Patent Grant
10524956
The present disclosure is related to cooling of tissue, such as in the context of cryolipolysis and cryolysis.
The following commonly assigned U.S. patent applications and U.S. patents are incorporated herein by reference in their entireties:
U.S. Patent Publication No. 2008/0287839 entitled “METHOD OF ENHANCED REMOVAL OF HEAT FROM SUBCUTANEOUS LIPID-RICH CELLS AND TREATMENT APPARATUS HAVING AN ACTUATOR”;
U.S. Pat. No. 6,032,675 entitled “FREEZING METHOD FOR CONTROLLED REMOVAL OF FATTY TISSUE BY LIPOSUCTION”;
U.S. Patent Publication No. 2007/0255362 entitled “CRYOPROTECTANT FOR USE WITH A TREATMENT DEVICE FOR IMPROVED COOLING OF SUBCUTANEOUS LIPID-RICH CELLS”;
U.S. Pat. No. 7,854,754 entitled “COOLING DEVICE FOR REMOVING HEAT FROM SUBCUTANEOUS LIPID-RICH CELLS”;
U.S. Patent Publication No. 2011/0066216 entitled “COOLING DEVICE FOR REMOVING HEAT FROM SUBCUTANEOUS LIPID-RICH CELLS”;
U.S. Patent Publication No. 2008/0077201 entitled “COOLING DEVICES WITH FLEXIBLE SENSORS”;
U.S. Patent Publication No. 2008/0077211 entitled “COOLING DEVICE HAVING A PLURALITY OF CONTROLLABLE COOLING ELEMENTS TO PROVIDE A PREDETERMINED COOLING PROFILE”;
U.S. Patent Publication No. 2009/0118722, filed Oct. 31, 2007, entitled “METHOD AND APPARATUS FOR COOLING SUBCUTANEOUS LIPID-RICH CELLS OR TISSUE”;
U.S. Patent Publication No. 2009/0018624 entitled “LIMITING USE OF DISPOSABLE SYSTEM PATIENT PROTECTION DEVICES”;
U.S. Patent Publication No. 2009/0018623 entitled “SYSTEM FOR TREATING LIPID-RICH REGIONS”;
U.S. Patent Publication No. 2009/0018625 entitled “MANAGING SYSTEM TEMPERATURE TO REMOVE HEAT FROM LIPID-RICH REGIONS”;
U.S. Patent Publication No. 2009/0018627 entitled “SECURE SYSTEM FOR REMOVING HEAT FROM LIPID-RICH REGIONS”;
U.S. Patent Publication No. 2009/0018626 entitled “USER INTERFACES FOR A SYSTEM THAT REMOVES HEAT FROM LIPID-RICH REGIONS”;
U.S. Pat. No. 6,041,787 entitled “USE OF CRYOPROTECTIVE AGENT COMPOUNDS DURING CRYOSURGERY”;
U.S. Pat. No. 8,285,390 entitled “MONITORING THE COOLING OF SUBCUTANEOUS LIPID-RICH CELLS, SUCH AS THE COOLING OF ADIPOSE TISSUE”;
U.S. Pat. No. 8,275,442 entitled “TREATMENT PLANNING SYSTEMS AND METHODS FOR BODY CONTOURING APPLICATIONS”;
U.S. patent application Ser. No. 12/275,002 entitled “APPARATUS WITH HYDROPHILIC RESERVOIRS FOR COOLING SUBCUTANEOUS LIPID-RICH CELLS”;
U.S. patent application Ser. No. 12/275,014 entitled “APPARATUS WITH HYDROPHOBIC FILTERS FOR REMOVING HEAT FROM SUBCUTANEOUS LIPID-RICH CELLS”;
U.S. Patent Publication No. 2010/0152824 entitled “SYSTEMS AND METHODS WITH INTERRUPT/RESUME CAPABILITIES FOR COOLING SUBCUTANEOUS LIPID-RICH CELLS”;
U.S. Pat. No. 8,192,474 entitled “TISSUE TREATMENT METHODS”;
U.S. Patent Publication No. 2010/0280582 entitled “DEVICE, SYSTEM AND METHOD FOR REMOVING HEAT FROM SUBCUTANEOUS LIPID-RICH CELLS”;
U.S. Patent Publication No. 2012/0022518 entitled “COMBINED MODALITY TREATMENT SYSTEMS, METHODS AND APPARATUS FOR BODY CONTOURING APPLICATIONS”;
U.S. Publication No. 2011/0238050 entitled “HOME-USE APPLICATORS FOR NON-INVASIVELY REMOVING HEAT FROM SUBCUTANEOUS LIPID-RICH CELLS VIA PHASE CHANGE COOLANTS, AND ASSOCIATED DEVICES, SYSTEMS AND METHODS”;
U.S. Publication No. 2011/0238051 entitled “HOME-USE APPLICATORS FOR NON-INVASIVELY REMOVING HEAT FROM SUBCUTANEOUS LIPID-RICH CELLS VIA PHASE CHANGE COOLANTS, AND ASSOCIATED DEVICES, SYSTEMS AND METHODS”;
U.S. Publication No. 2012/0239123 entitled “DEVICES, APPLICATION SYSTEMS AND METHODS WITH LOCALIZED HEAT FLUX ZONES FOR REMOVING HEAT FROM SUBCUTANEOUS LIPID-RICH CELLS”;
U.S. patent application Ser. No. 13/830,413 entitled “MULTI-MODALITY TREATMENT SYSTEMS, METHODS AND APPARATUS FOR ALTERING SUBCUTANEOUS LIPID-RICH TISSUE”;
U.S. patent application Ser. No. 13/830,027 entitled “TREATMENT SYSTEMS WITH FLUID MIXING SYSTEMS AND FLUID-COOLED APPLICATORS AND METHODS OF USING THE SAME”;
U.S. patent application Ser. No. 11/528,225 entitled “COOLING DEVICE HAVING A PLURALITY OF CONTROLLABLE COOLING ELEMENTS TO PROVIDE A PREDETERMINED COOLING PROFILE;” and
U.S. Pat. No. 8,285,390 entitled “MONITORING THE COOLING OF SUBCUTANEOUS LIPID-RICH CELLS, SUCH AS THE COOLING OF ADIPOSE TISSUE.”
To the extent the foregoing commonly assigned U.S. patent applications and U.S. patents or any other material incorporated herein by reference conflicts with the present disclosure, the present disclosure controls.
Excess body fat, or adipose tissue, may be present at various locations of a subject's body and may detract from personal appearance. Excess subcutaneous fat under the chin and/or around the neck can be cosmetically unappealing and, in some instances, can produce a “double chin.” A double chin can cause stretching and/or sagging of skin and may also result in discomfort. Moreover, excess adipose tissue in superficial fat compartments can produce loose facial structures, such as loose jowls, that also cause an undesirable appearance. Excess body fat can also be located at the abdomen, thighs, buttocks, knees, and arms, as well as other locations.
