CA2463384A1 - Hydrating nasal gel and applicator - Google Patents
Hydrating nasal gel and applicator Download PDFInfo
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- CA2463384A1 CA2463384A1 CA002463384A CA2463384A CA2463384A1 CA 2463384 A1 CA2463384 A1 CA 2463384A1 CA 002463384 A CA002463384 A CA 002463384A CA 2463384 A CA2463384 A CA 2463384A CA 2463384 A1 CA2463384 A1 CA 2463384A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
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Abstract
A hydrating nasal gel for shooting nasal tissues within the nasal cavity is described. The gel remains inside the nasal cavity for a substantial period of time to provide the user with relief from dry nasal tissues caused by sickness or arid environmental conditions. The gel can be applied using an applicator tip that applies the gel to the nasal tissues within the nasal cavity, substantially without applying the gel within the nasal passage.
Description
HYDRATING NASAL GEL AND APPLICATOR
Technical Field During times of sickness, or when the local environment is low in humidity, the tissues of 1o the inside of the nose can become dried out. This nasal dryness may cause discomfort, soreness, congested breathing, and even bleeding and the associated possibility of nasal infections.
The present invention is directed to providing relief of dryness of the nasal tissues within the nasal cavity, and particularly to providing such relief over an extended period of time.
The present invention is able to provide such relief without the need for drug ingredients.
Disclosure of the Invention 2o The present invention is directed to solving the problems associated with dry nasal tissues by slowly releasing moisture or water directly to the internal nasal tissues and to the micro-environment of the nasal cavity. The present invention solves these problems by providing a nasal gel that is applied to the nasal tissue and remains inside the nose for a substantial period of time, and which can release water or moisture to the nasal tissues and cavity during this time. By doing so, the user is more comfortable and the nasal tissues are healthier, without the need to rely on drug ingredients. As used herein, the expression "drug ingredients" refers to ingredients classified as drugs by the United States Federal Drug Administration (U.S. FDA), with the ingredients being present at the levels at which such ingredients function as drugs as determined by the U.S. FDA.
The present invention solves these problems by providing a hydrating nasal gel comprising: water in an amount preferably ranging from about 50 wt-% to about 99 wt-%; a controlled-release agent in an amount effective to provide water to a nasal tissue at a rate of preferably between about 1 wt-% to 50 wt-% per hour at about 38°C;
and a gel-forming agent in an amount effective to provide a viscosity to the hydrating nasal gel of preferably between about 5,000 centipoise to 300,000 centipoise at about 25°C.
The present invention is also directed to a method of applying the hydrating nasal gel onto the nasal tissues using a device comprising a dispenser and an applicator. The applicator comprises a tip having sidewall openings and which preferably has a sealed end opposite a second end, which is in communication with a reservoir of the dispenser.
1o Brief Description of the Drawings FIG. 1 is a plot showing the percent weight loss over time of one embodiment of the nasal gel of the present invention.
FIG. 2 is a side view of one embodiment of the nasal gel applicator of the present invention.
FIG. 3 is another side view of the applicator embodiment shown in FIG. 2.
2o FIG. 3A is a cross-sectional view of the applicator embodiment shown in FIG. 3, taken along line A-A.
FIG. 3B is a top view of the applicator embodiment shown in FIG. 3.
FIG. 3C is a bottom view of the applicator embodiment shown in FIG. 3.
FIG. 4 is a perspective view of the applicator embodiment shown in FIG. 2.
FIG. S is a perspective view of an alternative embodiment of the nasal gel applicator of 3o the present invention.
FIG. 6 is a perspective view of another embodiment of the nasal gel applicator of the present invention.
Technical Field During times of sickness, or when the local environment is low in humidity, the tissues of 1o the inside of the nose can become dried out. This nasal dryness may cause discomfort, soreness, congested breathing, and even bleeding and the associated possibility of nasal infections.
The present invention is directed to providing relief of dryness of the nasal tissues within the nasal cavity, and particularly to providing such relief over an extended period of time.
The present invention is able to provide such relief without the need for drug ingredients.
Disclosure of the Invention 2o The present invention is directed to solving the problems associated with dry nasal tissues by slowly releasing moisture or water directly to the internal nasal tissues and to the micro-environment of the nasal cavity. The present invention solves these problems by providing a nasal gel that is applied to the nasal tissue and remains inside the nose for a substantial period of time, and which can release water or moisture to the nasal tissues and cavity during this time. By doing so, the user is more comfortable and the nasal tissues are healthier, without the need to rely on drug ingredients. As used herein, the expression "drug ingredients" refers to ingredients classified as drugs by the United States Federal Drug Administration (U.S. FDA), with the ingredients being present at the levels at which such ingredients function as drugs as determined by the U.S. FDA.
The present invention solves these problems by providing a hydrating nasal gel comprising: water in an amount preferably ranging from about 50 wt-% to about 99 wt-%; a controlled-release agent in an amount effective to provide water to a nasal tissue at a rate of preferably between about 1 wt-% to 50 wt-% per hour at about 38°C;
and a gel-forming agent in an amount effective to provide a viscosity to the hydrating nasal gel of preferably between about 5,000 centipoise to 300,000 centipoise at about 25°C.
The present invention is also directed to a method of applying the hydrating nasal gel onto the nasal tissues using a device comprising a dispenser and an applicator. The applicator comprises a tip having sidewall openings and which preferably has a sealed end opposite a second end, which is in communication with a reservoir of the dispenser.
1o Brief Description of the Drawings FIG. 1 is a plot showing the percent weight loss over time of one embodiment of the nasal gel of the present invention.
FIG. 2 is a side view of one embodiment of the nasal gel applicator of the present invention.
