Patent Application
20210137888
This application claims the benefit of US Design 29/712813 filed 12 Nov. 2019 which claims priority to the ECD 001471874 filed 14 May 2019, and EU 19209288.0 filed 14 Nov. 2019.
This invention relates to a novel combination product. The combination product comprises a nasal spray product containing a formulation for nasal administration and a balm holder element containing a skin-care balm.
Intranasal administration of a formulation, for example a drug formulation or a medicinal product formulation, frequently employs a primary packaging for such formulation that comprises a container and a dispensing mechanism with a nozzle that is suitable to be introduced into a user's nostril and from which such formulation is dispensed into the nostril. In particular for liquid formulations containing an active ingredient, where it is important that the desired dose of the ingredient is administered, metered dose spray pumps are commonly used as a dispensing mechanism.
Metered dose spray pumps are for example known from EP1768789B3, EP1954403B1, or WO2017191205A1. These documents are incorporated by reference.
The indications for which certain nasally administered drugs may be used are known in the art. For example, vasoconstrictors are used as nasal decongestants for alleviating the typical symptoms of the common cold or flu, like runny nose, obstructed nose etc., or for alleviating the symptoms of rhinitis or sinusitis. Antiallergic agents and corticosteroids are used in the treatment of allergic conditions, e.g. hay fever, or in asthmatic or inflammatory conditions.
Patients who suffer from any of these conditions frequently use tissues to blow their nose or to clean their nose. This often leads to skin irritation and redness around the nose, which generally occurs soon after the onset of the symptoms which are treated by the intranasal administration of a formulation. This irritation or redness can even be exacerbated by the formulation which has been administered.
Today, patients and consumers either leave this skin irritation untreated, or treat it with skin creams or balms sold separately or for different purposes, and/or conceal it with make-up or other cosmetic products. However, the use of concealer or make-up does not treat the condition, and might even worsen it. Furthermore, using a nasal spray and a separate product such as a cream or balm is not convenient, especially when both products need to be used several times per day, and users are traveling or commuting to their workplace, school or other locations.
Thus, there is a need for a solution allowing users to conveniently treat the skin irritation and redness around the nose occurring frequently together with nasal congestion or a runny nose.
Aspects of the present invention are directed to a novel combination product comprising a nasal spray dispenser containing a formulation for nasal administration, and a balm holder element attached to a bottom of the nasal spray dispenser containing a skin-care balm. According to an embodiment, the nasal spray dispenser comprises a dispensing head mounted on a top of a container.
In another embodiment, the combination product comprises a dispensing head mounted on a top of a container containing a liquid formulation for nasal administration, and a solidified skin-care balm for application around the nose contained in a balm holder element attached to a bottom of the container. In an embodiment, the balm holder element comprises a base element on which the balm is mounted, a balm cover with a cylindrical portion surrounding the balm, and a cover portion.
In an embodiment, the nasal spray dispenser containing the formulation is made from high density polyethylene (HDPE). According to an embodiment of the invention, the dispensing head is a metered dose spray pump.
According to an embodiment of the invention, the balm holder element comprises a base element on which the balm is mounted, a balm cover with a cylindrical portion surrounding the balm, and a cover portion. The balm cover may be removed from the base element, exposing the balm. The balm is then ready to be applied directly to the skin. In an embodiment, the cylindrical portion of the balm cover is aligned with a cylindrical wall of the nasal spray dispenser containing the formulation.
According to an embodiment of the invention, the balm cover is attached to the nasal spray dispenser. Preferably, the cover portion of the balm cover is attached to the bottom of the nasal spray dispenser.
In an embodiment, the cover portion of the balm cover is glued to the bottom of the nasal spray dispenser. In another embodiment, the balm cover is clipped or snap-fitted to the bottom of the nasal spray dispenser. Depending on the design of the connection, this can also allow for an assembly or disassembly by the consumer.
In an embodiment, the cover portion of the balm cover is dome-shaped and matches a recess in the bottom of the nasal spray dispenser. This improves the bond between the balm cover and the nasal spray dispenser.
According to an embodiment, the base element is attached to the bottom of the nasal spray dispenser. In an embodiment, the base element can be glued, clipped, or snap-fitted to the nasal spray dispenser, or attached in any other suitable way, either removable or non-removable for the consumer. In an embodiment, the balm holder element is detachably attached to the bottom of the nasal spray dispenser.
