Integrated cryosurgical device with thermally conductive interface for treatment of skin lesions

Abstract

The invention relates to an integrated cryosurgical device and a method of treatment that makes the application of cryogen to a targeted skin lesion on the surface of the skin for treatment more efficient through the use of a combination of a thermally conductive applicator tip, a conductive link, and an evaporative reservoir system. The combination of the thermally conductive applicator tip, the conductive link, and the evaporative reservoir system allows for the temperature of the thermally conductive applicator tip to be lower than the boiling point of a cryogen gas used with the integrated cryosurgical device when applied to a targeted skin lesion through heat of vaporization and evaporative cooling.

Description

[0001] PCT Application Attorney Docket No. 054.0020-WO00

[0002] INTEGRATED CRYOSURGICAL DEVICE WITH THERMALLY CONDUCTIVE INTERFACE FOR TREATMENT OF SKIN LESIONS

[0003] CROSS-REFERENCE TO RELATED APPLICATIONS

[0004]

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 684,589, filed on August 19, 2024; the disclosure of which is incorporated herein by reference.

[0005] TECHNICAL FIELD

[0006]

[0002] The invention relates to devices for and methods of treating the skin using extreme cold to destroy and remove unwanted topical skin lesions. More specifically, the invention relates to an integrated cryosurgical device comprising a thermally conductive interface comprising a thermally conductive applicator tip and a conductive link, and an evaporative reservoir system calibrated and balanced to the type and mass of the thermally conductive interface for optimal treatment temperature.

[0007] BACKGROUND OF THE INVENTION

[0008]

[0003] As the largest organ of the body, the skin has a number of functions; however, thermoregulation is one of the most important. The skin is composed of three major layers including the epidermis, the dermis, and subcutaneous tissue. The layers of the skin act, in part, to insulate the body against heat and water loss.

[0009]

[0004] Normally, tissue exists at a homeostatic or constant temperature. The human core temperature ranges from 97.7-99.5°F, with the surface temperature being several degrees cooler. When extreme cold is applied to the skin, any heat loss is offset for a time by the heat transfer from the surrounding tissue. When cryogen is applied for a sufficient period of time in a focused area and at a temperature exceeding the heat capacity for the tissue to return to homeostatic temperature, the tissue is frozen, and a cryosurgical effect is achieved. Namely, the cryosurgical effect is the destruction of targeted tissue using extreme cold. The precise temperature when cryosurgical destruction is achieved is debated in the literature, but, generally, it can be achieved at temperatures below -20°C, with temperatures below -50°C being most effective. The goal of the treatment is to destroy the targeted lesion where the extreme cold is applied; however, the overall effectiveness of the treatment is not only influenced by the low temperature, but also the hydration of the targeted lesion.

[0010]

[0005] Numerous types of benign lesions may be treated with cryosurgery and the peer reviewed literature is replete with many examples such as: verruca (warts), including flat, finger, vulgaris, plantar, and other PCT Application Attorney Docket No. 054.0020-WO00 superficial warts; lentigo (age spots); actinic keratoses (solar keratoses); seborrheic keratoses; achrochordon (skin tags); molluscum contagiosum; small keloids; dermatofibromas; keratocanthoma; granuloma annulare; angiomas; chondrodermatitis; epithelial nevus; porokeratosis plantaris discreta; leukoplakia; granuloma pyogenicum; and pyogenic granuloma.

[0011]

[0006] Warts are often discussed as a primary lesion treated using extreme cold or more commonly described as cryosurgery. Warts may be thickened and difficult to adequately freeze. Skin tags, in contrast, are soft and usually pedunculated. They often range in size from 2-6 mm and may or may not be pigmented. Skin tags pose no malignant threat, increase in number with age, and often appear where clothing rubs the skin. Being benign, they may simply be left alone; however, they are often removed for cosmetic reasons or because of irritation. The occurrence of skin tags in the general population is much higher than for warts, above 50 %. Several homeopathic treatments are available on the internet. However, when one reads the online reviews of these products and their poor performance, it is evident that they are not controlled nor effective. Cryosurgical treatments, however, have been shown to be 100 % effective when treating skin tags.

[0012]

[0007] Cryosurgical treatment of skin lesions is a well-established medical practice that utilizes controlled freezing to destroy unwanted tissue through precise thermal manipulation. The fundamental principle involves rapidly extracting heat from targeted lesions until cellular destruction occurs. When a cryogenic applicator is applied to skin tissue, heat flows from the warmer biological tissue (typically 32-37°C) to the colder applicator surface. The rate and extent of heat transfer depend on several factors:

[0013] • Temperature differential: Greater temperature differences accelerate heat extraction

[0014] • Thermal conductivity: Both of the applicator material and tissue characteristics

[0015] • Contact area and pressure: Affecting the thermal interface efficiency

[0016] • Duration of application: Determining depth and extent of thermal penetration

[0017]

[0008] Effective cryosurgical destruction occurs through multiple biological mechanisms when tissue temperatures drop below critical thresholds. Primary freezing effects (0°C to -10°C) involve initial ice crystal formation beginning in extracellular spaces, cellular dehydration as water migrates to form ice crystals, and osmotic stress on cellular membranes. Critical destruction temperature (-20°C and below) involves intracellular ice crystal formation causing membrane rupture, protein denaturation and enzyme inactivation, microvascular damage leading to ischemia and thrombosis, and direct mechanical damage from ice crystal expansion. Maximum destruction treatment temperature (-40°C to -50°C) involves complete cellular destruction with minimal recovery potential, extensive tissue necrosis ensuring permanent lesion removal, and reduced risk of incomplete treatment requiring retreatment. PCT Application Attorney Docket No. 054.0020-WO00

[0018]

[0009] Cryosurgical treatment initiates a predictable sequence of biological responses. Immediate phase (0-24 hours) involves tissue appearing white and frozen during application, gradual return to normal color as thawing occurs, initial inflammatory response with mild erythema and swelling, and possible blister formation, particularly with aggressive treatment. Inflammatory phase (1-7 days) involves progressive tissue necrosis becoming evident, formation of eschar (scab) over treated area, surrounding tissue may show mild irritation, and the lesion begins to darken and desiccate. Healing phase (1-3 weeks) involves natural sloughing of necrotic tissue, eschar separation revealing healthy underlying skin, progressive re- epithelialization from wound margins, gradual restoration of normal skin appearance. Resolution phase (2-6 weeks) involves complete healing typically achieved within 2-4 weeks for superficial lesions, deeper lesions may require 4-6 weeks for complete resolution, minimal scarring when properly performed, and potential temporary hypopigmentation that usually resolves over months.

[0019]

[0010] The success of cryosurgical treatment depends critically on achieving and maintaining adequate temperature for sufficient duration. Under treatment, such as insufficient time or temperature, may result in incomplete lesion destruction and recurrence. Over treatment, such as excessive temperature or duration, may cause unnecessary damage to surrounding healthy tissue and increased scarring. Optimal treatment requires precise temperature control and timing for complete lesion destruction with minimal collateral damage.

[0020]

[0011] Traditional devices typically use foam or cotton applicators that hold cryogen directly adjacent to the skin but are rapidly depleted of cryogen as heat transfers from the skin. Another important consideration in cryosurgical treatment is the method of cryogen delivery. When the cryogen is applied directly to the tissue, the minimum achievable temperature is inherently limited to the boiling point of the chosen cryogen. Consequently, the ability to achieve lower treatment temperatures— which can be crucial for the effective destruction of certain lesions— relies on the use of cryogens with lower boiling points. However, attaining these colder temperatures often necessitates the use of higher-pressure cryogen containers, as higher pressures enable the storage and delivery of cryogens that boil at lower temperatures. This approach introduces practical limitations, since the pressures required frequently exceed the safety ratings and regulatory limits of more affordable, Department of Transportation (DOT) approved containers. Therefore, while direct application methods offer simplicity, their temperature constraints and the associated equipment requirements must be weighed carefully when considering clinical and commercial viability. These conventional applicators, while of limited effectiveness, lack precise temperature control and provide limited thermal consistency throughout the treatment period, making it difficult for operators to ensure optimal treatment parameters. PCT Application Attorney Docket No. 054.0020-WO00

[0012] The use of metallic interfaces in cryosurgical applications has been explored in various forms, each with distinct limitations. U.S. Patent 4,022,215A to Gage (1977) disclosed one of the earliest cryosurgical systems incorporating metal components, describing a probe with "a resilient mass of porous material such as copper mesh positioned adjacent one end of the stem." The patent specified that semi-rigid rods or tubes could be "formed from a heat conductive malleable material such as copper or aluminum" to provide structural support and enhanced heat transfer. However, this design relied on membrane- enclosed copper mesh rather than a direct metal interface with the skin. The prior art evolved to include more sophisticated metal tip designs. U.S. Patent WO1992004872A1 described cryosurgical instruments with probe tips featuring "an outer hollow shell or casing, preferably of stainless steel or copper" designed for insertion into tissue. The patent noted that "the region downstream from the JT valve may be constructed from a metal with good thermal conductivity, such as gold plated copper," demonstrating recognition of metal's superior thermal properties. U.S. Patent 3,827,436A (Stumpf et al., 1974) disclosed a "multipurpose cryosurgical probe having a refrigerated tip with a plurality of surfaces" made of "heat conductive material," allowing for treatment of different bodily tissues with various geometrical configurations. This demonstrated early recognition that metal tips could be shaped for specific applications. U.S. Patent Application 20030024250A1 describes a cryoprobe system utilizing "a monolithic, insulated, hand-held thermal mass having an exposed tip for cryosurgical applications" that interfaces with a heat extraction base employing thermoelectric devices and copper application tips. These systems require complex charging stations and are cost-prohibitive for many applications.

[0021]

[0013] Several commercial products have successfully implemented metal tip technology. Compound W Advanced Freeze Off is a widely available consumer product that utilizes a nickel-plated metal tip that achieves cooling through direct cryogen application. However, laboratory testing referenced in this application demonstrates that the device does not achieve temperatures below the boiling point of its cryogen (dimethyl ether, -24°C), indicating limited utilization of heat of vaporization principles.

[0022]

[0014] The CryoPen Cryosurgical System, disclosed in U.S. Patents 6,430,956 and 6,629,417, represents a significant advancement using "a monolithic, insulated, hand-held thermal mass having an exposed tip" that is cooled through interfacing with a heat exchange system. However, this approach to cooling introduces significant drawbacks for consumer-oriented, over-the-counter use. The systems required to provide such precise and sustained temperature control— namely, complex refrigeration units or sizable thermal mass devices— are inherently bulky and costly. These attributes make them impractical for home or personal use, restricting their suitability primarily to physician offices or high-volume clinical environments, where the investment and operational complexity can be justified by frequent, professional PCT Application Attorney Docket No. 054.0020-WO00 application. The CryoPen achieves extremely low temperatures (-105°C) using Stirling Cryocooler technology with linear compression cooling. However, the system is noted to have "limited cooling capacity due to the cooling being solely provided by the thermal mass acting as a heat sink," requiring a separate charging base and limiting portability.