FIG. 3 is another side view of the applicator embodiment shown in FIG. 2.
2o FIG. 3A is a cross-sectional view of the applicator embodiment shown in FIG. 3, taken along line A-A.
FIG. 3B is a top view of the applicator embodiment shown in FIG. 3.
FIG. 3C is a bottom view of the applicator embodiment shown in FIG. 3.
FIG. 4 is a perspective view of the applicator embodiment shown in FIG. 2.
FIG. S is a perspective view of an alternative embodiment of the nasal gel applicator of 3o the present invention.
FIG. 6 is a perspective view of another embodiment of the nasal gel applicator of the present invention.
Best Mode for Carrying Out the Invention To provide moisture to the nasal tissues over a period of time, it is necessary to overcome the natural biological actions, such as sneezing, which function to flush out or remove foreign materials from the nasal cavity. It is also necessary to provide moisture in a way to that retains the water on the nasal tissue and does not simply drain out of the nose.
The present invention achieves these goals by providing a gelled product in the nasal cavity, which resists both flushing and draining out of the nose, and therefore remains in the nasal cavity and in contact with the nasal tissues for a substantial period of time.
To provide a gelled product, a gelling or gel-forming agent is used in the present invention. A wide variety of materials is available which can gel an aqueous solution.
The gel-forming agent should be safe for use on the nasal tissues, be non-irritating, and be able to form a gel that is stable over time. Preferably, the gel-forming agent should form a gel that has a viscosity sufficient to remain adhered to the nasal tissues after application, but that is not so viscous as to be unpleasant to the user, to be difficult to dispense and apply, or to interfere with the release of water to the nasal tissues and nasal cavity. More preferably, the gel-forming agent should form a thixotropic gel that is easy to apply in a thin layer and regains significant viscosity after application to remain on the nasal tissues for a prolonged period of time.
The hydrating nasal gels of the present invention are effective a viscosity preferably ranging from between about 5,000 centipoise to about 300,000 centipoise at room temperature, or about 25°C. More preferably, the viscosity of the hydrating nasal gel of the present invention is between about 100,000 centipoise to about 300,000 centipoise at about 25°C, and particularly preferred is a hydrating gel having a viscosity of about 100,000 centipoise at about 25°C. The viscosity ranges described herein are measured using a Brookfield viscometer at room temperature. At the lower end of the viscosity ranges, the Brookfield viscometer is fitted with a number 4 spindle operating at 10 rpm, and at the higher end of the range, the Brookfield viscometer is fitted with a TE
heliopathic spindle operating at 0.3 rpm.
In addition, the hydrating nasal gel of the present invention includes a controlled-release agent that physically or chemically entrains, retains or entraps water, so that moisture will be progressively released over a substantial period of time. If water is released too quickly, the product will be ineffective. If the water is released too slowly, the hydrating nasal gel will be ineffective in providing moisture to the nasal tissues.
Water should 1o preferably be released from the entraining or water binding agent at such a rate that it maintains moisture in the environment of the nasal cavity and/or in the nasal linings or tissues for a substantial period of time.
The controlled-release agent used in the present invention should be safe for use on the nasal tissues, be non-irritating, and should not substantially interfere with the gelling action of the gel-forming agent. Preferably, the controlled-release agent should be able to hold large quantities of water and release it at a relatively steady rate over a substantial period of time. In general, the nasal gel should release at least 0.1 gram of water per hour, for about two to four hours after application to the nasal tissue.
Preferably, the nasal gel of the present invention releases water at a rate of between about 1 wt-% to about 50 wt-% per hour at body temperature, or about 3~°C, based on the total weight of the gel. More preferably, the nasal gel of the present invention releases water at a rate of between about 1 wt-% to 10 wt-% per hour at body temperature.
It was surprisingly discovered that a nasal gel having a viscosity within the ranges described above was not substantially flushed out of the nose by natural biological functions, and remained in the nose for a substantial period of time without causing discomfort or an unpleasant sensation to the user.
3o In a preferred embodiment, the gel-forming function and the controlled-release function are provided by a single ingredient or component of the hydrating nasal gel.
The single component preferably has all the properties described above for each function.
Examples of materials that may be used to perform both functions in a single component include, but axe not limited to: hydrogel-forming agents, such as hydroxyethylcellulose; silica;
clay; a carbomer; and the like. Any material that produces a gel and then releases water over a period of minutes to hours would be effective in the hydrating nasal gel of the present invention.
The present invention achieves these goals by providing a gelled product in the nasal cavity, which resists both flushing and draining out of the nose, and therefore remains in the nasal cavity and in contact with the nasal tissues for a substantial period of time.
To provide a gelled product, a gelling or gel-forming agent is used in the present invention. A wide variety of materials is available which can gel an aqueous solution.
The gel-forming agent should be safe for use on the nasal tissues, be non-irritating, and be able to form a gel that is stable over time. Preferably, the gel-forming agent should form a gel that has a viscosity sufficient to remain adhered to the nasal tissues after application, but that is not so viscous as to be unpleasant to the user, to be difficult to dispense and apply, or to interfere with the release of water to the nasal tissues and nasal cavity. More preferably, the gel-forming agent should form a thixotropic gel that is easy to apply in a thin layer and regains significant viscosity after application to remain on the nasal tissues for a prolonged period of time.
The hydrating nasal gels of the present invention are effective a viscosity preferably ranging from between about 5,000 centipoise to about 300,000 centipoise at room temperature, or about 25°C. More preferably, the viscosity of the hydrating nasal gel of the present invention is between about 100,000 centipoise to about 300,000 centipoise at about 25°C, and particularly preferred is a hydrating gel having a viscosity of about 100,000 centipoise at about 25°C. The viscosity ranges described herein are measured using a Brookfield viscometer at room temperature. At the lower end of the viscosity ranges, the Brookfield viscometer is fitted with a number 4 spindle operating at 10 rpm, and at the higher end of the range, the Brookfield viscometer is fitted with a TE
heliopathic spindle operating at 0.3 rpm.