In one embodiment, the formulation is a liquid formulation containing a saline solution. In another embodiment, the formulation is a liquid formulation containing an active ingredient selected from a group of vasoconstrictors, antiallergic agents and corticosteroids. In one particular embodiment, the active ingredient is xylometazoline or a pharmaceutically acceptable salt thereof.
In one embodiment, the balm comprises one or several skin conditioning agents. In an embodiment, the balm comprises an active ingredient that is a botanical extract. In one embodiment, the botanical extract is Zanthoxylum bungeanum fruit husk extract.
In one embodiment, the balm comprises a blend of two or more waxes in an amount from 15%-45% (w/w). In one embodiment, the balm further comprises emollients in an amount from 45%-70% (w/w). In one embodiment, the blend of two or more waxes comprises a first wax having a melting point of 70° C.-90° C. and a second wax having a melting point of 30° C.-60° C. In one embodiment, the first wax is rice bran wax. In one embodiment, the balm has a melting point from 60° C. to 75° C.
In an embodiment, the balm has substantially a hemispherical shape.
An embodiment of the present invention is directed to a method for treating nasal discomfort whereby a cooling and soothing effect is provided to a perinasal skin area, comprising use of the combination product according to the invention by application of the balm to the perinasal skin area and administration of the formulation for nasal administration into a nostril.
Another embodiment of the present invention is directed to a method for treating runny nose whereby irritated skin is soothed, comprising use of a combination product according to the invention by application of the balm to an irritated perinasal skin area and administration of the formulation for nasal administration into a nostril.
An embodiment of the present invention is directed to a balm holder element comprising: a base element on which a balm is mounted, a balm cover with a cylindrical portion surrounding the balm, and a cover portion, wherein the balm holder element is attachable to a nasal spray dispenser. In an embodiment, the balm holder element is permanently attached to the nasal spray dispenser. In another embodiment, the balm holder is removably attached to the nasal spray dispenser. In an embodiment, the balm holder element is attachable to a bottom of the nasal spray dispenser.
The invention will now be described by way of example with reference to the accompanying figures.
The nasal spray dispenser containing the formulation may for example be made from high density polyethylene (HDPE), polypropylene (PP) or glass. Preferably, the nasal spray dispenser is made from HDPE.
The nasal spray dispenser may be manufactured in one piece or may be assembled from multiple pieces. Preferably, the nasal spray dispenser comprises a dispensing head 10 mounted on a top of a container 20. In embodiments of the invention, the balm holder element 30 is attached to the bottom of the container 20.
Preferably, the balm cover 32 corresponds to an outline or shape of the nasal spray dispenser. Therefore, when the nasal spray dispenser has an ellipsoid or ovoid outline or shape, the balm cover 32 has a corresponding elliptic or oval cylinder portion. When the nasal spray dispenser has a circular outline or shape, the balm cover 32 has a corresponding circular cylindrical portion.
According to a preferred embodiment of the invention, the balm holder element 30 comprises a balm cover 32 with a cylindrical portion surrounding the balm 50 and a cover portion, and a base element 34 on which the balm is mounted. Alternatively, the balm holder element 30 comprises a balm cover 32 with an elliptic cylinder portion surrounding the balm and a cover portion, and a base element 34 on which the balm is mounted. Preferably, the balm holder element is made from polypropylene (PP).
Protrusions protruding inwardly from the circumferential rim 52 can be used to hold the balm 50 in place, once it has been pressed on the base plate 37 and on the protrusions. Alternatively, the base element 34 and the balm 50 may be assembled upon moulding of the balm, whereby a molten balm formulation solidifies on the base element 34. In the first embodiment shown in
In a preferred embodiment, the balm cover 32 consists of a cylindrical portion 33 surrounding the balm 50, and a cover portion 36 which has a dome shape, as can be seen in
In a preferred embodiment, the cover portion 36 it is glued to the bottom 24 of the container 20. A user can take off the base element 34 comprising the balm 50 and apply the balm 50 without having to handle the nasal spray dispenser, or the container 20 and the dispensing head 10 during application. A suitable glue for attaching the balm cover to the nasal spray dispenser, in particular when the balm cover is made from polypropylene (PP) and the nasal spray dispenser is made from high density polyethylene (HDPE), is cyano-acrylate glue which is used together with a primer. No heating is necessary to create the bond, and such a glue is thus particularly suitable to be used with a pre-filled nasal spray dispenser, where the application of heat in an assembly process could compromise the stability of the formulation contained in the nasal spray dispenser.