[0023]

[0015] Despite these advances, existing metal tip cryosurgical devices suffer from several limitations. Metal tips generally provide excellent thermal conductivity; however, the degree of conductivity largely depends on the specific metal utilized. Once heat is extracted from the metal tip, it must be continuously replenished, or the device becomes ineffective. Existing solutions require either: complex refrigeration systems, external charging bases, or direct cryogen circulation through hollow metal structures. Current metal tip devices provide no visual indication of when optimal treatment temperature is achieved, whether adequate cryogen has been dispensed, risk of over-treatment or under-treatment, or treatment completion status. Existing systems rely heavily on operator experience and training to determine proper usage timing, leading to inconsistent treatment outcomes and potential safety issues. Advanced metal tip systems like the CryoPen require expensive infrastructure and maintenance, limiting accessibility for many healthcare providers and consumers.

[0024]

[0016] The prior art demonstrates that while metal tips offer superior thermal properties for cryosurgical applications, existing solutions fail to address the fundamental challenges of maintaining adequate cooling without complex infrastructure, providing real-time visual feedback for optimal treatment, ensuring consistent treatment outcomes across different operators, and balancing effectiveness with cost and simplicity for over-the-counter products. Current absorbent applicators, because of the constraint of a small treatment contact area, are limited to the chosen cryogen's boiling point. Current metal tip designs use thermal conductivity (and thermal storage) to transfer low temperatures to treatment. This still requires high pressures for low boiling points or complex Stirling or Thermo Electric Cooling (TEC) systems. Other existing cryo-treatment devices use applicators that contact the skin composed of cellulose, sponge, and foam materials. However, when used as applicators they hold cryogen directly adjacent to the skin but will rapidly be depleted of cryogen as heat transfers from the skin. These limitations create a significant need for an integrated solution that uses the thermal advantages of metal tips. Additionally, intelligent feedback systems and simplified cryogen management provide an improvement over the state of the art.

[0025] SUMMARY OF THE INVENTION

[0026]

[0017] The invention relates to an integrated cryosurgical device comprising a thermally conductive interface, which comprises a thermally conductive applicator tip and a conductive link. The thermally PCT Application

[0027] Attorney Docket No. 054.0020-WO00 conductive applicator tip is designed to interface directly with a targeted skin lesion and provide controlled and sustained heat transfer. The integrated cryosurgical device further comprises a holder and an evaporative reservoir system which contains a large evaporative area and is in thermal communication with the thermally conductive applicator tip via the conductive link. In some embodiments of the invention, the thermally conductive interface comprising the thermally conductive applicator tip and the conductive link can be attached to and detached from the holder of the integrated cryosurgical device. In some embodiments of the invention, the evaporative reservoir system can be applied to and removed from an outer portion of the conductive link of the thermally conductive interface. In some embodiments of the invention, the holder further comprises a plurality of fins. In some embodiments of the invention, the evaporative reservoir system surrounds at least a portion of the conductive link of the thermally conductive interface which is attached to the thermally conductive applicator tip of the thermally conductive interface. The evaporative reservoir system maintains the thermally conductive applicator tip at treatment temperatures below the boiling point of the cryogen being used for treatment through controlled evaporation and heat of vaporization principles via the conductive link. In some embodiments of the invention, the treatment temperature is below -20°C.

[0028]

[0018] The invention uniquely combines two physical phenomena. First is heat of vaporization cooling. Because of heat of vaporization, cryogen will produce temperatures well below their boiling points as long as evaporation is encouraged. Second, if a thermally conductive member, such as the conductive link of the thermally conductive interface of the integrated cryosurgical device, is placed between the limited treatment contact area, the thermally conductive applicator tip, and a sufficiently sized evaporative cooling area, the evaporative reservoir system, a treatment temperature below the cryogen's boiling point can be maintained. The invention allows cryogen to produce heat of vaporization temperatures below the boiling point of the cryogen being used, and then conduct that heat to a smaller treatment area. The invention balances the heat gain through the small treatment area with a larger evaporative area in the evaporative reservoir system which allows the integrated cryosurgical device to maintain temperatures below the boiling point of the cryogen.

[0029]

[0019] In some embodiments of the invention, the integrated cryosurgical device further comprises at least one integrated thermochromic indicator zone comprising at least one thermochromic material. The at least one integrated thermochromic indicator zones are strategically positioned throughout the integrated cryosurgical device to provide visual feedback to a user regarding: device readiness for treatment; optimal treatment temperature achievement; over-dispensation or excess cryogen warnings; and treatment completion. Different thermochromic indicator zones provide staged visual cues throughout the treatment PCT Application Attorney Docket No. 054.0020-WO00 process. The integrated visual guidance of the thermochromic indicator zones eliminates guesswork in cryogen dispensation amount and skin lesion treatment timing.

[0030]

[0020] The invention utilizes the superior thermal conductivity of metal while addressing its limitation of finite heat capacity through an innovative evaporative reservoir system design. In some embodiments of the invention, this innovative evaporative reservoir system design is combined with thermochromic materials that guide optimal usage. The invention leverages controlled cryogen evaporation to achieve treatment temperatures below the boiling point of the cryogen. Unlike other metal tip devices, the invention utilizes a proprietary absorbent evaporative reservoir system, the structure and capacity of which are calibrated and balanced to the type and mass of the thermally conductive applicator tip, maximizing thermal transfer and enabling reliably lower treatment temperatures for the appropriate amount of time for treatment. The thermally conductive applicator tip can have various tip shapes and be comprised of various materials in order to optimize heat transfer for different skin lesion types.

[0031]

[0021] The integrated cryosurgical device of the invention leverages controlled cryogen evaporation to achieve temperatures below the cryogen's boiling point. Unlike other metal tip devices that employ simple absorbent materials and fail to reach comparably low temperatures over similar periods of time, the integrated cryosurgical device of the invention utilizes a foam evaporative reservoir system. The foam evaporative reservoir structure and capacity are calibrated and balanced to the type and mass of the chosen thermally conductive applicator tip to maximize thermal transfer thereby enabling reliably lower treatment temperatures over longer periods of time. This integrated cryosurgical device with a thermally conductive interface comprising a thermally conductive applicator tip represents a significant advancement in topical skin lesion treatment technology. Additionally, by combining the thermal advantages of thermally conductive applicator tips with intelligent visual feedback systems like thermochromic indicator zones, the device addresses further key limitations of existing technology while improving safety, efficacy, and ease of use. The integration of multiple thermochromic indicator zones provides comprehensive guidance throughout the treatment process, from initial cooling to optimal temperature achievement to completion confirmation. This innovation reduces operator dependency on experience and judgment while enhancing treatment consistency and outcomes.

[0032]

[0022] The invention further relates to an integrated cryosurgical device for treating skin lesions comprising a holder, a thermally conductive interface, and an evaporative reservoir system. The thermally conductive interface comprises a conductive link and a thermally conductive applicator tip configured to contact a targeted skin lesion. The evaporative reservoir system is in thermal communication with the thermally conductive applicator tip via the conductive link, wherein the evaporative reservoir system comprises an PCT Application

[0033] Attorney Docket No. 054.0020-WO00 evaporative area sized to maintain a heat of vaporization temperature of the thermally conductive applicator tip below the boiling point of cryogen. In some embodiments of the invention, the integrated cryosurgical device further comprises at least one thermochromic indicator zone disposed on a visible portion of the integrated cryosurgical device. The at least one thermochromic indicator zone comprises at least one thermochromic material and visibly changes color when the thermally conductive applicator tip reaches a predetermined treatment temperature. In some embodiments of the invention, the integrated cryosurgical device further comprises a container of cryogen gas. In some embodiments of the invention, the holder further comprises a plurality of fins.

[0034]

[0023] The invention further relates to a method for treating skin lesion comprising: providing an integrated cryosurgical device of the invention, dispensing cryogen gas into the evaporative reservoir system, applying the thermally conductive applicator tip to a targeted skin lesion, contacting the targeted skin lesion with the thermally conductive applicator tip when the thermally conductive applicator tip reaches an optimal treatment temperature that is lower than the boiling point of the cryogen gas, and removing the thermally conductive applicator tip from the targeted skin lesion after a period of time.

[0035]

[0024] The invention further relates to a kit comprising an integrated cryosurgical device of the invention. In some embodiments of the invention, the integrated cryosurgical device is partially or fully assembled in the kit. In some embodiments of the invention, the integrated cryosurgical device is disassembled in the kit.

[0036] BRIEF DESCRIPTION OF THE FIGURES

[0037]

[0025] FIG. 1 shows an integrated cryosurgical device comprising an evaporative reservoir system, a thermally conductive applicator tip, a conductive link, a plurality of fins, and a container of cryogen in accordance with the invention.

[0038]

[0026] FIG. 2 shows a cross-sectional view of an integrated cryosurgical device comprising a container of cryogen, an evaporative reservoir system, a plurality of fins, a conductive link, and a thermally conductive applicator tip in accordance with the invention.

[0039]

[0027] FIG. 3A shows a diagram of how a user holds an integrated cryosurgical device in accordance with the invention.

[0040]

[0028] FIGS. 3B and 3C show a diagram of how a user dispenses cryogen using an integrated cryosurgical device in accordance with the invention.

[0041]

[0029] FIG. 4 shows an integrated cryosurgical device comprising a thermally conductive applicator tip and an evaporative reservoir system for remote application of cryogen to a targeted skin lesion in accordance with the invention. PCT Application Attorney Docket No. 054.0020-WO00

[0030] FIG. 5A shows the integrated cryosurgical device of FIG. 4 inserted into a container of cryogen during dispensation of the cryogen in accordance with the invention.

[0042]

[0031] FIG. 5B shows a cross-sectional view of the integrated cryosurgical device of FIG. 4 inserted into a container of cryogen, which represents two different sizes of possible containers of cryogen, during dispensation of the cryogen in accordance with the invention.

[0043]

[0032] FIG. 6 shows an integrated cryosurgical device comprising a container of cryogen, a thermally conductive applicator tip, an evaporative reservoir system, a plurality of fins, and a skin lesion targeting adapter in accordance with the invention.

[0044]

[0033] FIG. 7 shows a conductive link connected to a thermally conductive applicator tip comprising at least one large facet and at least one small facet in accordance with the invention.

[0045]

[0034] FIG. 8 shows a temperature comparison of an integrated cryosurgical device of the invention versus a commercially available product over a period of time.