In addition, the hydrating nasal gel of the present invention includes a controlled-release agent that physically or chemically entrains, retains or entraps water, so that moisture will be progressively released over a substantial period of time. If water is released too quickly, the product will be ineffective. If the water is released too slowly, the hydrating nasal gel will be ineffective in providing moisture to the nasal tissues.
Water should 1o preferably be released from the entraining or water binding agent at such a rate that it maintains moisture in the environment of the nasal cavity and/or in the nasal linings or tissues for a substantial period of time.
The controlled-release agent used in the present invention should be safe for use on the nasal tissues, be non-irritating, and should not substantially interfere with the gelling action of the gel-forming agent. Preferably, the controlled-release agent should be able to hold large quantities of water and release it at a relatively steady rate over a substantial period of time. In general, the nasal gel should release at least 0.1 gram of water per hour, for about two to four hours after application to the nasal tissue.
Preferably, the nasal gel of the present invention releases water at a rate of between about 1 wt-% to about 50 wt-% per hour at body temperature, or about 3~°C, based on the total weight of the gel. More preferably, the nasal gel of the present invention releases water at a rate of between about 1 wt-% to 10 wt-% per hour at body temperature.
It was surprisingly discovered that a nasal gel having a viscosity within the ranges described above was not substantially flushed out of the nose by natural biological functions, and remained in the nose for a substantial period of time without causing discomfort or an unpleasant sensation to the user.
3o In a preferred embodiment, the gel-forming function and the controlled-release function are provided by a single ingredient or component of the hydrating nasal gel.
The single component preferably has all the properties described above for each function.
Examples of materials that may be used to perform both functions in a single component include, but axe not limited to: hydrogel-forming agents, such as hydroxyethylcellulose; silica;
clay; a carbomer; and the like. Any material that produces a gel and then releases water over a period of minutes to hours would be effective in the hydrating nasal gel of the present invention.
One preferred component of the nasal gel that can perform both the gel-forming function and the controlled-release function is glyceryl polymethacrylate. Useful formulations of the hydrating nasal gel of the present invention comprising glyceryl polymethacrylate are summarized in Table I:
1o Table I
Ingredient Weight Percent Water 50%-99%
Glyceryl polymethacrylate1 %-50%
Other ingredients 0%- 25%
One preferred formulation of the present invention comprised about 65 wt-%
water, 25 wt-% glyceryl polyrnethacrylate, and 10 wt-% other ingredients.
Other ingredients or components in the nasal gel may include, but are not limited to:
humectants; preservatives; buffers; coloring agents; fragrances; solubilizing agents;
stabilizing agents; gel modifiers; herbal materials; and vitamins. Each of these ingredients can be present in any amount that does not substantially interfere with the gel-forming and controlled-release functions of the gel, preferably between about 0 wt-% to 10 wt-%. The preservative, if used, can more preferably be present in amounts ranging from 0.1 wt-% to 1.0 wt-%, depending on the preservative.
If any non-water soluble ingredients are used in the gel of the present invention, it may be useful or necessary to entrain such ingredients in microvesicles such as liquid crystals, micelles, liposomes, encapsulates, and the like.
If a fragrance is used, preferably it is one that provides cold symptom relief itself, such as camphor, menthol, or eucalyptus.
Example I
A hydrating nasal gel was prepared according to the formula shown in Table II.
1o Table I
Ingredient Weight Percent Water 50%-99%
Glyceryl polymethacrylate1 %-50%
Other ingredients 0%- 25%
One preferred formulation of the present invention comprised about 65 wt-%
water, 25 wt-% glyceryl polyrnethacrylate, and 10 wt-% other ingredients.
Other ingredients or components in the nasal gel may include, but are not limited to:
humectants; preservatives; buffers; coloring agents; fragrances; solubilizing agents;
stabilizing agents; gel modifiers; herbal materials; and vitamins. Each of these ingredients can be present in any amount that does not substantially interfere with the gel-forming and controlled-release functions of the gel, preferably between about 0 wt-% to 10 wt-%. The preservative, if used, can more preferably be present in amounts ranging from 0.1 wt-% to 1.0 wt-%, depending on the preservative.
If any non-water soluble ingredients are used in the gel of the present invention, it may be useful or necessary to entrain such ingredients in microvesicles such as liquid crystals, micelles, liposomes, encapsulates, and the like.
If a fragrance is used, preferably it is one that provides cold symptom relief itself, such as camphor, menthol, or eucalyptus.
Example I
A hydrating nasal gel was prepared according to the formula shown in Table II.
Table II
Brand Weight Ingredient Function Tested Percent Water Medium; provides moisture34.955%
59.00%
Glyceryl 1 Gel-forming agent; [29.5%-36.58%
Lubrajel water MS
water polymethacrylate release agent 22.42% -29.5%
glyceryl olymethacrylate]
Fragrance oil Fragrance 2.25%
Liposorb Polysorbate 20 Solubilizer 2 00%
L-202 .
Preservative Germaben Preservative 0.80%
II' Propylene glycol Humectant 0.50%
Glycerin Humectant 0.50%
-LubrajelC~ MS is a product of International Specialty Products, Wayne, NJ.
zLiposorb~ L-20 is a product of Lipo Chemicals, Inc., Patterson, NJ.
3Germaben~ II is a product of Sutton Laboratories, Inc., Chatham, NJ.
