HK1227009A1 - Spray delivery device - Google Patents

Description

Spray delivery device

RELATED APPLICATIONS

This application claims priority to serial No. 61/939,830, U.S. provisional application serial No. filed on date 2, month 14, 2014, which is incorporated herein by reference in its entirety.

Background

Many people have experienced skin conditions such as rashes, pressure ulcers, or wounds such as incisions or first degree burns that require topical application of creams or ointments to aid in the healing process. Generally, these conditions are more prevalent in infants, the elderly and the infirm. For example, infants, the elderly, and infirm may easily develop incontinent dermatitis, which occurs when the skin is exposed to prolonged moisture, causes an increase in skin pH due to contact with urine and excrement, and causes the stratum corneum or the outermost layer of the skin to break down. Meanwhile, pressure ulcers, also known as decubitus ulcers or bedsores, are also a concern. Pressure ulcers are localized lesions of the skin and/or underlying tissue that typically occur over bony prominences due to pressure or pressure in combination with shear and/or friction. The most common sites are the sacrum, coccyx, heel or hip, but other sites such as the elbow, knee, ankle or posterior skull can also be affected. Pressure ulcers occur due to pressure applied to soft tissue resulting in a fully or partially occluded blood flow to the soft tissue. Factors that can contribute to the formation of ulcers include protein caloric malnutrition, microclimate (skin wetness due to perspiration or incontinence), diseases that reduce blood flow to the skin such as arteriosclerosis, or diseases that reduce sensation on the skin such as paralysis or neuropathy.

These and other skin conditions can be prevented or treated, for example, by applying an active agent to the affected area of the skin. Active agents may, for example, help to accelerate the wound healing process and may also limit exposure of the skin to excessive moisture. Thus, one method for treating these skin conditions is to block moisture from reaching the skin, for example, by applying an oil-based protectant or protective cream, such as various over-the-counter creams or ointments containing moisture-resistant active agent particles, to the affected area. However, some of these oil-based protectants and creams may actually seal moisture to the inside of the skin rather than to the outside if the skin does not dry out. Further, such protectants and creams are very sticky and may be greasy, resulting in difficulty in removing the protectants and creams from the hands after application to the affected area of the skin. Furthermore, rubbing these products into the skin can cause additional discomfort or pain, and if the caregiver or health care provider must apply the product to the patient, this can cause embarrassment to the patient and caregiver depending on the location of application.

Thus, there is a need for compositions that provide a uniform coating of active agent to the skin, are easy to apply, and do not cause discomfort. One approach is to use an active agent in conjunction with a propellant to produce a sprayable composition. However, the high viscosity of the resulting aerosol spray compositions often means that it can be difficult to formulate the compositions into a medium that can be sprayed due to clogging problems of the active agent particles in the valves and nozzles of the dispenser. Meanwhile, to combat this problem, other sprayable compositions are formulated to have a low viscosity that allows spraying, but this can result in compositions that are not sufficiently viscous when applied to the surface of the skin, resulting in a flowable product that does not coat evenly or contact the skin effectively.

Yet another problem associated with the above-described spraying is that the active agent of the sprayable composition is particulate-based and typically settles to the bottom of the container in which the composition is stored, especially when the viscosity is low, resulting in clumping of the active agent in the container and failure to deliver the active agent in a uniform manner.

Thus, there is a need for stable sprayable compositions comprising active agent particles that remain substantially uniformly distributed and are capable of being uniformly sprayed as a fine mist onto the skin without clogging.

Summary of The Invention

In accordance with one embodiment of the present invention, a spray delivery system is disclosed. The system includes an active agent composition and a container. The active agent composition has a viscosity of about 500 centipoise to about 10,000 centipoise and includes a hydrofluoro-based propellant, a carrier fluid, and active agent particles. While the container comprises a straw; a valve assembly including a valve body, a valve stem including a valve stem bore, and an air vent; and an actuator, wherein the suction tube is connected to the actuator through the valve assembly. Depressing the actuator dispenses the active agent composition stored in the container.

Other features and aspects of the present invention are set forth in more detail below.

Brief Description of Drawings

A full and enabling disclosure of the present invention, including the best mode thereof, directed to one of ordinary skill in the art, is set forth more particularly in the remainder of the specification, which makes reference to the appended figures in which:

fig. 1 is a cross-sectional side view of a spray delivery system according to one embodiment of the present disclosure;

fig. 2A is a front view of an actuator that may be used with a spray delivery system according to one embodiment of the present disclosure;

FIG. 2B is a cross-sectional side view of the actuator of FIG. 2A;

FIG. 3 is a cross-sectional side view of a spray assembly according to one embodiment of the present disclosure; and

fig. 4 is a cross-sectional side view of a spray delivery system according to another embodiment of the present disclosure using the spray assembly of fig. 3.

Repeat use of reference characters in the present specification and drawings is intended to represent same or analogous features or elements of the invention.

Detailed description of representative embodiments

It is to be understood by one of ordinary skill in the art that the present discussion is a description of exemplary embodiments only, and is not intended as limiting the broader aspects of the present invention.

The present invention relates generally to spray delivery systems that may be used, for example, to treat various skin conditions or any other condition requiring topical application of an active agent. The spray delivery system includes a sprayable active agent composition contained in a container. The sprayable active agent composition comprises a hydrofluoro-based propellant, a carrier fluid, and active agent particles, and has a viscosity of about 500 centipoise to about 10,000 centipoise. The container comprises a straw; a valve assembly including a valve body, a valve stem including a valve stem bore, and an air vent; and an actuator. The straw is connected to an actuator through a valve assembly, and the actuator is depressed to dispense the sprayable active agent composition. By selectively controlling the viscosity of the components and compositions used, as well as the arrangement and size of the container components, the active agent particles resist settling, thereby maintaining a substantially uniform distribution of particles. Thus, the composition may be stable and dispensed uniformly from the container as a fine mist without clogging. For example, the spray delivery system includes a sprayable active agent composition that can be stable such that less than about 3 wt.%, such as less than about 2 wt.%, such as less than about 1 wt.% of the active agent particles in the composition settle when stored in a container for 3 days at 21 ℃. This results in a composition that can be uniformly sprayed onto a surface as a substantially uniform coating of the active agent particles.

First, the components of the container used in the spray delivery system are selected to prevent clogging of the sprayable active agent composition and to promote uniform spraying. For example, an actuator that is depressed to dispense a composition from a container may have an exit orifice having a diameter of from about 0.3 mm to about 0.6 mm, such as from about 0.35 mm to about 0.55 mm, such as from about 0.4 mm to about 0.5 mm to prevent the exit orifice from being clogged by particles of the active agent. Additionally, the actuator may be a non-mechanical disruption actuator, as a mechanical disruption actuator includes a channel that tends to clog when used in conjunction with a spray composition containing particles. Additionally, the valve stem orifice member of the container may have a diameter of from about 0.5 mm to about 0.75 mm, such as from about 0.55 mm to about 0.7 mm, such as from about 0.6 mm to about 0.65 mm, which may also prevent clogging as the active agent particles pass up through the straw and through the valve stem orifice.

Also, the diameter of the pores used to facilitate mixing of the propellant, carrier fluid and active agent particles in the composition in the valve body may be from about 0.1 mm to about 0.5 mm, such as from about 0.15 mm to about 0.45 mm, such as from about 0.2 mm to about 0.4 mm. This results in a substantially uniform distribution of propellant and active agent particles in the sprayable composition throughout the valve body. Such a distribution prevents clogging in the valve body and actuator and allows for even spraying from the open orifice.