[0046] DETAILED DESCRIPTION OF THE INVENTION

[0047]

[0035] The invention relates to the use of a thermally conductive interface comprising a conductive link and a thermally conductive applicator tip, wherein the thermally conductive applicator tip interfaces with the skin during a cryo-treatment with the purpose of destroying a targeted skin lesion. In some embodiments of the invention, the thermally conductive applicator tip is ceramic. In some embodiments of the invention, the thermally conductive applicator tip is metallic. Metal has a controlled rate of heat transfer and is predictable when applied to a defined heat source. The disadvantage of metal is that it is a limited source of heat and must have a method to maintain its low temperature. The invention provides an integrated cryosurgical device to continuously and effectively treat a targeted skin lesion using a cryogen source, including an evaporative reservoir system to hold the cryogen and cool the thermally conductive applicator tip, and a thermally conductive applicator tip that can be applied to the surface of the skin and effectively transfer heat from the skin effecting the freeze. The thermally conductive applicator tip is continuously cooled by the adjacent evaporative reservoir system which contains cryogen. The thermally conductive applicator tip is in thermal communication with the evaporative reservoir system via the conductive link. The invention also provides a method capable of sufficiently conducting heat from the targeted skin lesion for the period of time necessary to facilitate the targeted destruction of the skin lesion. The primary mechanism of the invention is the use of heat of vaporization to allow contact temperatures below the boiling point of the cryogen being used. When a cryogen directly contacts the skin (heat source), the heat from the skin brings the temperature of the cryogen to its boiling point. If cryogen is allowed to PCT Application Attorney Docket No. 054.0020-WQ00 freely evaporate, its temperature will drop below its boiling point due to heat of vaporization. The thermally conductive applicator tip, which is in thermal communication with the cryogen evaporative area via the conductive link, takes advantage of heat of vaporization to produce a treatment temperature below the boiling point of the cryogen being used. Lower temperatures provide better treatment outcomes. The thermally conductive applicator tip transfers heat of the treatment site. The heat conducts through the conductive link from the thermally conductive applicator tip and into the absorbent evaporative reservoir system. The cryogen in the absorbent evaporative reservoir system evaporates, dropping the temperature below the cryogen's normal boiling point. The thermally conductive applicator tip maintains its ability to draw heat due to the evaporative reservoir system over a sufficient amount of time to destroy the targeted tissue.

[0048]

[0036] The invention relates to an integrated cryosurgical device for treating skin lesions comprising a thermally conductive interface comprising a conductive link and a thermally conductive applicator tip utilizing cryogen to treat topical skin lesions by way of freezing. The integrated cryosurgical device further comprises a holder and an evaporative reservoir system which comprises an evaporative area. The thermally conductive applicator tip contacts a targeted skin lesion for treatment when the integrated cryosurgical device is in use. The thermally conductive applicator tip is in thermal communication with the evaporative reservoir system via the conductive link. In some embodiments of the invention, the evaporative reservoir system surrounds at least a portion of the conductive link. In some embodiments of the invention, the thermally conductive applicator tip, the conductive link, and the evaporative reservoir system are connected in series. The thermally conductive interface comprising the thermally conductive applicator tip and the conductive link can be attached to and detached from the holder. In some embodiments of the invention, the evaporative reservoir system can be applied to and removed from an outer portion of the conductive link of the thermally conductive interface. The thermally conductive applicator tip and the conductive link are integrated together as a single piece forming the thermally conductive interface of the integrated cryosurgical device. The holder is a portion of the integrated cryosurgical device that can be held by a user in order to apply the thermally conductive applicator tip to the targeted skin lesion without the user coming into contact with the thermally conductive applicator tip, the evaporative reservoir system, the conductive link, or cryogen gas. In some embodiments of the invention, the holder further comprises a plurality of fins that surround the cryogen reservoir system. In some embodiments of the invention, the integrated cryosurgical device is connected to a source of cryogen. In some embodiments of the invention, the source of cryogen is a container of cryogen. In some embodiments of the invention, the integrated cryosurgical device is configured to receive the source of PCT Application Attorney Docket No. 054.0020-WO00 cryogen and dispense the cryogen to the evaporative reservoir system. In some embodiments of the invention, the integrated cryosurgical device comprises a first evaporative reservoir system and a second evaporative reservoir system. The first evaporative reservoir system and the second evaporative reservoir system each surround at least a portion of the conductive link increasing the evaporative area of the integrated cryosurgical device.

[0049]

[0037] The invention utilizes heat of vaporization through the combination of the thermally conductive interface comprising the thermally conductive applicator tip and the conductive link, and the evaporative reservoir system. The heat of vaporization allows the thermally conductive applicator tip to reach a temperature that is below the boiling point of a cryogen gas that is being used with the device. When cryogen directly contacts the skin which acts as a heat source, the heat from the skin brings the temperature of the cryogen to its boiling point. If the cryogen is allowed to freely evaporate, then the temperature of the cryogen will drop below its boiling point due to heat of vaporization. The invention of an integrated cryosurgical device comprising a thermally conductive applicator tip in thermal communication via a conductive link with an evaporative reservoir system comprising an evaporative area utilizes the heat of vaporization to produce a treatment temperature of the thermally conductive applicator tip below the boiling point of the cryogen being used. Lower treatment temperatures provide for better treatment outcomes. The thermally conductive applicator tip transfers heat from the skin at the treatment site into the integrated cryosurgical device. The heat conducts from the thermally conductive applicator tip through the conductive link and into the evaporative reservoir system. The cryogen will then evaporate from the evaporative reservoir system, dropping the temperature of the thermally conductive applicator tip to below the boiling point of the cryogen.

[0050]

[0038] The thermally conductive applicator tip of the thermally conductive interface comprises materials selected for optimal thermal conductivity. In some embodiments of the invention, the thermally conductive applicator tip is ceramic. In some embodiments of the invention, the thermally conductive applicator tip is metallic. In some embodiments of the invention, the thermally conductive applicator tip is made of copper which is an excellent thermal conductor. In some embodiments of the invention, the thermally conductive applicator tip is made of aluminum which provides good thermal conductivity with a lighter weight. In some embodiments of the invention, the thermally conductive applicator tip is made of stainless steel which is a biocompatible material with adequate thermal conductivity. In some embodiments of the invention, the thermally conductive applicator tip is made of gold. In some embodiments of the invention, the thermally conductive applicator tip is made of silver. In some embodiments of the invention, the thermally conductive applicator tip is made of nickel. In some PCT Application Attorney Docket No. 054.0020-WO00 embodiments of the invention, the thermally conductive applicator tip is made of a thermally conductive polymer, including liquid crystal polymers. In some embodiments of the invention, the thermally conductive applicator tip is made of a mixture of two or more of copper, aluminum, stainless streel, ceramic, gold, nickel, or a thermally conductive polymer. In some embodiments of the invention, the thermally conductive applicator tip is sterilizable.

[0051]

[0039] The conductive link of the thermally conductive interface also comprises materials selected for optimal thermal conductivity. The conductive link must have sufficient thermal conductivity to match the treatment heat flux (i.e., the heat flux from the skin at the treatment site). In some embodiments of the invention, the conductive link is ceramic. In some embodiments of the invention, the conductive link is metallic. In some embodiments of the invention, the conductive link is made of copper. In some embodiments of the invention, the conductive link is made of aluminum. In some embodiments of the invention, the conductive link is made of stainless steel. In some embodiments of the invention, the conductive link is made of gold. In some embodiments of the invention, the conductive link is made of silver. In some embodiments of the invention, the conductive link is made of nickel. In some embodiments of the invention, the conductive link is made of a thermally conductive polymer, including liquid crystal polymers. In some embodiments of the invention, the conductive link is made of a mixture of two or more of copper, aluminum, stainless streel, ceramic, gold, nickel, or a thermally conductive polymer. In some embodiments of the invention, the conductive link is sterilizable. In some embodiments of the invention, the conductive link and the thermally conductive applicator tip are made of the same material. In some embodiments of the invention, the conductive link and the thermally conductive applicator tip are made of different materials.

[0052]

[0040] The mass of the thermally conductive applicator tip of the thermally conductive interface also has an effect on the thermal conductivity of the applicator tip. A larger thermally conductive applicator tip will require more thermal transfer and therefore affect the size of the cryogen evaporation area. In a preferred embodiment, the thermally conductive applicator tip is hollow to decrease the mass of the thermally conductive applicator tip. The thickness of the material that comprises the thermally conductive applicator tip has a direct effect on the evaporation rate of the cryogen from the evaporative reservoir system. If the thermally conductive applicator tip is too thin, then the heat from the skin at the treatment site cannot properly transfer from the thermally conductive applicator tip to the evaporative reservoir system via the conductive link. In this case, the heat flux for the heat of vaporization will only come from environmental factors (e.g., ambient air) rather than both environmental factors and the skin at the treatment site, resulting in only the boiling point of the cryogen being reached. The thermally conductive applicator tip PCT Application Attorney Docket No. 054.0020-WO00 must be made of thick enough material for the heat from the skin at a treatment site to be transferred to the evaporative reservoir system via the conductive link for evaporation of the cryogen in order to bring the temperature of the thermally conductive applicator tip to an optimal treatment temperature that is below the boiling point of the cryogen. In some embodiments of the invention, the thermally conductive applicator tip is made of a material that is between 0.1 mm to 1 mm thick. In some embodiments of the invention, the thermally conductive applicator tip is made of material that is 0.35 mm thick.

[0053]

[0041] The mass of the conductive link of the thermally conductive interface also has an effect on the thermal conductivity of the applicator tip. A larger conductive link will require more thermal transfer and therefore affect the size of the cryogen evaporation area. In a preferred embodiment, the conductive link is hollow to decrease the mass of the conductive link. The thickness of the material that comprises the conductive link has a direct effect on the evaporation rate of the cryogen from the evaporative reservoir system. If the conductive link is too thin, then the heat from the skin at the treatment site cannot properly transfer from the thermally conductive applicator tip to the evaporative reservoir system via the conductive link. In this case, the heat flux for the heat of vaporization will only come from environmental factors (e.g., ambient air) rather than both environmental factors and the skin at the treatment site, resulting in only the boiling point of the cryogen being reached. The conductive link must be made of thick enough material for the heat from the skin at a treatment site to be transferred to the evaporative reservoir system from the thermally conductive applicator tip for evaporation of the cryogen in order to bring the temperature of the thermally conductive applicator tip to an optimal treatment temperature that is below the boiling point of the cryogen. In some embodiments of the invention, the conductive link is made of a material that is between 0.1 mm to 1 mm thick. In some embodiments of the invention, the conductive link is made of material that is 0.35 mm thick.

[0054]

[0042] In some embodiments of the invention, the thermally conductive applicator tip comprises multiple surface geometries, such as a flat surface, a curved surface, a faceted surface, or a combination thereof. In some embodiments of the invention, the surface geometry of the thermally conductive applicator tip is dependent on the type of skin lesion to be treated. In some embodiments of the invention, the thermally conductive applicator tip comprises multiple surface geometries of different sizes, such as a combination of large and small facets. In some embodiments of the invention, the thermally conductive applicator tip is hollow. In some embodiments of the invention, the thermally conductive applicator tip comprises a concaved surface for treatment of a raised skin lesion. In some embodiments of the invention, the thermally conductive applicator tip comprises a narrow point. PCT Application

[0055] Attorney Docket No. 054.0020-WO00

[0056]

[0043] The thermally conductive applicator tip can vary in size for precise targeting of the skin lesion. In some embodiments of the invention, the thermally conductive applicator tip has a diameter in the range of 1-15 mm. In some embodiments of the invention, the thermally conductive applicator tip has a diameter in the range of 1-12 mm. In some embodiment of the invention, the thermally conductive applicator tip has a diameter in the range of 2-8 mm. The size and surface geometry of the thermally conductive applicator tip is selected based on the size, shape, and type of skin lesion to be treated.

