CRYOPROTECTANT FOR USE WITH A TREATMENT DEVICE FOR IMPROVED COOLING OF SUBCUTANEOUS LIPID-RICH CELLS

A cryoprotectant for use with a treatment device for improved removal of heat from subcutaneous lipid-rich cells of a subject having skin is provided. The cryoprotectant is a non-freezing liquid, gel, or paste for allowing pre-cooling of the treatment device below 0° C. while preventing the formation of ice thereon. The cryoprotectant may also prevent freezing of the treatment device to the skin or ice from forming from moisture seeping out from the skin. The cryoprotectant may further be hygroscopic, thermally conductive, and biocompatible.

DETAILED DESCRIPTION

The present disclosure describes devices, systems, and methods for cooling subcutaneous lipid-rich cells with a heat exchanging element and a thermally conductive cryoprotectant. The term “subcutaneous tissue” means tissue lying beneath the dermis and includes subcutaneous fat, or adipose tissue, which primarily is composed of lipid-rich cells, or adipocytes. It may be appreciated that several of the details set forth below are provided to describe the following embodiments in a manner sufficient to enable a person skilled in the relevant art to make and use the disclosed embodiments. Several of the details and advantages described below, however, may not be necessary to practice certain embodiments of the invention. Additionally, the invention may include other embodiments that are within the scope of the claims but are not described in detail with respect to the Figures.

B. System for Selectively Reducing Lipid-Rich Cells

FIG. 1is an isometric view of a treatment system100for exchanging heat from subcutaneous lipid-rich cells of a subject101in accordance with an embodiment of the invention. The treatment system100may include a treatment device104placed at an abdominal area102of the subject101or another area where reduction of the subcutaneous fat, or fat layer, is desired. The treatment device104may be fastened to the subject101using, for example, a mechanical fastener (e.g., a belt105), an adhesive (e.g., an epoxy), suction (e.g., a vacuum or reduced pressure), or any other mechanisms. The treatment device104may be configured to heat and/or cool the subject101. In certain embodiments, the treatment device104may contain a non-freezing cryoprotectant to, among other advantages, allow pre-cooling of the treatment device104to a temperature around or below the freezing point of water (0° C.) while preventing ice from forming. Various embodiments of the treatment device104are described in more detail below with reference toFIGS. 7-10. In other embodiments, the treatment system100may also include a coupling device (not shown inFIG. 1) for supplying the cryoprotectant to the treatment device104or the skin of the subject101, as described in more detail below with reference toFIG. 2andFIG. 3.

In one embodiment, the treatment device104is configured to cool subcutaneous lipid-rich cells of the subject101. In such cases, the treatment system100may further include a fluid source106and fluid lines108a-bconnecting the treatment device104to the fluid source106. The fluid source106may remove heat from a coolant to a heat sink and provide the chilled coolant to the treatment device104via the fluid lines108a-b. Examples of the circulating coolant include water, glycol, synthetic heat transfer fluid, oil, a refrigerant, and any other suitable heat conducting fluids. The fluid lines108a-bmay be hoses or other conduits constructed from polyethylene, polyvinyl chloride, polyurethane, steel, aluminum, copper and other materials that may accommodate the particular circulating coolant. The fluid source106may be a refrigeration unit, a cooling tower, a thermoelectric chiller, or any other device capable of removing heat from a coolant or municipal water supply.

The treatment device104may also include one or more thermoelectric elements, such as Peltier-type thermoelectric elements. In such cases, the treatment system100may further include a power supply110and a processing unit114operatively coupled to the treatment device104via electrical cables112,116. In one embodiment, the power supply110may provide a direct current voltage to the treatment device104remove heat from the subject101. The processing unit114may monitor process parameters via sensors (not shown inFIG. 1) placed proximate to the treatment device104and adjust the heat removal rate based on the process parameters. The processing unit114may include any processor, Programmable Logic Controller, Distributed Control System, and the like.

The processing unit114may be in electrical communication with an input device118, an output device120, and/or a control panel122. The input device118may include a keyboard, a mouse, a touch screen, a push button, a switch, a potentiometer, and any other device suitable for accepting user input. The output device120may include a display screen, a printer, a medium reader, an audio device, and any other device suitable for providing user feedback. The control panel122may include indicator lights, numerical displays, and audio devices. In the embodiment shown inFIG. 1, the processing unit114, power supply110, control panel122, fluid source106, input device118, and output device120are carried by a rack124with wheels126for portability. In another embodiment, the various components may be fixedly installed at a treatment site.

As explained in more detail below, a cryoprotectant applied to the treatment device104may allow the treatment device104to be pre-cooled prior to being applied to the subject101for more efficient treatment. Further, the cryoprotectant can also enable the treatment device104to be maintained at a desired temperature while preventing ice from forming on a surface of the treatment device104, and thus reduces the delay in reapplying the treatment device104to the subject. Yet another advantage is that the cryoprotectant may prevent the treatment device104from freezing to the skin of the subject. If the cryoprotectant is hygroscopic, it can adsorb moisture from the atmosphere and/or from the skin, which might otherwise form ice.

The treatment device104, the cryoprotectant, and/or other components of the treatment system100can be included in a kit (not shown) for removing heat from subcutaneous lipid rich cells of the subject101. The cryoprotectant can have a freezing point in the range of about −40° C. to about 0° C. and be configured to be applied to an interface between the treatment device104and the skin of the subject101. The kit can also include instruction documentation containing information regarding how to (a) apply the cryoprotectant to a target region and/or a heat exchanging surface of the treatment device104and (b) reduce a temperature of the target region such that lipid rich cells in the region are affected while preserving non-lipid rich cells proximate to the heat exchanging surface.