In addition, the components of the sprayable active agent composition components of the spray delivery system can be selectively controlled to provide a spray delivery system that is resistant to clogging and provides a uniform spray. For example, based on the nature and type of components selected, the viscosity of the composition may be from about 500 centipoise to about 10,000 centipoise, such as from about 1000 centipoise to about 8000 centipoise, such as from about 1500 centipoise to about 6000 centipoise, such as from about 2000 centipoise to about 4000 centipoise, which results in a composition that is not so thick as to clog a spray delivery system, but not so thin that the resulting spray does not coat uniformly onto a surface.

Turning now to the specific components of the compositions utilized in spray delivery systems, hydrofluoro-based propellants may be used in conjunction with a base active agent composition that includes active agent particles and a carrier fluid. The ratio of the specific gravity of the propellant to the specific gravity of the overall composition may be selected from about 0.7 to about 1.6, such as from about 0.8 to about 1.5, such as from about 0.9 to about 1.4. Such a ratio of specific gravities produces a propellant having a specific gravity similar to that of the overall composition, meaning that the propellant can be substantially uniformly distributed throughout the emulsion composition. Since the propellant is distributed throughout the composition in this manner. Since the propellant is distributed throughout the composition in this manner, settling of the active agent particles in the composition can be prevented, which aids the ability of the spray delivery system to resist clogging and deliver a uniform spray on a surface.

The various components of the spray delivery system are discussed in more detail below.

I.Sprayable active agent composition

a.Propellant

The spray delivery system of the present invention comprises a sprayable active agent composition that includes a propellant to provide the energy necessary to assist in the delivery of active agent particles to the surface of the skin affected by a skin condition such as a rash, ulcer, wound or trauma. In other words, the propellant may provide the propulsive force necessary to spray the active agent onto the skin. Thus, the propellant has sufficient dispersion energy to overcome the surface tension of the liquid component of the composition.

As noted above, the composition contains a propellant that is particularly useful for facilitating the spraying of the active agent particles. The present inventors have discovered that by selectively controlling certain aspects of the propellant, such as specific gravity, vapor pressure, and/or molecular weight, compositions having a substantially uniform distribution of active agent particles can be obtained.

The ratio of the specific gravity of the propellant to the specific gravity of the sprayable composition may be from about 0.7 to about 1.6, such as from about 0.8 to about 1.5, such as from about 0.9 to about 1.4. Such a ratio of specific gravities results in the propellant having a specific gravity similar to that of the overall composition, which means that the propellant may be substantially uniformly distributed throughout the composition. Since the propellant is distributed throughout the composition in this manner, the particles of active agent and other particles contained in the composition are prevented from settling. Further, the propellant may have a specific gravity of from about 1.03 to about 1.3, such as from about 1.05 to about 1.25, such as from about 1.07 to about 1.2, as determined at 21 ℃ and having a density of 1.0 at 21 ℃ based on water. Also, the sprayable composition may have a specific gravity of from about 0.8 to about 1.3, such as from about 0.85 to about 1.25, such as from about 0.9 to about 1.2, as measured at 21 ℃.

In addition, the propellant may provide a vapor pressure that is high enough for the composition to be nebulized and sprayed in aerosol form, but not so high that when sprayed onto the skin, the resulting spray produces too much fly or discomfort, or requires a specially designed aerosol container. For example, the vapor pressure may be less than about 60psi at room temperature (21 ℃). In some embodiments, for example, the vapor pressure can be from about 30psi to about 60psi, such as from about 35psi to about 55psi, such as from about 40psi to about 50 psi. Without being limited by theory, it is believed that by using a propellant having a lower vapor pressure at room temperature compared to other propellants, the propellant can be used in large quantities in sprayable compositions, which will produce a smoother, more easily controlled spray and also ensure complete evacuation of the container in which the sprayable composition is stored. In addition, because of the low vapor pressure of the propellant, it is not necessary to use high pressure aerosol containers, which is required when other propellants are used.

Further, the molecular weight of the propellant may be greater than 100 grams per mole, such as from about 100 grams per mole to about 400 grams per mole, such as from about 105 grams per mole to about 300 grams per mole, such as from about 110 grams per mole to about 200 grams per mole. By using a propellant having a molecular weight within this range, sedimentation of the active agent particles can be further prevented.

In one embodiment, the propellant may comprise at least one hydrofluoroolefin. In a particular embodiment, the propellant comprises a hydrofluoroolefin containing 3 to 4 carbon atoms, such as three carbon atoms. When the hydrofluoroolefin propellant of the present invention contains at least one hydrogen, at least one fluorine and no chlorine, it may be referred to as "HFO". HFO is a derivative of an olefin. In some embodiments, the HFO propellant may comprise two carbon-carbon double bonds.

In a particular embodiment, the sprayable active agent composition of the present invention comprises a propellant represented by formula I below:

wherein each R is independently hydrogen or halogen, such as fluorine (F), bromine (Br), iodine (I) or chlorine (Cl), and preferably fluorine (F),

r' is (CR)₂)_nY，

Y is CRF₂And are and

n is 0 or 1.

In addition, in a specific embodiment, Y is CF₃N is 0 and at least one of the remaining R is F. In another specific embodiment, Y is CF₃At least one R on the unsaturated terminal carbon is H, and at least one of the remaining Rs is F. In yet another embodiment, the fluoroolefin propellants of the present invention may comprise one or more tetrafluoropropenes, and such propellants may be referred to herein as HFO-1234 propellants. Examples of tetrafluoropropenes contemplated by the present invention are HFO-1234yf (specific gravity at 21 ℃ of 1.092) and HFO-1234ze (specific gravity at 21 ℃ of 1.17) in cis and/or trans form. It is to be understood that HFO-1234ze refers to 1,1,1, 3-tetrafluoropropene, whether in cis-or trans-form, and the terms "cis HFO-1234 ze" and "trans HFO-1234 ze" are used herein to describe the cis and trans forms of 1,1,1, 3-tetrafluoropropene, respectively.

In some embodiments, HFO-1234ze may comprise a combination of transHFO-1234 ze and cisHFO-1234 ze, such as from about 90% to about 99% of the trans isomer based on total HFO-1234ze, and from about 1% to about 10% of the cis isomer on the same basis. Thus, in some embodiments, the propellant of the present invention may comprise a combination of cis HFO-1234ze and transhfo-1234 ze, preferably in a cis to trans weight ratio of about 1: 99 to about 10: 99, such as about 1: 99 to about 5: 95, such as about 1: 99 to about 3: 97.

while the nature of cisHFO-1234 ze and transHFO-1234 ze differ in at least some respects, it is contemplated that each of these compounds is suitable for use as a propellant in the sprayable compositions of the present invention, either alone or in combination with other compounds, including stereoisomers thereof. For example, although transHFO-1234 ze has a relatively low boiling point (-19 ℃), it is contemplated that cis HFO-1234ze having a boiling point of 9 ℃ may also be used as a propellant in the sprayable compositions of the present invention. Further, it is understood that the terms HFO-1234ze and 1,1,1, 3-tetrafluoropropene both refer to stereoisomers and that the use of these terms covers the cis and trans forms.

Another type of propellant that may be used is a hydrofluoroalkane, which may be referred to as "HFA". HFA propellants are also known as hydrofluorocarbon or "HFC" propellants. One example of a suitable HFC propellant is 1,1,1, 2-tetrafluoroethane, which may also be referred to as HFC-134 a. Another type of HFC propellant that may be used is 1,1,1,2,3,3, 3-heptafluoropropane, which may also be referred to as HFC-227 ea.