[0057]

[0044] In some embodiments of the invention, the thermally conductive interface comprising the conductive link and the thermally conductive applicator tip attaches to the holder of the integrated cryosurgical device in a way that makes it easy to be interchanged during procedures. In some embodiments of the invention, the thermally conductive interface comprises a threaded attachment to attach to the holder of the integrated cryosurgical device. In some embodiments of the invention, the thermally conductive interface comprises a snap-fit attachment to attach to the holder of the integrated cryosurgical device. In some embodiments of the invention, the evaporative reservoir system surrounds at least a portion of the conductive link and may be in contact with the holder. In some embodiments of the invention, the plurality of fins of the holder is in contact with and surround the evaporative reservoir system. The evaporative reservoir system is held in place on at least a portion of the conductive link by the elasticity of the material of the evaporative reservoir system.

[0058]

[0045] In some embodiments of the invention, the evaporative reservoir system is an absorbent reservoir which is in thermal communication with the thermally conductive applicator tip via the conductive link. The evaporative reservoir system covers at least a portion of the conductive link and is held in place by the elasticity of the material of the evaporative reservoir system. The evaporative reservoir system is made of an absorbent material that protects the conductive link from ambient heat. In some embodiments of the invention, the adsorbent material is foam, cellulose, synthetic, or a combination thereof.

[0059]

[0046] In some embodiments of the invention, the evaporative reservoir system comprises an evaporative area. In some embodiments of the invention, cryogen is dispensed from a container of cryogen into the evaporative reservoir system. The cryogen then evaporates with controlled timing via the evaporative area of the evaporative reservoir system. The evaporative area is sized so that the evaporation rate of the cryogen from the evaporative reservoir system provides a heat flux that is equal to the treatment heat flux (i.e., heat flux from the skin) plus the environmental heat flux (i.e., heat flux from ambient air and the user of the device). The integrated cryosurgical device of the invention maintains a treatment temperature at the thermally conductive applicator tip below the boiling point of the cryogen being used through heat of vaporization and evaporative cooling. The integrated cryosurgical device minimizes heat flowing to the PCT Application Attorney Docket No. 054.0020-WO00 evaporative reservoir system from sources other than the thermally conductive applicator tip which is in contact with the skin. In some embodiments of the invention the evaporative reservoir system is made of a material that is between 0.25 mm to 2.5 mm thick. In some embodiments of the invention, the evaporative reservoir system is made of a material that is 1.5 mm thick.

[0060]

[0047] In some embodiments of the invention, at least a portion of the conductive link, which is attached to the thermally conductive applicator tip, is wrapped in the absorbent evaporative reservoir system. Cryogen is dispensed directly to the absorbent evaporative reservoir system wrapped around the conductive link. Evaporative cooling maintains the thermally conductive applicator tip temperature. The controlled exposure of the cryogen to the conductive link manages the duration of treatment of the targeted skin lesion.

[0061]

[0048] In some embodiments of the invention, the integrated cryosurgical device is a mobile device configured to be used for remote application of cryogen to a targeted skin lesion. This embodiment of the integrated cryosurgical device is used in conjunction with an external container of cryogen that is in thermal communication with a receptacle located on the top of the container of cryogen. The receptacle is configured to receive the integrated cryosurgical device for dispensation of the cryogen. Cryogen is dispensed from the container of cryogen into the receptacle and further dispensed into the evaporative reservoir system upon insertion of the integrated cryosurgical device. The evaporative reservoir system surrounds at least a portion of the conductive link which is attached to the thermally conductive applicator tip thereby cooling it down. After dispensation, the thermally conductive applicator tip is then remotely applied to a targeted skin lesion.

[0062]

[0049] In some embodiments of the invention, the integrated cryosurgical device further comprises a skin lesion targeting adapter. The skin lesion targeting adapter is configured to provide more precise and targeted application of the thermally conductive applicator tip to a targeted skin lesion while decreasing exposure of the surrounding skin to the thermally conductive applicator tip. The targeted skin lesion is positioned in the skin lesion targeting adapter during use.

[0063]

[0050] In some embodiments of the invention, the integrated cryosurgical device further comprises a plurality of fins. In some embodiments of the invention, the plurality of fins is disposed on one end of the holder and surrounds the evaporative reservoir system. In some embodiments of the invention, the plurality of fins covers at least a portion of the evaporative reservoir system. In some embodiments of the invention, each fin is spaced equidistant from the other fins so that there is an opening of the same width located between fins through which the evaporative reservoir system is visible. The width of the opening is optimized to allow enough ventilation for the evaporative area of the evaporative reservoir system and PCT Application Attorney Docket No. 054.0020-WO00 to decrease the hazard of an operator of the integrated cryosurgical device coming into contact with the evaporative reservoir system. In some embodiments of the invention, the width of the opening is less than 4 mm.

[0064]

[0051] In some embodiments of the invention, the integrated cryosurgical device further comprises at least one thermochromic indicator zone. The at least one thermochromic indicator zone comprises at least one thermochromic material that senses the presence of cryogen and visually informs the operator of the device via the at least one thermochromic indicator zone that the integrated cryosurgical device is ready to be applied to the skin lesion by changing color. The at least one thermochromic material of the integrated cryosurgical device may be located at various portions of the device and may be mixed into a materials matrix, for example foam or plastic, of the device or coated onto the external surface of the device. In some embodiments of the invention, the at least one thermochromic material is disposed on or mixed into at least one visible portion of the plurality of fins. In some embodiments of the invention, the at least one thermochromic material is disposed on or mixed into at least one visible portion of the holder. In some embodiments of the invention, the at least one thermochromic material is disposed on or mixed into at least one visible portion of the conductive link. In some embodiments of the invention, the at least one thermochromic material is disposed on or mixed into at least one visible portion of the thermally conductive applicator tip. In some embodiments of the invention, the at least one thermochromic material is disposed on or mixed into at least one visible portion of the evaporative reservoir system. The at least one thermochromic indicator zone is the portion where the color change from the at least one thermochromic material occurs. In some embodiments of the invention, the at least one thermochromic material comprises organic chemicals. In some embodiments of the invention, the at least one thermochromic material comprises crystalline inorganic material. In some embodiments of the invention, there is one thermochromic indicator zone associated with one thermochromic material within or on one portion of the integrated cryosurgical device. In some embodiments of the invention, there are two thermochromic indicator zones associated with thermochromic materials within or on two portions of the integrated cryosurgical device, wherein the thermochromic materials within or on the two portions of the integrated cryosurgical device may be the same or different. In some embodiments of the invention, there are three thermochromic indicator zones associated with thermochromic materials within or on three portions of the integrated cryosurgical device, wherein the thermochromic materials within or on the three portions of the integrated cryosurgical device may be the same or different. In some embodiments of the invention, there are four or more thermochromic indicator zones associated with thermochromic materials within or on four or more portions of the integrated cryosurgical device, wherein the PCT Application Attorney Docket No. 054.0020-WO00 thermochromic materials within or on the four or more portions of the integrated cryosurgical device may be the same or different.

[0065]

[0052] In some embodiments of the invention, the at least one thermochromic indicator zone acts as a readiness indicator zone. For example, in some embodiments of the invention, the readiness indicator zone comprises at least one thermochromic material. In some embodiments of the invention, the at least one thermochromic material of the readiness indicator zone is located on the holder of the integrated cryosurgical device and indicates that the thermally conductive applicator tip has reached a lowest effective treatment temperature. In some embodiments of the invention, the at least one thermochromic material of the readiness indicator zone is located on at least a portion of the plurality of fins of the holder of the integrated cryosurgical device. In some embodiments of the invention, the readiness indicator zone changes from colorless to blue or green when the thermally conductive applicator tip reaches the maximum effective treatment temperature in the range of 0°C to 5°C.

[0066]

[0053] In some embodiments of the invention, the at least one thermochromic indicator zone acts as an optimal temperature indicator zone. For example, in some embodiments of the invention, the optimal temperature indicator zone comprises at least one thermochromic material. In some embodiments of the invention, the at least one thermochromic material of the optimal temperature indicator zone is located near or on the thermally conductive applicator tip and indicates when the thermally conductive applicator tip has reached optimal treatment temperature by visibly changing color, such as blue. In some embodiments of the invention, the optimal treatment temperature ranges from -20°C to -25°C.

[0067]

[0054] In some embodiments of the invention, the at least one thermochromic indicator zone acts as an over-dispensation warning zone. For example, in some embodiments of the invention, the overdispensing warning zone comprises at least one thermochromic material. In some embodiments of the invention, the at least one thermochromic material of the over-dispensing warning zone is located on the thermally conductive applicator tip or conductive link and prevents over treatment of the targeted skin lesion or waste of the cryogen by changing color, such as to blue, if excess cryogen is present due to the temperature detected. In some embodiments of the invention, the at least one thermochromic material of the over-dispensing warning zone is located on at least a portion of the plurality of fins of the holder of the integrated cryosurgical device. In some embodiments of the invention, the at least one thermochromic material of the over-dispensing warning zone is red in a concentration of 1-5 %.

[0068]

[0055] In some embodiments of the invention, the at least one thermochromic indicator zone acts as a treatment completion indicator zone. For example, in some embodiments of the invention, the treatment completion indicator zone comprises at least one thermochromic material. In some embodiments of the PCT Application Attorney Docket No. 054.0020-WO00 invention, the at least one thermochromic material of the treatment completion indicator zone is located on a visible surface of the integrated cryosurgical device and indicates completion of a treatment cycle by visibly returning to the original color as the integrated cryosurgical device warms. The original color is the color of the integrated cryosurgical device before the thermochromic material detected the change in temperature and changed color.

[0069]

[0056] In some embodiments of the invention, the integrated cryosurgical device comprises a readiness indicator zone. In some embodiments of the invention, the integrated cryosurgical device comprises an optimal temperature indicator zone. In some embodiments of the invention, the integrated cryosurgical device comprises an over-dispensation warning zone. In some embodiments of the invention, the integrated cryosurgical device comprises a treatment completion indicator zone. In some embodiments of the invention, the integrated cryosurgical device comprises at least one of a readiness indicator zone, an optimal temperature indicator zone, an over-dispensation warning zone, or a treatment completion indicator zone. In some embodiments of the invention, the integrated cryosurgical device comprises at least two of a readiness indicator zone, an optimal temperature indicator zone, an over-dispensation warning zone, or a treatment completion indicator zone. In some embodiments of the invention, the integrated cryosurgical device comprises at least three of a readiness indicator zone, an optimal temperature indicator zone, an over-dispensation warning zone, or a treatment completion indicator zone. In some embodiments of the invention, the integrated cryosurgical device comprises all four of a readiness indicator zone, an optimal temperature indicator zone, an over-dispensation warning zone, and a treatment completion indicator zone.

[0070]

[0057] The at least one thermochromic indicator zone comprises at least one thermochromic material and may be located at various portions of the integrated cryosurgical device. In some embodiments of the invention, the at least one thermochromic material is an organic chemical. In some embodiments of the invention, the at least one thermochromic material is an inorganic chemical. In some embodiments of the invention, the at least one thermochromic material may be mixed into a materials matrix of at least one portion of the integrated cryosurgical device or coated onto a surface of at least one portion of the integrated cryosurgical device. In some embodiments of the invention, the materials matrix is, for example, foam, plastic, or a resin or substrate forming the device components, or coated onto the external surface of the device. In some embodiments of the invention, the at least one thermochromic material is applied to the exterior of the device using adhesives, paints, or tapes. In some embodiments of the invention, the at least one thermochromic material is a microencapsulated thermochromic. In some embodiments of the invention, the at least one thermochromic material is an organic dye. In some PCT Application Attorney Docket No. 054.0020-WO00 embodiments of the invention, the at least one thermochromic material is a metallic chemical. In some embodiments of the invention, the at least one thermochromic material is a crystalline inorganic material. In one embodiment of the invention, the at least one thermochromic material is a leuco-dye. In some embodiments of the invention, the at least one thermochromic material is a pigment crystal. In some embodiments of the invention, the at least one thermochromic material is one or more of an organic dye, a metallic chemical, a crystalline inorganic material, a leuco-dye, and a pigmented crystal. Leuco-dyes are organic compounds which provide reversible color change. Crystalline inorganic materials have high- temperature stability. Microencapsulated thermochromics have enhanced durability and protection.

