Patent Grant
8215822
The present disclosure relates generally to systems for ultrasonically mixing antimicrobials into various formulations. More particularly an ultrasonic mixing system is disclosed for ultrasonically mixing antimicrobial agents, typically being hydrophobic antimicrobial agents, into formulations to prepare antimicrobial formulations.
Preservatives, pesticides, antivirals, antifungals, antibacterials, xenobiotics, hydrophobic drugs or pharmaceuticals, anti-protozoal, antimicrobials, antibiotics, and biocides (referred to herein collectively as antimicrobial agents) are commonly added to formulations to provide antimicrobial formulations for use on animate (e.g., skin, hair, and body of a user) and inanimate surfaces (e.g., countertops, floors, glass), as well as in agricultural and industrial applications. Although antimicrobial agents are useful, many antimicrobial agents are hydrophobic and current mixing procedures have multiple problems such as poor solubility and dispersibility of the antimicrobial agents within the formulation, which can lead to decreased efficacy, and which can waste time, energy, and money for manufacturers of these formulations.
Specifically, formulations are currently prepared in a batch-type process, either by a cold mix or a hot mix procedure. The cold mix procedure generally consists of multiple ingredients (including the antimicrobial agents) or phases being added into a kettle in a sequential order with agitation being applied via a blade, baffles, or a vortex. The hot mix procedure is conducted similarly to the cold mix procedure with the exception that the ingredients or phases are generally heated above room temperature, for example to temperatures of from about 40 to about 100° C., prior to mixing, and are then cooled back to room temperature after the ingredients and phases have been mixed. In both procedures, antimicrobial agents are added to the other ingredients manually by one of a number of methods including dumping, pouring, and/or sifting.
Historically, these conventional batch-type methods have not been very effective in mixing hydrophobic antimicrobial agents into aqueous-type formulations. As such, hydrophobic antimicrobial agents have been added into emulsions delivery vehicles or oils. The produced-emulsions have not been sufficiently mixed into the formulation, hindering the antimicrobial activity of the antimicrobial agent. Furthermore, the antimicrobial agents are not well dispersed within the emulsions and/or formulation, thereby forming larger particle-sized agents that can also lead to less antimicrobial activity against microbes.
These conventional methods of mixing antimicrobial agents into formulations have several additional problems. For example, as noted above, all ingredients are manually added in a sequential sequence. Prior to adding the ingredients, each needs to be weighed, which can create human error. Specifically, as the ingredients need to be weighed one at a time, misweighing can occur with the additive amounts. Furthermore, by manually adding the ingredients, there is a risk of spilling or of incomplete transfers of the ingredients from one container to the next.
One other major issue with conventional methods of mixing antimicrobial agents into formulations is that batching processes require heating times, mixing times, and additive times that are entirely manual and left up to the individual compounders to follow the instructions. These practices can lead to inconsistencies from batch-to-batch and from compounder to compounder. Furthermore, these procedures require several hours to complete, which can get extremely expensive.
Based on the foregoing, there is a need in the art for a mixing system that provides ultrasonic energy to enhance the mixing of antimicrobial agents, particularly hydrophobic antimicrobial agents, into formulations. Furthermore, it would be advantageous if the system could be configured to enhance the cavitation mechanism of the ultrasonics, thereby increasing the probability that the antimicrobial agents will be effectively mixed/dispersed within and throughout the formulations.
In one aspect, an ultrasonic mixing system for mixing antimicrobial agents into a formulation generally comprises a treatment chamber comprising an elongate housing having longitudinally opposite ends and an interior space. The housing of the treatment chamber is generally closed at at least one of its longitudinal ends and has at least a first inlet port for receiving a formulation into the interior space of the housing, a second inlet port for receiving at least one antimicrobial agent into the interior space of the housing, and at least one outlet port through which an antimicrobial formulation is exhausted from the housing following ultrasonic mixing of the formulation and antimicrobial agents. The outlet port is spaced longitudinally from the inlet port such that the formulation (and antimicrobial agents) flows longitudinally within the interior space of the housing from the first and second inlet ports to the outlet port. In one embodiment, the housing further includes two separate ports for receiving separate components of the formulation. At least one elongate ultrasonic waveguide assembly extends longitudinally within the interior space of the housing and is operable at a predetermined ultrasonic frequency to ultrasonically energize and mix the formulation and the antimicrobial agents flowing within the housing.
The waveguide assembly comprises an elongate ultrasonic horn disposed at least in part intermediate the inlet ports and the outlet port of the housing and has an outer surface located for contact with the formulation and antimicrobial agents flowing within the housing from the inlet ports to the outlet port. A plurality of discrete agitating members are in contact with and extend transversely outward from the outer surface of the horn intermediate the inlet ports and the outlet port in longitudinally spaced relationship with each other. The agitating members and the horn are constructed and arranged for dynamic motion of the agitating members relative to the horn upon ultrasonic vibration of the horn at the predetermined frequency and to operate in an ultrasonic cavitation mode of the agitating members corresponding to the predetermined frequency and the formulation being mixed with antimicrobial agents in the chamber.
