JP2014515666A - Method for producing a substance with a supersaturated gas, transdermal delivery device and use thereof - Google Patents

Abstract

This document describes non-invasive transdermal administration of non-invasive gases, generally associated with portable mechanical devices for large and small water-soluble (hydrophilic) drugs, vitamins and other transdermal drugs. A skin delivery device has been disclosed. Not only a method for generating such a delivery device component or a substance containing a supersaturated amount of dissolved gas, but also a method for administering a transdermal agent using such a delivery device, using such a delivery device A method or condition for treating a disease is also disclosed.
[Selection] Figure 4C

Description

  Delivery of drugs through the skin to obtain a therapeutic effect is generally known as transdermal drug delivery. Transdermal drug delivery systems are dosage forms that facilitate the delivery of therapeutic agents through the blood circulation to the living epidermis and / or dermal tissue of the skin not only for the whole body but for local therapeutic effects. Transdermal delivery of therapeutic agents offers several advantages over injection and oral routes. For example, transdermal delivery of therapeutic agents improves the bioavailability of the drug by preventing gastrointestinal absorption and hepatic first pass metabolism, increasing the therapeutic effect of the drug by providing controlled and constant drug administration, Maintaining a stable plasma concentration of the drug by providing continuous drug administration, reducing pharmacological dose through higher drug absorption, and better overall therapeutic value through greater dosing flexibility And improve patient compliance. Disadvantages of transdermal delivery include, for example, difficulties in administering a therapeutic agent having a molecular weight greater than 500 Daltons, or using a therapeutic agent that has a very low or high partition coefficient.

  The transdermal drug delivery system may be active or passive. Common dosage forms for passive transdermal drug delivery systems include, for example, ointments, creams, gels, and transdermal patches. Passive systems require an additional careful selection of bases and penetration enhancers and are applied to the skin surface to carry specific doses of the drug into the bloodstream. Because of the imperviousness of the skin, passive transdermal drug delivery systems are generally used with lipophilic transdermal drugs.

  Active transdermal drug delivery systems use mechanical energy to transdermal drug transport across the skin by changing the skin barrier (mainly stratum corneum) or increasing the energy of the drug. Improve. Such active systems include, for example, microneedle that punctures the stratum corneum or otherwise physically breaks the stratum corneum and very small skin peeling, photochemical waves that break down the stratum corneum using chemicals. , Ion photolysis to transfer charged drugs through the skin using low-voltage current, electroporation and reverse electroporation to create transient aqueous pores in the skin using short high-voltage electropulses, ultra-low frequency Sonophoresis that breaks the stratum corneum using sonic energy, thermal ablation that uses heat to make the skin more permeable, increases the energy of the drug, and magnetophoresis that increases the flow of the drug across the skin using magnetic force Including.

  The skin has two important layers, the dermis and the epidermis. The outermost layer, the epidermis, is about 100-150 micrometers thick, has no blood flow, and contains a layer known as the stratum corneum. This layer is important for transdermal delivery because the tissue provides moisture retention and foreign body protection. Under the epidermis, the dermis contains a capillary system that carries blood through the body. If the drug has the ability to penetrate the stratum corneum, it can enter the bloodstream. Sweat tubes and hair follicles are also entrance passages to the blood flow system, but these passages have been considered less important. For example, see Non-Patent Document 1 below.

Aulton, Pharmaceutics: The Science of Dosage Form Design (2d edition, Churchill Livingston, Harcourt publishers, 2002)

  The transdermal route has become one of the most successful and innovative focal points for research in drug delivery. More than 35 transdermal drugs are approved for sale in the United States, and approximately 16 active ingredients are approved for use worldwide. However, there is still a need for better ways of delivering transdermal drugs by the transdermal route. For example, transdermal delivery systems on the market today are limited to small molecular weight drugs with very small daily doses that are often accompanied by various patient discomforts. The present specification discloses a transdermal delivery system using a device that administers a vapor comprising liquid particles containing a supersaturated amount of a dissolved transdermal drug that enters the circulatory system through the sweat gland pores and sweat duct system.

  Therefore, aspects herein disclose a transdermal device. The transdermal delivery device disclosed herein may comprise a pressure cylinder, a permeation valve, an exchange chamber, and a treatment chamber. The above components can be housed inside the housing.

  Another aspect of the present specification discloses a steam generation assembly within an exchange chamber. The vapor generation assembly disclosed herein may comprise a permeation valve and a fluid chamber assembly. The steam generation assembly disclosed herein may optionally comprise a regulation switch assembly.

  Yet another aspect of the present specification discloses a method of producing a material comprising a supersaturated amount of dissolved gas. A method of producing a substance disclosed herein includes, as disclosed herein, placing a substance in an airtight container and exposing the substance to a gas, wherein upon exposure, the substance A greater amount of gas dissolves in the material than can be dissolved at 25 ° C. and 1 atmosphere. The gas may be carbon dioxide. The resulting material that becomes supersaturated by the dissolved gas can then be administered to an individual to treat the disease as disclosed herein. In another aspect, the present specification discloses the use of a material comprising a supersaturated amount of dissolved gas to produce a medicament. Such agents can then be administered to an individual to treat the disease as disclosed herein.

  Yet another aspect of the present specification discloses a method of transdermally administering a therapeutically effective amount of a therapeutic agent to an individual. The method of transdermal administration disclosed herein comprises administering to an individual a substance comprising a supersaturated amount of dissolved gas by using the transdermal delivery device disclosed herein. In another aspect, a method of transdermal administration disclosed herein comprises a supersaturated amount of dissolved gas at a rate set by a permeation valve by using a transdermal delivery device disclosed herein. And administering a substance containing the therapeutic agent to the individual. Administration of gas and / or therapeutic agents generally treats symptoms associated with the disease. In certain aspects, the present specification discloses the use of a substance comprising a supersaturated amount of dissolved gas to treat a disease by using the transdermal device disclosed herein. Embodiments also include the use of a transdermal delivery device disclosed herein that transdermally administers a therapeutically effective amount of a therapeutic agent to an individual.

  A further aspect of the specification discloses a method of treating a disease by using the transdermal device disclosed herein. A method of treating a disease disclosed herein uses a transdermal delivery device as disclosed herein to treat a composition comprising a substance containing a supersaturated amount of dissolved gas with a disease. Administering to a body part of an individual, the administration of the composition relieves symptoms associated with the disease. The method of treating a disease disclosed herein also provides a composition comprising a substance comprising a supersaturated amount of dissolved gas and a therapeutic agent by using the transdermal delivery device disclosed herein. Administering to a body part of an individual suffering from, the administration of the composition relieves symptoms associated with the disease. The material may be a liquid aerosol, foam, emulsion, gel, sol, or other material that can be supersaturated by the amount of dissolved gas. Diseases include, but are not limited to, treating ischemia, hypertension, heart disease, diabetic disease, trauma, chronic inflammation, arthritis, migraine, cellulite disease, pallor, and cosmetic disorders . In certain embodiments, the present specification discloses the use of a substance comprising a supersaturated amount of dissolved gas to treat a disease. The transdermal device disclosed herein can be used to administer a substance over a set period of time at a set rate based on the gas cylinder pressure and the speed of the permeation valve. Embodiments also include the use of a transdermal delivery device disclosed herein wherein a therapeutically effective amount of a therapeutic agent for treating a disease in an individual is transdermally administered to the individual.