[0071]

[0058] In some embodiments of the invention, the at least one thermochromic material is mixed with a secondary concentrate to mask undesirable room temperature tints of the device or to match the required device aesthetics. The secondary concentrate is mixed in such a way that it does not mask the color change of the thermochromic material. In some embodiments of the invention, the secondary concentrate is a white pigment. In some embodiments of the invention, the secondary concentrate is 0.25-1 %. In some embodiments of the invention, the secondary concentrate is 1 %. In some embodiments of the invention, the secondary concentrate is 0.5 %. In some embodiments of the invention, the secondary concentrate is 0.25 %. In some embodiments of the invention, the secondary concentrate is 0 %.

[0072]

[0059] In some embodiments of the invention, the at least one thermochromic material is blue. In some embodiments of the invention, the at least one thermochromic material is green. In some embodiments of the invention, the at least one thermochromic material is red. In some embodiments of the invention, the at least one thermochromic material is yellow. In some embodiments of the invention, the thermochromic concentrate is 0.5 %. In some embodiments of the invention, the thermochromic concentrate is within the range of 0.5-3 %. In some embodiments of the invention, the thermochromic concentrate is 1 %. In some embodiments of the invention, the thermochromic concentrate is within the range of 1-5 %. In some embodiments of the invention, the thermochromic concentrate is 5 %. In some embodiments of the invention, the thermochromic concentrate is 3 %. In some embodiments of the invention, the at least one thermochromic material is green in a concentration of 0.5-3 %. In some embodiments of the invention, the at least one thermochromic material is red in a concentration of 1-5 %.

[0060] In some embodiments of the invention, the integrated cryosurgical device is connected to a source of cryogen. In some embodiments of the invention, the source of cryogen is a container of cryogen. In some embodiments of the invention, the integrated cryosurgical device is configured to receive the source of cryogen and dispense the cryogen to the evaporative reservoir system. In some embodiments of the invention, the integrated cryosurgical device further comprises a container of cryogen which dispenses PCT Application Attorney Docket No. 054.0020-WQ00 cryogen gas into the evaporative reservoir system. In some embodiments of the invention, the container of cryogen is inserted into the holder of the integrated cryosurgical device. In some embodiments of the invention, the cryogen is dispensed when an operator applies pressure to the container of cryogen in a downward direction. In some embodiments of the invention, this applied pressure dispenses the cryogen from the container of cryogen into the evaporative reservoir system. In some embodiments of the invention, the cryogen is dispensed when an operator squeezes the sides of a top end of the holder surrounding the container of cryogen towards each other. In some embodiments of the invention, this squeezing movement dispenses the cryogen from the container of cryogen into the evaporative reservoir system. In some embodiments of the invention, the cryogen gas is selected from the group consisting of dimethyl ether, propane, butane, R410A refrigerant (difluoromethane and pentafluoroethane), R404A refrigerant (pentafluoroethane, 1,1,1-trifluoroethane, and 1,1,2,2-tetrafluoroethane), R152A refrigerant (1,1-difluoroethane), carbon dioxide, nitrous oxide, and liquid nitrogen. In some embodiments of the invention, the container is filled with a composition of multiple cryogen gases. In some embodiments of the invention, the composition of cryogen gases is made of one or more of the following: dimethyl ether, propane, butane, R410A, R404A, R152A, carbon dioxide, nitrous oxide, and / or liquid nitrogen. In some embodiments of the invention, the cryogen gas is dispensed as liquefied cryogen gas. In some embodiments of the invention, the cryogen gas is dispensed as an aerosol cryogen gas. The specific thermochromic material and the evaporative reservoir system, conductive link, and thermally conductive applicator tip designs for optimal performance depend on which type of cryogen is used for treatment.

[0073]

[0061] The invention can be used to treat skin lesions located anywhere on the dermis. In some embodiments of the invention, the targeted skin lesion is located on the neck. In some embodiments of the invention, the targeted skin lesion is located on the chest. In some embodiments of the invention, the targeted skin lesion is located on the hands. In some embodiments of the invention, the targeted skin lesion is located on the arms. In some embodiments of the invention, the targeted skin lesion is located on or around the groin. In some embodiments of the invention, the targeted skin lesion is located on or around the breasts. In some embodiments of the invention, the targeted skin lesion is located on or around the knees or feet. In some embodiments of the invention, the skin lesion is a skin tag (acrochordon). In some embodiments of the invention, the skin lesion is a common wart (verruca vulgaris). In some embodiments of the invention, the skin lesion is a plantar wart, which is a thicker lesion requiring sustained treatment. In some embodiments of the invention, the skin lesion is an age spot (solar lentigo). In some embodiments of the invention, the skin lesion is a seborrheic keratoses. In some embodiments of the invention, the skin lesion is a small keloid. In some embodiments of the invention, the skin lesion is PCT Application Attorney Docket No. 054.0020-WO00 selected from the group consisting of actinic keratoses (solar keratoses), molluscum contagiosum, dermatofibromas, keratoacanthoma, granuloma annulare, angiomas, chondrodermatitis, epithelial nevus, porokeratosis plantaris discreta, leukoplakia, granuloma pyogenicum, pyogenic granuloma, and other topical skin lesions.

[0074]

[0062] In some embodiments of the invention, the integrated cryosurgical device comprises a thermally conductive interface comprising a conductive link and a thermally conductive applicator tip made of copper with a 8 mm diameter and flat surface geometry, an absorbent evaporative reservoir system made of foam that is in thermal communication with the thermally conductive applicator tip via a conductive link and surrounds at least a portion of the conductive link, and a single thermochromic indicator zone comprising a thermochromic material disposed on a holder of the integrated cryosurgical device. This embodiment may be used in conjunction with dimethyl ether. The thermochromic material may be green leuco-dye (1 % concentration) which activates at -20°C to indicate optimal treatment temperature achieved.

[0075]

[0063] In another embodiment of the invention, the integrated cryosurgical device comprises interchangeable thermally conductive interfaces comprising conductive links and thermally conductive applicator tips including ones made of copper, aluminum, and steel, a conductive link, a dual reservoir system comprising a first evaporative reservoir system and a second evaporative reservoir system, and four thermochromic indicator zones comprising at least one thermochromic material in each zone. This embodiment may be compatible with multiple types of cryogen. This embodiment involves graduated temperature feedback, cryogen over-dispensation prevention, treatment timing guidance, and sterilizable components for reusability. The first evaporative reservoir system and the second evaporative reservoir system each surround at least a portion of the conductive link increasing the evaporative area of the integrated cryosurgical device.

[0076]

[0064] In another embodiment of the invention, the integrated cryosurgical device comprises a thermally conductive interface comprising a conductive link and a thermally conductive applicator tip that is made of stainless steel and that is fixed in the device and in thermal communication with an evaporative reservoir system, a pre-filled container of cryogen, and two thermochromic indicator zones (a readiness indicator zone and an over-dispensation warning zone) comprising at least one thermochromic material in each zone. The readiness indicator zone may visually alert the user that the device is ready for use by turning green and the over-dispensation warning zone may visually alert the user of over-dispensation of cryogen by turning red. This embodiment involves clear visual instructions, foolproof operation, and safety mechanisms to prevent over-treatment. PCT Application Attorney Docket No. 054.0020-WO00

[0077]

[0065] In another embodiment of the invention, the integrated cryosurgical device comprises a narrow thermally conductive applicator tip that is made of copper and has a diameter of 3 mm, a small evaporative reservoir system for small cryogen volumes, a conductive link, and a high sensitivity thermochromic indicator zone. This embodiment may be used for pedunculated lesions and involves enhanced precision for small targeted skin lesions, reduced collateral tissue exposure, and optimization for soft tissue treatment.

[0078]

[0066] The invention further relates to a method for treating skin lesions comprising providing an integrated cryosurgical device of the invention, for example comprising a holder, a thermally conductive interface comprising a thermally conductive applicator tip and a conductive link, and an evaporative reservoir system. Depending on the size and type of skin lesion to be treated, a user of the integrated cryosurgical device must select an appropriate sized and shaped thermally conductive interface comprising the conductive link and the thermally conductive applicator tip. The user of the integrated cryosurgical device may be a health care professional or a general consumer. The thermally conductive interface comprising the conductive link and the thermally conductive applicator tip must then be attached to the holder of the integrated cryosurgical device. The evaporative reservoir system is attached to the thermally conductive interface by being stretched to surround and cover at least a portion of the conductive link of the thermally conductive interface. Cryogen is dispensed into the evaporative reservoir system and the thermally conductive applicator tip is then applied to and contacts the targeted skin lesion after the thermally conductive applicator tip reaches the optimal treatment temperature. In some embodiments of the invention, the optimal treatment temperature is in the range of -20°C to -25°C. Contact between the thermally conductive applicator tip and the targeted skin lesion is maintained for a period of time. In some embodiments of the invention, the period of time is greater than 1 second. In some embodiments of the invention, the period of time is between 10-40 seconds. After the period of time expires, the user then removes the thermally conductive applicator tip from the targeted skin lesion. In some embodiments of the invention, the integrated cryosurgical device is reusable for further treatments. In some embodiments of the invention, if the targeted skin lesion is a skin tag, the period of time is 10-40 seconds and the optimal treatment temperature is -25°C or lower. In some embodiments of the invention, if the targeted skin lesion is a wart, the period of time is 20-40 seconds and the optimal treatment temperature is -30°C. In some embodiments of the invention, if the targeted skin lesion is an age spot, the period of time is 15-40 seconds and the optimal treatment temperature is -20°C.

[0079]

[0067] In some embodiments of the invention, the method for treating skin lesions comprises providing the integrated cryosurgical device according to the invention that further comprises at least one PCT Application Attorney Docket No. 054.0020-WO00 thermochromic indicator zone comprising at least one thermochromic material. In this embodiment, when the thermally conductive interface comprising the conductive link and the thermally conductive applicator tip is selected and attached to the holder, the user verifies that the at least one thermochromic indicator zone is in a neutral, colorless state. In some embodiments of the invention, the neutral state of the at least one thermochromic indicator zone is a color, such as white. After dispensation of the cryogen into the evaporative reservoir system, the user optionally monitors the at least one thermochromic indicator zone acting as readiness indicator zone for a change in color. The user dispenses the cryogen until the at least one thermochromic indicator zone acting as an optimal temperature indicator zone changes color to indicate that the optimal treatment temperature of the thermally conductive applicator tip is achieved. During application of the thermally conductive applicator tip to the targeted skin lesion, the user optionally monitors the at least one thermochromic indicator zone acting as an over-dispensation warning zone for a color change, such as to red, indicating over dispensation of the cryogen to the device. After treatment is complete, the user optionally monitors the at least one thermochromic indicator zone acting as a treatment completion indicator zone for a return to a neutral, colorless state or to the original color, e.g. white, as the device warms before either reusing the device or storing the device. The original color is the color of the integrated cryosurgical device before the thermochromic material detected the change in temperature and changed color.