Aesthetic improvement of the human body may involve the selective removal of adipose tissue. Invasive procedures (e.g., liposuction) for this purpose, however, tend to be associated with relative high costs, long recovery times, and increased risk of complications. Injection of drugs for reducing adipose tissue, such as submental or facial adipose tissue, can cause significant swelling, bruising, pain, numbness, and/or induration. Conventional non-invasive treatments for reducing adipose tissue may include regular exercise, application of topical agents, use of weight-loss drugs, dieting, or a combination of these treatments. One drawback of these non-invasive treatments is that they may not be effective or even possible under certain circumstances. For example, when a person is physically injured or ill, regular exercise may not be an option. Topical agents and orally administered weight-loss drugs are not an option if, as another example, they cause an undesirable reaction (e.g., an allergic or other negative reaction). Additionally, non-invasive treatments may be ineffective for selectively reducing specific regions of adiposity. For example, localized fat loss around the neck, jaw, cheeks, etc. often cannot be achieved using general or systemic weight-loss methods.
Furthermore, aesthetic and/or therapeutic improvement of the human body may involve treatment or alteration of non-lipid rich tissue as well as lipid rich tissue, and again conventional treatments sometimes are not suitable for many subjects and cannot effectively target certain regions of tissue necessary for an effective treatment. For at least the foregoing reasons, there is a need for innovation in this field of aesthetic and/or therapeutic improvement of the human body.
Many aspects of the present invention can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale. Instead, emphasis is placed on illustrating clearly the principles of the present invention. For ease of reference, throughout this disclosure identical reference numbers may be used to identify identical, similar, or analogous components or features of more than one embodiment of the present invention.
Overview
During a cooling treatment, it can be useful to maintain stable thermal and physical contact between an applicator and a tissue region receiving the treatment. When this thermal and physical contact is broken or altered, the tissue region or portions thereof may rewarm prematurely, thereby causing the treatment to have a diminished effect or even no effect. Additionally, the applicator oftentimes includes various sensors that depend on stable contact between the tissue region and the applicator. These sensors, for example, are used to detect conditions such as applicator temperature, tissue temperature, quality of contact between the applicator and the tissue, and tissue properties (e.g., impedance, acoustic, and optical properties, etc.). The sensor readings are sometimes used to detect freeze events which causes treatment parameters to be changed in response thereto. When physical contact between the applicator and the tissue region is disrupted for any reason, such as by patient motion, any resulting X, Y, or Z axis motion between the applicator and the tissue region can create a serious signal artifact from at least some of these sensors. This, in turn, can lead to false sensor readings and incorrect corrective action, such as under or over cooling, a premature alarm, premature cessation of treatment, incorrect freeze event detections, etc.
Conventional approaches to maintaining stable thermal and physical contact between an applicator and a subject's skin during cooling treatments include use of suction and/or restraints (e.g., straps). While effective in many cases, these conventional approaches have limitations. For example, suction is applied to a subject's skin via an air gap that reduces a skin area available for thermal and physical contact with an applicator. The area of a subject's skin in contact with an air gap is directly proportional to the strength of the suction. Thus, when significant holding strength is desirable, achieving such holding strength by suction may require a large skin area to be in contact with an air gap and, therefore, not available for thermal and physical contact with an applicator. In the context of transdermal cooling, decreasing the area of a subject's skin available for thermal and physical contact with an applicator is typically undesirable. Furthermore, strong suction may be uncomfortable during long-duration treatments. Restraints may lessen or eliminate the need for suction, but only in limited cases. For example, unlike suction, restraints are typically not well suited for pulling and holding skin and underlying tissue in contact with three-dimensional surfaces. Also, use of suction and restraints generally allows for undue relative movement between the applicator and the tissue region when the subject moves for any of a variety of reasons which, as mentioned above, can cause false sensor readings, false alarms, and ineffective treatments.
Methods for cooling tissue and related structures and systems in accordance with embodiments of the present invention can at least partially address one or more problems associated with conventional technologies as discussed above and/or other problems whether or not such problems are stated herein. Methods in accordance with at least some embodiments of the present invention include use of temperature-dependent adhesive bonding to promote stable thermal and physical contact between an applicator and a tissue region. An adhesive that causes this bonding can be applied to one or more of a subject's skin, a heat transfer surface of an applicator, and an intervening structure (e.g., a liner). Furthermore, the adhesive can be applied independently (e.g., as a viscous layer) or carried by an absorbent substrate as part of a composite structure. The subject's skin and the heat-transfer surface of the applicator can then be brought together with the adhesive therebetween. The applicator can be used to cool the tissue region via the subject's skin, via the heat-transfer surface of the applicator, via the adhesive, and via various other intervening structures or materials when present at the treatment interface.
While the tissue region is cooled, the adhesive can also be cooled. This cooling of the adhesive can significantly strengthen the adhesion between the subject's skin and the heat-transfer surface of the applicator via the adhesive, thereby reducing or eliminating relative movement between the subject's skin and the heat-transfer surface of the applicator during the treatment. By way of theory, and without wishing to be bound to such theory, both increasing the viscosity of the adhesive and increasing the tackiness of the adhesive in response to cooling may contribute to the strengthened adhesion. Furthermore, the adhesive can have a viscosity and tackiness during application low enough to conform readily to irregularities in the subject's skin, but still high enough to maintain its shape. The viscosity and tackiness during application can also be low enough to allow an applicator to be ideally placed on the skin and moved into an optimal position. At a chilled temperature during tissue cooling, the viscosity and tackiness of the adhesive can be high enough to promote stable thermal and physical contact between the heat-transfer surface of the applicator and the tissue region and to keep the applicator fixed in position relative to the skin regardless of patient motion during the treatment. Thus, relative to conventional counterparts, methods for cooling tissue and related structures and systems in accordance with at least some embodiments of the present invention have less or no need for suction, restraints, and/or other mechanisms for maintaining stable thermal and physical contact between an applicator and a tissue region.
Specific details of methods for cooling tissue and related structures and systems in accordance with several embodiments of the present invention are described herein with reference to
The term “treatment system,” as used generally herein, refers to cosmetic, therapeutic or other medical treatment systems, as well as to any treatment regimens or medical device usage. At least some treatment systems configured in accordance with embodiments of the present invention are useful for reducing or eliminating excess adipose tissue or other undesirable tissue or enhancing the appearance of skin. In many cases, the treatment systems can be used at various locations, including, for example, a subject's face, neck, abdomen, thighs, buttocks, knees, back, arms, and/or ankles. Treatment systems in accordance with at least some embodiments of the present invention are well suited for cosmetically beneficial alterations of tissue at targeted anatomical regions. Some cosmetic procedures may be for the sole purpose of altering a target region to conform to a cosmetically desirable look, feel, size, shape, and/or other desirable cosmetic characteristic or feature. Accordingly, at least some embodiments of the cosmetic procedures can be performed without providing an appreciable therapeutic effect (e.g., no therapeutic effect). For example, some cosmetic procedures may not include restoration of health, physical integrity, or the physical well-being of a subject. The cosmetic methods can target subcutaneous or dermal regions to change a subject's appearance and can include, for example, procedures performed on subject's submental region, face, neck, ankle region, or the like. In other embodiments, however, desirable treatments may have therapeutic outcomes, such as alteration of vascular malformations, treatment of glands including sebaceous and sweat glands, treatment of nerves, alteration of body hormones levels (by the reduction of adipose tissue), etc.
