description
COMPOSITIONS FOR NASAL ADMINISTRATION
The present invention relates to a novel composition for nasal administration of medicaments.
The nasal passages may be used as a route of administration, for instance an ointment such as Bactroban Nasal may be applied to the anterior nares of the nose for a local topical effect. Spray formulations may applied to the nostrils. In addition, medicaments may administered to the lungs via the nostrils, using an aerosol or nebuliser. The nasal passages comprise mucosal tissues which might be used as means of systemically delivering a medicament. Such local topical or systemic delivery would be enhanced if the formulation was to have a prolonged residence time in the nasal passages.
Accordingly, the present invention provides a sprayable composition adapted for prolonged residence in the nasal passage, in particular the nasal pharynx, which comprises:
(a) an amphiphilic agent that increases in viscosity on contact with water;
(b) a non-aqueous diluent for the ampiphilic agent,
(c) a powdered medicament in suspension.
Amphiphilic agents are substances containing both hydrophilic and lipophilic groups. In liquid form, these agents are generally capable of spontaneous self-association in the presence of water, with a consequent increase in viscosity. This self-association results in a change in properties ranging from the formation of viscous liquids to semi-rigid gels. This behaviour has been characterised as due to the formation of long range order in the liquid system giving several distinct phases which have been called "liquid crystalline phases".
Materials known to exhibit such properties and which are suitable for use in a medicament formulation include mono-glycerides such as mono-olein and mono-linolein, phospholipids such as phosphatidyl cholines, and galactolipids such as galactoyl- diglycerides.
Typically the monoglycerides are long-chain fatty acid monoglycerides, optionally comprising up to 10% (w/w) of a long-chain fatty acid diglyceride and/or a small amount by weight of a free long-chain fatty acid. The mono- and di-glycerides may each include blends of different long-chain fatty acid mono- and di-glycerides. Suitable long-chain fatty acid monoglycerides include glycerol monooleate, glycerol monopalmitate and
glycerol monostearate. Suitable commercially available examples of such include the products available under the trade names MYVEROL, such as MYVEROL 18-99, MYVATEX, MYVAPLEX, and GMORPHIC 80 respectively, from Eastman Kodak Chemicals, Rochester, New York. A further useful long-chain fatty acid monoglyceride- containing product is ARLACEL 186 (available from ICI Americas Inc.) which includes, in addition to glycerol monooleate, propylene glycol (10%). The main fatty acids of MYVEROL 18-99 are oleic acid (61%), linoleic acid (21%), linolenic acid (9%) and palmitic acid (4%). Suitably in such long-chain monoglycerides, the major fatty acid component is a Ci g-saturated, monounsaturated or polyunsaturated fatty acid, preferably a C i g-monounsaturated or polyunsaturated fatty acid. Suitably the monoglyceride will have an HLB value in the range of about 2.5 to 6. The HLB value of the product MYVEROL 18-99 is 3.7.
In the present invention the amphiphilic substance is preferably glyceryl mono-oleate (mono-olein). As indicated above, in its commercially available form, glyceryl monooleate is a material which is predominantly glyceryl mono-oleate but also contains minor amounts of related mono and di-glycerides. Accordingly, the amount that is effective in a particular spray formulation will vary dependent on the level of glyceryl mono-oleate in the commercial material used.
To obtain a sprayable formulation, the amphiphilic substance is combined with a liquid diluent. The diluent is selected on the basis of compatibility e.g. producing a stable blend with the amphiphilic agent, and the ability to achieve a sprayable blend without excessive dilution that will reduce the self-association on contact with water and detract from the desired viscosity increase. Typically, a diluent is a pharmaceutically acceptable oil, most preferably a fatty acid triglyceride, typically vegetable (i.e. plant derived) oil, since mineral oils such as paraffin oil have been implicated in undesirable side effects when inhaled. Suitable vegetable oils include coconut oil, sesame oil and soya bean oil. In this invention, the preferred diluent is a vegetable oil, most preferably coconut oil, that has been fractionated so that it is predominantly medium chain length triglycerides.
Typically the proportion of amphiphilic agent to oil is from 2:1 to 1 :4, preferably 1 :1 to 1 :2. Ideally, the amount of diluent is adjusted so that the formulation is of a viscosity that is suitable for spray delivery at 20°C or above.