As such, the present disclosure is directed to an ultrasonic mixing system for preparing an antimicrobial formulation. The mixing system comprises a treatment chamber for mixing an antimicrobial agent with a formulation. The treatment chamber generally comprises an elongate housing having longitudinally opposite ends and an interior space, and an elongate ultrasonic waveguide assembly extending longitudinally within the interior space of the housing and being operable at a predetermined ultrasonic frequency to ultrasonically energize and mix the formulation and antimicrobial agents flowing within the housing. The housing is generally closed at at least one of its longitudinal ends and has a first inlet port for receiving a formulation into the interior space of the housing, a second inlet port for receiving at least one antimicrobial agent into the interior space of the housing, and at least one outlet port through which an antimicrobial formulation is exhausted from the housing following ultrasonic mixing of the formulation and antimicrobial agents. The outlet port is spaced longitudinally from the first and second inlet ports such that the formulation flows longitudinally within the interior space of the housing from the first and second inlet ports to the outlet port.
The waveguide assembly comprises an elongate ultrasonic horn disposed at least in part intermediate the first and second inlet ports and the outlet port of the housing and having an outer surface located for contact with the formulation and antimicrobial agents flowing within the housing from the first and second inlet ports to the outlet port. Additionally, the waveguide assembly comprises a plurality of discrete agitating members in contact with and extending transversely outward from the outer surface of the horn intermediate the first and second inlet ports and the outlet port in longitudinally spaced relationship with each other. The agitating members and the horn are constructed and arranged for dynamic motion of the agitating members relative to the horn upon ultrasonic vibration of the horn at the predetermined frequency and to operate in an ultrasonic cavitation mode of the agitating members corresponding to the predetermined frequency and the formulation and antimicrobial agents being mixed in the chamber.
The present disclosure is further directed to an ultrasonic mixing system for preparing an antimicrobial formulation. The mixing system comprises a treatment chamber for mixing an antimicrobial agent with a formulation. The treatment chamber generally comprises an elongate housing having longitudinally opposite ends and an interior space, and an elongate ultrasonic waveguide assembly extending longitudinally within the interior space of the housing and being operable at a predetermined ultrasonic frequency to ultrasonically energize and mix the formulation and antimicrobial agents flowing within the housing. The housing is generally closed at at least one of its longitudinal ends and has a first inlet port for receiving a formulation into the interior space of the housing, a second inlet port for receiving an antimicrobial agent, and at least one outlet port through which an antimicrobial formulation is exhausted from the housing following ultrasonic mixing of the formulation and antimicrobial agents. The outlet port is spaced longitudinally from the first and second inlet ports such that the formulation flows longitudinally within the interior space of the housing from the first and second inlet ports to the outlet port.
The waveguide assembly comprises an elongate ultrasonic horn disposed at least in part intermediate the first and second inlet ports and the outlet port of the housing and having an outer surface located for contact with the formulation and antimicrobial agents flowing within the housing from the first and second inlet ports to the outlet port; a plurality of discrete agitating members in contact with and extending transversely outward from the outer surface of the horn intermediate the first and second inlet ports and the outlet port in longitudinally spaced relationship with each other; and a baffle assembly disposed within the interior space of the housing and extending at least in part transversely inward from the housing toward the horn to direct longitudinally flowing formulation in the housing to flow transversely inward into contact with the agitating members. The agitating members and the horn are constructed and arranged for dynamic motion of the agitating members relative to the horn upon ultrasonic vibration of the horn at the predetermined frequency and to operate in an ultrasonic cavitation mode of the agitating members corresponding to the predetermined frequency and the formulation and antimicrobial agents being mixed in the chamber.
The present disclosure is further directed to a method for preparing an antimicrobial formulation using the ultrasonic mixing system described above. The method comprises delivering the formulation via the first inlet port into the interior space of the housing; delivery the antimicrobial agent via the second inlet port into the interior space of the housing; and ultrasonically mixing the antimicrobial agents and formulation via the elongate ultrasonic waveguide assembly operating in the predetermined ultrasonic frequency.
Other features of the present disclosure will be in part apparent and in part pointed out hereinafter.
Corresponding reference characters indicate corresponding parts throughout the drawings.
With particular reference now to
It is generally believed that as ultrasonic energy is created by the waveguide assembly, increased cavitation of the formulation occurs, creating microbubbles. As these microbubbles then collapse, the pressure within the formulation is increased forcibly dispersing the antimicrobial agents within and throughout the formulation.
The term “liquid” and “formulation” are used interchangeably to refer to a single component formulation, a formulation comprised of two or more components in which at least one of the components is a liquid such as a liquid-liquid formulation or a liquid-gas formulation or a liquid emulsion in which particulate matter is entrained, or other viscous fluids.