Reference throughout this specification to “one example,” “an example,” “one embodiment,” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the example is included in at least one example of the present invention. Thus, the occurrences of the phrases “in one example,” “in an example,” “one embodiment,” or “an embodiment” in various places throughout this specification are not necessarily all referring to the same example. Furthermore, the particular features, structures, routines, stages, or characteristics may be combined in any suitable manner in one or more examples of the invention. The headings provided herein are for convenience only and are not intended to limit or interpret the scope or meaning of the invention.
Treatment Systems
The connector 114 can include an elongate main body 126 and lines 128 (individually identified as lines 128a-128e) within the main body 126. The lines 128 can extend longitudinally between the control module 112 and the applicator 104. In the illustrated embodiment, the lines 128 include a supply fluid line 128a operably connected to the fluid system 118, a return fluid line 128b also operably connected to the fluid system 118, a power line 128c operably connected to the power supply 120, a suction line 128d operably connected to the suction system 122, and a control line 128e operably connected to the controller 124. In other embodiments, a counterpart of the connector 114 can carry other suitable lines in addition to or instead of the illustrated lines. Furthermore, the control module 112 and the applicator 104 can be configured to communicate wirelessly in addition to or instead of communicating via the connector 114.
When in use, the treatment system 102 can deliver heat-transfer fluid continuously or intermittently from the control module 112 to the applicator 104 via the supply fluid line 128a. Within the applicator 104, the heat-transfer fluid can circulate to absorb heat from the treatment site 105. The heat-transfer fluid can then flow from the applicator 104 back to the control module 112 via the return fluid line 128b. For warming periods, the control module 112 can actively heat the heat-transfer fluid such that warm heat-transfer fluid is circulated through the applicator 104. Alternatively or in addition, the heat-transfer fluid can be allowed to warm passively. In the illustrated embodiment, the applicator 104 relies on circulation of heat-transfer fluid to maintain a thermal gradient at the treatment site 105 and thereby drive cooling or heating. In other embodiments, a counterpart of the applicator 104 can include a thermoelectric element that supplements or takes the place of circulation of heat-transfer fluid to maintain this thermal gradient. The thermoelectric element can be configured for cooling (e.g., by the Peltier effect) and/or heating (e.g., by resistance). For example, in some embodiments, a counterpart of the applicator 104 can rely on circulation of heat-transfer fluid to drive cooling and a thermoelectric element to drive heating.
The control module 112 can control the suction system 122 to apply suction at the treatment site 105 via the applicator 104 and via the suction line 128d. Suction can be useful for securing a liner (not shown) to the applicator 104 and/or for drawing and holding skin 111 and underlying tissue at the treatment site 105 into contact with the applicator 104 or the applicator liner, and/or for other purposes. Suitable suction levels can be selected based on characteristics of the tissue at the treatment site 105, patient comfort, and/or the holding power of a temperature-dependent adhesive (not shown) at the treatment site 105. The power supply 120 can be configured to provide a direct current voltage for powering electrical elements (e.g., thermal and sensor devices) of the applicator 104 via the power line 128c. For example, the control module 112 can include an input/output device 130 (e.g., a touchscreen) operably connected to the controller 124. The input/output device 130 can display a state of operation of the treatment system 102 and/or a progress of a treatment protocol.
The controller 124 can be in communication with the applicator 104 and can have instructions for causing the treatment system 102 to use the applicator 104 to cool tissue at the treatment site 105. In at least some embodiments, the controller 124 exchanges data with the applicator 104 via the control line 128e, via a wireless communication link, via an optical communication link, and/or via another suitable communications link. The controller 124 can monitor and adjust a treatment based on, without limitation, one or more treatment profiles and/or patient-specific treatment plans, such as those described, in commonly assigned U.S. Pat. No. 8,275,442, which is incorporated herein by reference in its entirety. Suitable treatment profiles and patient-specific treatment plans can include one or more segments, each including a temperature profile, a vacuum level, and/or a duration (e.g., 1 minute, 5 minutes, 10 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, etc.).
The heat-transfer surface 134 can be temperature controlled, such as via the controller 124. In the illustrated embodiment, the heat-transfer surface 134 is three-dimensional. In other embodiments, the heat-transfer surface 134 can be two-dimensional. As shown in
Suction at the slot 139 can draw the tissue 135 into the cavity 132 and hold the tissue 135 within the cavity 132 with the assistance of the adhesive 136. As discussed below, the tensile adhesion and viscosity of the adhesive can increase with decreasing temperature such that the initial adhesion provided by the adhesive may be relatively weak. In other embodiments, a counterpart of the applicator 104 can be configured for use without a removable liner, and suction at the side and end suction ports 140, 142 and the slot 139 can draw the tissue 135 into the cavity 132 and hold the tissue 135 within the cavity 132. In still other embodiments, a counterpart of the applicator 104 can have other suitable suction configurations. Furthermore, counterparts of the applicator 104 can be without suction functionality, such as when drawing the tissue 135 into the cavity 132 and holding the tissue 135 within the cavity 132 is not needed. For example, a counterpart of the applicator 104 that is substantially flat or slightly curved may be placed directly on the subject's skin 111 without use of any suction and held in place with only straps and the adhesive 136 or with just the adhesive 136.
With reference again to
In the embodiment illustrated in
In some embodiments, the absorbent substrate 160 is tubular and stretchable so that it can be fitted around the subject's neck, arm, leg, torso, etc. In other embodiments, the absorbent substrate 160 can be a flat or curved pad or have other suitable forms for making optimum contact with a treatment site and yet be easy to apply and remove. The absorbent substrate 160 can include a stretchable fabric, mesh, or other porous material suitable for carrying the adhesive 136. Cotton, rayon, and polyurethane cloth are a few examples of suitable materials for use in the absorbent substrate 160. Furthermore, the absorbent substrate 160 can include a thermally conductive material that at least partially compensates for a lower thermal conductivity of the corresponding adhesive 136. Thus, in some cases, the composite structure 162 is more thermally conductive than the adhesive 136 alone. Higher thermal conductivity can be useful, for example, to facilitate detection of the thermal signature of a freeze event during a cooling procedure. When the absorbent substrate 160 include stretchable fabric, some or all of the fibers of the fabric can be made of thermally conductive material. For example, the fabric can include metal fibers, carbon fibers, and/or fibers having a thermally conductive coating. Carbon fiber fabric is available, for example, under the FLEXZORB trademark from Calgon Carbon (Pittsburgh, Pa.). These and other forms of the absorbent substrate 160 can be configured for single-use or multiple-use, and can be packaged with or without being preloaded with the adhesive 136. When the absorbent substrate 160 is preloaded with the adhesive 136, the corresponding composite structure 162 can be encased in moisture impermeable packaging (not shown) to protect the constituent adhesive 136 from the environment. Furthermore, the composite structure 162 can be packaged separately from or together with the liner 131. In a particular embodiment, the composite structure 162 is pre-positioned on the liner 131 such that the composite structure 162 and the liner 131 can simply be brought into contact with the subject's skin 111 without any need to separately position the composite structure 162. In another embodiment, the composite structure 162 is independent of the liner 131 and configured to be placed on the subject's skin 111 before establishing thermal and physical contact with the applicator 104.