In another embodiment, the balm cover 32 is clipped or snap-fitted to the bottom of the container 20. On the outer surface of the rim 52, several protrusions 56 are foreseen, which make a snap-fit connection with the cylindrical portion 33 of the balm cover 32 and help to keep the base element 34 connected to the balm cover 32, and thus to the container 20. In a preferred embodiment, the balm cover 32 and the base element 34 are made of Polypropylene (PP).
An example of a balm formulation that may be utilized in the present invention is provided in Example 1. Preferably, the formulation comprises a moisturizing agent, in particular selected from the group comprising dexpanthenol, sorbitol and hydroxypropylmethylcellulose. Preferably, the balm comprises an active ingredient having skin soothing properties, in particular selected from the group comprising ectoin, dexpanthenol, aloe vera, calendula, bisabolol and niacinamide.
In another embodiment, the balm comprises an active ingredient that is a botanical extract. A botanical extract may be an extract from any part of a plant, e.g. an herbal extract. Botanical extracts are widely accepted by consumers, can be sourced in an environmentally friendly manner and do not need to be chemically synthesized. Botanical extracts from edible plants are preferred as they are non-toxic and can be used in the perinasal and perioral area, such as the upper lip region, without limitation. The ingredients of the extracts can be controlled such that desired and effective ingredients are enriched and undesirable ingredients are reduced or eliminated.
In one embodiment, the botanical extract is Zanthoxylum bungeanum fruit husk extract. This extract is rich in lipophilic alkylamides such as hydroxy-alpha-sanshools and hydroxy-beta-sanshools. These agents are believed to act as agonists on receptors of sensory neurons, such as the transient receptor potential cation channel subfamily V member 1 TRPV1 (also known as capsaicin receptor, or vanilloid receptor) and the transient receptor potential cation channel subfamily A member 1, 1TRPA1. The interaction of the ingredients of the extract with the somatosensory neurons in the skin provides a soothing, numbing and anti-itching effect that is especially suitable for the balm of the present invention. It provides a mild tingling effect and gives an immediate relief. Furthermore, it gives a cooling sensation. Its soothing or paresthesial effect relieves the discomfort of the user, reduces the sensitivity of the skin and reduces the body's response to irritation such as a runny nose, tearing and skin reddening.
Zanthoxylum bungeanum fruit husk extract is not believed to be irritating to the skin and does not cause sensitization. Additionally it has a pleasant smell that can mask the odour inherent to the other balm components. The balm can therefore be formulated without perfume, which is preferred as perfumes can cause skin irritation or burning sensation, especially when used on damaged skin.
Preferably, the Zanthoxylum bungeanum fruit husk extract is obtained by a mild, solvent free extraction method such as CO2 extraction. This provides the advantage of a high yield of the lipophilic alkylamides with no residual organic solvents.
The Zanthoxylum bungeanum fruit husk extract may typically have a content of total alkylamides from 4% to 7% by weight and may be used in the formulation of the balm in an amount from 0.05% to 1.0% by weight.
In another embodiment, the botanical extract comprises Aloe barbadensis leaf extract. Aloe barbadensis leaf extract has a moisturizing effect that is beneficial for roughened and cracked skin and helps to soothe irritated skin. The Aloe barbadensis leaf extract may be used in the formulation of the balm in an amount from 0.05% to 1% by weight.
Alternatively or in addition to such an active ingredient, the balm can contain skin conditioning or moisturizing agents or emollients.
Preferably, the balm is a non-aqueous formulation. This reduces the risk of contamination of the balm upon contact with the skin and allows the formulation to be preservative-free. This is beneficial as the balm may be used on irritated skin with an impaired barrier-function. Furthermore, a non-aqueous formulation forms a waterproof film or barrier layer on the irritated perinasal skin that has an occlusive, thus hydrating effect and protects the skin from nasal discharge and wiping with tissues that typically exacerbate irritation of the skin. Such a lipophilic film is furthermore preferred as it may serve as a substitute for a disrupted natural skin barrier and aid to restore the natural skin barrier which prevents the skin from being damaged further.