The ultrasonic mixing system 121 is illustrated schematically in
As noted above, the antimicrobial agents can be any agent that can control the growth of microbes and/or kill microbes upon contact. Typically, the antimicrobial agents are solid particulates, however, it should be understood that the antimicrobial agents can be particulate powders, liquid dispersions, encapsulated liquids, and the like. Exemplary antimicrobial agents can include, but are not limited to antibacterial agents, antifungal agents, antiviral agents, antiprotozoal agents, antihelminth agents, xenobiotics, hydrophobic drugs and/or pharmaceuticals, pesticides, herbicides, insecticides, moluscsides, and rodencides. More specifically, examples of suitable antimicrobial agents to mix with the formulations using the ultrasonic mixing system of the present disclosure can include water-insoluble antimicrobial agents (e.g., isothiazolinone (Kathon), isothiazolone, triazole, phthalimide, benzimidazol carbamate tetrachloroisophalonitrile, iodopropargyl butyl carbamate (IPBC), benzisothiazolone (BIT), propiconazole, N(trichloromethyhlthio)pthalimide, methyl benzimidazol-2-yl carbamate, tetrachloroisophalonitrile, methylene bistiocyanate, polystyrene hydantoins, poly[3-chloro-2,2,5,5-tetramethyl-1-(4′-vinylbenzyl)imidazolidin-4-one] (Poly-p-VBD-Cl), poly[acrylonitrile-co-(1,3-dichloro-5-methhyl-5-(4′-vinylbenzyl)barbituric acid)] (Poly-AN-Barb-Cl), 1-bromo-3-ethoxycarbonyloxy-1,2-diiodo-1-propene (BECDIP), 4-chlorophenyl-3-iodopropargylformal (CPIP), hexetidine, cyprocomazole, proiconaxzole, tebucaonazole 2-[thiocyanomethlthio]benzothiazole TCMTB, polyoxymethylene, parabens, phenols, parachlorometaxylenol, cresols (Lysol), halogenated (chlorinated, brominated) phenols, hexachlorophene, triclosan, triclocarbon, trichlorophenol, tribromophenol, pentachlorophenol, dibromol, sulfones, salicylic acid, benzoyl peroxide, zinc pyrithione, hexetidine, benzoic acid, chloroxylenol, chlorhexidine, dehydroacetic acid, sorbic acid, iodopropynyl butylcarbamate, 5-bromo-nitro-1,3 dioxane, ortho phenylphenol, selium disulfide, piroctone, olamine, and the like}; water-insoluble complexes (e.g., chitosan, silver protein complexes, silver iodide, zinc oxide, and the like); water-insoluble oils (e.g., essential oils such as Picea excelsa oil, neem oil, myrrh oil, cedarwood oil, and tea tree oil and the like); water-insoluble antibiotics (e.g., N-thiolated β-lactam acrylate, polyene antibiotics such as amphotericin and nystatin, erythromycin, nalidixic acid, chloramphenicol, pyridomycin, labilomycin, griseoluteins A and B, usnic acid, thiostrepton, aglycones, anthracylcline, Fumagillin, azalide azithromycin, quinolone, dapsone, Nigericin, Polyetherin A, Azalomycin, domperidone, pyridostigmine, Alendronate, Dihydroergotamine, Labetalol, Ganciclovir, Saquinavir, Acyclovir, ritonavir, Pamidronamte, alendronate, and the like); rodenticides (e.g., coumarin-type rodenticides such as difenacoum); insecticides (e.g., pyrethroids such as cypermethrin and d-phenothrin, chlorthalonil, dichlofuanid, imidacloprid, and the like); and combinations thereof. One particularly preferred antimicrobial agent is triclosan. As used herein “water-insoluble” refers to an agent that is substantially hydrophobic so that less than 5 grams of the agent dissolves in 100 milliliters of water. More suitably, the water-insoluble agent is such that less than 2 grams of the agent dissolves in 100 milliliters of water.
In some embodiments, the antimicrobial agents can be coated or encapsulated. The coatings can be hydrophobic or hydrophilic, depending upon the individual antimicrobial agents and the formulation with which the antimicrobial agents are to be mixed. Examples of encapsulation coatings include cellulose-based polymeric materials (e.g., ethyl cellulose), carbohydrate-based materials (e.g., cationic starches and sugars), polyglycolic acid, polylactic acid, and lactic acid-based aliphatic polyesters, and materials derived therefrom (e.g., dextrins and cyclodextrins) as well as other materials compatible with human tissues.
The encapsulation coating thickness may vary depending upon the antimicrobial agent's composition, and is generally manufactured to allow the encapsulated antimicrobial agent to be covered by a thin layer of encapsulation material, which may be a monolayer or thicker laminate layer, or may be a composite layer. The encapsulation coating should be thick enough to resist cracking or breaking of the coating during handling or shipping of the product (i.e., end-product formulation). The encapsulation coating should be constructed such that humidity from atmospheric conditions during storage, shipment, or wear will not cause a breakdown of the encapsulation coating and result in a release of the antimicrobial agent.
Encapsulated antimicrobial agents should be of a size such that the user cannot feel the encapsulated antimicrobial agent in the formulation when used on the skin. Typically, the encapsulated antimicrobial agents have a diameter of no more than about 25 micrometers, and desirably no more than about 10 micrometers. At these sizes, there is no “gritty” or “scratchy” feeling when the antimicrobial formulation contacts the skin.
In one particularly preferred embodiment, as illustrated in
The terms “upper” and “lower” are used herein in accordance with the vertical orientation of the treatment chamber 151 illustrated in the various drawings and are not intended to describe a necessary orientation of the chamber in use. That is, while the chamber 151 is most suitably oriented vertically, with the outlet end 127 of the chamber below the inlet end 125 as illustrated in the drawing, it should be understood that the chamber may be oriented with the inlet end below the outlet end (see
The terms “axial” and “longitudinal” refer directionally herein to the vertical direction of the chamber 151 (e.g., end-to-end such as the vertical direction in the illustrated embodiment of
The inlet end 125 of the treatment chamber 151 may be in fluid communication with at least one suitable delivery system, generally indicated at 129, that is operable to direct one or more formulations to, and more suitably through, the chamber 151. Typically, the delivery system 129 may comprise one or more pumps 130 operable to pump the respective formulation from a corresponding source thereof to the inlet end 125 of the chamber 151 via suitable conduits 132.