Regardless of the specific propellant used, the amount of propellant included in the sprayable active agent compositions of the present invention may be from about 5 wt.% to about 95 wt.%, such as from 10 wt.% to about 80 wt.%, such as from about 15 wt.% to about 60 wt.%, based on the total weight of the composition.

b.Active agent particles

The sprayable compositions of the present invention also comprise particles of active agents, which can refer to any compound or mixture of compounds that produces a physiological result upon contact with a living organism (e.g., mammal), such as a human. The active agent particles can be distinguished from other components of the sprayable composition, such as preservatives, conditioning agents, emollients, viscosity modifiers, emulsifiers and the like. The active agent particles may include any molecule capable of modulating a biological process, as well as binding portions or fragments thereof. In some embodiments, the active agent particles may be used in the diagnosis, treatment or prevention of disease, or as a component of a pharmaceutical, cosmetic or cosmeceutical. Additionally, the active agent particles may be compounds that interact with, or affect or otherwise modulate a target in a living subject. The target can be a number of different types of naturally occurring structures, wherein the target of interest includes both intracellular and extracellular targets. The active agent particles can include, for example, moisture barriers, antifungal agents, antibacterial agents, analgesic agents, antibacterial agents, anesthetic agents, anti-inflammatory agents, antipruritic agents, and the like. The active agent particles can have an average particle size of from about 20 nanometers to about 1000 nanometers, such as from about 25 nanometers to about 500 nanometers, such as from about 30 nanometers to about 250 nanometers.

In one embodiment, the active agent particles may include zinc oxide particles that repel moisture and create a barrier between the skin and the environment to protect the skin from excess moisture. The zinc oxide particles can have an average particle size of from about 20 nanometers to about 200 nanometers, such as from about 25 nanometers to about 150 nanometers, such as from about 30 nanometers to about 100 nanometers.

The zinc oxide particles may be hydrophobic, for example, by applying a hydrophobic coating on the surface of the zinc oxide particles, as described in more detail below. The particles may also carry an inorganic coating, either alone or in combination with the hydrophobic coating, as described in more detail below. The zinc oxide particles may be coated with alumina, silica, organic materials, polysiloxanes, or combinations thereof. Other suitable surface treatments may include: phosphate esters (including lecithin), perfluoroalkyl alcohol phosphate esters, fluorosilanes, isopropyl titanium triisostearate, stearic acid or other fatty acids, silanes, dimethicone and related silicone polymers or combinations thereof.

For example, the zinc oxide particles may be coated with oxides of other elements, such as oxides of aluminium, zirconium or silicon or mixtures thereof, such as alumina and silica. Alternatively, the zinc oxide particles may be treated with boron nitride or other known inorganic coatings, alone or in combination, prior to embedding the zinc oxide particles in the pores of the particles. The inorganic coating may be applied using techniques known in the art. A typical process may include forming an aqueous dispersion of zinc oxide particles in the presence of a soluble salt of an inorganic element whose oxide will form the coating. The dispersion is generally acidic or basic, depending on the nature of the salt selected, and settling of the inorganic oxide is achieved by adjusting the pH of the dispersion by adding acid or base as appropriate. The inorganic coating, if present, can be applied as a first layer to the surface of the zinc oxide particles.

In another embodiment, the zinc oxide particles may include an organic coating that provides hydrophobicity. The organic coating may be applied to the inorganic coating (if present), or directly to the zinc oxide. The hydrophobic coating agent may be, for example, a polysiloxane, a silane, a metal soap, a titanate, an organic wax, or a combination thereof. The hydrophobic coating may alternatively comprise a fatty acid, for example, a fatty acid containing 10 to 20 carbon atoms, such as lauric acid, stearic acid, isostearic acid and salts of these fatty acids. The fatty acid may be titanium isopropoxide triisostearate. For polysiloxanes, the hydrophobic coating may be polymethylsiloxane, dimethicone, copolymers thereof, or mixtures thereof. The polysiloxane may also be an organosilicon compound, for example with recurring-Me₂Dimethylpolysiloxanes of SiO-unit skeleton ("Me" is methyl, CH)₃) Methylhydrogenpolysiloxanes having a repeating skeleton of units-MeHSiO-and of the formula R_nOSiH_(4-n)Wherein "R" is an alkyl group and "n" is an integer of 1,2 or 3. For silanes, the hydrophobic coating agent may be an alkoxysilane, such as available from OSI Specialties or PCRAlkyl triethoxy or alkyl trimethoxy silane. The alkoxysilane may be of C₃To C₁₂Alkyl triethoxycaprylylsilane or perfluoroalkylethyltriethoxysilane, which may be linear or branched. The zinc oxide particles with a coating of triethoxycaprylylsilane may be referred to by the name ZANO^TM10Plus is commercially available from Umicore Zinc Chemicals.

Other active agent particles that may be used in the sprayable composition may include paraffin, microcrystalline wax, petrolatum, beeswax, or a combination thereof. Such active agent particles may act as a moisture barrier material.

Regardless of the type of active agent particles utilized, the amount of active agent particles included in the sprayable compositions of the present invention may be from about 0.1 wt.% to about 30 wt.%, such as from 1 wt.% to about 25 wt.%, such as from about 2 wt.% to about 20 wt.%, based on the total weight of the composition.

c.Carrier fluid

The sprayable active agent composition may also include a carrier fluid in which the propellant and active agent particles may be substantially uniformly dispersed. In some embodiments, the carrier fluid may comprise an oil phase and an aqueous phase. The oil phase and the aqueous phase may form a water-in-oil emulsion or an oil-in-water emulsion. In other embodiments, the carrier fluid may be oil or water.

Suitable oils that may be used in the carrier fluid include mineral oil, vegetable oil, silicone oil, or combinations thereof. Examples of commercially available mineral oils (which are derivatives of liquid petroleum oils) that may be used in accordance with the present invention may include carnotion from Witco Corporation^TMMineral oil or DRAKEOL from Penreco corporation^TMA mineral oil. Suitable vegetable oils which may be used are non-petroleum biomass derived oils including vegetable or fruit oils such as almond oil (almond oil), peanut oil, wheat germ oil, linseed oil, jojoba oil, apricot kernel oil, walnut oil, palm fruit oil, pistachio oil, sesame seed oil, rapeseed oil, juniper oil, corn oil, peach kernel oil, poppy oil, pine oilCastor oil, soybean oil, avocado oil, safflower oil, coconut oil, hazelnut oil, olive oil, grape seed oil, sunflower oil, almond oil, geranium oil, rice bran oil and mixtures thereof. Silicone oils that may be used include disiloxanes, cyclomethicones, dimethicone and derivatives thereof, and dimethicone fluids. Cyclomethicone is a volatile compound and evaporates when applied to the surface of the skin, so that the resulting coating is drier to the touch. Other similar volatile compounds that may be used include isododecane.

Water may also be used as the carrier fluid alone or in combination with any of the oils described above in a water-in-oil emulsion or an oil-in-water emulsion. Of course, the carrier fluid is not intended to be limited to the materials described above.

When the carrier fluid comprises both oil and water, the oil may be present in the emulsion in an amount of from about 1 wt.% to about 35 wt.%, such as from about 3 wt.% to about 30 wt.%, such as from about 5 wt.% to about 25 wt.%, based on the total weight of the composition. Meanwhile, the water may be present in an amount of less than about 50 wt.%, such as from about 1 wt.% to about 50 wt.%, such as from about 5 wt.% to about 45 wt.%, such as from about 10 wt.% to about 40 wt.%, based on the total weight of the composition. Additionally, the total amount of carrier fluid present in the composition may be from about 10 wt.% to about 70 wt.%, such as from about 15 wt.% to about 65 wt.%, such as from about 20 wt.% to about 60 wt.%, based on the total weight of the composition.

d.Emulsifying system

The sprayable composition may also comprise an emulsifying system. The emulsifying system may comprise one or more emulsifiers to help establish a stable, substantially homogeneous, homogeneous dispersion of the propellant and the active agent particles by preventing the sprayable composition from separating into the constituent phases. The emulsifying system also comprises one or more nonionic, anionic and/or amphoteric emulsifiers, including mixtures comprising different species or mixtures of different surfactants within the same species. In a particular embodiment, the emulsifying system comprises one or more non-ionic emulsifiers.