The balm formulation preferably comprises a blend of two or more waxes in an amount from 15%-45% by weight of the composition. The use of a blend of two or more waxes lowers the melting point which eases application to the skin. The use of a blend also reduces the tendency of the waxes to form large crystals, which would make the balm grainy or brittle.
The terms wax and waxes, as used herein, include waxes and pseudo-waxes. Numerous waxes or pseudo-waxes of animal, plant or petroleum origin known in the art are suitable for the formulation of the balm. Pseudo-waxes are excipients that have physical properties similar to those of waxes but are not waxes in the chemical sense, i.e. esters of fatty acids with fatty alcohols. They may be mixtures of carbohydrates and/or fatty acids and/or fatty alcohols and/or fatty acid esters and/or hydrogenated or unhydrogenated oils (triglycerides). Examples for carbohydrates are petrolatum and paraffin.
In one embodiment, the balm comprises a blend of petrolatum and paraffin. Petrolatum and paraffin are non-irritating, well-established and abundant carbohydrates.
Preferably, the melting point of the balm is in the range of 60° C. to 75° C. Melting point is determined according to the method monographed in the European Pharamcopoeia, Method Ph. Eur. 2.2.15. This melting point of the balm reduces the tendency of sweating or creaming of some ingredients included in the balm. It also provides firm adhesion of the balm to the balm base and structural integrity of the balm shape even in warm temperatures. At the same time, it is still soft enough for easy application to the skin and a convenient application on the desired area. This melting point is achieved, according to a preferred embodiment, by combining a first wax having a melting point of 70° C.-90° C. and a second wax having a melting point of 30° C.-60° C.
In a preferred embodiment, the first wax is rice bran wax. Rice bran wax gives the balm formulation a matt finish and reduces shine and greasiness when applied to the skin.
In a preferred embodiment, the balm comprises of a blend of two or more waxes in an amount of 15%-45% (w/w) and emollients in an amount of 45%-70% (w/w). The emollients hydrate the roughened skin of the perinasal area and soothe irritation. Furthermore, emollients reduce the hardness of the balm and lower the crystallization tendency of the waxes, which makes spreading more gentle and ensures the texture of the balm remains stable over time. Emollients are well-known in the art.
Preferably, the emollients comprise powdered hydrogenated castor oil. The powdered form of the hydrogenated castor oil reduces shine and greasiness of the balm when applied to the skin. Examples of other suitable emollients are botanical butters such as Butyrospermum Parkii (Shea) Butter and Theobroma Cacao (Cocoa) Seed Butter, oils such as castor oil and avocado oil, octyldodecanol, caprylic/capric triglyceride, behenyl alcohol, isopropyl lanolate, isopropyl myristate, isocetyl stearate and myristyl myristate.
Emollients comprising unsaturated fatty acids are preferred, for example shea butter and/or avocado oil. Avocado oil is especially preferred as it has a specific composition comprising free fatty acids that provides an excellent compatibility with the natural hydrolipidic film on the skin.
The balm may optionally comprise further excipients used in the art such as antioxidants, wetting agents, matting agents, rheology additives, hydrating agents and cooling agents.
Preferably, the balm has substantially a hemispherical shape, thus allowing for easy application to the desired area.
The balm may be applied to damaged, cracked, roughened, dry and irritated skin. It is especially beneficial for application in the perinasal area, i.e. the skin around the nose and the nostrils and the upper lip region. This area suffers primarily from wiping and nose blowing, nasal discharge, leakage of nasal formulation from the nose and other effects of nasal symptoms. It may also be beneficial for application to the perioral area and the lips. The perioral area and the lips also suffer from the effects of nasal symptoms, such as leakage of nasal formulation or frequent licking.
According to a preferred embodiment, the balm is applied to the skin around the nose. In another preferred embodiment, the balm is applied to the skin around the nostrils. The balm may be applied when needed. For example, the balm may be applied after each cleaning of the nose or multiple times daily.
In an embodiment, the formulation for nasal administration may be in a powdered (dry) form. Intranasal administration of powders, and nasal spray dispensers adapted for the intranasal administration of powders are known in the art. For example, intranasal administration of powdered cellulose derivates is used to block allergens, and intranasal administration of powdered corticosteroids is used for the treatment of allergy and asthma. These conditions often cause symptoms such as runny nose, and therefore those formulations are suitable for the present combination product.