Suitable medium-chain fatty acid triglycerides for use in the present invention may be of natural, semi-synthetic or synthetic origin and may include blends of different medium chain fatty acid triglycerides. The term "medium-chain fatty acid" as used herein refers to a fatty acid having from 6 to 12, preferably 8 to 10 carbon atoms which may be branched
or unbranched, preferably unbranched and which may be optionally substituted. Certain neutral plant oils, such as fractionated coconut oils, provide convenient sources of medium-chain fatty acid triglycerides. The triglyceride suitably comprises from 50 to 100%> (w/w) of caprylic (Cg) acid and from 0 to 50% (w/w) of capric (Ci Q) acid triglycerides. Suitable examples include those available under the trade names MYRITOL; CAPTEX (Karlshams Lipid Specialties, Columbus OH), for instance CAPTEX 355, CAPTEX 300, CAPTEX 350, CAPTEX 850 and CAPTEX 8000; MIGLYOL (BASF), for instance the grades MIGLYOL 810, MIGLYOL 812 AND MIGLYOL 818 (which also comprises a linoleic acid triglyceride) and MAZOL 1400 (Mazer Chemical, Guernee, II). The fatty acid content of representative products is: CAPTEX 355™ - CAPROIC ACID (2%), CAPRYLIC ACID (55%) and capric acid (42%); CAPTEX 8000 - at least 98% caprylic acid, MYGOL 810 - caproic acid (2%), caprylic acid (65-75%), capric acid (25-35%) and MIGLYOL 812 - caproic acid (3%), caprylic acid (50-65%), capric acid (30-45%) and lauric acid (5%) (manufacturer's data).
The sprayable formulations of this invention are especially suitable for nasal delivery, because in the humid environment of the nasal passages they increase in viscosity by contact with water, and so are better able to resist wash-out when in contact with nasal surfaces. The prolonged residence time of formulations of the present invention in the nasal passages, especially the nasal pharynx, makes them particularly suitbable for topical treatment with local action or, since it provides prolonged contact of the formulation with an absorptive region, systemic delivery of a medicament.
Suitable medicaments include antibiotics, for instance mupirocin or a pharmaceutically acceptable salt or ester thereof
An antibiotic such as mupirocin may be used in the prophylactic treatment of recurrent sinusitis, and otitis media.
Suitable pharmaceutically acceptable salts of mupirocin are well known in the art and include alkali metal salts such as sodium and lithium and alkaline earth metal salts such as calcium, of which the calcium salt is preferred, in particular the crystalline dihydrate from thereof described in EP 0 167 856-A (Beecham Group). Other suitable salts include silver and aluminium salts and ammonium and substituted- ammonium salts. The salts may be anhydrous or may be in the form of pharmaceutically acceptable solvates, for instance alcoholates and, especially, hydrates. Preferred salts include the calcium, silver and lithium salts, in particular the calcium salt. In the case of the calcium salt of
mupirocin, the crystalline salt is preferably used, especially the crystalline hydrated calcium salt, more preferably the crystalline dihydrate salt.
Suitable pharmaceutically acceptable esters of mupirocin are well known in the art and include lower alkyl esters, especially the methyl and ethyl esters.
Since the medicament is suspended in a non-aqueous carrier, it is preferably present as a finely divided powder. This may be achieved by milling, and most suitably by micronising (fluid energy milling) so that the medicament has a particle size less than 100 μm, preferably less than 10 μm.
Typically an antibiotic will be used at between 0.1 and 10%, preferably 2 and 8%, typically about 4-6%, by weight of the formulation. It is preferred to use a relatively high dosage level, to reduce the risk of the development of bacterial resistance. Also, to avoid excessive spray volumes which will be uncomfortable in nasal administration, the medicament is preferably present at a relatively high loading compared to other topical administration formulations. For example, mupirocin may be added at a level of 4% w/w to a carrier based on coconut oil and glycerylmono-oleate, so that a sprayed dose of 125 μl will deliver approximately 5 mg approximately 5 mg of mupirocin.
Formulations of the present invention may be administered by a conventional pump dispenser suitable for nasal administration. For treatment of recurrent sinusitis and otitis media the formulation is preferably sprayed into the nasal passages where natural processes carry the medicament through the nasal passages to reach deep seated sites of infection. The viscosity increase on contact with moisture prolongs the residence of the medicament and prevents early wash-out.
In the use and method of this invention, the amphiphilic agent and non-aqueous diluent are typically in the preferred forms described above.
The composition of this invention may be produced by conventional pharmaceutical techniques. Thus, for example, amphiphilic substance and diluent may be blended by mixing together at an elevated temperature. The mixture may then be cooled to room temperature, and, after the addition of any further optional ingredients, stirred to ensure adequate dispersion. The medicament may be added during hot preparation of the base, or may be added with additional ingredients after cooling of the base. If necessary, the composition may be provided in sterile condition.
Optional ingredients that may be added if desired include colourings and flavourings.
Surprisingly it has been found that the addition of the calcium salt of Mupirocin to a mixture of glyceryl mono-oleate and fractionated coconut oil improves the physical stability and rheology of the resulting blend.
The invention is illustrated by the following Example.
Example A carrier for a nasal spray formulation was prepared by forming a blend of 67% w/w fractionated coconut oil (medium chain length)* and 33% w/w of glyceryl mono-oleate **. To this blend was added 0.2% w/w of powdered lemon juice flavour, followed by 4% w/w of micronized calcium Mupirocin.