It is understood that the delivery system 129 may be configured to deliver more than one formulation, or more than one component for a single formulation, such as when mixing the components to create the formulation, to the treatment chamber 151 without departing from the scope of this disclosure. It is also contemplated that delivery systems other than that illustrated in
Typically, the delivery system 129 is operable to deliver the formulation to the interior space of the treatment chamber at a flow rate of from about 0.1 liters per minute to about 100 liters per minute. More suitably, the formulation is delivered to the treatment chamber at a flow rate of from about 1 liter per minute to about 10 liters per minute.
In the illustrated embodiment of
Similar to the delivery system 129 to deliver the formulation to the treatment chamber 151, it should be understood that the delivery system 141 may be configured to deliver more than one antimicrobial agent to the treatment chamber 151 without departing from the scope of this disclosure. For example, in an alternative embodiment when the antimicrobial agent is in solid and/or particulate form, the ultrasonic mixing system 321 is illustrated schematically in
Typically, the flow rate of antimicrobial agents into the treatment chamber is from about 1 gram per minute to about 1,000 grams per minute. More suitably, the antimicrobial agents are delivered to the treatment chamber at a flow rate of from about 5 grams per minute to about 500 grams per minute.
Amounts of antimicrobial agents to be mixed with the formulations using the ultrasonic mixing system of the present disclosure will typically depend on the type of formulation, type of antimicrobial agent, and desired end product to be produced. In one example, the formulation is a cosmetic formulation having triclosan added thereto. In such an embodiment, typically from about 0.3% (by weight formulation) to about 0.6% (by weight formulation) triclosan is added to the formulation. It should be understood that the amounts of antimicrobial agent can be less than 0.3% (by weight formulation) or more than 0.6% (by weight formulation) without departing from the scope of the present disclosure.
It is also contemplated that delivery systems other than that illustrated in
The treatment chamber 151 comprises a housing defining an interior space 153 of the chamber 151 through which a formulation and antimicrobial agents delivered to the chamber 151 flow from the inlet end 125 to the outlet end 127 thereof. The housing 151 suitably comprises an elongate tube 155 generally defining, at least in part, a sidewall 157 of the chamber 151. The tube 155 may have one or more inlet ports (generally indicated in
Furthermore, it should be understood by one skilled in the art that the inlet end of the housing may include more than two ports, more than three ports, and even four inlet ports or more. For example, although not shown, the housing may comprise three inlet ports, wherein the first inlet port and the second inlet port are suitably in parallel, spaced relationship with each other, and the third inlet port is oriented on the opposite sidewall of the housing from the first and second inlet ports.
As shown in
In the illustrated embodiment of
A waveguide assembly, generally indicated at 203, extends longitudinally at least in part within the interior space 153 of the chamber 151 to ultrasonically energize the formulation (and any of its components) and the antimicrobial agents flowing through the interior space 153 of the chamber 151. In particular, the waveguide assembly 203 of the illustrated embodiment extends longitudinally from the lower or inlet end 125 of the chamber 151 up into the interior space 153 thereof to a terminal end 113 of the waveguide assembly disposed intermediate the outlet port (e.g., outlet port 160 where it is present). Although illustrated in
Referring again to
The waveguide assembly 203, and more particularly the booster is suitably mounted on the chamber housing 151, e.g., on the tube 155 defining the chamber sidewall 157, at the lower end thereof by a mounting member (not shown) that is configured to vibrationally isolate the waveguide assembly (which vibrates ultrasonically during operation thereof) from the treatment chamber housing. That is, the mounting member inhibits the transfer of longitudinal and transverse mechanical vibration of the waveguide assembly 203 to the chamber housing 151 while maintaining the desired transverse position of the waveguide assembly (and in particular the horn assembly 133) within the interior space 153 of the chamber housing and allowing both longitudinal and transverse displacement of the horn assembly within the chamber housing. The mounting member also at least in part (e.g., along with the booster and lower end of the horn assembly) closes the inlet end 125 of the chamber 151. Examples of suitable mounting member configurations are illustrated and described in U.S. Pat. No. 6,676,003, the entire disclosure of which is incorporated herein by reference to the extent it is consistent herewith.
In one particularly suitable embodiment the mounting member is of single piece construction. Even more suitably, the mounting member may be formed integrally with the booster (and more broadly with the waveguide assembly 203). However, it is understood that the mounting member may be constructed separately from the waveguide assembly 203 and remain within the scope of this disclosure. It is also understood that one or more components of the mounting member may be separately constructed and suitably connected or otherwise assembled together.
In one suitable embodiment, the mounting member is further constructed to be generally rigid (e.g., resistant to static displacement under load) so as to hold the waveguide assembly 203 in proper alignment within the interior space 153 of the chamber 151. For example, the rigid mounting member in one embodiment may be constructed of a non-elastomeric material, more suitably metal, and even more suitably the same metal from which the booster (and more broadly the waveguide assembly 203) is constructed. The term “rigid” is not, however, intended to mean that the mounting member is incapable of dynamic flexing and/or bending in response to ultrasonic vibration of the waveguide assembly 203. In other embodiments, the rigid mounting member may be constructed of an elastomeric material that is sufficiently resistant to static displacement under load but is otherwise capable of dynamic flexing and/or bending in response to ultrasonic vibration of the waveguide assembly 203.