FIG. 2is a side elevation view illustrating a coupling device502suitable to be used in the treatment system100ofFIG. 1and configured in accordance with an embodiment of the invention. The coupling device502may be placed adjacent to a treatment region501of the subject101. The coupling device502may include attachment features510for releasably or fixedly attaching the coupling device502to a heat exchanging element130of the treatment device104(FIG. 1). In the illustrated embodiment, the attachment features510include tensioning clips. During assembly, the coupling device502may be snapped onto the heat exchanging element130with the backside portion504facing the treatment device104. In other embodiments, the attachment features510may include screws, pins, hinges, and/or any other suitable attachment devices.

The coupling device502may include a backside portion504proximate to the heat exchanging element130, a front side portion508spaced apart from the backside portion504, and an intermediate portion506between the backside portion504and the front side portion508. In certain embodiments, the coupling device502optionally may include a protective layer (e.g., a polymeric film, not shown) attached to the front side portion508. The protective layer may isolate the front side portion508from the environment and may be peeled off to expose the front side portion508before treatment.

The backside portion504may be a film, a plate, a sheet, or other structure constructed from a metal, a metal alloy, ceramics, a polymeric material, or other suitable conductive material. The backside portion504may transfer heat between the heat exchanging element130and the treatment region501. The backside portion504may also isolate the heat exchanging element130from the treatment region501for sanitation purposes.

The intermediate portion506may be a reservoir constructed from a mesh, a foam material, a porous plastic and/or metal, or other materials that may at least temporarily contain a fluid and/or a gel. In one embodiment, the intermediate portion506contains, or is loaded with, a cryoprotectant before a treatment process begins. In another embodiment, the intermediate portion506may be generally empty before a treatment process begins and only loaded with cryoprotectant immediately before and/or during the treatment process. In any of these embodiments, the intermediate portion506may be pressurized with the cryoprotectant or may be at a generally atmospheric pressure during treatment.

The front side portion508may be a film constructed from a polymeric material, a plastic material, or other material that is at least partially flexible. The front side portion508may include one or more apertures516in fluid communication with the intermediate portion506. During treatment, the aperture or apertures516may allow the cryoprotectant contained in the intermediate portion506to escape to the treatment region501of the subject101through capillary actions or other mechanisms. For example, the intermediate portion506may continually supply the cryoprotectant to the treatment region501during treatment. In certain embodiments, the intermediate portion506is pre-loaded with excess cryoprotectant. As a portion of the cryoprotectant escapes from the apertures516, additional cryoprotectant may be supplied from the intermediate portion506to the skin of the subject during treatment. In other embodiments, the intermediate portion506may be constantly replenished to provide a continuous supply of the cryoprotectant. The cryoprotectant can be absorbed by the skin in the treatment region501. The degree of cryoprotectant absorption by the skin depends on a number of factors, the most important of which are cryoprotectant concentration, duration of contact, solubility, and the physical condition of the skin.

The coupling device502optionally may include at least one sensor514proximate to the front side portion508to measure at least one parameter of the treatment process. The sensor514may be a temperature sensor, a pressure sensor, a transmissivity sensor, a bio-resistance sensor, an ultrasound sensor, an optical sensor, an infrared sensor, a heat flux sensor, any other desired sensors, or any combination thereof. An operator may adjust the treatment process based on the measured parameter.

In the illustrated embodiment, the treatment device104optionally may include a supply device520connected to a port515of the coupling device502by a conduit522for supplying and/or replenishing the cryoprotectant in the intermediate portion506. In the illustrated embodiment, the supply device520is a syringe holding a volume of the cryoprotectant. In other embodiments, the supply device520may include a pump coupled to a cryoprotectant storage (not shown), or other suitable supply configurations.

Optionally, a pressure sensor524(shown schematically) may be used for monitoring a cryoprotectant pressure in the intermediate portion506. The pressure sensor524may be operatively coupled to the conduit522, the intermediate portion506, or the supply device520. During treatment, the pressure sensor524may provide an electric, visual, or other signal indicating the cryoprotectant pressure in the intermediate portion506. In one embodiment, an operator may manually adjust the output of the supply device520based on the indicated pressure. In another embodiment, the signal from the pressure sensor524may be used as a process variable to automatically control the output of the supply device520.

Several embodiments of the treatment system100may continually protect the skin of the subject against freezing damage. According to conventional techniques, a cryoprotectant may be topically applied to the skin before a treatment begins. The skin then absorbs the applied cryoprotectant, which dissipates over a period of time. After the cryoprotectant dissipates, in conventional techniques, the skin may be subject to freezing damage. As a result, by continually replenishing the dissipated cryoprotectant from the intermediate portion506, the treatment system100may at least reduce the risk of freezing damage, or even prevent such freezing damage, during treatment.

Several embodiments of the treatment system100may also reduce the risk of air pockets that can reduce the heat transfer efficiency between the treatment region501and the treatment device104. As the cryoprotectant escapes through the aperture or apertures516during treatment, the pressure in the intermediate portion506decreases, and air pockets may form. The air pockets may interfere with the heat transfer efficiency between the treatment region501and the treatment device104. As a result, maintaining the intermediate portion506at a constant pressure may at least reduce the risk of air pocket formation, and thus improve the efficiency of such heat transfer.

Even though the coupling device502is illustrated as having the attachment features510, in certain embodiments, the attachment features510may be omitted, and the coupling device502may be configured and/or incorporated into other structures. For example,FIG. 3illustrates another embodiment, in which the coupling device502is incorporated into a sleeve162that attaches to the heat exchanging element130. The coupling device502can define a first sleeve portion164, and the sleeve162can also have a second sleeve portion166. For example, the first sleeve portion164may include the backside portion504, the front side portion508, and the intermediate portion506(FIG. 3). The second sleeve portion166may be an isolation layer extending from the first sleeve portion164. For example, the second sleeve portion166may be constructed from latex, rubber, nylon, polyimide, polyethylene, Kevlar®, or other substantially impermeable or semi-permeable material. The second sleeve portion166may prevent any contact between the skin of the subject and the heat exchanging element130. In one embodiment, the sleeve162may be reusable. In other embodiments, the sleeve162may be disposable. The sleeve162may be provided sterile or non-sterile. In one embodiment, the sleeve is fabricated from a flex circuit material such as polyimide or polyethylene, with etched traces to connect sensors to electronics resident in, e.g., the processing unit114.