In the embodiment illustrated in
In the embodiment illustrated in
Treatment Methods
When the skin 111 and the underlying tissue 135 first move into thermal and physical contact with the heat-transfer surface 134, the adhesive 136 can form a weak adhesive bond between the skin 111 and the heat-transfer surface 134. Thus, in at least some cases, the applicator 104 is readily repositionable before cooling begins. Repositioning the applicator 104 can be useful, for example, when an initial position of the applicator 104 is suboptimal. Once the applicator 104 is properly positioned and the tissue 135 and the heat-transfer surface 134 are in thermal and physical contact with one another (and in direct physical contact with one another when the liner 131 is not present), the applicator 104 can be activated to draw heat (represented by arrows 194 in
After the adhesive bond between the skin 111 and the heat-transfer surface 134 has been cryogenically strengthened, the applicator 104 may no longer be readily repositionable. In at least some cases, cooling the adhesive 136 from an application temperature to a chilled temperature in conjunction with a cooling treatment can at least increase a tensile strength of the adhesive bond between the skin 111 and the heat-transfer surface 134 by a factor of more than 1.25×, 1.5×, 2×, 3×, 4×, 5×, 6×, 7×, 10×, 20×, or 30×. For example, a force required to break adhesion between the skin 111 and the heat-transfer surface 134 in a direction normal to the heat-transfer surface 134 when the adhesion is cryogenically strengthened can be at least a factor of more than 1.25×, 1.5×, 2×, 3×, 4×, 5×, 6×, 7×, 10×, 20×, or 30× a corresponding force required to break the adhesion before the adhesion is cryogenically strengthened. Similarly, cooling the adhesive 136 from an application temperature to a chilled temperature in conjunction with the cooling treatment can at least increase a shear strength of the adhesive bond between the skin 111 and the heat transfer surface 134 by a factor of more than 1.25×, 1.5×, 2×, 3×, 4×, 5×, 6×, 7×, 10×, 20×, or 30× a shear strength of the adhesive bond between the skin 111 and the heat-transfer surface 134 before the shear strength is cryogenically strengthened. For example, a force required to break the adhesion between the skin 111 and the heat-transfer surface 134 in a direction parallel to the heat-transfer surface 134 when the adhesion is cryogenically strengthened can be at least a factor of more than 1.25×, 1.5×, 2×, 3×, 4×, 5×, 6×, 7×, 10×, 20×, or 30× such a force required to break adhesion before the adhesion is cryogenically strengthened. An increase in shear strength can be important to prevent any X, Y axis relative movement between the skin 111 and the heat transfer surface 134 during a cooling treatment.
For “cup-type” applicators (e.g., the applicator 104 shown in
In addition to using adhesives as described which exhibit a large reversible change in adhesive power and viscosity in response to a change in temperature, those skilled in the art will appreciate that any material used to form an adhesive absorbent (when used), liner (when used), heat transfer surface, and any other components that may come in contact with the adhesive should be compatible with the adhesive. For example, these other structures and materials can be selected to preferably wet to the adhesive and form strong bonds thereto at treatment temperatures. For at least one tested adhesive formation, it has been found that aluminum, cotton, rayon, and polyurethane are compatible with the formation of strong adhesive bonds. Bonding strength has been found to increase when an absorbent substrate carrying an adhesive has a surface that is at least somewhat porous.
After the adhesive bond between the skin 111 and the heat-transfer surface 134 is cryogenically strengthened, a level of suction and/or compression initially used to urge the tissue 135 into the cavity 132 may be unneeded to maintain a position of the tissue 135 within the cavity 132. Accordingly, the level of suction and/or compression can be reduced, which can be beneficial, for example, to enhance patient comfort during long-duration treatments and/or to reduce undesirable side effects of the suction and/or compression. In some cases, thermal and physical contact between the tissue 135 and the heat-transfer surface 134 occurs primarily or solely by adhesion while the tissue 135 is cooled. In other cases, maintaining thermal and physical contact between the tissue 135 and the heat-transfer surface 134 can occur primarily by suction supplemented by adhesion while the tissue 135 is cooled.
In at least some embodiments, cooling the adhesive 136 from an application temperature to a chilled temperature in conjunction with a cooling treatment increases a viscosity of the adhesive 136 by at least 1,000% (e.g., at least 10,000%) on a centipoise scale. In these and other embodiments, cooling the adhesive 136 in this manner can cause the adhesive 136 to have a viscosity within a range from 3,000,000 centipoise to a maximum viscosity of the adhesive 136 at temperatures warmer than a glass transition temperature of the adhesive 136. Cooling the adhesive 136 to colder than its glass transition temperature can weaken the adhesion between the skin 111 and the heat-transfer surface 134 via the adhesive 136. Accordingly, the adhesive 136 can be selected to have a glass transition temperature colder than a coldest temperature to which the adhesive 136 is to be cooled during a cooling treatment. For example, the adhesive 136 can be selected to have a glass transition temperature colder than −20° C., such as colder than −30° C.
According to a particular embodiment, at room temperature or another suitable application temperature, the adhesive 136 has minimal adhesive force such that the applicator 104 can be readily placed on and removed from the skin 111 and moved sideways or twisted as need be to correctly position the applicator 104. For example, the adhesive force before cooling can be insufficient to keep the applicator 104 in a precise position and fixed in that position for a significant period of time without the use of some other holding force. However, at a treatment temperature, the adhesive force is dramatically increased such that the adhesive force alone is strong enough to keep the applicator 104 in place without any other attachment force. Other attachment forces that may become unnecessary can include suction, straps, or even the support of the subject's tissue 135 with the assistance of gravity (e.g., if the subject 100 is lying down and the applicator 104 is resting on top of the subject 100). In other words, the adhesive 136 is strong enough to secure the applicator 104 in place in any orientation. So even if the subject 100 is standing and the applicator 104 is simply hanging from the subject 100, such as from the subject's abdomen or side flank, the adhesive 136 is strong enough to secure the applicator 104 and keep it in place and non-movable relative to the skin 111 at the treatment site being treated by the applicator 104. Furthermore, the adhesive 136 can be strong enough to not only hold the applicator 104 in place and keep it from moving relative a subject's skin 111 when the subject is standing and the applicator 104 is hanging from the subject, but could do so even if the subject moves, shivers, or were to jump up and down.