  The drawings are illustrative of different aspects of the presently disclosed subject matter. Each illustrated aspect is not intended to limit the scope of the subject matter disclosed herein, but rather to be exemplary of its scope and spirit. Similar components in the drawings share the same reference numerals.

FIG. 2 shows a block flow chart diagram of an exemplary delivery device configuration disclosed herein. FIG. 3 shows a cross-sectional view of an exemplary housing. 2 illustrates an exemplary permeation valve and fluid chamber structure. Fig. 3 shows another exemplary permeation valve and fluid chamber structure. FIG. 4 illustrates a fluid chamber structure including yet another exemplary permeation valve and actuator assembly. FIG. 1 shows a perspective view of an exemplary transdermal delivery device. FIG. 1 shows a cross-sectional view of an exemplary transdermal delivery device. FIG. 6 shows a cross-sectional view of another exemplary transdermal delivery device that includes an actuator. FIG. 4 shows a cross-sectional view of an exemplary permeation valve with a gas cartridge that is not fully engaged with the piercing member. Figure 3 shows a gas cartridge engaged with a piercing member. FIG. 3 shows a cross-sectional view of an exemplary adjustment switch assembly. FIG. 3 shows a cross-sectional view of an exemplary fluid chamber assembly.

  The average diameter of most human sweat glands provides enough space for most drug molecules to pass through. According to various studies, the average density of sweat pores varies greatly depending on the individual and body part. The palmer surface, ie palm and finger, and the sole surface, ie the back of the toes and toes, averages 2700 skin flicks of skin surface pores per square inch. Have. This compares to about 400 holes per square inch for other parts of the body's skin surface. The total number of sweat pores distributed throughout the body has been estimated to be 1.6 million to 4 million. Sweat gland dimensions vary by up to 5 times from individual to individual, but on average it has been found that the pore size in human skin is 50 micrometers. The dimensions of the coil that goes into the back from the opening in the epidermis are about 2-5 mm in length, about 60-80 micrometers in diameter, and the tube has a slightly smaller diameter.

  The present specification discloses a lightweight and portable mechanical device designed to transdermally administer a therapeutic agent to an individual. The device delivers a vapor containing a supersaturated amount of dissolved gas, which is a non-invasive delivery through the skin through a pore and duct system contained within the skin, such as a sweat gland and sweat duct system. Can be generated. In normal operation, a removable cartridge containing a compressed gas such as carbon dioxide is attached to the port of the permeation valve. The permeation valve can reduce the pressure and thus reduce the gas flow rate to a predetermined speed without mechanical adjustment. Control of gas pressure can also reduce the temperature of the gas.

  In the case where the gas is a therapeutic agent, this low pressure, atmospheric gas then flows to a fluid chamber assembly containing a liquid, such as water, physiological buffer or other suitable liquid, where it is It can be dissolved in the liquid to produce a liquid that is supersaturated with gas. The therapeutic gas is then administered to the individual by evaporating the supersaturated liquid and blowing a vapor onto the skin surface where the liquid particles containing the supersaturated amount of the dissolved therapeutic agent enter the body through the pores of the skin. In the case where the therapeutic agent is not a gas, this low pressure, atmospheric temperature gas is transferred to the fluid chamber assembly containing the therapeutic agent in which the gas is dissolved in a liquid that produces a liquid containing a supersaturated amount of dissolved gas. Can be washed away. The therapeutic agent can then be administered transdermally to the individual as a vapor.

  Aspects herein disclose, in part, a transdermal delivery device. A flow chart of such a device is shown in FIG. Such a device may include at least one pressure cylinder 102, at least one permeation valve 104, a fluid chamber 106, and a treatment chamber 108. Each of these components can be directly coupled or can include additional components in between. For example, a button may be disposed between the permeation valve 104 and the fluid chamber 106 to actuate the valve. Other additional valves or ports may also be included.

  The transdermal delivery device disclosed herein comprises a housing (see, for example, housing 200 of FIG. 2) and a steam generation assembly, which can accommodate the steam generation assembly. Such devices can be designed to be lightweight and portable devices that provide a practical and comfortable experience for the user during operation of the device. The overall shape of the transdermal delivery device disclosed herein is generally cylindrical, although other shapes can be used. In certain embodiments, a transdermal delivery device disclosed herein is less than about 20 inches long, less than about 18 inches long, less than about 16 inches long, less than about 14 inches long, Less than about 12 inches long, less than about 10 inches long, or less than about 8 inches long, with a width of less than 2 inches, less than 1.5 inches, less than 1 inch, or less than 0.5 inches . In certain aspects of this embodiment, the transdermal delivery device disclosed herein may have a length of less than about 12 inches and a width of about 1 inch.

  The housing disclosed herein includes an outer body shell (see, eg, outer body shell 202 of FIG. 2), one or more internal compartments, and a cartridge holder that is removably engaged with the outer body shell. A container (see, for example, cartridge holding container 212 in FIG. 2). The outer shell disclosed herein can be made from any durable material that provides robustness, safety and portability, including metals or alloys, high strength plastics or composite materials. The shape of the outer shell encompasses the steam generation assembly disclosed herein and is designed to provide a practical and comfortable feel when held in the user's hand and during operation of the device.

  The housing disclosed herein may optionally include a fluid chamber assembly access cover that is removably engaged with the outer body shell. The fluid chamber assembly access cover disclosed herein is designed to provide access to the fluid chamber assembly disclosed herein. The fluid chamber assembly access cover disclosed herein is designed to be removed from the outer body shell of the transdermal delivery device. Such removal, for example, allows the user to remove the fluid chamber assembly or its components as well as reattach the fluid chamber assembly or its components. In certain aspects, the fluid chamber assembly access cover disclosed herein can be completely removed from the housing of the transdermal delivery device to allow access as disclosed herein. Designed. In another aspect, the fluid chamber assembly access cover disclosed herein is designed to provide access to the fluid chamber assembly as disclosed herein, but nevertheless It remains attached to the outer body shell of the body. As a non-limiting example, the fluid chamber assembly access cover may include a threaded portion that may be capable of screwing or unscrewing the outer body shell threaded portion. In such an embodiment, the access cover can be completely removed from the housing. As another non-limiting example, the fluid chamber assembly access cover includes a passage and groove structure and the outer body shell allows the access cover to slide back and forth from an open position to a closed position. Such a structure may include a locking member that allows complete removal of the access cover or prevents complete removal, but provides access as disclosed herein. Can be designed to. As yet another non-limiting example, the fluid chamber assembly access cover can include a hinge assembly having an outer body shell that the access cover can open and close. In such a structure, the access cover generally remains attached to the housing. Other structures that allow access are known to those skilled in the art, as disclosed herein.