The second sleeve portion166may also include attachment features to affix the sleeve162to the treatment device104. In the illustrated embodiment, the second sleeve portion166includes four brackets172(identified individually as172a-d), each located at a corner of the second sleeve portion166. Individual brackets172include an aperture174(identified individually as174a-d) that corresponds to an attachment point170of the treatment device104. During assembly, the apertures174of the brackets172may fit over the attachment point170such that the second sleeve portion166at least partially encloses the heat exchanging element130.

In another embodiment, the second sleeve portion166may include brackets that may engage each other. For example, the bracket172amay include a pin that may engage the aperture174dof the bracket172d. During assembly, the second sleeve portion166may wrap around the treatment device104and be held in place by engaging the brackets172with each other. In a further embodiment, the second sleeve portion166may include a flexible member (not shown, e.g., an elastic band) at an outer edge176of the second sleeve portion166that may hold the sleeve162over the treatment device104during assembly. In a further embodiment, the second sleeve portion166may include a releasable attachment member (not shown, e.g., Velcro® or snaps) at the outer edge176-ofthe second sleeve portion166that may hold the sleeve162over the treatment device104during assembly. In yet another embodiment, adhesive may hold the second sleeve portion166to the treatment device104.

In addition to the expected advantages described above, one expected advantage of using the sleeve162is the improved sanitation of using the treatment device104. The sleeve162may prevent cross-contamination between the skin of the subject and the heat exchanging element130because the sleeve162is substantially impermeable. Also, operating expense of the treatment device104may be reduced because the heat exchanging element130does not need to be sanitized after each use.

The sleeve162may have many additional embodiments with different and/or additional features without detracting from its operation. For example, the first and second sleeve portions164,166may be constructed from the same material (e.g., polyimide) or different materials. The sleeve162may include an adhesive layer (not shown) that binds the sleeve162to the treatment device104.

D. Method of Pre-Cooling a Treatment Device Using a Cryoprotectant

FIG. 4is a flow chart illustrating a method suitable to be performed in the treatment system100ofFIG. 1and in accordance with an embodiment of the invention. The method may include applying a cryoprotectant to a heat exchanging element contained in a treatment device (block10). In certain embodiments, the cryoprotectant may be applied to the skin of a subject or both the skin and the heat exchanging element. The temperature of the heat exchanging element may be reduced to a desired temperature (block12). Once the temperature of the heat exchanging element is reduced to a desired temperature, for example, around or below the freezing point of water (0° C.), the heat exchanging element may be placed adjacent to the skin of a subject (block14). Placing the heat exchanging element adjacent to the skin of a subject reduces the temperature of a region such that lipid-rich cells in the region are selectively affected while non-lipid-rich cells in the epidermis and/or dermis are not generally affected (block16). In certain embodiments, the temperature of the treatment device optionally may be further reduced to a treatment temperature once the heat exchanging element is placed adjacent to the skin of a subject (block15).

After a selected period of time, the treatment device may then be removed from the skin of the subject (block18), and the process may then end (block20). Once the treatment device is removed from the skin of the subject, the reduced temperature of the heat exchanging element optionally may be maintained at a desired temperature (block22). In certain embodiments, the heat exchanging element optionally may be placed adjacent to another region of the skin of the subject to selectively affect lipid-rich cells in a different region of the skin of the subject (block24). Once the heat exchanging element is placed adjacent to another region of the skin of the subject, the lipid-rich cells are affected (block16). The treatment device may then be removed from the skin of the subject (block18) and then the process may end (block20). Optionally, the cryoprotectant may be reapplied to the heat exchanging element, the skin of the subject, or to an interface between the treatment device and the skin of the subject (block28) prior to placing the heat exchanging element on another region of the skin of the subject.

In another embodiment, a cryoprotectant may be applied to the heat exchanging element, the skin of the subject, or an interface between the treatment device and the skin of the subject to prevent the formation of ice (block10) as the temperature of the heat exchanging element is reduced to a desired temperature. The heat exchanging element is placed adjacent to the skin of the subject in a desired region (block14), and the lipid-rich cells are selectively affected (block16). After a selected period of time, the heat exchanging element may then be removed from the skin of the subject (block18). Optionally, the cryoprotectant is reapplied to the heat exchanging element, the skin of the subject, and/or an interface between the treatment device and the skin of the subject (block28), and the temperature of the heat exchanging element is maintained at a desired temperature (block22). The process of treating the selected region of the skin of the subject optionally may be repeated to selectively affect the lipid-rich cells in a region of the subject while non-lipid-rich cells in the epidermis and/or dermis are not generally affected (block26).

FIG. 5illustrates another method for pre-cooling the heat exchanging element by applying a cryoprotectant on the heat exchanging element prior to decreasing the temperature of the heat exchanging element to prevent icing. In one embodiment, a cryoprotectant is placed on the heat exchanging element to prevent the heat exchanging element from icing (block50). The heat exchanging element is then pre-cooled by decreasing the temperature to at or below 0° C. (block52). The heat exchanging element is applied to the skin of the subject in a first treatment region (block54), to selectively affect lipid-rich cells in the treatment region (block56). In certain embodiments, the temperature of the heat exchanging element may be further decreased (block68). The heat exchanging element is then removed from the treatment region (block58) and the treatment may then end (block64). In certain embodiments, the temperature of the heat exchanging element may be maintained at a target temperature (block60), and the heat exchanging element may be applied to a second treatment region on the skin of the subject (block62), to selectively affect the lipid-rich cells. Once the heat exchanging element is removed from the treatment region (block58), the temperature of the heat exchanging element may be allowed to return to an ambient temperature (block66), or the temperature of the heat exchanging element may be maintained at or below 0° C. (block60). In yet another embodiment, the temperature of the heat exchanging element may be maintained at a target temperature (block70). The heat exchanging element may then be applied to a second treatment region on the skin of the subject (block72), or may be reapplied to the first treatment region on the skin of the subject to selectively affect the lipid-rich cells (block54).