When the tissue 135 is in thermal and physical contact with the heat-transfer surface 134 via the skin 111 and via the adhesive 136, the method 200 can include cooling the adhesive 136 (block 206) and cooling the tissue 135 (block 208). Cooling the adhesive 136 can include cooling the adhesive 136 to a temperature no colder than a glass transition temperature of the adhesive 136, such as a temperature within a range from 1° C. warmer than the glass transition temperature of the adhesive 136 to 10° C. warmer than the glass transition temperature of the adhesive 136, e.g., to a temperature warmer by more than either of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10° C. In at least some cases, the temperature to which the adhesive 136 is cooled is within a range from either −25° C. to −1° C., −25° C. to −5° C., −20° C. to −8° C., or −18° C. to −10° C. Cooling the adhesive 136 can cryogenically strengthen an adhesive bond between the skin 111 and the heat-transfer surface 134. Cooling the tissue 135 can occur during cryogenic strengthening of the adhesive bond and/or after cryogenic strengthening of the adhesive bond. Cooling the tissue 135 can include cooling the tissue 135 via a viscous layer of the adhesive 136, via the composite structure including the absorbent substrate 160 and adhesive 136 (
While cooling the tissue 135, the method 200 can include maintaining thermal and physical contact between the tissue 135 and the heat-transfer surface 134 (block 210). The adhesive 136 can cause this thermal and physical contact to be more reliable than it would be if the adhesive 136 were not present. In at least some cases, the adhesive bond between the skin 111 and the heat-transfer surface 134 may become strong enough while cooling the tissue 135 to at least partially or totally substitute for suction and/or compression used to urge the tissue 135 into the cavity 132. In these and other cases, the method 200 can include reducing or eliminating suction and/or compression after cryogenically strengthening the adhesive bond and while cooling the tissue 135. The method 200 can further include maintaining a position of the liner 131 within the cavity 132 (block 212) while cooling the tissue 135. For example, the position of the liner 131 within the cavity 132 can be maintained at least primarily by suction and/or by another adhesive, which can but does not need to have any special properties. If rapid release of the tissue 135 from the applicator 104 is necessary while a strong adhesive bond between the skin 111 and the heat-transfer surface 134 is present via the adhesive 136, suction holding the liner 131 within the cavity 132 can be released and the tissue 135 can be removed from the cavity 132 with the liner 131 when a liner adhesive is not present. When a liner adhesive is present or when the liner 131 is not used, if rapid release of the tissue 135 from the applicator 104 is necessary, the applicator 104 can be rapidly re-warmed to warm the adhesive 136 to a temperature high enough such that the tissue 135 can be readily removed from the cavity 132.
As shown in
Cooling treatments in accordance with at least some embodiments of the present invention can be used to reduce or eliminate targeted tissue in either the skin, subcutaneous layer, or other layers, and thereby cause the tissue to have a desired appearance. For example, treatment systems in accordance with embodiments of the present invention can perform medical treatments to provide therapeutic effects and/or cosmetic procedures for cosmetically beneficial effects. Without being bound by theory, the selective effect of cooling is believed to result in, for example, membrane disruption, cell shrinkage, disabling, disrupting, damaging, destroying, removing, killing, reducing, and/or other methods of lipid-rich cell and non-lipid rich cell alteration, and alteration of other tissue, either in the skin, subcutaneous tissue, or other tissue. Such alteration is believed to stem from one or more mechanisms acting alone or in combination. It is thought that such mechanism(s) trigger an apoptotic cascade, which is believed to be the dominant form of lipid-rich cell death by non-invasive cooling. In any of these embodiments, the effect of tissue cooling can be the selective reduction of lipid-rich cells by a desired mechanism of action, such as apoptosis, lipolysis, or the like. In some procedures, an applicator 104 can cool targeted tissue of a subject to a temperature in a range of from about −25° C. to about 20° C. In other embodiments, the cooling temperatures can be from about −20° C. to about 10° C., from about −18° C. to about 5° C., from about −15° C. to about 5° C., or from about −15° C. to about 0° C. In further embodiments, the cooling temperatures can be equal to or less than −5° C., −10° C., −15° C., or in yet another embodiment, from about −15° C. to about −25° C. Other cooling temperatures and temperature ranges can be used.
Apoptosis, also referred to as “programmed cell death”, is a genetically-induced death mechanism by which cells self-destruct without incurring damage to surrounding tissues. An ordered series of biochemical events induce cells to morphologically change. These changes include cellular blebbing, loss of cell membrane asymmetry and attachment, cell shrinkage, chromatin condensation and chromosomal DNA fragmentation. Injury via an external stimulus, such as cold exposure, is one mechanism that can induce cellular apoptosis in cells, Nagle, W. A., Soloff, B. L., Moss, A. J. Jr., Henle, K. J. “Cultured Chinese Hamster Cells Undergo Apoptosis After Exposure to Cold but Nonfreezing Temperatures” Cryobiology 27, 439-451 (1990).
One aspect of apoptosis, in contrast to cellular necrosis (a traumatic form of cell death causing local inflammation), is that apoptotic cells express and display phagocytic markers on the surface of the cell membrane, thus marking the cells for phagocytosis by macrophages. As a result, phagocytes can engulf and remove the dying cells (e.g., the lipid-rich cells) without eliciting an immune response. Temperatures that elicit these apoptotic events in lipid-rich cells may contribute to long-lasting and/or permanent reduction and reshaping of subcutaneous adipose tissue.
One mechanism of apoptotic lipid-rich cell death by cooling is believed to involve localized crystallization of lipids within the adipocytes at temperatures that do not induce crystallization in non-lipid-rich cells. The crystallized lipids selectively may injure these cells, inducing apoptosis (and may also induce necrotic death if the crystallized lipids damage or rupture the bi-lipid membrane of the adipocyte). Another mechanism of injury involves the lipid phase transition of those lipids within the cell's bi-lipid membrane, which results in membrane disruption or dysfunction, thereby inducing apoptosis. This mechanism is well-documented for many cell types and may be active when adipocytes, or lipid-rich cells, are cooled, Mazur, P., “Cryobiology: the Freezing of Biological Systems” Science, 68: 939-949 (1970); Quinn, P. J., “A Lipid Phase Separation Model of Low Temperature Damage to Biological Membranes” Cryobiology, 22: 128-147 (1985); Rubinsky, B., “Principles of Low Temperature Preservation” Heart Failure Reviews, 8, 277-284 (2003).
Other possible mechanisms of adipocyte damage, described in U.S. Pat. No. 8,192,474, relate to ischemia/reperfusion injury that may occur under certain conditions when such cells are cooled as described herein. For instance, during treatment by cooling as described herein, the targeted adipose tissue may experience a restriction in blood supply and thus be starved of oxygen due to isolation as a result of applied pressure, cooling which may affect vasoconstriction in the cooled tissue, or the like. In addition to the ischemic damage caused by oxygen starvation and the buildup of metabolic waste products in the tissue during the period of restricted blood flow, restoration of blood flow after cooling treatment may additionally produce reperfusion injury to the adipocytes due to inflammation and oxidative damage that is known to occur when oxygenated blood is restored to tissue that has undergone a period of ischemia. This type of injury may be accelerated by exposing the adipocytes to an energy source (via, e.g., thermal, electrical, chemical, mechanical, acoustic, or other means) or otherwise increasing the blood flow rate in connection with or after cooling treatment as described herein. Increasing vasoconstriction in such adipose tissue by, e.g., various mechanical means (e.g., application of pressure or massage), chemical means or certain cooling conditions, as well as the local introduction of oxygen radical-forming compounds to stimulate inflammation and/or leukocyte activity in adipose tissue may also contribute to accelerating injury to such cells. Other yet-to-be understood mechanisms of injury may exist.
In addition to the apoptotic mechanisms involved in lipid-rich cell death, local cold exposure is also believed to induce lipolysis (i.e., fat metabolism) of lipid-rich cells and has been shown to enhance existing lipolysis which serves to further increase the reduction in subcutaneous lipid-rich cells, Vallerand, A. L., Zamecnik. J., Jones, P. J. H., Jacobs, I. “Cold Stress Increases Lipolysis, FFA Ra and TG/FFA Cycling in Humans” Aviation, Space and Environmental Medicine, 70, 42-50 (1999).