[0080]

[0068] In some embodiments of the invention, the method for treating skin lesions comprises providing an integrated cryosurgical device that further comprises a container of cryogen. The container of cryogen is inserted into the holder of the integrated cryosurgical device and the user dispenses the cryogen into the evaporative reservoir system by applying pressure to the container of cryogen.

[0081]

[0069] FIG. 1 shows an exemplary embodiment of an integrated cryosurgical device 100 of the invention comprising a holder 101, a container of cryogen 102, an evaporative reservoir system 103, a plurality of fins 105, and a thermally conductive interface 107 comprising a conductive link 106 and a thermally conductive applicator tip 104. FIG. 2 shows a cross-sectional view of the same exemplary embodiment of the integrated cryosurgical device 100 comprising the holder 101, the container of cryogen 102, the evaporative reservoir system 103, the plurality of fins 105, and the thermally conductive interface 107 comprising the conductive link 106 and the thermally conductive applicator tip 104. The evaporative reservoir system 103 is in thermal communication with the thermally conductive applicator tip 104 via the conductive link 106. The evaporative reservoir system 103 surrounds at least a portion of the conductive link 106. The thermally conductive interface 107 comprising the conductive link 106 and the thermally conductive applicator tip 104 is attached to the bottom end of the holder 101. The container of cryogen PCT Application Attorney Docket No. 054.0020-WO00

[0082] 102 is enclosed in the holder 101 of the integrated cryosurgical device 100. In some embodiments of the invention, the cryogen gas is dispensed from the container of cryogen 102 into the evaporative reservoir system 103. The thermally conductive applicator tip 104 transfers heat from skin at a treatment site into the integrated cryosurgical device 100. The heat conducts through the conductive link 106 from the thermally conductive applicator tip 104 into the evaporative reservoir system 103. The cryogen then evaporates from the evaporative reservoir system 103, dropping the temperature of the thermally conductive applicator tip 104 to below the boiling point of the cryogen. The plurality of fins 105 is disposed at the bottom end of the holder 101 and surrounds at least a portion of the evaporative reservoir system 103. Each of the plurality of fins 105 is spaced equidistant from the other of the plurality of fins 105 so that there is an opening of the same width located between fins through which the evaporative reservoir system 103 is visible. The width of the opening is optimized to allow enough ventilation for the evaporative reservoir system 103 and to decrease the hazard of an operator of the integrated cryosurgical device 100 coming into contact with the evaporative reservoir system 103. In some embodiments of the invention, the width of the opening is less than 4 mm. The thermally conductive applicator bp 104 is applied to a targeted skin lesion of a patient when the integrated cryosurgical device 100 is in use after reaching an optimal treatment temperature. In some embodiments of the invention, the integrated cryosurgical device

[0083] 100 further comprises at least one thermochromic indicator zone 108 comprising at least one thermochromic material. In some embodiments of the invention, the at least one thermochromic material is disposed on or mixed into at least one visible portion of the plurality of fins 105, as shown in FIGS. 1 and 2.

[0084]

[0070] FIG. 3A shows a diagram of how a user holds an exemplary embodiment of an integrated cryosurgical device 100 of the invention by gripping a holder 101 of the integrated cryosurgical device 100. The integrated cryosurgical device 100 further comprises a thermally conductive applicator tip 104, an evaporative reservoir system 103, a plurality of fins 105, and a container of cryogen 102. The evaporative reservoir system 103 is in thermal communication with the thermally conductive applicator dp 104 via a conductive link (not visible in FIG. 3A). The combination of the thermally conductive applicator tip 104 and the conductive link forms a thermally conductive interface (not visible in FIG. 3A). The thermally conductive interface comprising the conductive link and the thermally conductive applicator tip 104 is attached to the bottom end of the holder 101. At least a portion of the conductive link is surrounded by the evaporative reservoir system 103. The plurality of fins 105 is disposed at the bottom end of the holder

[0085] 101 and surrounds the evaporative reservoir system 103. Each of the plurality of fins 105 is spaced equidistant from the other of the plurality of fins 105 so that there is an opening of the same width located PCT Application Attorney Docket No. 054.0020-WO00 between fins through which the evaporative reservoir system 103 is visible. The width of the opening is optimized to allow enough ventilation for the evaporative reservoir system 103 and to decrease the hazard of a finger of an operator of the integrated cryosurgical device 100 coming into contact with the evaporative reservoir system 103. In some embodiments of the invention, the width of the opening is less than 4 mm. As shown in FIG. 3A, the user may hold the integrated cryosurgical device 100 in one hand by the holder 101 with the thermally conductive applicator tip 104 pointing in a downward direction. The holder 101 encloses the container of cryogen 102. FIGS. 3B and 3C show a diagram of how a user dispenses cryogen using the exemplary embodiment of the integrated cryosurgical device 100 as shown in FIG. 3A comprising the holder 101, the thermally conductive applicator tip 104, the evaporative reservoir system 103, the plurality of fins 105, and the container of cryogen 102. In some embodiments of the invention, the user applies pressure to the container of cryogen 102 in a downward direction as shown in FIG. 3B. In some embodiments of the invention, this applied pressure dispenses the cryogen from the container of cryogen 102 into the evaporative reservoir system 103. The thermally conductive applicator tip 104 transfers heat from skin at a treatment site into the integrated cryosurgical device 100. The heat conducts through the conductive link from the thermally conductive applicator tip 104 into the evaporative reservoir system 103. The cryogen then evaporates from the evaporative reservoir system 103, dropping the temperature of the thermally conductive applicator tip to 104 below the boiling point of the cryogen. In some embodiments of the invention, the user squeezes the sides of the top end of the holder 101 surrounding the container of cryogen 102 towards each other as shown in FIG. 3C. In some embodiments of the invention, this squeezing movement dispenses the cryogen from the container of cryogen 102 into the evaporative reservoir system 103. The thermally conductive applicator tip 104 transfers heat from skin at a treatment site into the integrated cryosurgical device 100. The heat conducts through the conductive link from the thermally conductive applicator tip 104 into the evaporative reservoir system 103. The cryogen then evaporates from the evaporative reservoir system 103, dropping the temperature of the thermally conductive applicator tip to 104 below the boiling point of the cryogen. The thermally conductive applicator tip 104 is applied to a targeted skin lesion of a patient when the integrated cryosurgical device 100 is in use after reaching an optimal treatment temperature.

[0086]

[0071] FIG. 4 shows an integrated cryosurgical device 200 comprising a holder 201, a thermally conductive applicator tip 204, and an evaporative reservoir system 203 for remote application of cryogen to a targeted skin lesion. As shown in FIG. 4, an external container of cryogen 202 is used in conjunction with the integrated cryosurgical device 200. The container of cryogen 202 is in thermal communication with a receptacle 205 on the top of the container of cryogen 202 that receives the thermally conductive PCT Application Attorney Docket No. 054.0020-WO00 applicator tip 204 for dispensation of the cryogen. Cryogen is dispensed from the container of cryogen 202 into the receptacle 205. The evaporative reservoir system 203 is in thermal communication with the thermally conductive applicator tip 204 via a conductive link (not visible in FIG. 4). The combination of the thermally conductive applicator tip 204 and the conductive link forms a thermally conductive interface (not visible in FIG. 4). The thermally conductive interface comprising the conductive link and the thermally conductive applicator tip 204 is attached to the bottom end of the holder 201. At least a portion of the conductive link is surrounded by the evaporative reservoir system 203. The combination of the thermally conductive interface comprising the thermally conductive applicator tip 204 and the conductive link, and the evaporative reservoir system 203 is inserted into the receptacle 205 to begin dispensation of the cryogen. In some embodiments of the invention, the evaporative reservoir system 203 is filled with the cryogen. After dispensation, the cryogen-filled integrated cryosurgical device 200 is then removed from the receptacle 205 and remotely applied to a targeted skin lesion. The thermally conductive applicator tip

[0087] 204 transfers heat from skin at a treatment site into the integrated cryosurgical device 200. The heat conducts through the conductive link from the thermally conductive applicator tip 204 into the evaporative reservoir system 203. The cryogen then evaporates from the evaporative reservoir system 203, dropping the temperature of the thermally conductive applicator tip 204 below the boiling point of the cryogen.

[0088]

[0072] FIG. 5A shows an exemplary embodiment of the integrated cryosurgical device 200 of FIG. 4 inserted into the receptacle 205 of the container of cryogen 202. FIG. 5B shows a cross-sectional view of that same exemplary embodiment of the integrated cryosurgical device 200 of FIG. 4 inserted into the receptacle

[0089] 205 of the container of cryogen 202. FIG. 5B shows two different sizes of containers of cryogen (202a and 202b) to be used in conjunction with the integrated cryosurgical device 200 of FIG. 4. As shown in FIGS. 5A and 5B, the integrated cryosurgical device 200 is inserted into the receptacle 205 with the thermally conductive applicator tip 204 (shown in FIG. 5B) being inserted in a downward direction. The thermally conductive applicator tip 204 is in thermal communication with the evaporative reservoir system 203 via the conductive link 206 (shown in FIG. 5B). The combination of the thermally conductive applicator tip 204 and the conductive link 206 forms a thermally conductive interface 207 (shown in FIG. 5B). The thermally conductive interface 207 comprising the conductive link 206 and the thermally conductive applicator tip 204 is attached to the bottom end of the holder 201. The evaporative reservoir system 203 surrounds at least a portion of the conductive link 206. The combination of the thermally conductive interface 207 comprising the thermally conductive applicator tip 204 and the conductive link 206, and the evaporative reservoir system 203 is inserted into the receptacle 205 to begin dispensation of the cryogen and the PCT Application Attorney Docket No. 054.0020-WO00 cryogen is dispensed from the container of cryogen 202 into the receptacle 205 via cryogen dispensation means 209. During dispensation of the cryogen, the holder 201 is not exposed to the cryogen and remains outside the receptacle 205 (as shown in FIG. 5A) while the combination of the thermally conductive interface 207 comprising the thermally conductive applicator tip 204 and the conductive link 206, and the evaporative reservoir system 203 are inside the receptacle 205 (as shown in FIG. 5B). In some embodiments of the invention, the evaporative reservoir system 203 is filled with the cryogen. After dispensation, the cryogen-filled integrated cryosurgical device 200 is then removed from the receptacle 205 and remotely applied to a targeted skin lesion. The thermally conductive applicator tip 204 transfers heat from skin at a treatment site into the integrated cryosurgical device 200. The heat conducts through the conductive link 206 from the thermally conductive applicator tip 204 into the evaporative reservoir system 203. The cryogen then evaporates from the evaporative reservoir system 203, dropping the temperature of the thermally conductive applicator tip 204 below the boiling point of the cryogen. In some embodiments of the invention, the integrated cryosurgical device 200 further comprises at least one thermochromic indicator zone 208 comprising at least one thermochromic material. In some embodiments of the invention, the at least one thermochromic material is disposed on or mixed into at least one visible portion of the holder 201 as shown in FIG. 5B.