By cooling the subcutaneous tissues to a temperature lower than 37° C., subcutaneous lipid-rich cells may be selectively affected. In general, the epidermis and dermis of a subject have lower amounts of unsaturated fatty acids compared to the underlying lipid-rich cells forming the subcutaneous tissues. Because non-lipid-rich cells usually withstand colder temperatures better than lipid-rich cells, the subcutaneous lipid-rich cells may be selectively affected while maintaining the non-lipid-rich cells in the dermis and epidermis. For example, a range for the heat exchanging elements may be from about −20° C. to about 20° C., preferably from about −20° C. to about 10° C., more preferably from about −15° C. to about 5° C., more preferably from about −10° C. to about 0° C.

The lipid-rich cells may be affected by affecting, shrinking, disabling, destroying, removing, killing, or otherwise being altered. Without being bound by theory, selectively affecting lipid-rich cells is believed to result from localized crystallization of highly saturated fatty acids at temperatures that do not induce crystallization in non-lipid-rich cells. The crystals may rupture the bi-lipid membrane of lipid-rich cells to selectively necrose these cells. Thus, damage of non-lipid-rich cells, such as dermal cells, may be avoided at temperatures that induce crystal formation in lipid-rich cells. Cooling is also believed to induce lipolysis (e.g., fat metabolism) of lipid-rich cells to further enhance the reduction in subcutaneous lipid-rich cells. Lipolysis may be enhanced by local cold exposure, inducing stimulation of the sympathetic nervous system.

One expected advantage of several of the embodiments described above is that the treatment device may selectively reduce subcutaneous lipid-rich cells without unacceptably affecting the dermis, epidermis, and/or other tissues. Another expected advantage is that the treatment device may simultaneously selectively reduce subcutaneous lipid-rich cells while providing beneficial effects to the dermis and/or epidermis. These effects may include: fibroplasias, neocollagenesis, collagen contraction, collagen compaction, collagen density increase, collagen remodeling, and acanthosis (epidermal thickening).

Another expected advantage of several of the embodiments described above is that the heat exchanging element may be pre-cooled in advance of treatment to more efficiently treat the skin of the subject. Further, the embodiments allow the treatment device to be maintained at a temperature at or below 0° C. or at a target temperature because the cryoprotectant may prevent icing on the heat exchanging element and/or on the skin of the subject.

E. Method of Protecting the Skin of a Subject Using Cryoprotectant

FIG. 6is a flow chart illustrating another method suitable to be performed in the treatment system100ofFIG. 1and in accordance with an embodiment of the invention. The method80ofFIG. 6may be applied separately or in combination with the methods shown inFIG. 4and/orFIG. 5. For example, a cryoprotectant may be applied to both the skin of the subject for protecting the skin from freezing damage and the heat exchanging surface of the treatment device for pre-cooling the treatment device.

In the illustrated embodiment, the method80may include applying a cryoprotectant to a treatment region of the skin of the subject (block82). For example, applying the cryoprotectant may include spraying or smearing the cryoprotectant onto the skin using an instrument including, e.g., a spatula, a spray bottle, and/or a coupling device as shown inFIG. 2. In another embodiment, the cryoprotectant may be injected into the skin of the subject using, e.g., a syringe.

A heat exchanging element is subsequently placed adjacent to the skin of the subject (block84). The heat exchanging element may cool the treatment region that is in contact with the cryoprotectant to selectively affect lipid-rich cells in the region (block86). During treatment, the cryoprotectant may be continually supplied to the skin of the subject (block88). The continually supplied cryoprotectant may maintain a sufficient concentration of absorbed cryoprotectant in the epidermis and/or dermis of the subject for reducing the risk of freezing damage. The cryoprotectant may be continually supplied using an absorbent (e.g., a cotton pad, a gauze, or other absorbents) pre-loaded with the cryoprotectant, or using a coupling device releasably attached to the treatment device.

A decision is made to determine whether the treatment should be continued (block90). The determination may be based on time, skin temperatures, and/or other parameters of the treatment process. If the treatment is continued, then the process returns to block86; otherwise, the process ends.

The applied cryoprotectant may at least reduce the risk of freezing damage in the epidermis and/or dermis of the subject during treatment and may even prevent such freezing damage. Without being bound by theory, it is believed that low temperatures may potentially cause damage in the epidermis and/or dermis via at least intracellular and/or extracellular ice formation. Intracellular ice formation occurs when ice forms inside a cell. The ice may expand and rupture the cell as the ice grows through the cellular wall, thus causing cell death. When extracellular ice formation occurs, extracellular water freezes to form ice. As a result, the remaining extracellular fluid becomes concentrated with solutes. The high concentration of the extracellular fluid may cause intracellular fluid to permeate through the semi-permeable cellular wall and eventually cause cell dehydration and death. The high concentration of the extracellular fluid may also interrupt electrical and/or ionic interactions among neighboring cells to cause irreversible protein damage.

Applying a cryoprotectant may at least reduce the risk of intracellular and/or extracellular ice formation, or even prevent such ice formation, by reducing the freezing point of water in the body fluid affected by the cryoprotectant. It is believed that after the cryoprotectant is absorbed into the epidermis and/or dermis, the cryoprotectant dissolves in or otherwise combines with water of the intracellular and/or extracellular fluid to delay the onset of ice formation by lowering the freezing point of the solution in which it resides. For example, the cryoprotectant may reduce the freezing point of the body fluid from, e.g., about −2° C. to about −5° C., −10° C., −16° C., or other temperatures suitable for a particular treatment. In some embodiments, the cryoprotectant may have a sufficient concentration in the body fluid such that water in the body fluid does not freeze but instead vitrifies under low temperature conditions. As a result, the onset of intracellular and/or extracellular ice formation may be prevented in these embodiments.