One expected advantage of the foregoing techniques is that the subcutaneous lipid-rich cells in the target region can be reduced generally without collateral damage to non-lipid-rich cells in the same region. In general, lipid-rich cells can be affected at low temperatures that do not affect non-lipid-rich cells. As a result, lipid-rich cells, such as those associated with highly localized adiposity (e.g., submental adiposity, submandibular adiposity, facial adiposity, etc.), can be affected while non-lipid-rich cells (e.g., myocytes) in the same generally region are not damaged. The unaffected non-lipid-rich cells can be located underneath lipid-rich cells (e.g., cells deeper than a subcutaneous layer of fat), in the dermis, in the epidermis, and/or at other locations.
In some procedures, the treatment system can remove heat from underlying tissue through the upper layers of tissue and create a thermal gradient with the coldest temperatures near the cooling surface, or surfaces, of the applicator (i.e., the temperature of the upper layer(s) of the skin can be lower than that of the targeted underlying cells). It may be challenging to reduce the temperature of the targeted cells low enough to be destructive to these target cells (e.g., induce apoptosis, cell death, etc.) while also maintaining the temperature of the upper and surface skin cells high enough so as to be protective (e.g., non-destructive). The temperature difference between these two thresholds can be small (e.g., approximately, 5° C. to about 10° C., less than 10° C., less than 15° C., etc.). Protection of the overlying cells (e.g., typically water-rich dermal and epidermal skin cells) from freeze damage during dermatological and related aesthetic procedures that involve sustained exposure to cold temperatures may include improving the freeze tolerance and/or freeze avoidance of these skin cells by using, for example, cryoprotectants for inhibiting or preventing such freeze damage. In at least some cases, the adhesive 136 acts as such a cryoprotectant. The adhesive can be used when tissue is cooled to temperatures above a freezing point of the tissue, when tissue is cooled to temperatures below a freezing point of the tissue where freezing does not occur due to supercooling, or alternatively be used in procedures where freezing of tissue is intended and caused to occur. Additional details regarding cryotherapies compatible with at least some embodiments of the present invention can be found, for example, in U.S. Patent Application Publication No. 2005/0251120, which is incorporated herein by reference in its entirety.
Adhesive Formulations
Adhesives in accordance with embodiments of the present invention (e.g., the adhesive 136 described above) can include a bonding agent that significantly increases in viscosity and tack (i.e., stickiness) when cooled. The adhesives can further include a viscosity-reducing agent mixed with the bonding agent to modify the viscosity temperature-dependence of the resulting adhesive, to modify that tack temperature-dependence of the resulting adhesive, and/or to lower the glass transition temperature of the resulting adhesive.
The relative proportions of the bonding agent and the viscosity-reducing agent in the adhesive can be selected to cause a cooling temperature range in which the adhesive significantly increases in viscosity and stickiness to correspond to a cooling temperature range of a treatment in which the adhesive is to be used. The targeted temperature range, for example, can extend from an application temperature (e.g., room temperature or body temperature) to a chilled temperature suitable for damaging or otherwise disrupting subcutaneous lipid-rich cells and/or any other targeted structures in the skin or subcutaneous layer (e.g., −20° C., −15° C., −10° C., or −5° C.). The relative proportions of the bonding agent and the viscosity-reducing agent in the adhesive can additionally or alternatively be selected based on the solubility limit of the bonding agent in the viscosity-reducing agent. For example, the concentration of the bonding agent in the adhesive can be selected to be a maximum concentration (thereby maximizing the viscosity and the tack of the adhesive) that still adequately suppresses recrystallization of the bonding agent during normal storage and use of the adhesive.
Adhesives in accordance with at least some embodiments of the present invention have a viscosity less than 500,000 centipoise (e.g., within a range from 5,000 centipoise to 500,000 centipoise) at 20° C. and a viscosity greater than 3,000,000 centipoise at −15° C. In these and other cases, the viscosities of the adhesives at −10° C. can be greater than the viscosities of the adhesives at 20° C. by at least 1,000% (e.g., by at least 3,000%, 5,000%, or 10,000%) on a centipoise scale. Furthermore, the adhesives can have a first level of tensile adhesion to human skin at 20° C. and a second level of tensile adhesion to human skin at −10° C. greater that the first level of tensile adhesion by a factor of more than 1.25×, 1.5×, 2×, 3×, 4×, 5×, 6×, 7×, 10×, 20×, or 30×. This tensile adhesion to human skin can be tested by applying a normal pulling force to a flat layer of adhesive disposed between an applicator and a skin analog.
The bonding agent can be a modified or unmodified saccharide. These compounds can be well suited for this application because they tend to become both increasingly viscous and increasingly sticky when cooled to temperatures above their glass transition temperatures. As discussed above, this behavior is desirable for enhancing adhesion between skin and an applicator during a cooling treatment that involves using the applicator to cool and thereby damage or otherwise disrupt subcutaneous lipid-rich cells and/or any other targeted structures in the skin or subcutaneous layer. The strength of the bond between the skin and the applicator may benefit from both high viscosity (e.g., for maintaining the internal integrity of the bond) and high tack (e.g., for maintaining the integrity of the bonded interface between the adhesive and the skin). Saccharides also tend to be biocompatible, nontoxic, and water soluble, with the latter being useful to facilitate cleaning. Examples of saccharides suitable for use in methods in accordance with at least some embodiments of the present invention include modified and unmodified monosaccharides (e.g., glucose and fructose) and modified and unmodified disaccharides (e.g., sucrose, maltose, and trehalose). Although experimental data for glucose, fructose, and sucrose acetate isobutyrate (SAIB) are described below, it should be understood that other modified and unmodified saccharides are also expected to be suitable for use in methods in accordance with embodiments of the present invention.
The tendency of saccharides and saccharide derivatives to become both increasingly viscous and increasingly sticky when cooled typically does not apply below their glass transition temperatures. For example, when pure SAIB, pure glucose, or pure fructose transitions to its glass state, it becomes brittle and no longer sticky. The glass transition temperatures for pure SAIB, pure glucose, and pure fructose are all at or above 0° C. Thus, these saccharides would turn to glass if used in their pure forms in cooling procedures that involve cooling to below 0° C., which is typical of cooling procedures that disrupt subcutaneous lipid-rich cells. To address this problem, the bonding agent can be mixed with a viscosity-reducing agent at a ratio that moves the glass-transition temperature of the resulting adhesive to be colder than a chilled temperature characteristic of a cooling procedure in which the adhesive is to be used. In at least some cases, the glass transition temperature of the bonding agent is modified in this manner such that the glass transition temperature of the corresponding adhesive is colder than −20° C., such as colder than −30° C. Suitable viscosity-reducing agents include glycols (e.g., propylene glycol, dipropylene glycol, and glycerol) and other polar, biocompatible oil-like compounds. These compounds tend to be good solvents of saccharides and to have relatively low glass transition temperatures.
Adhesives in accordance with at least some embodiments of the present invention contain less than 3% w/w water. For example, bonding agents, viscosity-reducing agents, and adhesives in accordance with embodiments of the present invention can be anhydrous. The presence of water as a co-solvent tends to reduce the solubility limit of viscosity-reducing agents for modified or unmodified saccharides. Thus, reducing or eliminating water from adhesives including saccharide-based bonding agents may increase the solubility limits of these adhesives for their constituent bonding agents. This, in turn, may increase the maximum viscosity and tack of the adhesives within targeted temperature ranges for cooling procedures while still adequately suppressing recrystallization of the bonding agents during normal storage and use of the adhesives. Reducing or eliminating water from adhesives including saccharide-based bonding agents also may enhance the antimicrobial properties of the adhesives. In the absence of water, saccharide-based bonding agents typically do not support the growth of bacteria and fungi. This can facilitate manufacturing and storage of adhesives including these bonding agents.