A suitable ultrasonic drive system 131 including at least an exciter (not shown) and a power source (not shown) is disposed exterior of the chamber 151 and operatively connected to the booster (not shown) (and more broadly to the waveguide assembly 203) to energize the waveguide assembly to mechanically vibrate ultrasonically. Examples of suitable ultrasonic drive systems 131 include a Model 20A3000 system available from Dukane Ultrasonics of St. Charles, Ill., and a Model 2000CS system available from Herrmann Ultrasonics of Schaumberg, Ill.
In one embodiment, the drive system 131 is capable of operating the waveguide assembly 203 at a frequency in the range of about 15 kHz to about 100 kHz, more suitably in the range of about 15 kHz to about 60 kHz, and even more suitably in the range of about 20 kHz to about 40 kHz. Such ultrasonic drive systems 131 are well known to those skilled in the art and need not be further described herein.
In some embodiments, however not illustrated, the treatment chamber can include more than one waveguide assembly having at least two horn assemblies for ultrasonically treating and mixing the formulation and antimicrobial agents. As noted above, the treatment chamber comprises a housing defining an interior space of the chamber through which the formulation and antimicrobial agents are delivered from an inlet end. The housing comprises an elongate tube defining, at least in part, a sidewall of the chamber. As with the embodiment including only one waveguide assembly as described above, the tube may have two or more inlet ports formed therein, through which one or more formulations and antimicrobial agents to be mixed within the chamber are delivered to the interior space thereof, and at least one outlet port through which the antimicrobial formulation exits the chamber.
In such an embodiment, two or more waveguide assemblies extend longitudinally at least in part within the interior space of the chamber to ultrasonically energize and mix the formulation and antimicrobial agents flowing through the interior space of the chamber. Each waveguide assembly separately includes an elongate horn assembly, each disposed entirely within the interior space of the housing intermediate the inlet ports and the outlet port for complete submersion within the formulation being mixed with the antimicrobial agents within the chamber. Each horn assembly can be independently constructed as described more fully herein (including the horns, along with the plurality of agitating members and baffle assemblies).
Referring back to
In one embodiment (not shown), the agitating members 137 comprise a series of five washer-shaped rings that extend continuously about the circumference of the horn in longitudinally spaced relationship with each other and transversely outward from the outer surface of the horn. In this manner the vibrational displacement of each of the agitating members relative to the horn is relatively uniform about the circumference of the horn. It is understood, however, that the agitating members need not each be continuous about the circumference of the horn. For example, the agitating members may instead be in the form of spokes, blades, fins or other discrete structural members that extend transversely outward from the outer surface of the horn. For example, as illustrated in
By way of a dimensional example, the horn assembly 133 of the illustrated embodiment of
It is understood that the number of agitating members 137 (e.g., the rings in the illustrated embodiment) may be less than or more than five without departing from the scope of this disclosure. It is also understood that the longitudinal spacing between the agitating members 137 may be other than as illustrated in
In particular, the locations of the agitating members 137 are at least in part a function of the intended vibratory displacement of the agitating members upon vibration of the horn assembly 133. For example, in the illustrated embodiment of
In the illustrated embodiment of
It is understood that the horn 105 may be configured so that the nodal region is other than centrally located longitudinally on the horn member without departing from the scope of this disclosure. It is also understood that one or more of the agitating members 137 may be longitudinally located on the horn so as to experience both longitudinal and transverse displacement relative to the horn upon ultrasonic vibration of the horn 105.
Still referring to
As used herein, the ultrasonic cavitation mode of the agitating members refers to the vibrational displacement of the agitating members sufficient to result in cavitation (i.e., the formation, growth, and implosive collapse of bubbles in a liquid) of the formulation being treated at the predetermined ultrasonic frequency. For example, where the formulation (and antimicrobial agents) flowing within the chamber comprises an aqueous liquid formulation, and the ultrasonic frequency at which the waveguide assembly 203 is to be operated (i.e., the predetermined frequency) is about 20 kHZ, one or more of the agitating members 137 are suitably constructed to provide a vibrational displacement of at least 1.75 mils (i.e., 0.00175 inches, or 0.044 mm) to establish a cavitation mode of the agitating members.
It is understood that the waveguide assembly 203 may be configured differently (e.g., in material, size, etc.) to achieve a desired cavitation mode associated with the particular formulation and/or antimicrobial agents to be mixed. For example, as the viscosity of the formulation being mixed with the antimicrobial agents changes, the cavitation mode of the agitating members may need to be changed.
In particularly suitable embodiments, the cavitation mode of the agitating members corresponds to a resonant mode of the agitating members whereby vibrational displacement of the agitating members is amplified relative to the displacement of the horn. However, it is understood that cavitation may occur without the agitating members operating in their resonant mode, or even at a vibrational displacement that is greater than the displacement of the horn, without departing from the scope of this disclosure.
In one suitable embodiment, a ratio of the transverse length of at least one and, more suitably, all of the agitating members to the thickness of the agitating member is in the range of about 2:1 to about 6:1. As another example, the rings each extend transversely outward from the outer surface 107 of the horn 105 a length of about 0.5 inches (12.7 mm) and the thickness of each ring is about 0.125 inches (3.2 mm), so that the ratio of transverse length to thickness of each ring is about 4:1. It is understood, however that the thickness and/or the transverse length of the agitating members may be other than that of the rings as described above without departing from the scope of this disclosure. Also, while the agitating members 137 (rings) may suitably each have the same transverse length and thickness, it is understood that the agitating members may have different thicknesses and/or transverse lengths.