One expected advantage of several of the embodiments of the method80is that an operator may use lower treatment temperatures for selectively affecting lipid-rich cells of the subject without causing freezing damage to the epidermis and/or dermis of the subject. The applied cryoprotectant may lower the freezing point of the skin of the subject or body fluid in the target region to at least reduce the risk of intracellular and/or extracellular ice formation at such low treatment temperatures.

Another expected advantage is that the epidermis and/or dermis of the subject may be continually protected against freezing damage. It is believed that a topically administered cryoprotectant may protect the treatment region of the skin of the subject. After the cryoprotectant is applied to the skin of the subject, the cryoprotectant is believed to enter the epidermis, the dermis, and eventually the blood stream of the subject. The subject's blood stream then may carry the cryoprotectant away from the treatment region. As a result, the cryoprotectant concentration in the treatment region drops, and the freezing point of the subject's affected body fluid increases to heighten the risk of freezing damage. Accordingly, continually supplying the cryoprotectant to the skin of the subject may at least reduce or even prevent such a risk.

Another expected advantage of several of the embodiments is that cooling the skin of the subject may increase the residence time of the cryoprotectant and may reduce local and/or systemic side effects of the cryoprotectant. It is believed that the skin of the subject absorbs the cryoprotectant at a slower rate under low temperature conditions than under normal temperature (e.g., body temperature) conditions. Thus, the reduced absorption rate may increase the amount of time it takes for the subject's blood stream to remove the cryoprotectant, and thus prolong the efficacy of the cryoprotectant. It is also believed that certain cryoprotectants at certain concentration levels may be toxic to the subject by causing, for example, denaturation of proteins (e.g., enzymes). Thus, reducing the absorption rate of the cryoprotectant may reduce the cryoprotectant concentration in deeper tissues, and thus may reduce the associated local or systemic side effects.

A cryoprotectant suitable to be used in the treatment system100ofFIG. 1is a substance that may protect biological tissues of a subject from freezing damage (e.g., damage due to ice formation). The cryoprotectant may contain a temperature depressant along with a thickening agent, a pH buffer, a humectant, a surfactant, and/or other additives. The cryoprotectant may be formulated as a liquid (e.g., an aqueous solution or a non-aqueous solution), a gel, a hydrogel, or a paste. The cryoprotectant may be hygroscopic, thermally conductive, and is ideally biocompatible. In certain embodiments, the cryoprotectant may be formulated to be ultrasonically acoustic to allow ultrasound to pass through the cryoprotectant, such as a water-based gel described in U.S. Pat. No. 4,002,221 issued to Buchalter and U.S. Pat. No. 4,459,854 issued to Richardson et al., the entire disclosures of which are incorporated herein by reference.

The temperature depressant may include polypropylene glycol (PPG), polyethylene glycol (PEG), propylene glycol, ethylene glycol, dimethyl sulfoxide (DMSO), or other glycols. The temperature depressant may also include ethanol, propanol, iso-propanol, butanol, and/or other suitable alcohol compounds. The temperature depressant may lower the freezing point of a solution (e.g., body fluid) to about 0° C. to −40° C., and more preferably to about −10° C. to −16° C. Certain temperature depressants (e.g., PPG, PEG, etc.) may also be used to improve smoothness of the cryoprotectant and to provide lubrication.

The thickening agent may include carboxyl polyethylene polymer, hydroxyethyl xylose polymer, and/or other viscosity modifiers to provide a viscosity in the range of about 1 cP to about 10,000 cP, more preferably in the range of about 4,000 cP to about 8,000 cP, and most preferably from about 5,000 cP to about 7,000 cP. The cryoprotectant with a viscosity in this range may readily adhere to the treatment device, the skin of the subject, and/or the interface between the treatment device and the skin of the subject during treatment.

The pH buffer may include cholamine chloride, cetamidoglycine, tricine, glycinamide, bicine, and/or other suitable pH buffers. The pH buffer may help the cryoprotectant to have a consistent pH of about 3.5 to about 11.5, more preferably about 5 to about 9.5, and most preferably about 6 to about 7.5. In certain embodiments, the pH of the cryoprotectant may be close to the pH of the skin of the subject.

The surfactant may include sodium dodecyl sulfate, ammonium lauryl sulfate, sodium lauryl sulfate, alkyl benzene sulfonate, sodium lauryl ether sulfate, and other suitable surfactants. The surfactant may promote easy spreading of the cryoprotectant when an operator applies the cryoprotectant to the treatment device, the skin of the subject, and/or the interface between the treatment device and the skin of the subject during treatment.

The cryoprotectant may also include other additives in addition to or in lieu of the ingredients described above. For example, the cryoprotectant may also include a coloring agent, perfume, emulsifier, an anesthetic agent, and/or other ingredient.

In a particular embodiment, the cryoprotectant may include about 30% polypropylene glycol, about 30% glycerin, and about 40% ethanol. In another embodiment, the cryoprotectant may include about 40% propylene glycol, about 0.8% hydroxyethylcellulose, and about 59.2% water. In a further embodiment, the cryoprotectant may include about 50% polypropylene glycol, about 40% glycerin, and about 10% ethanol.

G. Treatment Devices with Rotatable Heat Exchanging Elements

FIG. 7is an isometric view of a treatment device104in accordance with one embodiment of the invention suitable for use in the treatment system100. In this embodiment, the treatment device104includes a support128having a first portion129aand a second portion129b, a first heat exchanging element130alocated at the first portion129a, and a second heat exchanging element130blocated at the second portion129b. The treatment device104is generally configured to be a handheld unit for manual operation, and/or it may be strapped or otherwise configured to be releasably attached to the subject. The first heat exchanging element130aand/or the second heat exchanging element130bmay be configured to move along the support128and/or rotate to position the heat exchanging elements130a-bfor applying pressure to the treatment region during operation.