  One or more internal compartments disclosed herein are designed to hold the vapor generating assembly or its components correctly in a manner that ensures proper operation of the transdermal delivery device. The internal compartment is not limited and includes a delivery outlet that is open at the end (see, eg, delivery outlet 206 that is open at the end of FIG. 2) and a steam generation assembly compartment (eg, steam generation in FIG. 2). Assembly compartment 208). Such compartments may include internal struts that enhance the structural integrity of the devices and / or foundations that ensure proper placement and function of the steam generation assembly or components thereof disclosed herein.

  The cartridge holding container disclosed herein may include an outer cover shell (see, eg, outer cover shell 214 in FIG. 2) and an inner cartridge compartment (see, eg, inner cartridge compartment 216 in FIG. 2). The cartridge holding container disclosed herein is designed to properly place, mount and secure the compressed gas cartridge in the lance housing of the permeation valve during operation of the transdermal delivery device.

  The cartridge holding container disclosed herein can removably engage the outer body shell of the housing. In other embodiments, the cartridge can be incorporated into the device and can be disposable, after which the device can be discarded. The cartridge holding container disclosed herein can be designed to be completely removed from the transdermal delivery device housing to obtain an unengaged position, as disclosed herein. . In another aspect, the cartridge holding container disclosed herein is designed to obtain an unengaged position as disclosed herein, but still attached to the housing. . By way of non-limiting example, the cartridge holding container may include a threaded portion that can be screwed or unscrewed to the threaded portion of the outer body shell. In such a structure, the cartridge holding container can be completely removed from the housing in which the compressed gas cartridge is inserted into the internal cartridge compartment. The cartridge holding container is then screwed back into the housing so that proper insertion of the cartridge into the device is possible. As another non-limiting example, the cartridge holding container includes a hinge assembly with an outer body shell in which the cartridge holding container can be positioned so that the compressed gas cartridge can be properly inserted into the device. In such a structure, the cartridge holding container generally remains attached to the housing. Other structures are known that allow for proper cartridge insertion and cartridge holding container attachment as disclosed herein.

  The cartridge holding container disclosed herein can be removably engaged with the outer body shell of the transdermal delivery device. This is achieved because the cartridge holding container disclosed herein can be in one of two operating positions. In the disengaged position (or removed or open position), the cartridge holding container disclosed herein allows the compressed gas cartridge to be placed in the internal cartridge compartment of the cartridge holding container or the cartridge holding container is Expose the lance housing present in the permeation valve disclosed herein for the compressed gas cartridge and / or allow both. In the engaged position (or attached or closed position), the compressed gas is released from the cartridge, and the released gas is compressed so that the gas flows through a permeation valve through the valve at a predetermined flow rate. The cartridge holding container disclosed herein is designed to place, mount and secure the gas cartridge in the lance housing of the permeation valve.

  The housing disclosed herein may optionally include a leg stand (see, eg, leg stand 204 in FIG. 2) or other protrusion attached to the outer body shell. The leg stand disclosed herein may generally be positioned near the end where the delivery outlet, which is open at the end, is located. The leg stand disclosed herein is designed to tilt the fluid container assembly to provide a tilt of no more than 30 ° relative to the horizontal position of the transdermal delivery device to facilitate gas and liquid mixing. Can be done. The leg stand can also be stored in the outer body for ease of storage.

  Thus, in certain aspects, as disclosed herein, the housing includes an outer body shell, a delivery outlet that is open at a termination that includes a treatment chamber, and a vapor generation assembly that includes a fluid exchanger. A compartment, a permeation valve, and a cartridge holding container removably engaged with the outer body shell, wherein the vapor generating assembly compartment is located between the delivery outlet open at the end and the cartridge holding container. Can do. The delivery outlet, which is open at the end, is designed to accommodate an individual's body part, such as a finger, toe or hand. Alternatively, the delivery outlet with an open end may simply be placed on or near the skin surface. The steam generation assembly compartment itself may be divided into different compartments that are designed to include the components of the steam generation assembly disclosed herein.

  In another aspect, a housing disclosed herein includes an outer body shell, a delivery outlet having an open end, a vapor generation assembly compartment comprising a fluid chamber assembly compartment and a permeation valve, and an outer body. A cartridge holding container removably engaged with the shell, wherein the linear arrangement of the inner compartment is a delivery outlet with an open end adjacent to the fluid chamber assembly compartment next to the permeation valve; It has become.

  An exemplary device is shown in FIG. 2, wherein the housing 200 includes an outer body shell 202, a leg stand 204, a delivery outlet 206 that is open at the end, a steam generation assembly compartment 208, and an outer body shell 202. A permeate valve compartment 210 and a cartridge holding container 212 that are removably engaged with each other, and an outer cover shell 214 and an inner cartridge compartment 216.

  The transdermal device may optionally comprise a compressed gas cartridge that may be housed within the cartridge holding container 212. The compressed gas cartridges disclosed herein generally contain sufficient gas under pressure to produce a volume of liquid supersaturated with dissolved gas sufficient to produce a vapor that provides a therapeutic effect. It is a sufficient dimension. In some cases, a therapeutic effect can be obtained with a single administration of supersaturated gas. The compressed gas cartridge disclosed herein may have a pressure in excess of 40 psi at 21.1 ° C., or 104 psi at 54.4 ° C., regardless of the pressure at 21.1 ° C. A gas having a pressure greater than (approximately 717 kilopascals) or any liquid having an absolute vapor pressure greater than 40 psi (approximately 275 kilopascals) at 37.8 ° C. may be accommodated. For example, about 400 kilopascals (about 58 psi) at 21.1 ° C., about 600 kilopascals (about 87 psi) at 21.1 ° C., about 800 kilopascals (about 116 psi) at 21.1 ° C., or about 21.1 ° C. Under a pressure of 1000 kilopascals (about 145 psi), the compressed gas cartridge contains 16 grams, 8 grams or 1.3 grams of food industry or medical gas. In one embodiment, under about 800 kilopascals at 21.1 ° C., the compressed gas cartridge contains 16 grams of food industry or medical carbon dioxide. The compressed gas cartridge may be designed to be disposable. Such disposable compressed gas cartridges generally include a permeable seal that can be pierced to release gas. For example, as disclosed herein, the lance from the permeation valve punctures the permeation seal of the compressed gas cartridge, thereby ensuring proper operation of the transdermal delivery device. Compressed gas can be released from the cartridge.