In the above described embodiment, the transverse length of the agitating member also at least in part defines the size (and at least in part the direction) of the flow path along which the formulation and antimicrobial agents or other flowable components in the interior space of the chamber flows past the horn. For example, the horn may have a radius of about 0.875 inches (22.2 mm) and the transverse length of each ring is, as discussed above, about 0.5 inches (12.7 mm). The radius of the inner surface of the housing sidewall is approximately 1.75 inches (44.5 mm) so that the transverse spacing between each ring and the inner surface of the housing sidewall is about 0.375 inches (9.5 mm). It is contemplated that the spacing between the horn outer surface 107 and the inner surface 167 of the chamber sidewall 157 and/or between the agitating members 137 and the inner surface 167 of the chamber sidewall 157 may be greater or less than described above without departing from the scope of this disclosure.
In general, the horn 105 may be constructed of a metal having suitable acoustical and mechanical properties. Examples of suitable metals for construction of the horn 105 include, without limitation, aluminum, monel, titanium, stainless steel, and some alloy steels. It is also contemplated that all or part of the horn 105 may be coated with another metal such as silver, platinum, gold, palladium, lead dioxide, and copper to mention a few. In one particularly suitable embodiment, the agitating members 137 are constructed of the same material as the horn 105, and are more suitably formed integrally with the horn. In other embodiments, one or more of the agitating members 137 may instead be formed separate from the horn 105 and connected thereto.
While the agitating members 137 (e.g., the rings) illustrated in
As best illustrated in
Additionally, a baffle assembly, generally indicated at 245 is disposed within the interior space 153 of the chamber housing 151, and in particular generally transversely adjacent the inner surface 167 of the sidewall 157 and in generally transversely opposed relationship with the horn 105. In one suitable embodiment, the baffle assembly 245 comprises one or more baffle members 247 disposed adjacent the inner surface 167 of the housing sidewall 157 and extending at least in part transversely inward from the inner surface of the sidewall 167 toward the horn 105. More suitably, the one or more baffle members 247 extend transversely inward from the housing sidewall inner surface 167 to a position longitudinally intersticed with the agitating members 137 that extend outward from the outer surface 107 of the horn 105. The term “longitudinally intersticed” is used herein to mean that a longitudinal line drawn parallel to the longitudinal axis of the horn 105 passes through both the agitating members 137 and the baffle members 247. As one example, in the illustrated embodiment, the baffle assembly 245 comprises four, generally annular baffle members 247 (i.e., extending continuously about the horn 105) longitudinally intersticed with the five agitating members 237.
As a more particular example, the four annular baffle members 247 illustrated in
It will be appreciated that the baffle members 247 thus extend into the flow path of the formulation and antimicrobial agents that flow within the interior space 153 of the chamber 151 past the horn 105 (e.g., within the ultrasonic treatment zone). As such, the baffle members 247 inhibit the formulation and antimicrobial agents from flowing along the inner surface 167 of the chamber sidewall 157 past the horn 105, and more suitably the baffle members facilitate the flow of the formulation and antimicrobial agents transversely inward toward the horn for flowing over the agitating members of the horn to thereby facilitate ultrasonic energization (i.e., agitation) of the formulation and antimicrobial agents to initiate mixing the formulation and antimicrobial agents to form the antimicrobial formulation.
In one embodiment, to inhibit gas bubbles against stagnating or otherwise building up along the inner surface 167 of the sidewall 157 and across the face on the underside of each baffle member 247, e.g., as a result of agitation of the formulation, a series of notches (broadly openings) may be formed in the outer edge of each of the baffle members (not shown) to facilitate the flow of gas (e.g., gas bubbles) between the outer edges of the baffle members and the inner surface of the chamber sidewall. For example, in one particularly preferred embodiment, four such notches are formed in the outer edge of each of the baffle members in equally spaced relationship with each other. It is understood that openings may be formed in the baffle members other than at the outer edges where the baffle members abut the housing, and remain within the scope of this disclosure. It is also understood, that these notches may number more or less than four, as discussed above, and may even be completely omitted.
It is further contemplated that the baffle members 247 need not be annular or otherwise extend continuously about the horn 105. For example, the baffle members 247 may extend discontinuously about the horn 105, such as in the form of spokes, bumps, segments or other discrete structural formations that extend transversely inward from adjacent the inner surface 167 of the housing sidewall 157. The term “continuously” in reference to the baffle members 247 extending continuously about the horn does not exclude a baffle member as being two or more arcuate segments arranged in end-to-end abutting relationship, i.e., as long as no significant gap is formed between such segments. Suitable baffle member configurations are disclosed in U.S. application Ser. No. 11/530,311 (filed Sep. 8, 2006), which is hereby incorporated by reference to the extent it is consistent herewith.
Also, while the baffle members 247 illustrated in
In one embodiment, the ultrasonic mixing system may further comprise a filter assembly (not shown) disposed at the outlet end 127 of the treatment chamber 151. Many antimicrobial agents (particularly, hydrophobic antimicrobial agents), when initially added to a formulation, can attract one another and can clump together in large balls. As such, the filter assembly can filter out the large balls of antimicrobial agents that form within the antimicrobial formulation prior to the formulation being delivered to a packaging unit for consumer use, as described more fully below. Specifically, the filter assembly is constructed to filter out antimicrobial agents sized greater than about 0.2 microns.