The first and second heat exchanging elements130a-bmay have many similar features. As such, the features of the first heat exchanging element130aare described below with reference symbols followed by an “a”, and corresponding features of the second heat exchanging element130bare shown and noted by the same reference symbol followed by a “b.” The first heat exchanging element130amay include a housing139aand fluid ports138a-bcoupled to the fluid lines108a-b. The housing139amay be constructed from polymeric materials, metals, ceramics, woods, and/or other suitable materials. The housing139ashown inFIG. 7is generally rectangular, but it may have any other desired shape.

The first heat exchanging element130amay further include a first interface member132ahaving a first heat exchanging surface131afor transferring heat to/from the subject101. A cryoprotectant (not shown) may be applied to the heat exchanging surface131ato prevent ice from forming thereon when the temperature is reduced to a temperature around or below the freezing point of water (0° C.). In one embodiment, the first heat exchanging surface131ais generally planar, but in other embodiments, the first heat exchanging surface131ais non-planar (e.g., curved, faceted, etc.) The first interface member132amay be constructed from any suitable material with a thermal conductivity greater than 0.05 Watts/Meter ° Kelvin, and in many embodiments, the thermal conductivity is more than 0.1 Watts/Meter ° Kelvin. Examples of suitable materials include aluminum, other metals, metal alloys, graphite, ceramics, some polymeric materials, composites, or fluids contained in a flexible membrane. Portions of the first heat exchanging surface131amay be an insulating material with a thermal conductivity less than 0.05 Watts/Meter ° Kelvin.

The first heat exchanging element130amay also include at least one sensing element135aproximate to the first heat exchanging surface131a. The sensing element135a, for example, may be generally flush with the heat exchanging surface131a. Alternatively, it may be recessed or protrude from the surface. The sensing element135amay include a temperature sensor, a pressure sensor, a transmissivity sensor, a bio-resistance sensor, an ultrasound sensor, an optical sensor, an infrared sensor, a sensor for measuring blood flow, or any other desired sensor. In one embodiment, the sensing element135amay be a temperature sensor configured to measure the temperature of the first heat exchanging surface131aand/or the temperature of the skin of the subject. For example, the temperature sensor may be configured as a probe or as a needle that penetrates the skin during measurement. Examples of suitable temperature sensors include thermocouples, resistance temperature devices, thermistors (e.g., neutron-transmutation-doped germanium thermistors), and infrared radiation temperature sensors. In another embodiment, the sensing element135amay be an ultrasound sensor configured to measure the thickness of a fat layer in the subject or crystallization of subcutaneous fat in the treatment region of a subject. In yet another embodiment, the sensing element135amay be an optical or infrared sensor configured to monitor an image of the treatment region to detect, for example, epidermal physiological reactions to the treatment. In yet another embodiment, the sensing element135amay be a device to measure blood flow. The sensing element135amay be in electrical communication with the processing unit114via, for example, a direct wired connection, a networked connection, and/or a wireless connection.

The treatment device104may further include a mounting element136athat couples the first heat exchanging element130ato the first portion129aof the support128. The mounting element136a, for example, may be a pin, a ball joint, a bearing, or other types of rotatable joints. Suitable bearings include, but are not limited to, ball bearings, roller bearings, thrust bearings, and journal bearings. The mounting element136amay accordingly be configured to rotatably couple the first heat exchanging element130ato the support128. In certain embodiments, the first heat exchanging element130amay rotate relative to the support128in two dimensions (indicated by arrow A) such that the angle between the first and second heat exchanging surfaces131a-bmay be adjusted. In another embodiment, the first heat exchanging element130amay rotate in three dimensions relative to the support128(as indicated by arrows A and B).

A specific embodiment of the mounting element136aincludes a first mounting base134aand a flange137acoupled to the base134aby a rotatable or pivotable joint. By rotatably mounting at least one of the first and second heat exchanging elements130a-bto the support128, the angle between the first and second heat exchanging surfaces131a-bmay be adjusted. For example, the first and second heat exchanging elements130a-bmay be generally parallel to each other, i.e., have an angle of generally 0° between the first and second heat exchanging surfaces131a-b. The first and second heat exchanging elements130a-bmay also be generally co-planar, i.e., have an angle of generally 180° between the first and second heat exchanging surfaces131a-b. With the rotatable mounting elements136a-b, any angle of about 0° to about 180° between the first and second heat exchanging surfaces131a-bmay be achieved.

The treatment device104may further include a shaft133, and the first mounting base134amay be attached to the shaft133. As explained in more detail below, at least one of the heat exchanging elements130a-bmoves along the shaft133and/or the shaft133moves relative to the support128to adjust the distance between the first and second heat exchanging elements130a-b(shown by arrow C). The shaft133, more specifically, extends between the first and second heat exchanging elements130a-bto enable movement of at least one of the heat exchanging elements130a-brelative to the support128. In certain embodiments, the first mounting base134amay be fixedly attached to the shaft133, and a second mounting base134bof the second heat exchanging element130bis configured such that the second mounting base134bmay slide along the shaft133. In other embodiments, both the first mounting base134aand the second mounting base134bmay be configured to slide along the shaft133. The shaft133is generally constructed from polymeric materials, metals, ceramics, woods, or other suitable materials.

The treatment device104further includes a handle140slidably coupled to the shaft133or formed as a part of the shaft133. The handle140is configured to be held by a hand of an operator. For example, the handle140may have a grip with grooves to improve stability of the treatment device104when held by the operator. The handle140further includes an actuator142that operates with the shaft133to move the second heat exchanging element130brelative to the shaft133. The actuator142may be a lever that engages the shaft133to incrementally advance the second heat exchanging element130bin an axial motion (arrow C) along the shaft133.