Ten 0.2 gram dosage units of the gel released an average of 0.2 grams of water per hour for six hours.
The water release rate of the hydrating nasal gel of the present invention was measured by applying 100 grams of the gel as a 2mm thick layer onto a metal surface. The metal surface was then subjected to a temperature near body temperature, or about 100°F, or about 38°C, and the weight loss of the gel was measured over time. FIG.
1 shows the weight loss rate over time. The weight loss is attributable to the gel releasing moisture into the surrounding environment, such as a nasal cavity.
As seen in FIG. l, the weight loss rate during the first two hours was about 1 gram every 10 minutes, or about 0.1% per minute, or approximately 6% per hour. After the first two hours, the weight loss rate of the gel of the present invention tapered off, but still continued at a slower rate. This non-linear weight loss rate of the hydrating gel of the present invention was unexpected, since in general, water diffusion is a linear phenomenon. The advantage of the non-linear weight loss rate is that although the weight loss rate becomes slower over time, the gel remains on the surface and releases moisture for a longer period of time than it would have had the weight loss rate remained linear over time.
Although the primary function of the hydrating nasal gel of the present invention is to deliver water to the nasal membranes or tissues over a substantial period of time, the gel could also be used to simultaneously release other beneficial materials such as vitamins, herbal extracts, pharmaceutical materials, homeopathic materials, and the like. The gel of the present invention could also be used to deliver water-insoluble agents to the nasal membranes on a time-release basis, in that as the water in the gel evaporates, any water-insoluble components may be released into the nasal tissue as well.
The hydrating nasal gel of the present invention is preferably applied in a manner to provide a relatively uniform layer of the gel on the inner nasal tissues, and more preferably in such a way as to substantially avoid being directly inserted into the nasal passage, where the gel cannot function to hydrate the nasal membranes. This can be accomplished in a number of ways, such as by using a cotton swab, a finger tip, or other type of applicator. Preferably, a squeeze bottle fitted with an applicator tip of the present invention is used to apply the gel to the nasal tissues.
FIG. 2 shows one embodiment of the applicator tip 10 of the present invention.
Applicator tip 10 includes base 11, sidewall 12, closed end 14, open end 16 of base 11, and sidewall orifice 18.
Applicator tip 10 generally is of a length and diameter that is appropriate for the geometry of the nasal cavity, and is preferably tapered to comfortably fit within the nasal cavity.
Open end 16 is preferably flared to prevent insertion of tip 10 too deeply into the nasal cavity. Sidewall orifices 18 are preferably arranged so as to dispense the gel at an appropriate depth into the nasal cavity, with the orifices preferably longitudinally positioned along the length of the tip to dispense the gel comfortably and evenly over the length of the nasal cavity, substantially without dispensing the gel too far into the nasal length of the nasal cavity, substantially without dispensing the gel too far into the nasal cavity, where the gel could be dispensed directly into the nasal passages, or too little into the nasal cavity, where the gel would not remain in the nasal cavity for a period of time sufficient to provide relief from dryness. Sidewall orifices 18 are preferably radially positioned to dispense the gel substantially evenly over the perimeter of the nasal cavity.
1o Orifices 18 also preferably have relatively restricted openings to retard the flow of gel to allow for consistent dosage application amounts.
Preferably, applicator tip 10 has a length ranging from about 0.5 inch to 1.5 inches. In one particularly preferred embodiment, applicator tip 10 has a length of between about 0.75 inch and 0.85 inch.
Open end 16 of base 11 is preferably in communication with a reservoir, not shown, containing the hydrating nasal gel of the present invention. Applicator tip 10 and the reservoir together comprise the dispenser for dispensing the hydrating nasal gel. Sidewall 12 includes at least one orifice 18, and preferably includes a plurality of such orifices to facilitate dispensing the gel from the sidewall orifices onto the nasal tissues. FIGS. 3A, 3B, and 3C show a cross-sectional view, a top view, and a bottom view, respectively, of the applicator tip embodiment shown in FIG. 3. As can be seen in FIG. 3B, the sidewall orifices 18 can be positioned generally uniformly around sidewall 12 to provide relatively uniform application of the gel within the nasal cavity onto the nasal tissues.
In the preferred embodiment shown in FIG. 3B, sidewall orifices 18 are positioned 120° apart from each other. Other positions of the sidewall orifices 18 may be used to suitably dispense the gel within the nasal cavity.
3o FIG. 3A is a cross-sectional view of the applicator tip embodiment shown in FIG. 3, taken along line A-A of FIG. 3. In this preferred embodiment, the applicator tip 10 has a total length of about 0.8 inches, a sidewall 12 length of about 0.54 inches, and a base 11 width of about 0.37 inches. As stated previously, the dimensions of applicator tip 10 are selected to comfortably fit within the nasal cavity to apply the nasal gel of the present invention.
Brand Weight Ingredient Function Tested Percent Water Medium; provides moisture34.955%
59.00%
Glyceryl 1 Gel-forming agent; [29.5%-36.58%
Lubrajel water MS
water polymethacrylate release agent 22.42% -29.5%
glyceryl olymethacrylate]
Fragrance oil Fragrance 2.25%
Liposorb Polysorbate 20 Solubilizer 2 00%
L-202 .
Preservative Germaben Preservative 0.80%
II' Propylene glycol Humectant 0.50%
Glycerin Humectant 0.50%
-LubrajelC~ MS is a product of International Specialty Products, Wayne, NJ.
zLiposorb~ L-20 is a product of Lipo Chemicals, Inc., Patterson, NJ.
3Germaben~ II is a product of Sutton Laboratories, Inc., Chatham, NJ.
Ten 0.2 gram dosage units of the gel released an average of 0.2 grams of water per hour for six hours.