In one particularly preferred embodiment, the filter assembly covers the inner surface of the outlet port. The filter assembly includes a filter having a pore size of from about 0.5 micron to about 20 microns. More suitably, the filter assembly includes a filter having a pore size of from about 1 micron to about 5 microns, and even more suitably, about 2 microns. The number and pour size of filters for use in the filter assembly will typically depend on the antimicrobial agents and formulation to be mixed within the treatment chamber.
In operation according to one embodiment of the ultrasonic mixing system of the present disclosure, the mixing system (more specifically, the treatment chamber) is used to mix/disperse antimicrobials into one or more formulations. Specifically, a formulation is delivered (e.g., by the pumps described above) via conduits to one or more inlet ports formed in the treatment chamber housing. The formulation can be any suitable formulation known in the art. For example, suitable formulations can include hydrophilic formulations, hydrophobic formulations, siliphilic formulations, and combinations thereof. Examples of particularly suitable formulations to be mixed within the ultrasonic mixing system of the present disclosure can include aqueous dispersions, microemulsions, macroemulsions, and nanoemulsions including oil-in-water emulsions, water-in-oil emulsions, water-in-oil-in-water emulsions, oil-in-water-in-oil emulsions, water-in-silicone emulsions, water-in-silicone-in-water emulsions, glycol-in-silicone emulsion, high internal phase emulsions, hydrogels, and the like. High internal phase emulsions are well known in the art and typically refer to emulsions having from about 70% (by total weight emulsion) to about 80% (by total weight emulsion) of an oil phase. Furthermore, as known by one skilled in the art, “hydrogel” typically refers to a hydrophilic base that is thickened with rheology modifiers and or thickeners to form a gel. For example a hydrogel can be formed with a base consisting of water that is thickened with a carbomer that has been neutralized with a base.
Generally, from about 0.1 liters per minute to about 100 liters per minute of the formulation is typically delivered into the treatment chamber housing. More suitably, the amount of formulation delivered into the treatment chamber housing is from about 1.0 liters per minute to about 10 liters per minute.
In one embodiment, the formulation is prepared using the ultrasonic mixing system simultaneously during delivery of the formulation into the interior space of the housing and mixing with the antimicrobial agents. In such an embodiment, the treatment chamber can include more than one inlet port to deliver the separate components of the formulation into the interior space of the housing. For example, in one embodiment, a first component of the formulation can be delivered via a first inlet port into the interior space of the treatment chamber housing and a second component of the formulation can be delivered via a third inlet port into the interior space of the treatment chamber housing (as described above, the antimicrobial agents are typically delivered via the second inlet port; however, the numbering of ports is not substantially important and thus can be other than as described above without departing from the present disclosure). In one embodiment, the first component is water and the second component is a triclosan. The first component is delivered via the first inlet port to the interior space of the housing at a flow rate of from about 0.1 liters per minute to about 100 liters per minute, and the second component is delivered via the second inlet port to the interior space of the housing at a flow rate of from about 1 milliliter per minute to about 1000 milliliters per minute.
Typically, the multiple inlet ports are disposed in parallel along the sidewall of the treatment chamber housing. In an alternative embodiment, the multiple inlet ports are disposed on opposing sidewalls of the treatment chamber housing. While described herein as having two inlet ports to deliver one or more components of the formulation, it should be understood by one skilled in the art that more than two inlet ports can be used to deliver the various components of the formulations without departing from the scope of the present disclosure.
In one embodiment, the formulation (or one or more of its components) is heated prior to being delivered to the treatment chamber. With some formulations, while the individual components have a relatively low viscosity (i.e., a viscosity below 100 cps), the resulting formulation made with the components has a high viscosity (i.e., a viscosity greater than 100 cps), which can result in clumping of the formulation and clogging of the inlet port of the treatment chamber. For example, many water-in-oil emulsions can suffer from clumping during mixing. In these types of formulations, the water and/or oil components are heated to a temperature of approximately 40° C. or higher. Suitably, the formulation (or one or more of its components) can be heated to a temperature of from about 70° C. to about 100° C. prior to being delivered to the treatment chamber via the inlet port.
Additionally, the method includes delivering antimicrobial agents, such as those described above, to the interior space of the chamber to be mixed with the formulation. Specifically, the antimicrobial agents are delivered to the interior space of the housing via a second inlet port.
Typically, the one or more antimicrobial agents are delivered to the interior space of the housing at a flow rate of from about 1 gram per minute to about 1000 grams per minute. More suitably, one or more antimicrobial agents are delivered at a flow rate of from about 5 grams per minute to about 500 grams per minute.
In accordance with the above embodiment, as the formulation and antimicrobial agents continue to flow upward within the chamber, the waveguide assembly, and more particularly the horn assembly, is driven by the drive system to vibrate at a predetermined ultrasonic frequency. In response to ultrasonic excitation of the horn, the agitating members that extend outward from the outer surface of the horn dynamically flex/bend relative to the horn, or displace transversely (depending on the longitudinal position of the agitating member relative to the nodal region of the horn).
The formulation and antimicrobial agents continuously flow longitudinally along the flow path between the horn assembly and the inner surface of the housing sidewall so that the ultrasonic vibration and the dynamic motion of the agitating members causes cavitation in the formulation to further facilitate agitation. The baffle members disrupt the longitudinal flow of formulation along the inner surface of the housing sidewall and repeatedly direct the flow transversely inward to flow over the vibrating agitating members.