In operation, an operator may hold the treatment device104in one hand by grasping the handle140. Then, the heat exchanging elements130a-bmay be rotated via the mounting elements136a-bto achieve a desired orientation. The operator may place the treatment device104having the heat exchanging elements130a-bin the desired orientation proximate to the skin of the subject to remove heat from a subcutaneous region of the subject101. In one embodiment, the operator may clamp a portion of the skin of the subject between the heat exchanging surfaces131a-bwhen the surfaces131a-bare generally parallel to each other. In another embodiment, the operator may press the heat exchanging surfaces131a-bagainst the skin of the subject when the surfaces131a-bare generally co-planar. In certain embodiments, the operator may use thermoelectric coolers to remove heat from the subcutaneous region as described below with reference toFIG. 8. The operator may also monitor and control the treatment process by collecting measurements, such as skin temperatures, from the sensing element135a. By cooling the subcutaneous tissues to a temperature lower than 37° C., subcutaneous lipid-rich cells may be selectively affected. The affected cells are then reabsorbed into the subject through natural processes.

One expected advantage of using the treatment device104is that the treatment device may be applied to various regions of the subject's body because the two heat exchanging elements130a-bmay be adjusted to conform to any body contour. Another expected advantage is that by pressing the treatment device104against the skin of the subject, blood flow through the treatment region may be reduced to achieve efficient cooling. Yet another expected advantage is that by applying the cryoprotectant to prevent icing and to allow pre-cooling of the heat exchanging elements, the treatment duration may be shortened. Yet another expected advantage is that maintaining the temperature of the heat exchanging elements may reduce the power consumption of the device. Still another expected advantage is that the power requirement is reduced for each of the heat exchanging elements130a-bbecause heat is removed from the skin through the two heat exchanging surfaces131a-binstead of a single heat exchanging element.

The first and second heat exchanging elements130a-bmay have many additional embodiments with different and/or additional features without detracting from the operation of both elements. For example, the second heat exchanging element130bmay or may not have a sensing element proximate to the second heat exchanging surface131b. The second heat exchanging element130bmay be constructed from a material that is different from that of the first heat exchanging element130a. The second mounting base134bmay have a shape and/or a surface configuration different from that of the first mounting base134a. The first heat exchanging element130amay be rotatable, but the second heat exchanging element130bmay be non-rotatable.

The first and second heat exchanging elements130a-bmay further include a thermoelectric cooler (not shown), such as a Peltier-type element, proximate to the interface members132a-b. The thermoelectric cooler may be a single Peltier-type element or an array of Peltier-type elements. One suitable thermoelectric cooler is a Peltier-type heat exchanging element (model # CP-2895) produced by TE Technologies, Inc. in Traverse City, Mich.

H. Treatment Device Having a Plurality of Cooling Elements

FIGS. 8A-Bare isometric views of a treatment device104in accordance with embodiments of the invention suitable for use in the treatment system100. In this embodiment, the treatment device104includes a control system housing202and cooling element housings204a-g. The cooling element housings204a-gare connected to the heat exchanging elements (not shown) by attachment means206. The attachment means may be any mechanical attachment device such as a screw or pin as is known in the art. The plurality of cooling element housings204a-gmay have many similar features. As such, the features of the first cooling element housing204aare described below with reference symbols followed by an “a,” corresponding features of the second cooling element housing204bare shown and noted by the same reference symbol followed by a “b,” and so forth. The cooling element housing204amay be constructed from polymeric materials, metals, ceramics, woods, and/or other suitable materials. The cooling element housing204ashown inFIGS. 8A-Bis generally rectangular, but it may have any other desired shape.

The treatment device104is shown in a first relatively flat configuration inFIG. 8Aand in a second curved configuration inFIG. 8B. As shown inFIGS. 8B, each segment of the cooling element housings204a-gis rotatably connected to adjacent segments and moveable about connection207a-fto allow the treatment device104to curve. The connection207a-f, for example, may be a pin, a ball joint, a bearing, or other type of rotatable joints. The connection207may accordingly be configured to rotatably couple the first cooling element housing204ato the second cooling element housing204b. According to aspects of the invention, the first cooling element housing204amay rotate relative to the second cooling element housing204b(indicated by arrow A), each adjacent moveable pair of cooling elements being such that, for example, the angle between the first and second cooling element housings204aand204bmay be adjusted up to 45°. In this way, the treatment device is articulated such that it may assume a curved configuration as shown inFIG. 8B, conformable to the skin of a subject.

One advantage of the plurality of rotatable heat exchanging surfaces is that the arcuate shape of the treatment device may concentrate the heat transfer in the subcutaneous region. For example, when heat exchanging surfaces are rotated about a body contour of a subject, the arcuate shape may concentrate heat removal from the skin.

The control system housing202may house a processing unit for controlling the treatment device104and/or fluid lines108a-band/or electrical power and communication lines. The control system housing202includes a harness port210for electrical and supply fluid lines (not shown for purposes of clarity). The control system housing202may further be configured to serve as a handle for a user of the treatment device104. Alternatively, the processing unit may be contained at a location other than on the treatment device.

The treatment device104may further include at each end of the treatment device104retention devices208aand208b. The retention devices208aand208bare rotatably connected to a frame by retention device coupling elements212a-b. The retention device coupling elements212a-b, for example, may be a pin, a ball joint, a bearing, or other type of rotatable joints. In certain embodiments, the retention devices208aand208bmay be rigidly affixed to the end portions of the cooling element housings204aand204g. Alternately, the retention device may attach to control system housing202.

The retention devices208aand208bare each shown as tabs214, each having a slot216therein for receiving a band or elastomeric strap (not shown for purposes of clarity) to retain the treatment device104in place on a subject101during treatment. Alternatively, the treatment device may not contain any attached retention device and may be held in place by hand, may be held in place by gravity, or may be held in place with a band, elastomeric strap, or non-elastic fabric (e.g., nylon webbing) wrapped around the treatment device104and the subject101.

As shown inFIGS. 8A-B, the cooling element housings204a-ghave a first edge218and an adjacent second edge220of a reciprocal shape to allow the treatment device104to mate and, thus, configure in a flat configuration. The first edge218and the second edge220are generally angular in the Figures; however, the shape could be curved, straight, or a combination of angles, curves, and straight edges that provides a reciprocal shape between adjacent segments of the cooling element housings204a-g.