In at least some cases, it is desirable for the adhesives to be as viscous as possible. For example, in addition to having a sufficiently high chilled viscosity to adhere an applicator to a subject's skin during a cooling procedure, it may also be helpful for an adhesive to have a sufficiently high application viscosity (e.g., at room temperature and/or at body temperature) to facilitate application of the adhesive before cooling begins or before significant cooling is achieved. High application viscosity, for example, may suppress excessive dripping of the adhesive and/or squeezing of the adhesive out of an interface between an applicator and a subject's skin. Relatedly, the adhesive can include a gelling agent that enhances its ability to retain its shape upon application. Examples of suitable gelling agents include polysaccharides (e.g., agar) and proteins (e.g., gelatin). The gelling agent can be present at a relatively low concentration (e.g., less than 5% w/w) such that its presence does not unduly interfere with other desirable properties of the adhesive.
In addition to or instead of reducing or eliminating water as a co-solvent, adhesives in accordance with at least some embodiments of the present invention include bonding agents that include more than one modified or unmodified saccharide. For example, an adhesive in accordance with a particular embodiment of the present invention includes a bonding agent that is a combination of a modified or unmodified first saccharide (e.g., one of sucrose, fructose, and glucose) and a modified or unmodified second saccharide (e.g., another of sucrose, fructose, and glucose). Each of the modified or unmodified first saccharide and the modified or unmodified second saccharide can be present at a concentration relative to the overall bonding agent within a range from 5% w/w to 95% w/w. As with reducing or eliminating water, the presence of more than one modified or unmodified saccharide in the bonding agent can increase the solubility limit of the corresponding adhesive for the bonding agent. An adhesive in accordance a particular embodiment of the present invention includes a bonding agent that includes modified or unmodified fructose and modified or unmodified glucose. Other combinations of modified or unmodified saccharides are also expected to be desirable for use as bonding agents.
As discussed above in relation to the embedded thermal sensor 164 (
Adhesives in accordance with embodiments of the present invention can further include additives that enhances their thermal conductivity. For example, a given adhesive can include dispersed particles of a highly thermally conductive material, such as zinc oxide. The thermally conductive particles can be incorporated into the adhesive by sonication or a similar mixing process to avoid aggregation. Furthermore, the adhesive can include a stabilizing agent (e.g., a compatible electrostatic and/or steric stabilizing agent) that promotes even distribution of the particles throughout the adhesive. Accordingly, the adhesive can be a stable suspension at room temperature. In some cases, the particles are configured to enhance the thermal conductivity of the adhesive when in a random distribution within the adhesive. In other cases, the particles are configured to enhance the thermal conductivity of the adhesive when in an ordered distribution within the adhesive. For example, thermally conductive particles within an adhesive in accordance with a particular embodiment of the present invention are configured to be magnetically shifted in situ to increase the thermal conductivity of the adhesive. An applicator used with the adhesive can be configured to apply a magnetic field that causes the particles to form channels for preferential transmission of thermal energy between the applicator and a subject's skin. These and other thermally conductive particles in accordance with embodiments of the present invention can have an average effective diameter greater than 100 nanometers to reduce or eliminate their migration through a subject's skin during a cooling procedure.
Adhesives in accordance with embodiments of the present invention can have benefits in addition to providing adhesion between an applicator and a subject's skin during a cooling procedure. For example, the viscosity-reducing agents of some adhesives may suppress skin freezing by deactivating potential ice nucleation sites. As another example, the bonding agents of some adhesives may absorb into or even through a subject's skin and provide cryoprotection to non-targeted cells. Similarly, when a saccharide-based pretreatment is used on a subject's skin for cryoprotection, the presence of a saccharide-based bonding agent in an adhesive applied after the pretreatment may establish a concentration gradient that suppresses outgoing migration of a cryoprotective saccharide absorbed during the pretreatment. Other advantages of adhesives in accordance with embodiments of the present invention in addition to or instead of the foregoing advantages are also possible.
1.) Viscosity Dependence on Concentration (SAIB/DPG Adhesive)
Adhesives including sucrose acetate isobutyrate (SAIB) and dipropylene glycol (DPG) were prepared by mixing these two constituent materials at 60° C. Specifically, SAIB/DPG adhesives with 70, 75 and 80% v/v SAIB content were prepared and their viscosities were measured using a Brookfield viscometer. Table 1 below shows that by adding DPG to SAIB, the viscosity of the mixture can be tuned, with more DPG content leading to lower viscosity at a fixed temperature.
2.) Viscosity Dependence on Shear Rate (SAIB/DPG Adhesive)
The viscosity of adhesive including 70% v/v SAIB and 30% v/v DPG was tested using a Brookfield viscometer to determine shear-rate dependence. The results, shown in Table 2 below, indicate that the tested adhesive was shear-rate dependent, and thus could be modeled as a non-Newtonian fluid.
3.) Viscosity Dependence on Temperature (SAIB/DPG Adhesive)
The viscosity of adhesive including 70% v/v SAIB and 30% v/v DPG was tested using a Brookfield viscometer to determine temperature dependence. The results, shown in
4.) Glass Transition Temperature (SAIB/DPG Adhesive)
Glass transition was observed relative to temperature for SAIB/DPG adhesives of different SAIB concentrations. The results, shown in Table 3 below, indicate that the tested adhesive including 80% v/v SAIB and 20% v/v DPG was capable of supporting cooling treatments at temperatures as cold as −15° C., and that the tested adhesive including 70% v/v SAIB and 30% v/v DPG was capable of supporting cooling treatments at temperatures as cold as −20° C. In Table 3, Y=glassy state and N=non-glassy state.
5.) Freeze Prevention (SAIB/DPG Adhesive)
Adhesive including 70% v/v SAIB and 30% v/v DPG at −10° C. was found not to trigger an immediate, on-command skin freeze when contacted with supercooled skin at −10° C. The potential for the tested adhesive to cause freezes, therefore, was tested by cooling skin in the presence of the adhesive to −10° C. and holding the tissue at −10° C. until a freeze was detected by a thermal camera. The freezes that were detected in this manner were all initiated within the skin. This indicates that the tested adhesive likely had little if any role in initiating the freezes.
6.) Comparison to Non-Adhesive Cryoprotectant (SAIB/DPG Adhesive)
Adhesive including 70% v/v SAIB and 30% v/v DPG was compared to a non-adhesive cryoprotectant for spontaneous skin freezing temperature and thermal properties. The tested non-adhesive cryoprotectant was a mixture of 50% w/w propylene glycol, 1.5% w/w hydroxymethyl cellulose, and 48.5% w/w water. Skin to be tested was cleaned by pre-treatment skin wipes prior to application of 100 μL of either the tested adhesive or the non-adhesive cryoprotectant over the treatment sites (1 square inch). Cooling was applied using a temperature setpoint profile including an initial drop from 10° C. to −18° C., followed by a drop of 2° C. at about 2.4 minutes, a drop of 2° C. at about 3.6 minutes, a drop of 2° C. at about 4.8 minutes, and a drop of 1° C. at about 6.0 minutes, resulting in a temperature of −25° C. The tested adhesive and the non-adhesive cryoprotectant were found to correspond to mean spontaneous skin freeze temperatures of −22.79° C. and −23.26° C., respectively. The statistical test (two-tailed T-test) gave a p-value of p=0.93 using a significance level of α=0.05, indicating that the tested adhesive and the non-adhesive cryoprotectant likely correspond to the same skin spontaneous freezing temperature.