The resultant formulation has a viscosity which is sprayable at 20°C or above. When sprayed into the nose of a patient, the liquid coats the nasal passages and contact with moisture inside the nose (from the mucous membranes, and the humid environment generally) causes the carrier to thicken. This prolongs the residence time of the sprayed formulation on the nasal surfaces. A spray volume of about 125 μl contains approximately 5 mg Mupirocin.
* Commercial product Miglyol, obtainable from Huls
** Commercial product Myverol 18-99, obtainable from Eastman
Claims
1. A sprayable composition adapted for prolonged residence in the nasal passage, in particular the nasal pharynx, which comprises: (a) an amphiphilic agent that increases in viscosity on contact with water;
(b) a non-aqueous diluent for the amphiphilic agent,
(c) a powdered medicament in suspension.
2. A composition according to claim 1 , in which the amphiphilic agent is selected from mono-glycerides, phospholipids and galactolipids.
3. A composition according to claim 2, in which the amphiphilic agent is glyceryl mono-oleate (mono-olein).
4. A composition according to any one of claims 1 to 3, in which the diluent is a pharmaceutically acceptable oil.
5. A composition according to claim 4, in which the diluent is a fatty acid triglyceride oil.
6. A composition according to claim 5, in which the fatty acid triglyceride oil is coconut oil, sesame oil or soya bean oil.
7. A composition according to claim 5 or 6, in which the fatty acid triglyceride has been fractionated so that it is predominantly medium chain length triglycerides.
8. A composition according to any one of claims 4 to 7 in which the proportion of amphiphilic agent to oil is from 2: 1 to 1 :4.
9. A composition according to any one of claims 1 to 8, in which the medicament is an antibiotic.
10. A composition according to claim 9, in which the antibiotic is mupirocin, or a pharmaceutically acceptable salt or ester there of.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9716805.8A GB9716805D0 (en) | 1997-08-09 | 1997-08-09 | Novel composition and use |
GB9716805 | 1997-08-09 | ||
GB9806682 | 1998-03-27 | ||
GBGB9806682.2A GB9806682D0 (en) | 1998-03-27 | 1998-03-27 | Novel composition |
PCT/EP1998/004972 WO1999007341A1 (en) | 1997-08-09 | 1998-08-05 | Compositions for nasal administration |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1001747A1 true EP1001747A1 (en) | 2000-05-24 |
Family
ID=26312034
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP98940262A Withdrawn EP1001747A1 (en) | 1997-08-09 | 1998-08-05 | Compositions for nasal administration |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1001747A1 (en) |
JP (1) | JP2001513493A (en) |
CA (1) | CA2299298A1 (en) |
WO (1) | WO1999007341A1 (en) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040057907A1 (en) * | 2002-09-23 | 2004-03-25 | Leonard Mackles | Dri-nasal sprays |
ATE378038T1 (en) * | 2003-07-07 | 2007-11-15 | Nares Ab | MICROEMULSIONS AND THEIR USE FOR PREVENTING RESPIRATORY DISEASES |
US8211448B2 (en) | 2003-07-07 | 2012-07-03 | Nares Ab | Microemulsions and its use for preventing airway diseases |
DE102011010668A1 (en) * | 2011-02-08 | 2012-08-09 | Ursapharm Arzneimittel Gmbh | Aqueous pharmaceutical composition for the prevention and / or therapy of allergic irritated nasal mucosa and its use |
US20120219644A1 (en) * | 2011-02-28 | 2012-08-30 | Harrington Carolyn J | Coconut oil-based intranasal composition and use |
WO2015174910A1 (en) * | 2014-05-13 | 2015-11-19 | Aerosol Scandinavia Ab | Composition having improved spraying characteristics comprising vegetable oils and triglycerides and/or mineral oils |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IE59628B1 (en) * | 1986-06-26 | 1994-03-09 | Beecham Group Plc | Treatment of fungal infections |
EP0871489A1 (en) * | 1995-10-12 | 1998-10-21 | Gs Development Ab | A pharmaceutical composition for administration of an active substance to or through a skin or mucosal surface |
BR9711843A (en) * | 1996-10-01 | 2001-07-31 | Smithkline Beecham Corp | Use of mupirocin for the manufacture of a medicine for the treatment of bacterial infections associated with colonization of the nasopharynx by pathogenic organisms |
-
1998
- 1998-08-05 EP EP98940262A patent/EP1001747A1/en not_active Withdrawn
- 1998-08-05 JP JP2000506935A patent/JP2001513493A/en active Pending
- 1998-08-05 WO PCT/EP1998/004972 patent/WO1999007341A1/en not_active Application Discontinuation
- 1998-08-05 CA CA002299298A patent/CA2299298A1/en not_active Abandoned
Non-Patent Citations (1)
Title |
---|
See references of WO9907341A1 * |
Also Published As
Publication number | Publication date |
---|---|
WO1999007341A1 (en) | 1999-02-18 |
CA2299298A1 (en) | 1999-02-18 |
JP2001513493A (en) | 2001-09-04 |
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