The formulation for nasal administration may also be a liquid formulation such as a solution or a liquid suspension. Preferably, the formulation for nasal administration is a liquid formulation. Upon nasal administration of liquid formulations it often occurs that the formulation does not remain in the nose, but flows out of the nostrils. This requires wiping, and may cause skin irritation.
According to a preferred embodiment of the invention, the liquid formulation contains a saline solution and/or an active ingredient selected from the group of vasoconstrictors, antiallergic agents and corticosteroids.
The nasal administration of saline solutions which may in addition contain active ingredients is a widely used method of treatment. Active ingredients which come into consideration are, for example, vasoconstrictors, such as xylometazoline, or antiallergic agents, such as cromoglycic acid or H1 receptor antagonists, e.g. dimethindene maleate. Another group of possible active ingredients is e.g. corticosteroids, such as beclomethasone or fluticasone.
Examples for formulations for nasal administration are given below in Example 3.
Active substances suitable for nasal administration are e.g. vasoconstrictors, e.g. xylometazoline, e.g. xylometazoline hydrochloride; indanazoline, metizoline; naphazoline, e.g. naphazoline hydrochloride; fenoxazoline, e.g. fenoxazoline hydrochloride; oxymetazoline, e.g. oxymetazoline hydrochloride; tetrahydrozoline, tramazoline, tymazoline; phenylephrine, e.g. phenylephrine hydrochloride; ephedrine, e.g. d-pseudoephedrine hydrochloride; or epine-phrine; or antiallergic agents, such as (1) cromoglycic acid (=cromolyn) or a nasally acceptable salt thereof, e.g. the disodium salt (=disodium cromoglycate), or (2) H1 receptor antagonists, e.g. dimethindene or a nasally acceptable salt thereof, e.g. dimethindene maleate; acrivastine, brompheniramine, chlorpheniramine, dexchlorpheniramine, triprolidine, bromodiphenhydramine, clemastine, phenyltoloxamine, piprinhydrinate, pyrilamine, tripelennamine, cetirizine, hydroxyzine, methdilazine, promethazine, trimeprazine, azatadine, cyproheptadine, loratadine, astemizole, diphenhydramine, levocabastine or terfenadine. Examples for corticosteroids are e.g. beclomethasone, e.g. beclomethasone dipropionate, or fluticasone, e.g. fluticasone propionate. Mixtures of more than one active substance come also into consideration, e.g. a combination of a vasoconstrictor and an antiallergic agent, such as xylometazoline plus cromoglycic acid or phenylephrine plus dimethindene, or a combination of a vasoconstrictor and a corticosteroid, such as xylometazoline plus beclomethasone, among others.
According to a preferred embodiment, the active ingredient is xylometazoline or a pharmaceutically acceptable salt thereof. Xylometazoline is widely used in particular for treating symptoms of common cold and flu, where the skin irritation and redness issues arise frequently.
In another embodiment, the active ingredient is oxymetazoline or a pharmaceutically acceptable salt thereof. In yet another embodiment, the liquid formulation is a hypertonic saline solution. In still another embodiment, the liquid formulation is an isotonic saline solution.
While the invention has been described with reference to an exemplary embodiment(s), it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment(s) disclosed, but that the invention will include all embodiments falling within the scope of the appended claims.
The balm may be prepared as indicated below in Table 1. The names of the raw materials are given using the International Nomenclature of Cosmetic Ingredients (INCI). The % are indicated by weight.
The balm may be prepared by a conventional method. For example, it is prepared by melting of the solid components in a waterbath at a temperature sufficiently high to melt all ingredients, such as 60° C.-70° C. Subsequently, the liquid ingredients are added and the mixture is stirred to form a bulk. Any volatile ingredient are added after letting the bulk cool under stirring, but whilst the bulk is still fluid. The fluid bulk is poured into a stainless steel mold with an array of recesses of hemispheric shape. Excess bulk is scraped off. The mold filled with the bulk is let cool down at 5° C. for 20 minutes. The solidified balm hemispheres are removed from the mould by turning it upside down and placing it on a hard surface. To produce the combination product, the balm is pressed on the base element 34 and the base element is assembled with the remaining parts of the balm element and the container that contains the formulation.
| Number | Date | Country | Kind |
|---|---|---|---|
| 19209288.0 | Nov 2019 | EP | regional |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 29712813 | Nov 2019 | US |
| Child | 15930847 | US |