Nonionic surfactants which typically have a hydrophobic group (e.g., long chain alkyl or alkylated aryl) and a hydrophilic chain (e.g., a chain containing ethoxy and/or propoxy moieties) may be particularly suitable. Some suitable nonionic surfactants that may be used include, but are not limited to, ethoxylated alkylphenols, ethoxylated and propoxylated fatty alcohols, polyethylene glycol ethers of methyl glucose, polyethylene glycol ethers of sorbitol, ethylene oxide-propylene oxide block copolymers, fatty acids (C)₈-C₁₈) Ethoxylated esters of ethylene oxide, condensation products of ethylene oxide with long chain amines or amides, condensation products of ethylene oxide with alcohols, fatty acid esters, mono-or diglycerides of long chain alcohols and mixtures thereof. Particularly suitable non-ionic emulsifiers may include ethylene oxide condensates of fatty alcohols (for example, sold under the trade name Lubrol), fatty acids (in particular C)₁₂-C₂₀Fatty acids), polyoxyethylene sorbitan fatty acid esters (e.g., under the trade name polyoxyethylene ethers, polyoxyethylene sorbitan fatty acid esters)Sold under the trade name SPAN) and sorbitan fatty acid esters (e.g. SPAN^TMOrSold), etc. The fatty component used to form such emulsifiers may be saturated or unsaturated, substituted or unsubstituted, and may contain from 6 to 22 carbon atoms, in some embodiments from 8 to 18 carbon atoms, and in some embodiments, from 12 to 14 carbon atoms.

While any emulsifier may generally be used, the present inventors have found that certain combinations of hydrophilic and lipophilic nonionic emulsifiers are particularly effective in stabilizing the sprayable composition. As is known in the art, the relative hydrophilicity or lipophilicity of an emulsifier can be characterized by a hydrophilic/lipophilic balance ("HLB") scale that measures the balance between the hydrophilicity of the compound and the propensity of the lipophilic solution. The HLB scale ranges from 0.5 to about 20, with smaller numbers indicating a high lipophilicity propensity and higher numbers indicating a high hydrophilicity propensity. Desirably, the sprayable composition may comprise at least one "hydrophilic" emulsifier having an HLB value of from about 10 to about 20, in some embodiments from about 12 to about 19, and in some embodiments, from about 14 to about 18. Likewise, the sprayable composition may also comprise at least one "lipophilic" emulsifier having an HLB value of from about 0.5 to about 10, in some embodiments from about 1 to about 9, and in some embodiments, from about 2 to about 8. If desired, two or more surfactants may be used, which have HLB values above or below the desired value, but together have an average HLB value within the desired range. Regardless, the present inventors have found that the weight ratio of lipophilic emulsifier to hydrophilic emulsifier in the sprayable composition is generally in the range of from about 5 to about 30, in some embodiments from about 7.5 to about 25, and in some embodiments, from about 10 to about 20. Further, the inventors have found that the total HLB value of the sprayable composition is generally lipophilic and may range from about 2 to about 12, such as from about 3 to about 10, such as from about 4 to about 9, such as from about 5 to about 8.

One particularly useful group of "lipophilic" emulsifiers are sorbitan fatty acid esters (e.g., mono-, di-, tri-esters, etc.) which are prepared by dehydrating sorbitol to 1, 4-sorbitan and then reacting with one or more equivalents of fatty acid. The fatty acid substituted moiety can be further reacted with ethylene oxide to yield a second set of surfactants. The fatty acid-substituted sorbitan surfactant is prepared by reacting 1, 4-sorbitan with a fatty acid such as lauric acid, palmitic acid, stearic acid, oleic acid or similar long chain fatty acids to produce a 1, 4-sorbitan monoester, a 1, g-sorbitan sesquioleate or a 1, 4-sorbitan triester. Common names for these surfactants include, for example, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan monooleate, sorbitan sesquioleate, and sorbitan trioleate. Such thatSurfactant is named SPAN^TMOr ARLACEL^TMCommercially available, typically with letter or number designations distinguishing the various mono-, di-, and tri-ester substituted sorbitan. SPAN^TMAnd ARLACEL^TMSurfactants are lipophilic and are generally soluble or dispersible in oil, but generally insoluble in water. One particularly suitable surfactant is sorbitan monooleate, which can act as a SPAN^TM80 are commercially available. Typically these surfactants will have HLB values in the range of 1.8 to 8.6.

Other useful lipophilic emulsifiers that may be used may include, for example, silicone water-in-oil emulsifiers. Polysiloxane refers to a molecule comprising at least one siloxane (-Si-O-) repeat unit and additionally comprising a hydrophobic portion and a hydrophilic portion. The HLB value of silicone water-in-oil emulsifiers is relatively low. For example, in some embodiments, the silicone emulsifier may have an HLB value in the range of 2 to 9.

Examples of suitable silicone water-in-oil emulsifiers can include non-crosslinked dimethicone copolyols such as alkoxy dimethicone copolyols, silicones having pendant hydrophilic moieties such as linear silicones having pendant polyether groups, branched polyethers and alkyl modified silicones, branched glycerol polymers and alkyl modified silicones, and combinations thereof. Examples of commercially available non-crosslinked dimethicone copolyols include the following from Dow Corning of Midland, Michigan: cyclopentasiloxane and PEG/PPG-18/18 dimethicone, available as DC 5225C, and cyclopentasiloxane and PEG-12 dimethicone crosspolymer, available as DC 9011. Some of the non-crosslinked dimethicone copolyols are cetyl dimethicone copolyols such as the name ABIL^TMCetyl PEG/PPG-10/1 dimethicone sold under the name EM-90, branched polyethers and alkyl modified silicones such as dodecyl PEG-9 dimethiconoethyl dimethicone sold under the name KF-6038, and branched glycerol polymers and alkyl modified silicones such as dodecyl KF-6105Polyglycerol-3 dimethiconoethyl dimethicone. Other non-crosslinked dimethicone copolyols include, for example, those known by the name ABIL^TMbis-PEG/PPG-14/dimethicone copolyol sold by EM-97, and sold under the name ABIL^TMPolyglycerol-4 isostearate/cetyl dimethicone copolyol/hexyl laurate mixture sold by WE 09. ABIL^TMEM-90、ABIL^TMEM-97 and ABIL^TMWE 09 is available from espen, Germany, Evonik Goldschmidt GmbH. KF-6038 and KF-6105 are available from Shin-Etsu Silicones of Akron, Ohio. A particularly suitable emulsifier for use in the present invention is ABIL^TMWE 09, having an HLB value of about 5. Another particularly suitable emulsifier is ABIL^TMEM 90, which also has an HLB value of about 5.

Yet another suitable nonionic lipophilic emulsifier that may be included in the sprayable active agent compositions of the present invention is octyl dodecanol/octyl dodecanol xyloside/PEG-30, which is known by the name EASYNOV^TMCommercially available from Seppic s.a.

Also, sorbitan fatty acid esters (e.g., mono-, di-, tri-, etc.) that have been modified with polyethylene glycol are likewise a particularly useful group of "hydrophilic" emulsifiers. These materials are typically prepared by the addition of ethylene oxide to 1, 4-sorbitan esters. Addition of polyethylene glycol converts the lipophilic sorbitan ester surfactant to a hydrophilic surfactant, which is generally soluble or dispersible in water. Such materials are known under the name TWEEN^TM(e.g., TWEEN)^TM80. Polysorbate 80 or polyethylene (20) sorbitan monooleate). TWEEN^TMSurfactants typically have HLB values in the range of 9.6 to 16.7. For example, TWEEN^TM80 has an HLB value of 15. Still other suitable hydrophilic emulsifiers may include sucrose fatty acid esters such as sucrose monopalmitate (HLB of 15) and sucrose monostearate (HLB of 11) or PEG-32 glyceryl laurate (HLB of 14) and BRIJ^TMPolyethylene glycol (PEG) n-alkanol esters of the family, e.g. BRIJ^TM35. 56, 58, 76, 78 and 99 having a range of 12.4 to 16.9HLB of (1). BRIJ^TM56 is polyethylene glycol [10 ]]Cetyl ether, for example, has an HLB value of 12.9.