The water release rate of the hydrating nasal gel of the present invention was measured by applying 100 grams of the gel as a 2mm thick layer onto a metal surface. The metal surface was then subjected to a temperature near body temperature, or about 100°F, or about 38°C, and the weight loss of the gel was measured over time. FIG.
1 shows the weight loss rate over time. The weight loss is attributable to the gel releasing moisture into the surrounding environment, such as a nasal cavity.
As seen in FIG. l, the weight loss rate during the first two hours was about 1 gram every 10 minutes, or about 0.1% per minute, or approximately 6% per hour. After the first two hours, the weight loss rate of the gel of the present invention tapered off, but still continued at a slower rate. This non-linear weight loss rate of the hydrating gel of the present invention was unexpected, since in general, water diffusion is a linear phenomenon. The advantage of the non-linear weight loss rate is that although the weight loss rate becomes slower over time, the gel remains on the surface and releases moisture for a longer period of time than it would have had the weight loss rate remained linear over time.
Although the primary function of the hydrating nasal gel of the present invention is to deliver water to the nasal membranes or tissues over a substantial period of time, the gel could also be used to simultaneously release other beneficial materials such as vitamins, herbal extracts, pharmaceutical materials, homeopathic materials, and the like. The gel of the present invention could also be used to deliver water-insoluble agents to the nasal membranes on a time-release basis, in that as the water in the gel evaporates, any water-insoluble components may be released into the nasal tissue as well.
The hydrating nasal gel of the present invention is preferably applied in a manner to provide a relatively uniform layer of the gel on the inner nasal tissues, and more preferably in such a way as to substantially avoid being directly inserted into the nasal passage, where the gel cannot function to hydrate the nasal membranes. This can be accomplished in a number of ways, such as by using a cotton swab, a finger tip, or other type of applicator. Preferably, a squeeze bottle fitted with an applicator tip of the present invention is used to apply the gel to the nasal tissues.
FIG. 2 shows one embodiment of the applicator tip 10 of the present invention.
Applicator tip 10 includes base 11, sidewall 12, closed end 14, open end 16 of base 11, and sidewall orifice 18.
Applicator tip 10 generally is of a length and diameter that is appropriate for the geometry of the nasal cavity, and is preferably tapered to comfortably fit within the nasal cavity.
Open end 16 is preferably flared to prevent insertion of tip 10 too deeply into the nasal cavity. Sidewall orifices 18 are preferably arranged so as to dispense the gel at an appropriate depth into the nasal cavity, with the orifices preferably longitudinally positioned along the length of the tip to dispense the gel comfortably and evenly over the length of the nasal cavity, substantially without dispensing the gel too far into the nasal length of the nasal cavity, substantially without dispensing the gel too far into the nasal cavity, where the gel could be dispensed directly into the nasal passages, or too little into the nasal cavity, where the gel would not remain in the nasal cavity for a period of time sufficient to provide relief from dryness. Sidewall orifices 18 are preferably radially positioned to dispense the gel substantially evenly over the perimeter of the nasal cavity.
1o Orifices 18 also preferably have relatively restricted openings to retard the flow of gel to allow for consistent dosage application amounts.
Preferably, applicator tip 10 has a length ranging from about 0.5 inch to 1.5 inches. In one particularly preferred embodiment, applicator tip 10 has a length of between about 0.75 inch and 0.85 inch.
Open end 16 of base 11 is preferably in communication with a reservoir, not shown, containing the hydrating nasal gel of the present invention. Applicator tip 10 and the reservoir together comprise the dispenser for dispensing the hydrating nasal gel. Sidewall 12 includes at least one orifice 18, and preferably includes a plurality of such orifices to facilitate dispensing the gel from the sidewall orifices onto the nasal tissues. FIGS. 3A, 3B, and 3C show a cross-sectional view, a top view, and a bottom view, respectively, of the applicator tip embodiment shown in FIG. 3. As can be seen in FIG. 3B, the sidewall orifices 18 can be positioned generally uniformly around sidewall 12 to provide relatively uniform application of the gel within the nasal cavity onto the nasal tissues.
In the preferred embodiment shown in FIG. 3B, sidewall orifices 18 are positioned 120° apart from each other. Other positions of the sidewall orifices 18 may be used to suitably dispense the gel within the nasal cavity.
3o FIG. 3A is a cross-sectional view of the applicator tip embodiment shown in FIG. 3, taken along line A-A of FIG. 3. In this preferred embodiment, the applicator tip 10 has a total length of about 0.8 inches, a sidewall 12 length of about 0.54 inches, and a base 11 width of about 0.37 inches. As stated previously, the dimensions of applicator tip 10 are selected to comfortably fit within the nasal cavity to apply the nasal gel of the present invention.
FIG. 4 is a perspective view of the applicator tip embodiment shown in FIG. 1.
Other embodiments of the applicator tip of the present invention are shown in FIGS.
5 and 6.
As can be seen, the number and dimensions of orifice 18 can be varied depending on the viscosity of the gel being applied and the amount of gel to be dispensed per application.
FIG. 6 shows an embodiment in which sidewall orifice 18 has different dimensions to depending on the location of each orifice 18 along the sidewall 12.
Applicator tip 10 can be made of any material suitable for use with the hydrating nasal gel of the present invention. Such materials must be compatible with the hydrating nasal gel, must be safe for the intended use, and should be suitable for use in conjunction with a dispenser containing the nasal gel, such as a tube, bottle, sprayer, and the like. Such materials include, but axe not limited to, polyethylene, polypropylene, polyurethane, ABS, and the like. Preferably, injection molded polyethylene is used to make applicator tip 10 of the present invention.