As the mixed antimicrobial formulation flows longitudinally downstream past the terminal end of the waveguide assembly, an initial back mixing of the antimicrobial formulation also occurs as a result of the dynamic motion of the agitating member at or adjacent the terminal end of the horn. Further downstream flow of the antimicrobial formulation results in the agitated formulation providing a more uniform mixture of components (e.g., components of formulation and antimicrobial agents) prior to exiting the treatment chamber via the outlet port. Furthermore, the initial agitation and back-mixing caused by the ultrasonic vibration and cavitation limit the particle size of the antimicrobial agents within the antimicrobial formulation. Specifically, the ultrasonic mixing system of the present disclosure allows for antimicrobial formulations having significantly reduced particle sized-antimicrobial agents, allowing for a better antimicrobial effect and a more comfortable, less harsh end-product antimicrobial formulation.
In one embodiment, as illustrated in
The liquid recycle loop can be any system that is capable of recycling the liquid formulation from the interior space of the housing downstream of the intake zone back into the intake zone of the interior space of the housing. In one particularly preferred embodiment, as shown in
Typically, the formulation (and antimicrobial agents) is delivered back into the treatment chamber at a flow rate having a ratio of recycle flow rate to initial feed flow rate of the formulation (described below) of 1.0 or greater. While a ratio of recycle flow rate to initial feed flow rate is preferably greater than 1.0, it should be understood that ratios of less than 1.0 can be tolerated without departing from the scope of the present disclosure.
Once the antimicrobial formulation is thoroughly mixed, the antimicrobial formulation exits the treatment chamber via the outlet port. In one embodiment, once exited, the antimicrobial formulation can be directed to a post-processing delivery system to be delivered to one or more packaging units. Without being limiting, for example, the antimicrobial formulation is a skin cleansing formulation and the antimicrobial formulation can be directed to a post-processing delivery system to be delivered to a lotion-pump dispenser for use by the consumer.
The post-processing delivery system can be any system known in the art for delivering the antimicrobial formulation to end-product packaging units. Suitable packaging units can be any packaging unit for the formulations described above. For example, suitable packaging units include spray bottles, lotion tubes and/or bottles, wet wipes, and the like.
The present disclosure is illustrated by the following examples which are merely for the purpose of illustration and is not to be regarded as limiting the scope of the disclosure or manner in which it may be practiced.
In this Example, the water-insoluble antimicrobial agent, triclosan, was mixed with various aqueous formulations in the ultrasonic mixing system of
Four samples (Samples A-D) of triclosan in a diluted wet wipe formulation were mixed using the ultrasonic mixing system of
Four additional samples (Samples E-H) of triclosan in a water formulation were mixed using the ultrasonic mixing system of
Two control samples (I & J) of triclosan and diluted wet wipe formulation and two control samples (K & L) of triclosan and water were also prepared using either a homogenizing mixer or laboratory benchtop mixer to manually stir the antimicrobial formulation mixture together. Specifically, 398.8 grams of formulation (i.e., diluted wet wipe solution above) and 1.2 grams of triclosan were delivered to the mixing vessels and mixed by either IKA-Werke Eurostar lab benchtop mixer or Silverson L4RT-W lab homogenizer. The formulation and antimicrobial agents were then mixed for 5 minutes at a rate of either 500 rpm on the IKA lab mixer or 5000 rpm on the homogenizer.
All samples of antimicrobial formulations were visually observed immediately after mixing, 1 day after mixing, 2 days after mixing, 3 days after mixing, and 6 days after mixing. The various samples and visual observations are shown in Table 3.
As can be seen in Table 3, ultrasonic mixing with the ultrasonic mixing system of the present disclosure allowed for faster, and more efficient mixing. Specifically, the antimicrobial formulations were completely homogenous after a shorter period of time; that is the triclosan completely dissolved faster in the aqueous formulations, or dispersed more finely so the resultant particulate antimicrobial agents remained dispersed for much longer periods of time and did not reagglommerate into larger particles using the ultrasonic mixing system of the present disclosure as compared to manual mixing with either a homogenizer mixer or hand mixer. Furthermore, the ultrasonic mixing system produced antimicrobial formulations that remained stable, homogenous formulations for a longer period of time.
Subsequently, the samples were run through a filter and triclosan particles (if any) were separated from the formulation. Both volume mean particle diameter and particle size distribution were performed using Laser Light Scattering methods by Micromeritics Analytical Services (Norcross, Ga.). The results are shown in Table 4.
Furthermore, the samples were analyzed for their efficacy against Staphylococcus aureus. Specifically, approximately 104 colony forming units of S. aureus (ATCC#6538) were aliquoted into wells of a 96-well microtiter plate. The samples above were placed in the wells and parafilm sealed. The plates were incubated at 37° C. for 24 hours and then the MIC and the zone of inhibition were measured. The results are shown in Table 5.
As shown in Table 5, the samples that were ultrasonically mixed provided better antimicrobial activity compared to the control samples. Specifically, the ultrasonically mixed samples provided larger zones of inhibition and controlled the growth of S. aureus better than the control samples as represented by the MIC data in the table.
When introducing elements of the present disclosure or preferred embodiments thereof, the articles “a”, “an”, “the”, and “said” are intended to mean that there are one or more of the elements. The terms “comprising”, “including”, and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements.
As various changes could be made in the above constructions and methods without departing from the scope of the invention, it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.
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