I. Additional Embodiments of Treatment Device

FIG. 9is an isometric and exploded view of a treatment device104in accordance with another embodiment of the invention. The treatment device104may include a housing302, a cooling assembly308at least partially disposed in the housing302, and retention devices318configured for fastening the cooling assembly308to the housing302. The treatment device104may also include a vibration member disposed in the housing302, as described in more detail below with reference toFIG. 10.

The cooling assembly308may include a heat sink312, a thermally conductive interface member309, and a thermoelectric cooler314disposed between the heat sink312and the interface member309. The thermoelectric cooler314may be connected to an external power supply (not shown) via connection terminals316. In the illustrated embodiment, the heat sink312includes a U-shaped fluid conduit310at least partially embedded in a thermally conductive portion313of the heat sink312. The fluid conduit310includes fluid ports138a-bthat may be coupled to a circulating fluid source (not shown) via the fluid lines108a-b. In other embodiments, the heat sink312may include a plate-type heat exchanger, a tube and shell heat exchanger, and/or other types of heat exchanging device. The interface member309may include a plate constructed from a metal, a metal alloy, and/or other types of thermally conductive material. The thermoelectric cooler314may be a single Peltier-type element or an array of Peltier-type elements. One suitable thermoelectric cooler is a Peltier-type heat exchanging element (model # CP-2895) produced by TE Technology, Inc. in Traverse City, Mich.

Individual retention devices318may include a plate330and a plurality of fasteners306extending through a plurality of apertures332(two are shown for illustrative purposes) of the plate330. In the illustrated embodiment, the fasteners306are screws that may be received by the housing302. In other embodiments, the fasteners306may include bolts, clamps, clips, nails, pins, rings, rivets, straps, and/or other suitable fasteners. During assembly, the cooling assembly308is first at least partially disposed in the internal space303of the housing302. Then, the retention devices318are positioned proximate to the cooling assembly308, and the fasteners306are extended through the apertures332of the plate330to engage the housing302. The fasteners306, the plates330, and the housing302cooperate to hold the cooling assembly308together.

By applying power to the thermoelectric cooler314, heat may be effectively removed from the skin of the subject to a circulating fluid in the fluid conduit310. For example, applying a current to the thermoelectric cooler314may achieve a temperature generally below 37° C. on the first side315aof the thermoelectric cooler314to remove heat from the subject via the interface member309. The thermoelectric cooler314transfers the heat from the first side315ato the second side315b. The heat is then transferred to the circulating fluid in the fluid conduit310.

FIG. 10is an isometric and exploded view of a vibrator322disposed in the treatment device104ofFIG. 9. The vibrator322may include a frame324, a motor325carried by the frame324, a rotating member328operatively coupled to the motor325, and a plurality of fasteners326(e.g., screws) for fixedly attaching the frame324to the housing302. In the illustrated embodiment, the motor325has an output shaft (not shown) generally centered about a body axis327of the motor325. One suitable motor is a direct current motor (model # Pittman 8322S008-R1) manufactured by Ametek, Inc., of Harleysville, Pa. The rotating member328has a generally cylindrical shape and is off-centered from the body axis327. In other embodiments, the motor325may have an off-centered shaft that is operatively coupled to the rotating member328.

In operation, applying electricity to the motor325may cause the rotating member328to rotate around the body axis327of the motor325. The off-centered rotating member328causes the vibrator322to be off-balanced about the body axis327, and vibration in the frame324and the housing302may result.

The applicants conducted experiments to cool subcutaneous lipid-rich cells in a pig using a treatment device as shown inFIG. 9and a cryoprotectant. A first cryoprotectant composition used in the experiments included about 30% polypropylene glycol, about 30% glycerin, and about 40% ethanol (cryoprotectant I). A second cryoprotectant composition used in the experiments included about 40% propylene glycol, about 0.8% hydroxyethylcellulose, and about 59.2% water (cryoprotectant II). Skin surface temperatures investigated include −11° C., −12° C., −14° C., −16° C., and −20° C.

Each testing site was cleaned and shaved, and a surface thermocouple was placed on the skin of the pig to control the treatment device. A number of 3″X3″ squares of Webril® Undercast Padding #3175, supplied by Tyco Healthcare of Mansfield Mass. (“Webril”), were soaked with 8 milliliters of either cryoprotectant I or cryoprotectant II. The soaked Webril squares were then placed on the test sites for 5 minutes, and the treatment device was then applied to the Webril squares to achieve a desired surface temperature. Once the desired surface temperature was achieved, the surface temperature was maintained for a treatment period of up to about 30 minutes. After the treatment period, the skin of the pig was inspected for freezing.

The results of several experiments indicate that both cryoprotectant I and cryoprotectant II significantly lowered the freezing point of the skin of the pig. In particular, when the surface temperature was between about −12° C. to about −16° C., limited or no skin freezing was observed.

Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise,” “comprising,” and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in a sense of “including, but not limited to.” Words using the singular or plural number also include the plural or singular number, respectively. When the claims use the word “or” in reference to a list of two or more items, that word covers all of the following interpretations of the word: any of the items in the list, all of the items in the list, and any combination of the items in the list.

The above detailed descriptions of embodiments of the invention are not intended to be exhaustive or to limit the invention to the precise form disclosed above. While specific embodiments of, and examples for, the invention are described above for illustrative purposes, various equivalent modifications are possible within the scope of the invention, as those skilled in the relevant art may recognize. For example, while steps are presented in a given order, alternative embodiments may perform steps in a different order. The various embodiments described herein may be combined to provide further embodiments.

In general, the terms used in the following claims should not be construed to limit the invention to the specific embodiments disclosed in the specification, unless the above detailed description explicitly defines such terms. While certain aspects of the invention are presented below in certain claim forms, the inventors contemplate the various aspects of the invention in any number of claim forms. Accordingly, the inventors reserve the right to add additional claims after filing the application to pursue such additional claim forms for other aspects of the invention.