2o The applicator tip of the present invention is suitable for dispensing gels having a viscosity ranging from between about 5,000 cps to 300,000 cps at room temperature using a Brookfield viscometer. Particularly preferred for use with the applicator tip of the present invention are gels that are thixotropic and have a significant yield point, although flowable gels can be dispensed through this applicator tip as well.
Although the applicator tip has been described for use in the nasal cavity, it can be used to apply a gel to any cavity that has a geometry and requirements similar to those of the nasal cavity. Also, although the applicator tip has been described for dispensing a gel product, a similar applicator can be used to dispense a solid or liquid product.
Industrial Applicability Exam lp a II
A study was conducted using the hydrating nasal gel prepared according to the formula shown in Table II. The gel was placed in a dispensing tube to which the applicator tip shown in FIGS. 2-4 was attached. 115 study participants were asked to use the gel over a 3 to S day period. The results are shown below.
Other embodiments of the applicator tip of the present invention are shown in FIGS.
5 and 6.
As can be seen, the number and dimensions of orifice 18 can be varied depending on the viscosity of the gel being applied and the amount of gel to be dispensed per application.
FIG. 6 shows an embodiment in which sidewall orifice 18 has different dimensions to depending on the location of each orifice 18 along the sidewall 12.
Applicator tip 10 can be made of any material suitable for use with the hydrating nasal gel of the present invention. Such materials must be compatible with the hydrating nasal gel, must be safe for the intended use, and should be suitable for use in conjunction with a dispenser containing the nasal gel, such as a tube, bottle, sprayer, and the like. Such materials include, but axe not limited to, polyethylene, polypropylene, polyurethane, ABS, and the like. Preferably, injection molded polyethylene is used to make applicator tip 10 of the present invention.
2o The applicator tip of the present invention is suitable for dispensing gels having a viscosity ranging from between about 5,000 cps to 300,000 cps at room temperature using a Brookfield viscometer. Particularly preferred for use with the applicator tip of the present invention are gels that are thixotropic and have a significant yield point, although flowable gels can be dispensed through this applicator tip as well.
Although the applicator tip has been described for use in the nasal cavity, it can be used to apply a gel to any cavity that has a geometry and requirements similar to those of the nasal cavity. Also, although the applicator tip has been described for dispensing a gel product, a similar applicator can be used to dispense a solid or liquid product.
Industrial Applicability Exam lp a II
A study was conducted using the hydrating nasal gel prepared according to the formula shown in Table II. The gel was placed in a dispensing tube to which the applicator tip shown in FIGS. 2-4 was attached. 115 study participants were asked to use the gel over a 3 to S day period. The results are shown below.
Satisfaction with time for gel to take effect:
Extremely satisfied 17%
Very satisfied 42%
Somewhat satisfied 29%
Not very satisfied 5%
io Not at ALL satisfied 7%
Did the product soothe/relieve?
Yes 91 No 9%
is Duration of soothing effect (in those who said it was soothin Less than one hour 11 One to two hours 22%
Two to three hours 15%
2o More than three hours 44%
Mean duration of soothing effect: 3.6 hours As can be seen, the hydrating nasal gel of the present invention, applied with the applicator of the present invention, provided significant relief to subjects suffering from 25 nasal discomfort without the need for drug ingredients.
Although the foregoing is intended to describe the present invention, it is not meant to limit the full scope of the invention, which is set forth in the following claims.
Extremely satisfied 17%
Very satisfied 42%
Somewhat satisfied 29%
Not very satisfied 5%
io Not at ALL satisfied 7%
Did the product soothe/relieve?
Yes 91 No 9%
is Duration of soothing effect (in those who said it was soothin Less than one hour 11 One to two hours 22%
Two to three hours 15%
2o More than three hours 44%
Mean duration of soothing effect: 3.6 hours As can be seen, the hydrating nasal gel of the present invention, applied with the applicator of the present invention, provided significant relief to subjects suffering from 25 nasal discomfort without the need for drug ingredients.
Although the foregoing is intended to describe the present invention, it is not meant to limit the full scope of the invention, which is set forth in the following claims.
Claims (19)
1. A hydrating nasal gel comprising:
water in an amount ranging from about 50 wt-% to about 99 wt-%;
a controlled-release agent in an amount effective to provide water to a nasal tissue within a nasal cavity at a rate of between about 1 wt-% to 50 wt-% per hour at about 38°C; and a gel-forming agent in an amount effective to provide a viscosity to the hydrating nasal gel of between about 5,000 centipoise to 300,000 centipoise at about 25°C.
water in an amount ranging from about 50 wt-% to about 99 wt-%;
a controlled-release agent in an amount effective to provide water to a nasal tissue within a nasal cavity at a rate of between about 1 wt-% to 50 wt-% per hour at about 38°C; and a gel-forming agent in an amount effective to provide a viscosity to the hydrating nasal gel of between about 5,000 centipoise to 300,000 centipoise at about 25°C.
2. The hydrating nasal gel of claim 1, wherein the controlled-release agent and the gel-forming agent comprise one component of the gel.
3. The hydrating nasal gel of claim 2, wherein the component is selected from the group comprising: hydrogel-forming agents; hydroxymethylcellulose; silica;
clays; and carbomers.
clays; and carbomers.
4. The hydrating nasal gel of claim 2, wherein the component is glyceryl polymethacrylate.
5. The hydrating nasal gel of claim 1, wherein the controlled-release agent and the gel-forming agent are present in amounts effective to provide water to the nasal tissue in the nasal cavity for up to about six hours.
6. The hydrating nasal gel of claim 1, further comprising one or more additional components selected from the group comprising: humectants; preservatives;
buffers;
colors; fragrances; solubilizing agents; stabilizing agents; gel modifiers;
herbal materials;
and vitamins.
buffers;
colors; fragrances; solubilizing agents; stabilizing agents; gel modifiers;
herbal materials;
and vitamins.