Regardless of the particular emulsifier used in the emulsification system, the emulsification system may be present in the sprayable composition in an amount of from about 0.1 wt.% to about 20 wt.%, such as from about 0.5 wt.% to about 15 wt.%, such as from about 1 wt.% to about 10 wt.%, based on the total weight of the composition. Additionally, the present inventors have found that the weight ratio of lipophilic emulsifier to hydrophilic emulsifier in the emulsification system component of the sprayable composition typically ranges from about 5 to about 30, in some embodiments from about 7.5 to about 25, and in some embodiments, from about 10 to about 20.

e.Viscosity modifier

In addition, the sprayable composition may comprise one or more viscosity modifiers, which may also help prevent separation of the various components of the composition. For example, in some embodiments, such as when the carrier fluid comprises more than one component, one or more viscosity modifiers may be added to the oil or water phase of the emulsion to adjust the viscosity to make the separate components more miscible in the composition. In addition, the viscosity of the entire active agent composition can be adjusted so that it is not so high that the composition cannot be sprayed onto a surface, but not so low that the composition is too thin to be uniformly applied to the surface. Thus, the composition may have a viscosity of from about 500 centipoise to about 10,000 centipoise, such as from about 1000 centipoise to about 8000 centipoise, such as from about 1500 centipoise to about 6000 centipoise, such as from about 2000 centipoise to about 4000 centipoise.

When a water-in-oil emulsion or an oil-in-water emulsion is formed, one or more viscosity modifiers may be added to the water phase of the water-in-oil emulsion or the oil-in-water emulsion to enhance miscibility between the water phase and the oil phase, which facilitates substantially uniform distribution of the components of the sprayable composition. However, it is also understood that viscosity modifiers may be added to an already formed oil-in-water or water-in-oil emulsion as needed to adjust the viscosity.

Suitable viscosity modifiers include carboxylic acid polymers, which are crosslinked compounds comprising one or more monomers derived from acrylic acid, substituted acrylic acids, and salts and derivatives of these acrylic acids and substituted acrylic acids. They may be crosslinked homopolymers of acrylic acid or its derivatives, such as acrylamidopropanesulfonic acid. They may also be crosslinked copolymers having: (i) a first monomer selected from (meth) acrylic acid, derivatives thereof, short chains (i.e. C)₁-C₄) Acrylate monomers and mixtures thereof; and (ii) a second monomer which is long chain (i.e. C)₈-C₄₀) Substituted polyethylene glycol acrylate monomers.

Examples of commercially available carboxylic acid polymers include CARBOPOL available from Lubrizol corp^TM1342、PEMULEN^TMTR-1 and PEMULEN^TMTR-2; sepigel 305, SIMULGEL available from Seppic S.A^TMEG、SIMULGEL^TMNS and SIMULGEL^TM600, preparing a mixture; VISCOLAM available from Lamberti S.p.A^TMAT100P and VISCOLAM^TMAT 64/P. A commercially available viscosity modifier may be SIMULGEL^TMNS was obtained from Seppic s.a. SIMULGEL^TMThe NS comprises hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer, squalane, and polysorbate 60, which may be added to the oil phase of a water-in-oil or oil-in-water emulsion.

Other suitable viscosity modifiers that may be used include corn starch (topical starch), talc, rice starch, oat starch, tapioca starch, potato starch, legume starch, soy starch, radish starch, microcrystalline cellulose, kaolin, aluminum starch octenyl succinate, and mixtures thereof. The water soluble aluminum starch octenyl succinate can be prepared as DRY FLO^TMPure、DRY FLO^TMXT、DRY FLO^TMPC and/or DRY FLO^TMAF (aluminum free grade) is commercially available from National Starch&Chemical Co, and which are water soluble so that they may be included in the aqueous phase of a water-in-oil emulsion or an oil-in-water emulsion.

Regardless of the particular viscosity modifier used, the viscosity modifier may be present in the sprayable composition in an amount in the range of from about 0.05 wt.% to about 15 wt.%, such as from about 0.1 wt.% to about 10 wt.%, such as from about 0.5 wt.% to about 5 wt.%, based on the total weight of the sprayable composition.

f.Conditioning agent

The sprayable composition may also comprise one or more conditioning agents to help condition the skin. For example, the sprayable composition may comprise thymol iodide, sodium chloride, magnesium sulfate, lanolin oil, lanolin wax, lanolin alcohols, lanolin acids, isopropyl lanolate, ethoxylated lanolin alcohols, ethoxylated cholesterol, propoxylated lanolin alcohols, acetylated lanolin alcohols, lanolin alcohol linoleate, lanolin alcohol ricinoleate, acetate esters of lanolin alcohols, ricinoleate esters of ethoxylated alcohol esters, hydrogenolysis products of lanolin, ethoxylated hydrogenated lanolin, ethoxylated sorbitol lanolin, or combinations thereof. Thymol iodine and magnesium sulfate can be particularly useful. One or more conditioning agents may be present in the sprayable composition in an amount of from about 0.05 wt.% to about 10 wt.%, such as from about 0.1 wt.% to about 7.5 wt.%, such as from about 0.5 wt.% to about 5 wt.%, based on the total weight of the composition.

g.Additional Components

Other optional components in the sprayable composition may comprise skin care additives such as emollients as well as fragrances and preservatives. For example, emollients such as caprylic/capric triglyceride may be included in the sprayable composition. Other suitable emollients include stearyloxytrimethylsilane, cetyl lactate and alkanol lactate, e.g. C₁₂-C₁₅An alkyl lactate. When an emollient is used, the sprayable composition may be smooth to the touch when applied to the skin. One or more emollients may be present in about 0.1 wt.% to about 25 wt.%, such as about based on the total weight of the sprayable compositionThe sprayable composition is present in an amount of from 0.5 wt.% to about 20 wt.%, such as from about 1 wt.% to about 15 wt.%.

Additionally, fragrance may be present in the sprayable composition in an amount of from about 0.005 wt.% to about 2 wt.%, such as from about 0.01 wt.% to about 1.5 wt.%, such as from about 0.02 wt.% to about 1 wt.%, based on the total weight of the sprayable composition.

Also, the preservative may be present in the sprayable composition in an amount of from about 0.01 wt.% to about 6 wt.%, such as from about 0.02 wt.% to about 4 wt.%, such as from about 0.05 wt.% to about 1 wt.%, based on the total weight of the composition. Suitable preservatives include paraben-based preservatives, such as methyl paraben and propyl paraben.

Furthermore, the inventors have found that a freezing point depressant may be included in the composition to limit the amount of crystallization of any solid components, which may subsequently reduce or limit clogging of the composition when sprayed. If desired, one or more antifreeze agents such as glycols (e.g., ethylene glycol, propylene glycol, butylene glycol, triethylene glycol, hexylene glycol, polyethylene glycol, ethoxydiglycol, dipropylene glycol, etc.); glycol ethers (e.g., methyl glycol ether, ethyl glycol ether, isopropyl glycol ether, etc.); and so on. Such anti-freeze agents may be present in the composition in an amount of from about 0.1 wt.% to about 15 wt.%, such as from about 0.5 wt.% to about 10 wt.%, such as from about 1 wt.% to about 5 wt.%, based on the total weight of the composition.