[0090]

[0073] FIG. 6 shows an exemplary embodiment of an integrated cryosurgical device 300 of the invention comprising a container of cryogen 302, a thermally conductive applicator tip 304, an evaporative reservoir system 303, a holder 301, a plurality of fins 305, and a skin lesion targeting adapter 306 in accordance with the invention. The evaporative reservoir system 303 is in thermal communication with the thermally conductive applicator tip 304 via a conductive link (not visible in FIG. 6). The combination of the thermally conductive applicator tip 304 and the conductive link forms a thermally conductive interface (not visible in FIG. 6). The thermally conductive interface comprising the conductive link and the thermally conductive applicator tip 304 is attached to the bottom end of the holder 301. At least a portion of the conductive link is surrounded by the evaporative reservoir system 303. The plurality of fins 305 is disposed at the bottom end of the holder 301 and surrounds the evaporative reservoir system 303. Each of the plurality of fins 305 is spaced equidistant from the other of the plurality of fins 305 so that there is an opening of the same width located between fins through which the evaporative reservoir system 303 is visible. The width of the opening is optimized to allow enough ventilation for the evaporative reservoir system 303 and to decrease the hazard of an operator of the integrated cryosurgical device 300 coming into contact with the evaporative reservoir system 303. In some embodiments of the invention, the width of the opening is less than 4 mm. The container of cryogen 302 is enclosed in the holder 301 of the integrated cryosurgical PCT Application

[0091] Attorney Docket No. 054.0020-WO00 device 300. In some embodiments of the invention, the cryogen gas is dispensed from the container of cryogen 302 into the evaporative reservoir system 303. The thermally conductive applicator tip 304 transfers heat from skin at a treatment site into the integrated cryosurgical device 300. The heat conducts through the conductive link from the thermally conductive applicator tip 304 into the evaporative reservoir system 303. The cryogen then evaporates from the evaporative reservoir system 303, dropping the temperature of the thermally conductive applicator tip to 304 below the boiling point of the cryogen. A targeted skin lesion is positioned in the skin lesion targeting adapter 306. The thermally conductive applicator tip 304 is then applied to the targeted skin lesion of a patient when the integrated cryosurgical device 300 reaches an optimal treatment temperature. The skin lesion targeting adapter 306 provides more precise and targeted application of the thermally conductive applicator tip 304 to the targeted skin lesion while decreasing exposure of the surrounding skin to the thermally conductive applicator tip 304.

[0074] FIG. 7 shows an exemplary thermally conductive interface 404 comprising a thermally conductive applicator tip 400 and a conductive link 403 of the invention. This exemplary thermally conductive applicator tip 400 comprises a small facet 401 and a large facet 402. The multiple sized facets of the thermally conductive applicator tip 400 provide a user with a choice of surface sizes and configurations to better adapt to the size and type of a targeted skin lesion. For use, the thermally conductive interface 404 comprising the thermally conductive applicator tip 400 and the conductive link 403 may be attached to a holder of an integrated cryosurgical device.

[0092]

[0075] The invention further provides a kit comprising, consisting of, or consisting essentially of the integrated cryosurgical device disclosed herein; and instructions for administration of the integrated cryosurgical device. As used herein, the term "instructions" when used in the context of a kit includes a publication, a recording, a diagram, or any other medium of expression which can be used to communicate the usefulness of the kit for its designated use. The instructions can, for example, be affixed to or included within a container for the kit. The thermally conductive interface comprising the thermally conductive applicator tip and the conductive link, the holder, the evaporative reservoir system, optionally, the at least one thermochromic indicator zone, and / or optionally, the container of cryogen gas may be sealed as separate articles (i.e., fully or partially disassembled) or may be combined into one or more articles of manufacture (i.e., fully or partially assembled). The thermally conductive interface comprising the thermally conductive applicator tip and the conductive link, the holder, the evaporative reservoir system, optionally, the at least one thermochromic indicator zone, and / or optionally, the container of cryogen gas may also be packaged as separate articles of manufacture. For example, the thermally conductive interface comprising the thermally conductive applicator tip and the conductive link, the holder, the evaporative PCT Application

[0093] Attorney Docket No. 054.0020-WO00 reservoir system, and / or optionally, the at least one thermochromic indicator zone, may be packaged as a first article of manufacture, and the container of cryogen gas may be packaged as a second article of manufacture. Individual components of the integrated cryosurgical device may be packaged as their own articles of manufacture as well. Furthermore, more than one of any component of the integrated cryosurgical device and optional container of cryogen gas may be packaged in a single article of manufacture. For example, one article of manufacture may contain two or more thermally conductive interfaces comprising thermally conductive applicator tips and conductive links for more than one treatment application.

[0094]

[0076] The term "container" as used herein refers to any receptacle or applicator means capable of holding, storing, and / or applying the cryogen disclosed herein. Such a container may be in any container configuration known to a person skilled in the art, such as, but not limited to, a canister. The containers may be made of any material suitable for the materials contained therein and additionally suitable for short- and / or long-term storage under any kind of temperature. Such materials include, by way of example, inorganic materials, such as Type I glass (including amber colored glass), ceramics, metals (e.g., steel, aluminum, tin), etc., and organic materials such as inert polymers including polyolefins (e.g., high density polyethylene), fluorinated polyolefins, and the like. Suitable containers include those that maintain the sterility and integrity of their contents, for example, by providing a barrier to moisture.

[0095]

[0077] The term "disposed on" as used herein refers to any means for applying or depositing the at least one thermochromic material onto the desired portion of the integrated cryosurgical device. For example, the at least one thermochromic material disclosed herein can be applied to the desired portion of the integrated cryosurgical device by any method known in the art, including, without limitation, compounding, coating, painting, inking, spraying, brushing, dipping, taping, printing, or rolling, or mixed into desired portions of the integrated cryosurgical device. The at least one thermochromic material can be applied onto the desired portion of the integrated cryosurgical device using various tools and equipment, including, without limitation, a paint brush, a spray gun, a roller, or a dispensing system.

[0096]

[0078] Examples

[0097]

[0079] Compared to traditional foam applicators, the integrated cryosurgical device according to the invention has many performance advantages. The integrated cryosurgical device of the invention has a consistent temperature because the thermally conductive applicator tip provides a stable thermal interface. The integrated cryosurgical device of the invention has controlled heat transfer because of predictable cooling rates. The integrated cryosurgical device of the invention which further comprises at PCT Application

[0098] Attorney Docket No. 054.0020-WO00 least one thermochromic indicator zone provides visual confirmation which eliminates guesswork and reduced waste due to precise cryogen dispensation control.

[0099]

[0080] Example 1: Comparison of Integrated Cryosurgical Device of the Invention to Compound W Advanced Freeze Off

[0100]

[0081] FIG. 8 shows a temperature comparison of the exemplary embodiment of the integrated cryosurgical device of the invention shown in FIG. 1 versus a commercially available product over a period of time. Each device was tested for temperature and time performance using a Teflon mat and a thermocouple placed near the time of each device where it would contact the skin. The devices were then monitored over a period of time between 10 and 40 seconds. The data was then plotted with the mean and standard deviation included. The commercially available product is Compound W Advanced Freeze Off which uses a metal tip of a different design. As shown in FIG. 8, the integrated cryosurgical device of the invention achieved colder temperatures than the commercially available product, particularly over the critical treatment period of up to 40 seconds which correlated to the treatment period of time on the skin. Further, the commercially available product did not achieve a temperature colder than the boiling point of exemplary cryogen gases that were used in conjunction with the device. The commercially available product used dimethyl ether which has a boiling point of -24°C. Therefore, the design of the commercially available product was not influenced by the heat of vaporization. The integrated cryosurgical device of the invention reached a temperature of -40°C and lowered over the critical period of 40 seconds. The integrated cryosurgical device of the invention was able to reach temperatures below the boiling point of difluoroethane, for example, which has a boiling point of -24°C, through heat of vaporization and evaporative cooling.

[0101]

[0082] The testing of Example 1 showed that the integrated cryosurgical device of the invention as shown in FIG. 1 achieved: temperatures below -40°C (compared to -24°C for conventional devices); sustained cooling for 40+ seconds; and 30 % improvement in treatment efficacy. The integrated cryosurgical device of the invention further comprising at least one thermochromic indicator zone achieved 95 % reduction in operator error from visual feedback.

[0102]

[0083] Exemplary Embodiments of the Invention

[0103]

[0084] El. An integrated cryosurgical device for treating skin lesions comprising: a holder; a thermally conductive interface comprising a conductive link and a thermally conductive applicator tip configured to contact a targeted skin lesion; and an evaporative reservoir system in thermal communication with the thermally conductive applicator tip via the conductive link, wherein the evaporative reservoir system PCT Application

[0104] Attorney Docket No. 054.0020-WO00 comprises an evaporative area sized to maintain a heat of vaporization temperature of the thermally conductive applicator tip below the boiling point of a cryogen gas.

[0105]

[0085] E2. The integrated cryosurgical device of El, further comprising at least one thermochromic indicator zone disposed on or mixed into at least one visible portion of the integrated cryosurgical device, wherein the at least one thermochromic indicator zone comprises at least one thermochromic material, and wherein the at least one thermochromic indicator zone visibly changes color when exposed to cryogen at a specific temperature.

[0106]

[0086] E3. The integrated cryosurgical device of El, further comprising a container of the cryogen.

[0107]

[0087] E4. The integrated cryosurgical device of E2, further comprising a container of the cryogen.

[0108]

[0088] E5. The integrated cryosurgical device of any one of E1-E4, wherein the holder comprises a plurality of fins.

[0109]

[0089] E6. The integrated cryosurgical device of any one of E1-E5, wherein the thermally conductive interface comprising the conductive link and the thermally conductive applicator tip is mechanically attached to the holder.

[0110]

[0090] E7. The integrated cryosurgical device of any one of E1-E5, wherein the thermally conductive interface comprising the conductive link and the thermally conductive applicator tip is attached to the holder via a snap-fit attachment.

[0111]

[0091] E8. The integrated cryosurgical device of any one of E1-E7, wherein the thermally conductive applicator tip and the conductive link each independently comprise copper, aluminum, stainless steel, a thermally conductive polymer, ceramic, or a combination thereof.

[0112]

[0092] E9. The integrated cryosurgical device of any one of E1-E8, wherein the evaporative reservoir system comprises an absorbent material.

[0113]

[0093] E10. The integrated cryosurgical device of E9, wherein the absorbent material is foam, cellulose, synthetic, or a combination thereof.

[0114]

[0094] Ell. The integrated cryosurgical device of any one of E1-E10, wherein the evaporative reservoir system surrounds or is adjacent to at least a portion of the conductive link.

[0115]

[0095] E12. The integrated cryosurgical device of any one of E3-E11, wherein cryogen from the container of cryogen is dispensed into the evaporative reservoir system.

[0116]

[0096] E13. The integrated cryosurgical device of any one of E1-E12, wherein the thermally conductive applicator tip and the conductive link are each hollow.