  Non-limiting examples of gases useful for operating the transdermal delivery devices disclosed herein include food industry or medical carbon dioxide, food industry or medical oxygen, food industry Food industry or medical gas, including industrial or medical helium and food industry or medical argon. The compressed gas cartridge disclosed in the present specification may have a thread or may not have a thread. Compressed gas cartridges with threads can be secured to a pressure-temperature controller assembly without relying on a cartridge holding container as disclosed herein. Compressed gas cartridges without threads are secured to the permeation valve using a cartridge holding container, as disclosed herein. The compressed gas cartridge disclosed herein may be a standard industrial design or a custom design useful only for the transdermal delivery devices disclosed herein. In certain aspects, a compressed gas cartridge with or without threads includes a body, an internal gas compartment, and a pierceable seal. In another aspect, a compressed gas cartridge with or without threads includes a body, a neck, an internal gas compartment, and a pierceable seal.

  Aspects herein disclose, in part, a steam generation assembly. The vapor generation assembly disclosed herein comprises a permeation valve and a fluid chamber assembly. The steam generation assembly disclosed herein may optionally comprise a regulation switch assembly. In certain aspects, the vapor generation assembly disclosed herein comprises a permeation valve and a fluid chamber assembly, but does not comprise a regulating switch assembly. In another aspect, a vapor generation assembly disclosed herein comprises a permeation valve, a regulation switch assembly, and a fluid chamber assembly.

  In certain aspects, as shown in FIG. 3A, fluid chamber assembly 302 may be coupled to permeation valve 304 using a tube 306. A compressed gas cartridge (not shown) can be coupled to the permeation valve 304 and the screw attachment point 308. A first bamboo shoot connector 310 and a second bamboo shoot connector 312 can be used to connect the respective components to the tube 306. The tube 306 can be formed from any suitable material such as, for example, plastic or metal. The tube 306 can also be connected to a bamboo bar or other lock-type coupler using a gasket or O-ring. In other embodiments, the tube can simply be welded or directly attached to the component without the use of bamboo shoots.

  As shown in FIG. 3B, the fluid chamber assembly 302 and the permeation valve 304 can be directly connected without the use of a tube. Here, the male thread 314 of the fluid chamber assembly 302 can be screwed to the female thread 316 of the permeation valve 304. The opposite screw structure can also be used. In yet another aspect, the fluid chamber assembly 302 and the permeation valve 304 can be manufactured as one piece without the need for manual attachment.

  FIG. 3C shows a system that includes a steam generation assembly 318 comprising a fluid chamber 302 and a regulating switch assembly 320 coupled to the permeation valve 304 as shown in FIG. 3A. Adjustment switch assembly 320 is an optional feature that may or may not be used with the devices disclosed herein.

  As shown in FIG. 3A, the permeation valve 304 can be directly associated with two components. The first connecting device 322 is typically screwed to the permeation valve 304 and is used to tie it to the fluid chamber assembly 302 and eventually to the delivery area. The second connection device 324 is also screwed to the permeation valve 304 and is typically used to connect the permeation valve 304 with a compressed gas cylinder.

  In certain aspects, as shown in FIGS. 4A-C, transdermal delivery device 400 includes a housing 402 with a leg stand 404 and a fluid chamber access cover 406. The fluid chamber assembly access cover 406 is opened to show the delivery outlet 408 having an open end and the fluid chamber assembly 410. The fluid chamber assembly access cover includes a passage and groove structure 412 and the housing 402 allows the access cover 406 to slide back and forth. In other aspects, the hinge 414 may move the access cover 406 upward to expose the delivery outlet 408 and fluid chamber access cover 410 that are open at the ends.

  The cartridge holding container 416 can be removed from the transdermal delivery device 400 to expose the front end of the permeation valve 418 where the lance housing 420 is located. The cartridge holding container 416 can hold the compressed gas cartridge 422. The cartridge retaining container (not shown) has a threaded portion that can be screwed on or removed from the threaded portion of the outer body shell 320.

  In some aspects, the fluid chamber assembly access cover 406 can have a window 424 that can be used to view the contents of the fluid chamber 426 when the fluid chamber assembly access cover 406 is closed. In such embodiments, at least a portion of the fluid chamber 426 adjacent to the window 424 can be transparent.

  FIG. 3C comprises additional components and a regulation switch assembly 430 that may be the regulation switch assembly described in FIG. 6 or of a different design, but having the same function. 4 is a cross-sectional view of another transdermal delivery device 428. FIG. The adjustment switch 430 allows adjustment of the therapeutic drug delivery instant or period of delivery. In contrast, this is a device without an adjustment switch 430 that will flow the contents of the cartridge 422 until it is depleted. In other words, the adjustment switch 430 allows the device to be switched on and off.

  The permeation valve disclosed in the present specification includes at least one permeation member. The permeation valve disclosed herein is designed to reduce the pressure of gas entering from a compressed gas cartridge. In some examples, the permeation valve can increase the temperature of the gas so that the gas is dissolved as it enters the fluid chamber as disclosed herein. The permeation valve disclosed herein includes not only a lance but also a permeation member. The valve itself can be formed from an alloy, high strength glass reinforced nylon or other lightweight material that can withstand the high and low temperatures caused by the gas as it leaves the compressed gas cartridge. The permeation valve disclosed herein may further include an adapter for connecting other portions of the device assembly thereto. An exemplary permeation valve useful for operating the transdermal delivery device disclosed herein is described, for example, in US Pat. No. 7,857,167, named Hollars, Compressed Gas Cartridge permeation Dispenser having a Predictable Permeation Rate. And all that is disclosed in connection with permeation valves is incorporated herein by reference.

  In some embodiments, the permeation valves disclosed herein can be set to reduce the pressure of the compressed gas to less than about 40 psi (about 275 kilopascals) at 21.1 ° C. In aspects of this embodiment, the permeation valve can provide a compressed gas pressure of, for example, about 35 psi (about 241 kilopascals), about 30 psi (about 207 kilopascals), about 25 psi (about 172 kilopascals), about 20 psi (about about 138 kilopascals) or about 15 psi (about 103 kilopascals). In other aspects of this embodiment, the permeation valve can adjust the pressure of the compressed gas to, for example, less than 40 psi (about 275 kilopascals), less than 35 psi (about 241 kilopascals), less than 30 psi (about 207 kilopascals), 25 psi (25 psi). It can be set to decrease to less than about 172 kilopascals, less than 20 psi (about 138 kilopascals), or less than 15 psi (about 103 kilopascals). In yet another aspect of this embodiment, the permeation valve provides a compressed gas pressure of, for example, between about 15 psi (about 103 kilopascals) and about 40 psi (about 275 kilopascals), about 15 psi (about 103 kilopascals). ) And about 35 psi (about 241 kilopascals), between about 15 psi (about 103 kilopascals) and 30 psi (about 207 kilopascals), about 15 psi (about 103 kilopascals) and about 25 psi (about 172 kilopascals). ) Or between about 15 psi (about 103 kilopascals) and about 20 psi (about 138 kilopascals).