II.Formation of active agent compositions for spray delivery systems

In general, the spray delivery systems of the present invention can be prepared by first forming a sprayable active agent composition. The composition may be prepared by: a base active agent composition is formed from a carrier fluid and active agent particles, which is then introduced into a container component of a spray delivery system, and a propellant is injected into the container. For example, when the base active composition is in the form of a water-in-oil emulsion or an oil-in-water emulsion, and thus includes a carrier fluid comprising an oil phase and a water phase, the base active composition can be prepared by first forming the oil phase and the water phase separately.

The manner in which the composition is formed may vary as is known to those skilled in the art. In one embodiment, for example, the oil phase is formed by blending one or more oils with one or more components of the emulsification system described above. However, it is also understood that in another embodiment, one or more components of the emulsification system may be added to the aqueous phase. Emollients, conditioning agents, and the like may also be added to form the oil phase. In such embodiments, the oil phase may comprise oil in an amount of from about 30 wt.% to about 80 wt.%, such as from about 35 wt.% to about 70 wt.%, such as from about 40 wt.% to about 60 wt.%, based on the total weight of the oil phase. Further, the oil phase may comprise an emulsifier in an amount of from about 5 wt.% to about 35 wt.%, such as from about 10 wt.% to about 30 wt.%, such as from about 15 wt.% to about 25 wt.%, based on the total weight of the oil phase. The addition of the emulsifier may result in an oil phase having an HLB value of from about 6 to about 7. Further, the oil phase may comprise emollients in an amount of from about 10 wt.% to about 45 wt.%, such as from about 15 wt.% to about 40 wt.%, such as from about 20 wt.% to about 35 wt.%, based on the total weight of the oil phase. Further, the oil phase may comprise a conditioning agent in an amount of from about 0.5 wt.% to about 10 wt.%, such as from about 1 wt.% to about 7.5 wt.%, such as from about 1.5 wt.% to about 5 wt.%, based on the total weight of the oil phase.

Also, the aqueous phase may be formed by blending water and any water soluble components of the sprayable composition, such as conditioning agents, viscosity modifiers, emulsifiers, and the like. However, it is also understood that in other embodiments, the aqueous phase may comprise only water. Thus, the aqueous phase may comprise water in an amount of from about 50 wt.% to about 100 wt.%, such as from about 55 wt.% to about 99 wt.%, such as from about 60 wt.% to about 98 wt.%. The aqueous phase may also contain a conditioning agent in an amount of from about 0.5 wt.% to about 15 wt.%, such as from about 1 wt.% to about 10 wt.%, such as from about 1.5 wt.% to about 7.5 wt.%, based on the total weight of the aqueous phase. Further, the aqueous phase may comprise a viscosity modifier in an amount of from about 0.25 wt.% to about 10 wt.%, such as from about 0.5 wt.% to about 7.5 wt.%, such as from about 1 wt.% to about 5 wt.%, based on the total weight of the aqueous phase.

After the oil phase and the aqueous phase are separately formed, the aqueous phase may be added to the oil phase to form a water-in-oil emulsion. Phase bonding may be facilitated by agitation (e.g., stirring) and controlling the temperature of each mixture. The active agent particles may then be added to the water-in-oil emulsion. The active agent particles may be present in an amount of from about 0.25 wt.% to about 35 wt.%, such as from about 0.5 wt.% to about 30 wt.%, such as from about 1 wt.% to about 25 wt.%, such as from about 5 wt.% to about 15 wt.%, based on the total weight of the base active agent composition.

Other components such as fragrances, preservatives, antifreeze agents and additional viscosity modifiers may then be added to the base active agent composition if desired. The fragrance may be added in an amount of from about 0.01 wt.% to about 5 wt.%, such as from about 0.05 wt.% to about 2.5 wt.%, such as from about 0.1 wt.% to about 1 wt.%, based on the total weight of the base active agent composition. Likewise, the preservative may be added in an amount of about 0.01 wt.% to about 5 wt.%, such as about 0.05 wt.% to about 2.5 wt.%, such as about 0.1 wt.% to about 1 wt.%, based on the total weight of the base active agent composition. Additionally, the anti-freeze agent can be added in an amount of from about 0.5 wt.% to about 15 wt.%, such as from about 1 wt.% to about 10 wt.%, such as from about 2 wt.% to about 8 wt.%, based on the total weight of the base active agent composition. Additionally, the viscosity modifier can be added in an amount of from about 0.1 wt.% to about 15 wt.%, such as from about 0.5 wt.% to about 10 wt.%, such as from about 1 wt.% to about 8 wt.%, based on the total weight of the base active agent composition. Thus, it is understood that in some embodiments, a first viscosity modifier may be added during formation of the aqueous phase, while a second viscosity modifier may be added after the base active is formed by combining the water and oil phases.

Regardless of the phase formed, the temperature is from about 15 ℃ to about 40 ℃, such as from about 18 ℃ to about 35 ℃, such as from about 20 ℃ to about 30 ℃. After the separate phases are mixed as described above, the resulting base active agent composition may then be filled into a spray container, such as an aerosol spray container. The container may then be sealed after the propellant is introduced into the container, such as through a valve. The container can be filled with a propellant at a pressure of from about 130psi to about 230psi, such as from about 140psi to about 220psi, such as from about 150psi to about 210 psi.

III.Spray delivery system container

Various aerosol spray containers can be used in conjunction with the sprayable active agent composition to form the spray delivery system of the present invention, which can be used to spray the active agent composition onto a surface, such as skin. One embodiment of a spray delivery system contemplated by the present invention is described with reference to fig. 1. The spray delivery system 100 may include a spray container 101 formed of metal or reinforced plastic. The spray container 101 has an upper opening in which the spray head 102 is installed. The spray head 102 is secured to the spray container 101 in such a way that the flange 104 of the spray head is connected to a collar 103 formed by welding or other possible connection method around the edge of the upper opening in the spray container 101. This creates a sealed connection between the spray head 102 and the aerosol container 101.

The nozzle 102 provides a valve 105 retained by a flange 104. The valve 105 is kept closed in its normal state by the energy force (energizing force) provided by the spring 106, but it is opened when the spray head 102 is pressed. The spray head 102 also has a nozzle 107 which communicates with the valve 105 via a conduit 108. At the same time, a straw 109 is connected to the valve 105 and extends to the bottom of the aerosol container 101. By pressing spray head 102 down against spring 106, valve 105 opens to create a fluid path from the lower port of straw 109 to nozzle 107 through valve 105 and conduit 108.

Sprayable composition 110 formed as discussed above may be filled into spray container 101. The sprayable composition is then expelled from the nozzle 107 through the fluid passageways described above in the form of a fine mist by pressing the spray head 102 via pressure associated with the propellant that is substantially uniformly distributed in the sprayable composition 110.

Another embodiment of a spray delivery system is described with reference to fig. 2A, 2B, 3 and 4. Due to the use of active agent particles, it is possible that sprayable compositions may clog some spray delivery systems. For example, standard aerosol spray delivery systems typically use actuators (spray buttons) that are not intended to deliver compositions containing high concentrations of particulate materials, such as the active agent particles of the present invention. Such actuators typically use mechanical break-up inserts to finely atomize sprayable compositions containing low levels of particulates. For example, the actuator may contain small passages to induce a swirling effect, producing a fine mist spray. However, when a sprayable composition containing a higher amount of active agent particles is used, the active agent particles or any other particles can clog the actuator and prevent a smooth spray from the container. Thus, the spray delivery system of the present invention represented by fig. 2A, 2B, 3 and 4 does not include the above-described actuator channels and does not have a mechanical break-up insert. Instead, the spray delivery system uses a valve and valve stem system where the valve stem design allows the valve stem inside the valve to automatically wipe as the valve sprays, which prevents solids from building up inside the valve, thereby reducing the risk of clogging. In addition, the valve includes a valve orifice having a diameter large enough so that active agent particles and other particles of the sprayable composition do not clog the interior of the container and so that a smooth mist can be achieved. In addition, the valve includes a vent to allow enhanced blending of the propellant vapor during spraying and to prevent accumulation of particles inside the valve. The addition of air voids also produces a more uniform delivery of the sprayable composition from the spray delivery system. In addition, the pores allow for an increased weight percentage of propellant to be used, which helps to produce a drier, less fluid product when delivered to the surface of the skin. Further, the pores produce a warmer-feeling spray because it helps to volatilize the propellant and solvent before the composition reaches the surface of the skin.