7. The hydrating nasal gel of claim 6, wherein the additional component is selected from the group comprising camphor, menthol and eucalyptus.
8. The hydrating nasal gel of claim 1, wherein the controlled-release agent is present in an amount effective to provide water to the nasal tissue at a rate of between about 1 wt-% to 10% per hour at about 38°C.
9. The hydrating nasal gel of claim 1, wherein the gel-forming agent is present in an amount effective to provide a viscosity to the hydrating nasal gel of about 100,000 cps at 25°C.
10. A hydrating nasal gel comprising:
water in an amount ranging from about 50 wt-% to about 99 wt-%;
a controlled-release agent in an amount effective to provide water to a nasal tissue within a nasal cavity at a rate of between about 1 wt-% to 50 wt-% per hour at about 38°C; and a gel-forming agent in an amount effective to provide a viscosity to the hydrating nasal gel of between about 5,000 centipoise to 300,000 centipoise at about 25°C;
wherein the controlled-release agent and the gel-forming agent are present in amounts effective to provide water to the nasal tissue within the nasal cavity for up to about six hours.
water in an amount ranging from about 50 wt-% to about 99 wt-%;
a controlled-release agent in an amount effective to provide water to a nasal tissue within a nasal cavity at a rate of between about 1 wt-% to 50 wt-% per hour at about 38°C; and a gel-forming agent in an amount effective to provide a viscosity to the hydrating nasal gel of between about 5,000 centipoise to 300,000 centipoise at about 25°C;
wherein the controlled-release agent and the gel-forming agent are present in amounts effective to provide water to the nasal tissue within the nasal cavity for up to about six hours.
11. The hydrating nasal gel of claim 10, wherein the gel is substantially free of drug ingredients.
12. A method for hydrating a nasal tissue, comprising the steps of a) providing a hydrating nasal gel comprising: water in an amount ranging from about 50 wt-% to about 99 wt-%; a controlled-release agent in an amount effective to provide water to the nasal tissue at a rate of between about 1 wt-% to 50 wt-% per hour at about 38°C; and a gel-forming agent in an amount effective to provide a viscosity to the hydrating nasal gel of between about 5,000 centipoise to 300,000 centipoise at 25°C;
b) administering said nasal gel to a nasal tissue.
b) administering said nasal gel to a nasal tissue.
13. The method of claim12, wherein the nasal gel is administered to the nasal tissue by a dispenser comprising an applicator tip including a plurality of sidewall orifices.
14. The method of claim 13, wherein the applicator tip comprises one sealed end and one open end, the open end being in fluid communication with a reservoir of the dispenser.
15. The method of claim 13, wherein the sidewall orifices are radially positioned around the tip, and longitudinally positioned along the tip to administer the gel to the nasal tissue in an approximately uniform amount.
16. The method of claim 13, wherein the sidewall orifices have a dimension sufficient to permit dispensing a thixotropic gel.
17. The method of claim 13, wherein the sidewall orifices are of a dimension sufficient to permit dispensing a gel having a viscosity of between about 5,000 centipoise to 300,000 centipoise at 25°C.
18. An applicator tip for dispensing a thixotropic material to an inner surface of a cavity, comprising a sidewall, an open end, and a sealed end, the open end being in fluid communication with a reservoir containing the thixotropic material, and the sidewall comprising a plurality of orifices longitudinally positioned along the applicator tip to dispense the thixotropic material onto the inner surface.
19. The applicator tip of claim 18, wherein the inner surface of the cavity comprises a nasal tissue within a nasal cavity, and the sealed end substantially prevents dispensing the thixotropic material into a nasal passage.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32912201P | 2001-10-12 | 2001-10-12 | |
| US32912301P | 2001-10-12 | 2001-10-12 | |
| US60/329,122 | 2001-10-12 | ||
| US60/329,123 | 2001-10-12 | ||
| PCT/US2002/032606 WO2003030793A1 (en) | 2001-10-12 | 2002-10-11 | Hydrating nasal gel and applicator |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2463384A1 true CA2463384A1 (en) | 2003-04-17 |
Family
ID=26986653
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002463384A Abandoned CA2463384A1 (en) | 2001-10-12 | 2002-10-11 | Hydrating nasal gel and applicator |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1450739A4 (en) |
| JP (1) | JP2005505587A (en) |
| CA (1) | CA2463384A1 (en) |
| MX (1) | MXPA04003359A (en) |
| WO (1) | WO2003030793A1 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2709588A1 (en) * | 2011-05-15 | 2014-03-26 | Trimel Biopharma SRL | Controlled release nasal testosterone gels, methods and pre-filled multi-dose applicator systems for pernasal administration |
| US9757388B2 (en) | 2011-05-13 | 2017-09-12 | Acerus Pharmaceuticals Srl | Intranasal methods of treating women for anorgasmia with 0.6% and 0.72% testosterone gels |
| US10111888B2 (en) | 2011-05-13 | 2018-10-30 | Acerus Biopharma Inc. | Intranasal 0.15% and 0.24% testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder |
| US10668084B2 (en) | 2011-05-13 | 2020-06-02 | Acerus Biopharma Inc. | Intranasal lower dosage strength testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder |
| US11090312B2 (en) | 2013-03-15 | 2021-08-17 | Acerus Biopharma Inc. | Methods of treating hypogonadism with transnasal testerosterone bio-adhesive gel formulations in male with allergic rhinitis, and methods for preventing an allergic rhinitis event |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6949262B1 (en) | 2003-05-27 | 2005-09-27 | Lousal Enterprises, Inc. | Skin and mucosal treatment formulation |
| GB2431874A (en) * | 2005-11-03 | 2007-05-09 | Cst Medical Ltd | Lubricant |
| NL2001342C2 (en) * | 2008-02-20 | 2009-08-24 | Cornelis Boegem | Balm for covering mucous membranes against allergenic substances present in the air, the use of the balm and an applicator for the balm. |
| CN106727277A (en) * | 2015-11-22 | 2017-05-31 | 中国人民解放军第三军医大学 | A kind of mentholated nasal cavity in-situ gel spray and preparation method thereof |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4863725A (en) * | 1982-10-27 | 1989-09-05 | Deckner George E | Novel clear oil-free moisturizer composition |
| GB2133691B (en) * | 1983-01-21 | 1986-05-21 | Leo Ab | Smoking substitutes for nasal administration |
| US4724231A (en) * | 1985-04-16 | 1988-02-09 | Nastech Pharmaceutical, Inc. | Nasel compositions containing vitamin B12 |
| US4781923A (en) * | 1987-07-20 | 1988-11-01 | Pellico Michael A | Antiseptic gels |
| ATE181824T1 (en) * | 1989-10-31 | 1999-07-15 | Columbia Lab Inc | AGENTS FOR MOISTURIZING TISSUES AND METHOD |
| GB9109775D0 (en) * | 1991-05-04 | 1991-06-26 | Procter & Gamble | Cosmetic compositions |
| IL101056A (en) * | 1992-02-24 | 1997-03-18 | Res & Dev Co Ltd | Composition for nasal treatment |
| FR2694189B1 (en) * | 1992-07-30 | 1994-09-02 | Sederma Sa | New method intended to increase the viscosity of cosmetic compositions. |
| GB9218834D0 (en) * | 1992-09-05 | 1992-10-21 | Procter & Gamble | Nasal spray products |
| GB9324250D0 (en) * | 1993-11-25 | 1994-01-12 | Minnesota Mining & Mfg | Inhaler |
| FR2744919B1 (en) * | 1996-02-21 | 1998-03-27 | Stoa Sa | NOVEL COMPOSITIONS FOR THE TREATMENT AND PROTECTION OF Udders OF MILKING ANIMALS |
| JPH09253208A (en) * | 1996-03-21 | 1997-09-30 | Unisia Jecs Corp | Medicator for nasal cavity |
| JPH11511180A (en) * | 1996-06-12 | 1999-09-28 | ストア ソシエテ アノニマ | Physical disinfecting gel for cosmetics |
| US5989535A (en) * | 1997-08-15 | 1999-11-23 | Soma Technologies | Polymeric bioadhesive emulsions and suspensions and methods of treatment |
| US6080783A (en) * | 1998-09-01 | 2000-06-27 | Gum Tech International, Inc. | Method and composition for delivering zinc to the nasal membrane |
| AU2862200A (en) * | 1999-01-27 | 2000-08-18 | Bruce H. Levin | Compositions, kits, apparatus, and methods for inhibiting cerebral neurovasculardisorders and muscular headaches |
| DE19961307A1 (en) * | 1999-12-18 | 2001-07-12 | Krewel Meuselbach Gmbh | Medical device for moisturizing and cleaning the nasal mucosa |
| WO2001070270A2 (en) * | 2000-03-23 | 2001-09-27 | Collaborative Technologies, Inc. | Base compositions for preparing surfactant free topical compositions |
-
2002
- 2002-10-11 JP JP2003533828A patent/JP2005505587A/en active Pending
- 2002-10-11 WO PCT/US2002/032606 patent/WO2003030793A1/en active Application Filing
- 2002-10-11 CA CA002463384A patent/CA2463384A1/en not_active Abandoned
- 2002-10-11 MX MXPA04003359A patent/MXPA04003359A/en unknown
- 2002-10-11 EP EP02769063A patent/EP1450739A4/en not_active Withdrawn
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9757388B2 (en) | 2011-05-13 | 2017-09-12 | Acerus Pharmaceuticals Srl | Intranasal methods of treating women for anorgasmia with 0.6% and 0.72% testosterone gels |
| US10111888B2 (en) | 2011-05-13 | 2018-10-30 | Acerus Biopharma Inc. | Intranasal 0.15% and 0.24% testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder |
| US10668084B2 (en) | 2011-05-13 | 2020-06-02 | Acerus Biopharma Inc. | Intranasal lower dosage strength testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder |
| EP2709588A1 (en) * | 2011-05-15 | 2014-03-26 | Trimel Biopharma SRL | Controlled release nasal testosterone gels, methods and pre-filled multi-dose applicator systems for pernasal administration |
| EP2709588B1 (en) * | 2011-05-15 | 2021-08-25 | Acerus Biopharma Inc. | Controlled release nasal testosterone gels, methods and pre-filled multi-dose applicator systems for pernasal administration |
| US11090312B2 (en) | 2013-03-15 | 2021-08-17 | Acerus Biopharma Inc. | Methods of treating hypogonadism with transnasal testerosterone bio-adhesive gel formulations in male with allergic rhinitis, and methods for preventing an allergic rhinitis event |
| US11744838B2 (en) | 2013-03-15 | 2023-09-05 | Acerus Biopharma Inc. | Methods of treating hypogonadism with transnasal testosterone bio-adhesive gel formulations in male with allergic rhinitis, and methods for preventing an allergic rhinitis event |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2005505587A (en) | 2005-02-24 |
| WO2003030793A1 (en) | 2003-04-17 |
| EP1450739A4 (en) | 2008-12-17 |
| EP1450739A1 (en) | 2004-09-01 |
| MXPA04003359A (en) | 2004-11-29 |
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