  In another aspect, the permeation valve disclosed herein is a compressed gas so that the gas does not freeze the liquid contained in the fluid chamber assembly as the gas passes through the permeation valve and enters the fluid chamber assembly. Increase the temperature. In aspects of this embodiment, the permeation valve provides the temperature of the compressed gas to, for example, about 0 ° C, about 2 ° C, about 4 ° C, about 5 ° C, about 8 ° C, about 10 ° C, about 12 ° C, about 15 ° C. , About 18 ° C, about 20 ° C or about 22 ° C. In another aspect of this embodiment, the permeation valve provides a temperature of the compressed gas, for example, at least 0 ° C, at least 2 ° C, at least 5 ° C, at least 8 ° C, at least 10 ° C, at least 12 ° C, at least 15 ° C, at least It can be raised to 18 ° C, at least 20 ° C or at least 22 ° C. In yet another aspect of this embodiment, the permeation valve provides a temperature of the compressed gas, for example, between about 0 ° C. and about 22 ° C., between about 2 ° C. and about 22 ° C., about 4 ° C. and about 22 ° C. Between about 8 ° C and about 22 ° C, between about 12 ° C and about 22 ° C, between about 0 ° C and about 18 ° C, between about 2 ° C and about 18 ° C, about 4 ° C. It can be raised to between about 0 ° C and about 18 ° C, between about 8 ° C and about 18 ° C, or between about 12 ° C and about 18 ° C.

  In another aspect, the permeation valve disclosed herein reduces the pressure of the compressed gas from about 40 psi (about 275 kilopascals) to about 15 psi (about 103 kilopascals) and reduces the temperature of the compressed gas to about 0. It can be set to increase from 0 ° C to about 22 ° C. In another aspect, the permeation valve disclosed herein reduces the pressure of the compressed gas from about 40 psi (about 275 kilopascals) to about 15 psi (about 103 kilopascals) and reduces the temperature of the compressed gas to about 4 psi. It can be set to increase from 0 ° C to about 22 ° C. In another aspect, the permeation valve disclosed herein reduces the pressure of the compressed gas from about 40 psi (about 275 kilopascals) to about 15 psi (about 103 kilopascals) and reduces the temperature of the compressed gas to about 8 psi. It can be set to increase from 0 ° C to about 22 ° C. In another aspect, the permeation valve disclosed herein reduces the pressure of the compressed gas from about 40 psi (about 275 kilopascals) to about 15 psi (about 103 kilopascals) and reduces the temperature of the compressed gas to about 12 psi. It can be set to increase from 0 ° C to about 22 ° C.

  In another aspect, the permeation valve disclosed herein is set to reduce the pressure of the compressed gas to less than about 40 psi (about 275 kilopascals) and raise the temperature of the compressed gas to at least 0 ° C. obtain. In another aspect, the permeation valve disclosed herein is set to reduce the pressure of the compressed gas to less than about 40 psi and increase the temperature of the compressed gas to at least 4 ° C. obtain. In another aspect, the permeation valve disclosed herein is set to reduce the pressure of the compressed gas to less than about 40 psi and increase the temperature of the compressed gas to at least 8 ° C. obtain. In another aspect, the permeation valve disclosed herein is set to reduce the pressure of the compressed gas to less than about 40 psi and to raise the temperature of the compressed gas to at least 12 ° C. obtain.

  In certain aspects, as shown in FIGS. 5A and 5B, the permeation valve assembly 500 includes a lance housing 502, a permeation member housing 504, a first attachment member 506, a second attachment member 508, Is provided. In some embodiments, each of the above-described members may be formed as a unitary unit, while in other embodiments, the members may be separately connectable. The connection points can be sealed using O-rings 510, 510 'or other means such as gaskets, bamboo shoots or compression fittings.

  The lance housing 502 may include a lance 512 located at the upstream end 514 of the permeate valve assembly 500. When the compressed gas cartridge seal 516 is brought into contact with the lance 512, the lance 512 may puncture the compressed gas cartridge seal 516 located at the neck of the compressed gas cartridge 518. The lance as disclosed herein can puncture the seal of the compressed gas cartridge and the compressed gas from the cartridge to the permeation valve assembly 500 to ensure proper operation of the transdermal delivery device. Any design that can release Such lance designs include, for example, hollow drilled lance designs and solid drilled lance designs.

  As shown in FIG. 5A, the compressed gas cartridge 518 can be screwed to the second attachment member 508. However, as shown in FIG. 5B, the compressed gas cartridge 518 may remain sealed until the compressed gas cartridge seal 516 reaches the lance 512. Once the lance 512 has punctured the compressed gas cartridge seal 516, gas can exit the cartridge and travel through the device.

  As the air exits the compressed gas cartridge 518, it passes through the hollow lance and / or the periphery of the lance member and travels through the device. In general, the lance 512 cannot substantially obstruct the airflow and cannot control the air pressure. The high pressure air can then travel through the lance housing 502 to the inner bore 520 until the high pressure air reaches the surface 522 of the permeable member housing 504. At the surface 522, the high pressure air enters the permeable member housing 504 through the hole in the surface 522. Just inside the hole, the high pressure air hits the permeable member 526. The transmissive member 526 can make a sealing portion by the surrounding wall 528.

  The purpose of the permeable member 526 is to adjust and / or reduce the air pressure. For example, the air entering the permeable member housing 504 can be at high pressure and the air that eventually exits the opposite permeable member housing 504 can be at a lower pressure. The permeable member 526 may be any semi-permeable material such as rubbers, corks, woven materials, porous polymer materials, densely sintered materials or any other suitable material that provides the appropriate and / or desired transmittance. Can also be configured.

  Air gradually permeates through the permeable member 526 at a rate specific to the material used to form the member. When the permeated air exits the permeable member 526, the pressure is lower than when air enters. This low pressure air can then pass through the permeate housing bore 530 and flow freely through the remaining permeate valve assembly 500.

  The transmissive member may also be in the form of an O-ring seal or other functional part of the device instead of or in addition to a single transmissive member. For example, a permeable member or other component of a permeable valve as described in US Pat. No. 7,857,167 is incorporated herein by reference for all that is disclosed for permeable valves.