The profile of skin temperature change over time for the tested adhesive and the non-adhesive cryoprotectant were also compared. Test treatments using the tested adhesive and the non-adhesive cryoprotectant at a ramping rate of 1.55° C./second and a target temperature of −18° C. were performed. The profiles of skin temperature change over time and the time to reach the target temperature were found to be approximately the same for the tested adhesive and the non-adhesive cryoprotectant.
7.) Viscosity Dependence on Temperature (Fructose/Glycerol Adhesive)
Adhesive including 43% w/w fructose and 57% w/w glycerol was tested using a Brookfield viscometer to determine temperature dependence. The results, shown in
8.) Glass Transition Temperature (Fructose/Glycerol Adhesive)
The glass transition temperature of adhesive including 43% w/w fructose and 57% w/w glycerol was determined theoretically and experimentally. The theoretical calculation, shown below, yielded a glass transition temperature of −45.082° C.
ω1=weight fraction of 1st component (fructose)=0.571
The experimental measurement of the glass transition temperature of the adhesive was performed by Differential Scanning calorimetry (DSC) Thermal Analysis. In a DSC apparatus, the difference in heat flow to the sample and to a reference sample at the same temperature, was recorded as a function of temperature. This allows the heat effects associated with phase transitions, including glass transition, to be measured as a function of temperature. The experimental measurement yielded a glass transition temperature of −45.35° C. for the tested adhesive, which agreed well with the theoretical calculation.
9.) Tensile Adhesion (Fructose/Glycerol Adhesive)
Pieces of rayon cloth loaded with adhesive including 43% w/w fructose and 57% w/w glycerol were placed between an applicator and a pulling block. The applicator was then used to cool the adhesive-loaded cloth to a pre-determined temperature. After the adhesive-loaded cloth equilibrated at the pre-determined temperature, normal pulling force was applied using an ESM303 Motorized Force Tester (Mark-10 Corporation of Copiague, N.Y.) at a constant velocity of 0.5 in/min and with a travel distance of 0.25 in. The peak force was recorded before the detachment of the pulling block. The results, shown in Table 4 below, indicate that the peak tensile adhesion force increased from 3.4 lbF to 34.3 lbF when the temperature of the adhesive decreased from 40° C. to −22° C.
10.) Thermal Properties (Fructose/Glycerol Adhesive)
The thermal properties of pieces of fabric loaded with adhesive including 43% w/w fructose and 57% w/w glycerol were tested using a Linseis Transient Hot Bridge (THB). The THB was able to measure thermal conductivity in the range of 0.01 to 1 W/mK. A cooling chamber was used to measure temperature dependent properties at equilibrium. The density of the tested adhesive was assumed to be 1.363 g/cm3. The results of this testing are shown in
11.) Glass Transition Temperature (Glucose/Glycerol Adhesive)
A piece of paper towel loaded with adhesive including 80% v/v glucose syrup with a dextrose equivalent of 44 and 20% v/v glycerol was placed between an applicator and a 500 g weight. The applicator was then used to cool the adhesive-loaded paper towel from 10° C. to −10° C. at a cooling rate of 0.5° C./s. After the cooling and after being held at −10° C. for 3 minutes, the applicator was inverted and the weight suspended. By this test, the tensile strength of the adhesive-loaded paper towel was found to be sufficient to prevent the weight from detaching from the applicator in response to gravity.
12.) Viscosity at 21.5° C. (Fructose/Glycerol Adhesive and Fructose/Glucose/Glycerol Adhesive)
The viscosity at 21.5° C. of adhesives having three different formulations were tested using a Brookfield viscometer. The results shown in Table 5 below indicate that increasing the total saccharide concentration from 43% w/w to 55% w/w significantly increases the viscosity of the adhesive at 21.5° C. Use of two different saccharides (fructose and glucose in this case) allowed for this increase while still adequately suppressing recrystallization of the saccharides.
12.) Thermal Properties (Fructose/Glucose/Glycerol Adhesive)
The thermal conductivity at −9.2° C., 6.4° C. and 22.4° C. of adhesives having three different formulations were tested as described in Example 10 above. The results shown in Table 6 below indicate that all three of the tested adhesives had sufficient thermal conductivity to allow for freeze detection during a cooling procedure.
13.) Other Tested Adhesives
In addition to the adhesive formulations discussed above, adhesives having the following formulations were tested for temperature-dependent adhesion: (a) 43% w/w fructose and 57% w/w propylene glycol, (b) 43% w/w fructose and 57% w/w di-propylene glycol, and (c) 33% w/w glucose and 67% w/w glycerol. These adhesives were all found to have temperature-dependent adhesion similar to that of the adhesive including 43% w/w fructose and 57% w/w glycerol, as described in Example 9 above.
Various embodiments of the invention are described above. It will be appreciated that details set forth above are provided to describe the 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, however, may not be necessary to practice some embodiments. Additionally, some well-known structures or functions may not be shown or described in detail, so as to avoid unnecessarily obscuring the relevant description of the various embodiments. Although some embodiments may be within the scope of the invention, they may not be described in detail with respect to the Figures. Furthermore, features, structures, or characteristics of various embodiments may be combined in any suitable manner. Moreover, one skilled in the art will recognize that there are a number of other technologies that could be used to perform functions similar to those described above. While processes or acts are presented in a given order, alternative embodiments may perform the processes or acts in a different order, and some processes or acts may be modified, deleted, and/or moved. The headings provided herein are for convenience only and do not interpret the scope or meaning of the described invention.
Unless the context clearly requires otherwise, throughout the description, 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. Use of the word “or” in reference to a list of two or more items 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. Furthermore, the phrase “at least one of A, B, and C, etc.” is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). In those instances where a convention analogous to “at least one of A, B, or C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.).
Any patents, applications and other references, including any that may be listed in accompanying filing papers, are incorporated herein by reference. Aspects of the described invention can be modified, if necessary, to employ the systems, functions, and concepts of the various references described above to provide yet further embodiments. These and other changes can be made in light of the above Detailed Description. While the above description details certain embodiments and describes the best mode contemplated, no matter how detailed, various changes can be made. Implementation details may vary considerably, while still being encompassed by the invention disclosed herein. As noted above, particular terminology used when describing certain features or aspects of the invention should not be taken to imply that the terminology is being redefined herein to be restricted to any specific characteristics, features, or aspects of the invention with which that terminology is associated.
The present application claims the benefit of the earlier filing date of U.S. Provisional Patent Application No. 62/276,131, filed Jan. 7, 2016, which is incorporated herein by reference in its entirety.
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| Number | Date | Country | |
|---|---|---|---|
| 20170196731 A1 | Jul 2017 | US |
| Number | Date | Country | |
|---|---|---|---|
| 62276131 | Jan 2016 | US |