The spray system is discussed in more detail below with reference to fig. 2A, 2B, 3, and 4. Fig. 2A shows a front view of a non-mechanical disruption actuator 200 that can be used with a spray delivery system according to an embodiment of the present disclosure. The actuator 200 is a component that may be used to depress a valve stem component of a valve assembly to initiate the introduction of a sprayable composition, as discussed in more detail below with reference to fig. 3 and 4. The actuator 200 includes a locking ring 201, an insert 202, and a dome 203. Locking ring 201 prevents the actuator from being inadvertently depressed. The actuator dome 203 may contain an insert 202, and the insert 202 may determine the spray characteristics of the sprayable composition. The insert 202 of fig. 2A and 2B is a non-mechanical crushing insert. The insert 202 defines an opening 204 from which the sprayable composition of the present invention can exit the actuator, and this opening is hereinafter referred to as the actuator orifice or outlet orifice 204. The outlet orifice 204 may have a diameter selected based on the particle size of particulate components, such as active agent particles, in the sprayable composition such that particles and other components of the sprayable composition may be sprayed from the outlet orifice 204 without causing clogging of the spray delivery system. Further, by selectively controlling the diameter of the outlet orifice 204, the magnitude of the resulting spray pattern may also be influenced. For example, too small a diameter may produce a very narrow spray pattern, while too large a diameter may produce a too wide spray pattern, producing an excessive amount of spray into the surrounding environment rather than the surface to be sprayed, such as clothing, bedding, and the like.

For example, the exit orifice 204 may have a diameter of about 0.3 millimeters to about 0.6 millimeters, such as about 0.35 millimeters to about 0.55 millimeters, such as about 0.4 millimeters to about 0.5 millimeters. Fig. 2B is a cross-sectional side view of the actuator of fig. 2A showing the arrangement of the exit orifice 204 in relation to the insert 202 located inside the dome 203. The outlet orifice is connected to a valve stem 302 of the valve assembly by an exit path 205, which will be discussed in more detail in FIG. 3.

Turning now to fig. 3 and 4, a cross-sectional side view of a spray delivery system including a spray valve member 300 and a mounting cup 301 is shown that can be used in conjunction with the actuator 200 of fig. 2A and 2B. The actuator 200 is connected to the valve assembly 300 by an exit path 205 as shown in fig. 2B. Aerosol valve assembly 300 includes a housing or body 305 that houses a valve stem 302, a valve stem gasket 304, and a spring 307. Suction pipe 311 is also connected to housing 305 through tailpipe 309. Mounting cup 301 holds aerosol valve assembly 300 together and is crimped onto container 401 to provide a seal. Generally, when the actuator 203 (see fig. 2A and 2B) disposed on the mounting cup 301 is pressed against the spring 307, the stem 302 of the valve assembly 300 moves downward, opening the seal between the stem gasket 303 and the stem 302 such that the stem bore 303 in the stem 302 passes below the stem gasket 304. This causes the propellant component of the sprayable composition to push the base active agent composition up the straw 311 through the tailpipe bore 310 and into the valve body 305. The gas vent 306 formed in the valve body 305 provides additional propellant to the valve body 305 and aids in mixing the liquid base active agent composition and propellant in the valve body 305, which can result in a more uniform distribution and reduce the risk of any active agent particles becoming clogged. Gas vent 306 also keeps the base active agent composition out of valve body 305 at rest as the steam pushes the base active agent composition downward and acts to prevent product settling. Once the sprayable composition (i.e., the substantially homogeneously blended propellant and base active agent composition) reaches the valve stem through the valve stem orifice 303, it passes through the exit path 205 and out the exit orifice 204 as a fine mist that does not clog the spray delivery system 400.

The dimensions of the various components may be selected to further reduce the risk of clogging. For example, the valve stem 302 may have a diameter of about 3 millimeters to about 5.5 millimeters, such as about 3.5 millimeters to about 5 millimeters, such as about 4 millimeters to about 4.5 millimeters. Meanwhile, the stem bore 303 may have a diameter of about 0.5 mm to about 0.75 mm, such as about 0.55 mm to about 0.7 mm, such as about 0.6 mm to about 0.65 mm. Further, the tailpipe bore 310 may have a diameter of about 0.75 mm to about 2 mm, such as about 1 mm to about 1.75 mm, such as about 1.25 mm to about 1.5 mm. Further, the air holes 306 may have a diameter of about 0.1 mm to about 0.5 mm, such as about 0.15 mm to about 0.45 mm, such as about 0.2 mm to about 0.4 mm. By selectively controlling the above-mentioned dimensions, the propellant of the sprayable active agent composition can remain substantially uniformly distributed throughout the composition to reduce settling of the active agent particles, and the sprayable composition can fly off less as a fine mist out of the outlet orifice 204 and can be more uniformly distributed than, for example, using an actuator.

IV.Use of sprayable compositions

Due to the combination of the characteristics of the container component system and the active agent composition used in the spray delivery system, a substantially uniform coating of the composition can be applied to a surface as a uniform mist that does not clog the container as it is dispensed from the container. For example, the compositions of the present invention may be applied to the surface of the skin as a uniform mist and may be used to treat various skin conditions or irritations, such as diaper rash, dry skin, ulcers, superficial cuts, scratches, wounds, first degree burns, and the like. The skin areas that can be treated include the buttocks, especially in the case of diaper rash/incontinent dermatitis, and the arms, elbows, hands, abdomen, back, sacrum, coccyx, hips, knees, feet, ankles, heels, and the like. When the composition reaches the surface of the skin, the propellant can evaporate, leaving a substantially uniform coating of the active agent particles on the skin. Additionally, the active agent particles can be distributed in a substantially uniform manner throughout the coating. After the composition is sprayed onto the skin in the form of a substantially uniform coating, the amount of active agent particles present in the composition on the skin is from about 0.25 wt.% to about 35 wt.%, such as from about 0.5 wt.% to about 30 wt.%, such as from about 1 wt.% to about 25 wt.%, such as from about 5 wt.% to about 15 wt.%, based on the total weight of the resulting coating (e.g., a sprayable composition that excludes volatile components, such as propellants).

The invention may be better understood by reference to the following examples.

Example 1

A sprayable composition is formed from a base active agent composition comprising a preservative phase, an oil phase, an aqueous phase, and active agent particles, to which a propellant is added. First, to prepare the preservative phase of the base active agent composition, the cryoprotectant was added to a beaker and agitated using a propeller. Then, the preservative was added to the beaker and mixing was started using a blender equipped with an anchor side-impact blender. Agitation was continued for at least 15 minutes until the solution was completely dissolved. The preservative phase was then allowed to stand.