  Depending on device requirements and configuration, the first mounting member 506 and the second mounting member 508 may be the same or different. 5A and 5B, the first attachment member 506 is a bamboo shoot connector 532 that is screwed to the transmission member housing 504 at an attachment portion 534 having a thread. 5A and 5B, the second attachment member 508 is an attachment portion having a thread for the cartridge holding container 536 having the opposite side thread. In another aspect, a cartridge holding container is not necessary. There, the compressed gas cartridge 518 can be screwed directly to the second mounting member 508 because it has threads.

  In some aspects, the permeable valve assembly 500 may not include moving parts and / or mechanical parts (eg, springs, actuators or moving bearings). In such an embodiment, the transmission is completely adjusted by the transmission member 526. In some cases, this adjustment can improve device safety, prevent unwanted mechanical problems, and improve simplicity and reduce the overall size of the device.

  To ensure that the proper amount of gas is dissolved in the liquid, the permeation valve assembly can be configured to inject the gas over a reasonable time (eg, for the size of the permeation member and / or the orifice). In some embodiments, for example, the permeation valve assembly is adjusted to inject gas for about 3 minutes, about 5 minutes, about 7 minutes, about 10 minutes, about 12 minutes, about 15 minutes, about 18 minutes, or about 20 minutes. Can be done. In another aspect, the permeation valve assembly is configured to inject gas over, for example, at least 3 minutes, at least 5 minutes, at least 7 minutes, at least 10 minutes, at least 12 minutes, at least 15 minutes, at least 18 minutes or at least 20 minutes. Can be adjusted. In yet another aspect, for example, from about 3 minutes to about 5 minutes, from about 3 minutes to about 10 minutes, from about 3 minutes to about 15 minutes, from about 3 minutes to about 20 minutes, from about 5 minutes to about 10 minutes, about The permeation valve assembly can be adjusted to inject gas for 5 minutes to about 15 minutes or about 5 minutes to about 20 minutes.

  In some embodiments, once the compressed gas cylinder is screwed into the permeate valve assembly and pierced by the lance, the permeation of gas through the permeable member is constant until the compressed gas is removed from the cylinder. In other words, once a compressed gas cylinder is drilled with a lance, in the absence of an “off” valve, the gas begins to flow without interruption until it is depleted.

  In other embodiments, a compressed gas cylinder may be provided that is permanently and / or non-removably attached to the device. In such an embodiment, a button can be used to puncture the cylinder with a lance at a predetermined time and the cylinder can be used to the end. When the gas is completely gone, the device can be discarded. Such an embodiment can be used as a disposable device. The patient receives a group of devices, each of which can be used once and discarded.

  In other embodiments, a regulating switch assembly that potentially and / or selectively stops airflow before the gas cylinder is completely depleted of gas can be inserted between the permeate valve assembly and the fluid chamber. Such an adjustment switch as disclosed herein comprises an actuator, a switch body, an inlet port and an outlet port and can be operated by a mechanical or electronic design. The regulating switch assembly disclosed herein is designed to regulate when low pressure gas exiting the controller assembly can enter the fluid chamber assembly.

  In one aspect, as shown in FIG. 6, the adjustment switch assembly 600 includes an actuator 602, a switch body 604, an inlet port 606, a flow ball seat valve 608, and a flow valve insert 610. The inlet port 606 can be coupled to the outlet port of the permeation valve disclosed herein. However, the actuator 602 can prevent gas flow to the flow ball seat valve 608. Activation of the actuator 602 creates a flow path that establishes communication between the inlet port 606 and the flowball seat valve 608, thereby allowing gas to enter the flowball seat valve 608. The flow ball seat valve 608 includes a ball seat valve body 610 that houses a seat valve ball 612, a ball spring 614, and a ball seat valve outlet port 616. Actuator 602 activation releases the tension in ball spring 614, thereby reducing the pressure on ball 612 that is forced against O-ring 618 by the tension of ball spring 614. When the actuator 602 is pressed, the clogged portion 620 moves downward, exposing the gap portion 622 connecting the inlet port 606 and the ball chamber 624, and pressure can cause the housing seat ball valve 612. The clogged portion 620 and the gap portion 622 are distinguished by one or more O-rings 626. When pushed down using a locking mechanism 628 that engages the bottom 630, the actuator 602 can be locked in the “open” position. By removing the pressure, gas can pass through the flow ball seat valve 608 and exit through the ball seat valve outlet port 616. Gas can flow to the fluid chamber assembly by way of the communication switch assembly 600 and the fluid chamber assembly disclosed herein. This communicated passage may be formed by the fluid chamber assembly inlet port and flow valve insert 610 as disclosed herein.

The fluid chamber assembly disclosed herein comprises a fluid container, an inlet port, and an outlet port. The fluid container may hold a liquid that will be supersaturated by the gas entering the chamber from the pressure-temperature controller assembly. The liquid may be water, physiological buffer or any other suitable liquid. Suitable liquids are: 1) dissolve a suitable amount of gas in the liquid to produce a vapor-containing liquid particle containing a supersaturated amount of the therapeutic agent, 2) retain, enable, or activate the therapeutic agent Ensuring that a therapeutically effective amount of the drug is received by the individual upon administration. For example, carbon dioxide comes out in gaseous and molecular forms. It is a molecular form of carbon dioxide that has the ability to dissolve in liquids such as water, allowing easy absorption of carbon dioxide through the skin. Conversely, at higher pH, carbon dioxide tends to turn into carboxylic acid (H ₂ CO ₃ ) and bicarbonate ions that are not readily absorbed through the skin. The lower the pH of the liquid, the more carbon dioxide in molecular form. Therefore, when the gas is carbon dioxide, the pH of the liquid should be weakly acidic, for example, about pH 6 or lower, about pH 5.5 or lower, about pH 5 or lower, about pH 4.5 or lower, or about pH 4 or lower. is there.

  Alternatively, another substance having the ability to dissolve a supersaturated amount of gas may be used instead of the liquid. Non-limiting examples of such materials include colloids such as foams, liquid aerosols, emulsions, gels and sols.

  The liquid disclosed herein contains a therapeutic agent. As used herein, the term “therapeutic agent” is synonymous with “active ingredient” and means used for any substance that has a beneficial effect on the individual to whom the therapeutic agent is administered.