[0117]

[0097] E14. The integrated cryosurgical device of E2, wherein the at least one thermochromic material is disposed on or mixed into at least one visible portion of the holder. PCT Application

[0118] Attorney Docket No. 054.0020-WO00

[0119]

[0098] E15. The integrated cryosurgical device of E2, wherein the at least one thermochromic material is disposed on or mixed into at least one visible portion of the thermally conductive applicator tip.

[0120]

[0099] E16. The integrated cryosurgical device of E2, wherein the at least one thermochromic material is disposed on or mixed into at least one visible portion of the evaporative reservoir system.

[0121]

[0100] E17. The integrated cryosurgical device of E2, wherein the at least one thermochromic material is disposed on or mixed into at least one visible portion of the conductive link.

[0122]

[0101] E18. The integrated cryosurgical device of E5, wherein the at least one thermochromic material is disposed on or mixed into at least one visible portion of the plurality of fins.

[0123]

[0102] E19. The integrated cryosurgical device of any one of E2 or E14-E18, wherein the at least one thermochromic material is configured to visibly indicate at least one of: when the integrated cryosurgical device reaches a maximum treatment temperature, when the integrated cryosurgical device reaches an optimal treatment temperature, when an excess of cryogen is present in the integrated cryosurgical device, or when treatment is complete and the temperature of the integrated cryosurgical device returns to a temperature prior to use.

[0124]

[0103] E20. The integrated cryosurgical device of E19, wherein the maximum treatment temperature is 0°C.

[0125]

[0104] E21. The integrated cryosurgical device of E19 or E20, wherein the optimal treatment temperature is -20°C and below.

[0126]

[0105] E22. The integrated cryosurgical device of any one of E2 or E14-E21, wherein the at least one thermochromic material comprises leuco-dyes, crystalline inorganic materials, microencapsulated thermochromic compounds, or a combination thereof.

[0127]

[0106] E23. The integrated cryosurgical device of any one of E1-E22, wherein the thermally conductive applicator tip comprises a surface geometry and a diameter based on a type and size of the targeted skin lesion.

[0128]

[0107] E24. The integrated cryosurgical device of E23, wherein the surface geometry of the thermally conductive applicator tip comprises at least one large facet and at least one small facet.

[0129]

[0108] E25. The integrated cryosurgical device of E23 or E24, wherein the diameter of the thermally conductive applicator tip ranges from 2-15 mm.

[0130]

[0109] E26. The integrated cryosurgical device of any one of E1-E25, wherein the cryogen gas is selected form the group consisting of: dimethyl ether, propane, butane, R152A refrigerant, R410A refrigerant, R404A refrigerant, carbon dioxide, nitrous oxide, and liquid nitrogen. PCT Application Attorney Docket No. 054.0020-WO00

[0131]

[0110] E27. The integrated cryosurgical device of any one of E1-E25, wherein cryogen gas is a composition of one or more of dimethyl ether, propane, butane, R152A refrigerant, R410A refrigerant, R404A refrigerant, carbon dioxide, nitrous oxide, and / or liquid nitrogen.

[0132]

[0111] E28. The integrated cryosurgical device of any one of E1-E27, wherein the targeted skin lesion is selected from the group consisting of a verruca (warts), lentigo (age spots), actinic keratoses (solar keratoses), seborrheic keratoses, achrochordon (skin tags), molluscum contagiosum, small keloids, dermatofibromas, keratocanthoma, granuloma annulare, angiomas, chondrodermatitis, epithelial nevus, porokeratosis plantaris discreta, leukoplakia, granuloma pyogenicum, pyogenic granuloma, and other topical skin lesions.

[0133]

[0112] E29. A method for treating skin lesions, the method comprising: providing the integrated cryosurgical device of any one of E1-E28; dispensing cryogen into the evaporative reservoir system; applying the thermally conductive applicator tip to a targeted skin lesion; contacting the targeted skin lesion with the thermally conductive applicator tip when the thermally conductive applicator tip reaches an optimal treatment temperature that is lower than the boiling point of the cryogen; and removing the thermally conductive applicator tip after a period of time.

[0134]

[0113] E30. The method of E29, wherein the period of time ranges from 10-40 seconds.

[0135]

[0114] E31. The method of E29 or E30, wherein the optimal treatment temperature ranges from -20°C to - 25°C.

[0136]

[0115] E32. The method of any one of E29-E31, wherein the targeted skin lesion is topically located on a patient.

[0137]

[0116] E33. A kit comprising the integrated cryosurgical device of any one of E1-E28.

[0138]

[0117] E34. The kit of E33, wherein the integrated cryosurgical device is partially or fully preassembled.

[0139]

[0118] E35. The kit of E33, wherein the integrated cryosurgical device is disassembled.

Claims

PCT ApplicationAttorney Docket No. 054.0020-WO00The claimed invention is:

1. An integrated cryosurgical device for treating skin lesions comprising: a holder; a thermally conductive interface comprising a conductive link and a thermally conductive applicator tip configured to contact a targeted skin lesion; and an evaporative reservoir system in thermal communication with the thermally conductive applicator tip via the conductive link, wherein the evaporative reservoir system comprises an evaporative area sized to maintain a heat of vaporization temperature of the thermally conductive applicator tip below the boiling point of a cryogen gas.

2. The integrated cryosurgical device of claim 1, further comprising at least one thermochromic indicator zone disposed on or mixed into at least one visible portion of the integrated cryosurgical device, wherein the at least one thermochromic indicator zone comprises at least one thermochromic material, and wherein the at least one thermochromic indicator zone visibly changes color when exposed to cryogen at a specific temperature.

3. The integrated cryosurgical device of claim 1, further comprising a container of the cryogen.

4. The integrated cryosurgical device of claim 2, further comprising a container of the cryogen.

5. The integrated cryosurgical device of any one of claims 1-4, wherein the holder comprises a plurality of fins.

6. The integrated cryosurgical device of any one of claims 1-4, wherein the thermally conductive interface comprising the conductive link and the thermally conductive applicator tip is mechanically attached to the holder.

7. The integrated cryosurgical device of any one of claims 1-4, wherein the thermally conductive interface comprising the conductive link and the thermally conductive applicator tip is attached to the holder via a snap-fit attachment.PCT ApplicationAttorney Docket No. 054.0020-WO008. The integrated cryosurgical device of any one of claims 1-4, wherein the thermally conductive applicator tip and the conductive link each independently comprise copper, aluminum, stainless steel, a thermally conductive polymer, ceramic, or a combination thereof.

9. The integrated cryosurgical device of any one of claims 1-4, wherein the evaporative reservoir system comprises an absorbent material.

10. The integrated cryosurgical device of claim 9, wherein the absorbent material is foam, cellulose, synthetic, or a combination thereof.

11. The integrated cryosurgical device of any one of claims 1-4 or 10, wherein the evaporative reservoir system surrounds or is adjacent to at least a portion of the conductive link.

12. The integrated cryosurgical device of claim 3 or 4, wherein cryogen from the container of cryogen is dispensed into the evaporative reservoir system.

13. The integrated cryosurgical device of any one of claims 1-4, wherein the thermally conductive applicator tip and the conductive link are each hollow.

14. The integrated cryosurgical device of claim 2, wherein the at least one thermochromic material is disposed on or mixed into at least one visible portion of the holder.

15. The integrated cryosurgical device of claim 2, wherein the at least one thermochromic material is disposed on or mixed into at least one visible portion of the thermally conductive applicator tip.

16. The integrated cryosurgical device of claim 2, wherein the at least one thermochromic material is disposed on or mixed into at least one visible portion of the evaporative reservoir system.

17. The integrated cryosurgical device of claim 2, wherein the at least one thermochromic material is disposed on or mixed into at least one visible portion of the conductive link.PCT Application Attorney Docket No. 054.0020-WO0018. The integrated cryosurgical device of claim 5, wherein the at least one thermochromic material is disposed on or mixed into at least one visible portion of the plurality of fins.

19. The integrated cryosurgical device of any one of claims 2 or 14-18, wherein the at least one thermochromic material is configured to visibly indicate at least one of: when the integrated cryosurgical device reaches a maximum treatment temperature, when the integrated cryosurgical device reaches an optimal treatment temperature, when an excess of cryogen is present in the integrated cryosurgical device, or when treatment is complete and the temperature of the integrated cryosurgical device returns to a temperature prior to use.

20. The integrated cryosurgical device of claim 19, wherein the maximum treatment temperature is 0°C.

21. The integrated cryosurgical device of claim 19, wherein the optimal treatment temperature is - 20°C and below.

22. The integrated cryosurgical device of any one of claims 2 or 14-18, wherein the at least one thermochromic material comprises leuco-dyes, crystalline inorganic materials, microencapsulated thermochromic compounds, or a combination thereof.

23. The integrated cryosurgical device of any one of claims 1-4, wherein the thermally conductive applicator tip comprises a surface geometry and a diameter based on a type and size of the targeted skin lesion.

24. The integrated cryosurgical device of claim 23, wherein the surface geometry of the thermally conductive applicator tip comprises at least one large facet and at least one small facet.

25. The integrated cryosurgical device of claim 23, wherein the diameter of the thermally conductive applicator tip ranges from 2-15 mm.PCT Application Attorney Docket No. 054.0020-WO0026. The integrated cryosurgical device of any one of claims 1-4, wherein the cryogen gas is selected form the group consisting of: dimethyl ether, propane, butane, R152A refrigerant, R410A refrigerant, R404A refrigerant, carbon dioxide, nitrous oxide, and liquid nitrogen.

27. The integrated cryosurgical device of any one of claims 1-4, wherein the cryogen gas is a composition of one or more of dimethyl ether, propane, butane, R152A refrigerant, R410A refrigerant, R404A refrigerant, carbon dioxide, nitrous oxide, and / or liquid nitrogen.

28. The integrated cryosurgical device of any one of claims 1-4, wherein the targeted skin lesion is selected from the group consisting of a verruca (warts), lentigo (age spots), actinic keratoses (solar keratoses), seborrheic keratoses, achrochordon (skin tags), molluscum contagiosum, small keloids, dermatofibromas, keratocanthoma, granuloma annulare, angiomas, chondrodermatitis, epithelial nevus, porokeratosis plantaris discreta, leukoplakia, granuloma pyogenicum, pyogenic granuloma, and other topical skin lesions.

29. A method for treating skin lesions, the method comprising: providing the integrated cryosurgical device of any one of claims 1-4; dispensing cryogen into the evaporative reservoir system; applying the thermally conductive applicator tip to a targeted skin lesion; contacting the targeted skin lesion with the thermally conductive applicator tip when the thermally conductive applicator tip reaches an optimal treatment temperature that is lower than the boiling point of the cryogen; and removing the thermally conductive applicator tip after a period of time.

30. The method of claim 29, wherein the period of time ranges from 10-40 seconds.

31. The method of claim 29, wherein the optimal treatment temperature ranges from -20°C to -25°C.

32. The method of claim 29, wherein the targeted skin lesion is topically located on a patient.

33. A kit comprising the integrated cryosurgical device of any one of claims 1-4.PCT ApplicationAttorney Docket No. 054.0020-WO0034. The kit of claim 33, wherein the integrated cryosurgical device is partially or fully preassembled.

35. The kit of claim 33, wherein the integrated cryosurgical device is disassembled.

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