Next, to prepare the oil phase of the base active agent composition, the emollient was added to a separate beaker and agitated using a propeller to initiate mixing while maintaining the temperature between 20 ℃ and 23 ℃, followed by the polyglyceryl-4 isostearate/cetyl dimethicone copolyol/hexyl laurate emulsifier, followed by cetyl PEG/PPG-10/1 dimethicone emulsifier, sorbitan oleate emulsifier, polysorbate 80 emulsifier and octyldodecanol/octyldodecanol xyloside/PEG-30 emulsifier. Mixing by stirring was continued while maintaining the temperature between 20 ℃ and 25 ℃. Next, silicone oil was added to the beaker while maintaining the temperature between 20 ℃ and 23 ℃. The temperature was then maintained between 20 ℃ and 25 ℃ using cooling water with agitation using a homogenizer, and then the conditioner was added. Agitation was continued for at least 15 minutes until the solution was completely dissolved, maintaining the temperature between 20 ℃ and 28 ℃. The resulting oil phase of the base active agent composition has an HLB value of 6 to 7.

Next, the aqueous phase of the base active agent composition was prepared in a separate beaker. Water was added to the beaker while maintaining the temperature at 20 ℃ to 28 ℃. Mixing was initiated using a stirrer equipped with a stainless steel three propeller blade. Add water soluble conditioner to beaker and continue mixing for at least 15 minutes until all solids are dissolved. The viscosity modifier comprising hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer, squalane and polysorbate 60 was then added to the beaker and mixing was continued for at least 15 minutes.

To prepare the base active agent composition, the temperature of the oil phase beaker was maintained at 20 ℃ to 25 ℃. The aqueous phase was then slowly transferred to an oil phase beaker with homogenizer agitation, wherein the transfer time was at least 20 minutes. The speed of the homogenizer is increased as necessary while maintaining the temperature at 20 ℃ to 25 ℃. The resulting water-in-oil emulsion was then covered and mixed for at least 30 minutes. The preservative phase was then added to the beaker while mixing was continued for at least 15 minutes, maintaining the temperature at 20 ℃ to 25 ℃. After ensuring that all of the powder is off the surface and increasing the mixing speed as necessary, the zinc oxide particles are added and mixed under homogenizer agitation for at least 5 minutes, increasing the speed as necessary, and maintaining the temperature at 20 ℃ to 25 ℃. The viscosity modifier aluminum starch octenylsuccinate is then added and mixed for at least 5 minutes with homogenizer agitation, increasing the speed as needed, and maintaining the temperature at 20 ℃ to 25 ℃. Thereafter, fragrance was added to the beaker under homogenizer agitation, and the emulsion was mixed for at least 15 minutes. The resulting base active agent composition had an HLB value of 7.42.

After the base active agent composition is formed, it is filled into an aerosol spray container, after which the valve of the container is sealed or crimped to the top of the container. HFO-1234ze propellant is then pressure filled into the container through a valve at a pressure of about 200 pounds. The resulting sprayable composition comprised a substantially homogeneous blend of propellant and active agent particles and comprised 22 wt.% propellant and 78 wt.% base active agent composition. The sprayable composition had a specific gravity of about 1.045. The weight percentages of the components used in the sprayable composition are summarized in table 1 below. Once sprayed as a substantially uniform coating onto a surface (e.g., skin), the composition contains 10.4 wt.% zinc oxide particles due to volatilization of the propellant.

TABLE 1 sprayable composition Components

These and other modifications and variations to the present invention may be practiced by those of ordinary skill in the art, without departing from the spirit and scope of the present invention. Further, it should be understood that aspects of the various embodiments may be interchanged both in whole or in part. Furthermore, those of ordinary skill in the art will appreciate that the foregoing description is by way of example only, and is not intended to limit the invention so further described in such appended claims.

Claims (26)

1. A spray delivery system comprising a sprayable composition having a viscosity of about 500 centipoise to about 10,000 centipoise and a container, wherein the composition comprises a hydrofluoro-based propellant, a carrier fluid, and active agent particles, wherein the container comprises a straw; a valve assembly including a valve body, a valve stem including a valve stem bore, and an air vent; and an actuator, wherein the straw is connected to the actuator through the valve assembly, wherein the actuator is depressed to dispense the active agent composition stored in the container.

2. The spray delivery system of claim 1, wherein the actuator comprises an exit orifice from which the composition is sprayed.

3. The spray delivery system of claim 2, wherein the exit orifice has a diameter of about 0.3 millimeters to about 0.6 millimeters.

4. The spray delivery system of any of the foregoing claims, wherein the actuator is a non-mechanical disruption actuator.

5. The spray delivery system of any of the foregoing claims, wherein the valve stem bore has a diameter of from about 0.5 millimeters to about 0.75 millimeters.

6. The spray delivery system of any of the foregoing claims, wherein the air holes have a diameter of from about 0.1 millimeters to about 0.5 millimeters.

7. The spray delivery system of any of the foregoing claims, wherein the sprayable composition is introduced into the valve body from a straw through the valve stem orifice and additional propellant is introduced into the valve body through the gas orifice, wherein active agent particles and the propellant are uniformly dispersed throughout the valve body.

8. The spray delivery system of any of the foregoing claims, wherein the composition comprises one or more nonionic lipophilic emulsifiers and one or more nonionic hydrophilic emulsifiers.

9. The spray delivery system of claim 8, wherein the weight ratio of the nonionic lipophilic emulsifier to the nonionic hydrophilic emulsifier is from about 5 to about 30.

10. The spray delivery system of claim 8 or 9, wherein the nonionic lipophilic emulsifier comprises a non-crosslinked dimethicone polyol, a sorbitan fatty acid ester, octyldodecanol, or a combination thereof.

11. The spray delivery system of any one of claims 8 to 10, wherein the non-ionic hydrophilic emulsifier comprises a sorbitan fatty acid ester modified with polyoxymethylene.

12. The spray delivery system of any of the foregoing claims, wherein the composition has a Hydrophilic Lipophilic Balance (HLB) value of from about 2 to about 12.

13. The spray delivery system of any of the foregoing claims, wherein the propellant is present in an amount of from about 5 wt.% to about 95 wt.%, based on the total weight of the composition, and the active agent particles are present in an amount of from about 0.5 wt.% to about 30 wt.%, based on the total weight of the composition.

14. The spray delivery system of any of the foregoing claims, wherein the carrier fluid is a water-in-oil emulsion or an oil-in-water emulsion.

15. The spray delivery system of any of the foregoing claims, wherein the carrier fluid comprises from about 1 wt.% to about 35 wt.% of an oil phase, and from about 1 wt.% to about 50 wt.% of a water phase, based on the total weight of the composition.

16. The spray delivery system of claim 15, wherein the oil phase comprises a silicone oil.

17. The spray delivery system of claim 15 or 16, wherein the aqueous phase comprises water.

18. The spray delivery system of any of the foregoing claims, wherein water is present in an amount of less than about 50 wt.%, based on the total weight of the composition.

19. The spray delivery system of any of the foregoing claims, wherein the composition further comprises a viscosity modifier.

20. The spray delivery system of claim 19, wherein the viscosity modifier comprises a carboxylic acid polymer, a starch, or a combination thereof.

21. The spray delivery system of any of the foregoing claims, wherein less than about 3 wt.% of the active agent particles in the composition settle when the composition is stored in a container at about 21 ℃ for 3 days.

22. The spray delivery system of any of the foregoing claims, wherein the propellant has a first specific gravity and the sprayable composition has a second specific gravity, wherein the ratio of the first specific gravity to the second specific gravity is from about 0.7 to about 1.6.

23. The spray delivery system of any of the foregoing claims, wherein the propellant has a vapor pressure of less than about 60psi at about 21 ℃.

24. The spray delivery system of any of the foregoing claims, wherein the propellant comprises a hydrofluoroalkene or a hydrofluoroalkane.

25. The spray delivery system of any of the foregoing claims, wherein the active agent particles comprise a moisture barrier, an antifungal, an antibacterial, an analgesic, an antibacterial, an anesthetic, an anti-inflammatory, an antipruritic, or a combination thereof.

26. The spray delivery system of any of the foregoing claims, wherein the composition further comprises one or more emollients, conditioning agents, freezing point depressants, preservatives, or combinations thereof.