  One type of therapeutic agent is a gas that is dissolved in a liquid as disclosed herein. An exemplary gas that is a therapeutic agent is carbon dioxide. Because these molecules are important biological messengers, the latest use of gases in medicine is rapidly being studied. For example, increasing the blood carbon dioxide concentration decreases the pH by conversion of carbon dioxide to bicarbonate. This reduced pH allows oxygen to more easily dissociate from hemoglobin, which is called the “Bohr effect”. Also, the elevated carbon dioxide concentration improves circulation and blood flow by triggering the release of vasodilators that dilate blood vessels for the purpose of increasing oxygen supply. Thus, increasing the carbon dioxide concentration increases tissue oxygen, and similarly, it increases vasodilation, which allows more nutrients to be delivered to the cells, and increases the supply of oxygen to the cells. By increasing the cell metabolism is increased. Thus, increasing the tissue oxygen concentration in this method includes, but is not limited to, promoting skin healing, improving skin texture, and providing anti-aging benefits to the skin. It has many beneficial effects that promote health.

  Another type of therapeutic agent that can be administered by the transdermal delivery device disclosed herein is either a drug that can be dissolved in the liquid disclosed herein or that can become part of the vapor upon vaporization. It is. Today, about half of the pharmaceuticals available on the market have a molecular affinity for water. This affinity is manifested in a tendency to dissolve in, mix with, or absorb water. Therapeutic agents with these properties are called hydrophilic therapeutic agents and include not only biologics but also small molecule drugs or chemical agents. Hydrophilic therapeutic agents include, but are not limited to, nicotine antihistamines, beta blockers, calcium antagonists, nonsteroidal anti-inflammatory drugs, contraceptives, antiarrhythmic drugs, insulin, antiviral drugs, analgesics, hormones, Contains alpha interferon, vitamins (eg, vitamin D) and chemotherapeutic agents. In some embodiments, the drug comprises one or more water soluble drugs.

  Another type of therapeutic agent that can be administered by the transdermal delivery device disclosed herein is a vitamin that can be dissolved in the liquid disclosed herein or become part of the liquid particle upon vaporization.

  In some embodiments, the amount of gas dissolved in the liquid is, for example, about 30000 ppm, about 35000 ppm, about 40000 ppm, about 45000 ppm, about 50000 ppm, about 55000 ppm or about 60000 ppm. In another aspect, the amount of gas dissolved in the liquid is, for example, at least 30000 ppm, at least 35000 ppm, at least 40000 ppm, at least 45000 ppm, at least 50000 ppm, at least 55000 ppm or at least 60000 ppm. In yet another aspect, the amount of gas dissolved in the liquid is, for example, at most 30000 ppm, at most 35000 ppm, at most 40000 ppm, at most 45000 ppm, at most 50000 ppm, at most 55000 ppm or at most 60000 ppm. In yet another aspect, the amount of gas dissolved in the liquid is, for example, between about 30000 ppm and about 35000 ppm, between about 30000 ppm and about 40000 ppm, between about 30000 ppm and about 45000 ppm, between about 30000 ppm and about 50000 ppm. Between about 35000 ppm to about 40000 ppm, between about 35000 ppm to about 45000 ppm, between about 35000 ppm to about 50000 ppm, between about 40000 ppm to about 45000 ppm, between about 40000 ppm to about 50000 ppm, or between about 50000 ppm to about 60000 ppm. It is.

  In certain embodiments where the therapeutic agent is not a dissolved gas or may not be a dissolved gas, the agent can be contained in a liquid located in the fluid container. The liquid located in the fluid container may also contain additional therapeutic agents as well as dissolved gases that also provide a therapeutic effect.

  The fluid chamber assembly may optionally include a fluid container cap that removably engages the fluid container disclosed herein. As disclosed herein, the ability to remove a fluid container allows for refilling of liquid as needed. For example, in applications involving wound healing, the liquid may include not only the dissolved molecular carbon dioxide, but also wound agents such as cyclosporine.

  As disclosed herein, the inlet port is designed to receive a low pressure gas flowing out of the permeation valve and allows the gas to flow to the fluid chamber assembly. In rare cases in a fluid chamber assembly, the gas will dissolve in the liquid contained within the fluid container, resulting in a liquid containing a supersaturated amount of dissolved gas molecules. As used herein, "supersaturation" when used in connection with "supersaturated amounts of dissolved gas molecules" can be accommodated by a liquid under atmospheric and atmospheric pressures, generally measured at 25 ° C and 1 atmosphere. Means a liquid disclosed herein that contains more dissolved gas. For example, in connection with the transdermal delivery device disclosed herein, the pressure of the dissolved gas in the fluid chamber assembly is greater than the pressure of the gas outside the assembly. In certain aspects, the inlet port comprises a check value, a spring and a poppet, as disclosed herein.

  As disclosed herein, an outlet port is a supersaturated amount of dissolved gas molecules at atmospheric pressure from a fluid chamber assembly toward a delivery outlet that is open at the end where it can be administered to an individual. And / or designed to release vapor containing therapeutic agents. In certain aspects, as disclosed herein, the outlet port comprises a check value, a spring, and a poppet. When the pressure inside the fluid container is sufficient to discharge liquid through the outlet port, vaporization of the liquid containing a supersaturated amount of dissolved gas is achieved. In certain aspects of this embodiment, a supersaturated amount of pressure when the pressure inside the liquid container is, for example, about 15 psi, about 20 psi, about 25 psi, about 30 psi, about 35 psi, about 40 psi, about 45 psi, or about 50 psi. Vaporization of a liquid containing dissolved gas is realized. In other aspects of this embodiment, the amount of supersaturation when the pressure inside the liquid container is, for example, at least 15 psi, at least 20 psi, at least 25 psi, at least 30 psi, at least 35 psi, at least 40 psi, at least 45 psi, or at least 50 psi. The vaporization of the liquid containing the dissolved gas is realized. In yet another aspect of this embodiment, the pressure inside the liquid container is, for example, at most 15 psi, at most 20 psi, at most 25 psi, at most 30 psi, at most 35 psi, at most 40 psi, at most 45 psi, or Vaporization of a liquid containing a supersaturated amount of dissolved gas is achieved at most 50 psi. In yet another aspect of this embodiment, the pressure inside the liquid container is, for example, from about 15 psi to about 50 psi, from about 20 psi to about 50 psi, from about 25 psi to about 50 psi, from about 30 psi to about 50 psi, from about 35 psi to about 50 psi, About 15 psi to about 45 psi, about 20 psi to about 45 psi, about 25 psi to about 45 psi, about 30 psi to about 45 psi, about 35 psi to about 45 psi, about 15 psi to about 40 psi, about 20 psi to about 40 psi, about 25 psi to about 40 psi, about 30 psi Vaporization of liquids containing supersaturated amounts of dissolved gas at about 40 psi, about 15 psi to about 35 psi, about 20 psi to about 35 psi, about 25 psi to about 35 psi, about 15 psi to about 30 psi, or about 20 psi to about 30 psi. Realized

  As disclosed herein, the vapor may include liquid particles and a supersaturated amount of dissolved gas molecules. The vapor can be a solution comprising a liquid aerosol, which is a liquid and gas or a colloidal composition comprising a liquid and a gas. When the therapeutic agent is not a dissolved gas, the vapor also includes a therapeutic agent, as disclosed herein.

  Vaporization can create liquid particles having an average dimension that is small enough to enter the skin pores. In some embodiments, the average size of the liquid particles can be, for example, about 100 micrometers, about 75 micrometers, about 50 micrometers, or about 25 micrometers. In another aspect, the average size of the liquid particles is, for example, 100 micrometers or less, 75 micrometers or less, 50 micrometers or less, or 25 micrometers or less. In yet another aspect, the average size of the liquid particles is, for example, from about 1 micrometer to about 100 micrometers, from about 1 micrometer to about 75 micrometers, from about 1 micrometer to about 50 micrometers, about 1 micrometer. To about 25 micrometers, about 5 micrometers to about 100 micrometers, about 5 micrometers to about 75 micrometers, about 5 micrometers to about 50 micrometers, about 5 micrometers to about 25 micrometers, about 10 micrometers. To about 100 micrometers, about 10 micrometers to about 75 micrometers, about 10 micrometers to about 50 micrometers, or about 10 micrometers to about 25 micrometers.

  The fluid chamber assembly may optionally include a pressure relief valve as a safety measure to prevent overpressure of the steam generation assembly or its components. In some embodiments, the pressure relief valve is, for example, a 30 psi valve, a 35 psi valve, a 40 psi valve, a 45 psi valve, or a 50 psi valve. In other embodiments, the pressure relief valve may not be required because the permeation valve is not mechanical and provides a predetermined constant airflow / pressure towards the fluid chamber.

  The fluid chamber assembly may optionally comprise a baffle assembly comprising one or more conical baffles or mixing elements. The baffle assembly is connected to a fluid container or a fluid container cap. The baffles are arranged in a cylindrical structure, with each overlying baffle partially overlapping other baffles, with their circular base side facing outwards from the inlet port. A narrow connecting piece at the periphery of the cylinder places the baffle in place. As the low pressure gas enters the fluid container via the inlet port, the airflow passes through the baffle and enhances the mixing of the gas and liquid. Thus, the baffle is designed to increase the rate of the amount of gas dissolved in the liquid and / or increase the amount of gas. In some embodiments, the fluid chamber assembly does not comprise a baffle assembly.

  In one aspect, as shown in FIG. 7, a fluid chamber assembly 700 includes a fluid container 702, a fluid container cap 704 that includes an inlet poppet 708, an inlet spring 710 and an inlet port 706 that includes an inlet check value 712, and an outlet. A poppet 716, an outlet spring 718 and an outlet port 714 including an outlet check value 720. Liquid 722 as disclosed herein is disposed in fluid container 702 and attached to fluid container cap 704 via screw 724. Screws are used for non-limiting illustration purposes and can be replaced by any securing means known to those skilled in the art. Via the inlet port 706, the gas enters the fluid chamber assembly 700 where the gas dissolves in the liquid. The air pressure there moves the inlet poppet 708 relative to the inlet spring 710 until the seal between the inlet poppet and the inner surface 726 is broken and gas can enter the chamber 726 and dissolve in the liquid 722. After a predetermined time, or after a certain or predetermined amount of pressure has been built, the pressure overcomes the force of the outlet spring 718 on the outlet poppet 716, and the outlet port face that seals the outlet poppet 716 and the O-ring When the seal with 728 breaks, a liquid containing a supersaturated amount of gas dissolved gas can be released. If the seal is broken, the gas can escape as vapor.

  Embodiments herein disclose a method of producing a material that includes a portion, a supersaturated amount of dissolved gas. As used herein, the term “substance” includes any material capable of dissolving a supersaturated amount of gas. Non-limiting examples of materials include liquids and colloids such as foams, liquid aerosols, emulsions, gels and sols. In the methods disclosed herein, the substance is placed in an airtight container and then the substance is exposed to the gas. During such exposure, a greater amount of gas dissolves in the material than can be dissolved at 25 ° C. and 1 atmosphere. The resulting material supersaturated with dissolved gas can then be administered to an individual and treated under conditions as disclosed herein.

  In some embodiments, the amount of gas dissolved in the material can be, for example, about 30000 ppm, about 35000 ppm, about 40000 ppm, about 45000 ppm, about 50000 ppm, about 55000 ppm, or about 60000 ppm. In another aspect, the amount of gas dissolved in the material can be, for example, at least 30000 ppm, at least 35000 ppm, at least 40000 ppm, at least 45000 ppm, at least 50000 ppm, at least 55000 ppm or at least 60000 ppm. In yet another aspect, the amount of gas dissolved in the material can be, for example, at most 30000 ppm, at most 35000 ppm, at most 40000 ppm, at most 45000 ppm, at most 50000 ppm, at most 55000 ppm or at most 60000 ppm. . In yet another aspect, the amount of gas dissolved in the material is, for example, between about 30000 ppm and about 35000 ppm, between about 30000 ppm and about 40000 ppm, between about 30000 ppm and about 45000 ppm, between about 30000 ppm and about 50000 ppm. Between about 35000 ppm to about 40000 ppm, between about 35000 ppm to about 45000 ppm, between about 35000 ppm to about 50000 ppm, between about 40000 ppm to about 45000 ppm, between about 40000 ppm to about 50000 ppm, or between about 50000 ppm to about 60000 ppm. Can be between.

  In another aspect, the method of producing a substance comprising a supersaturated amount of dissolved gas disclosed herein is performed by using a transdermal delivery device disclosed herein. For example, the fluid chamber assembly can be filled with a liquid or colloid, as disclosed herein, and the device is activated to produce a liquid or colloid containing a supersaturated amount of dissolved gas.

  Aspects herein further disclose, in part, a method of transdermally administering a therapeutically effective amount of a therapeutic agent disclosed herein. In certain aspects, the methods disclosed herein comprise administering to an individual a substance comprising a supersaturated amount of dissolved gas using the transdermal delivery device disclosed herein. The administration of dissolved gas treats symptoms associated with the disease and is therefore a therapeutically effective amount. A substance is a vapor, liquid, or foam that can be supersaturated with a certain amount of dissolved gas. It can be a liquid aerosol, emulsion, gel, sol, or other substance. In certain aspects of this embodiment, the substance containing a supersaturated amount of dissolved gas does not have another therapeutic agent. In another aspect of this embodiment, the dissolved gas is a carbon dioxide molecule. In yet another aspect of this embodiment, the dissolved gas is a carbon dioxide molecule that also serves as a therapeutic agent.

  In another aspect, a method disclosed herein comprises administering to an individual a substance comprising a supersaturated amount of dissolved gas and a therapeutic agent using a transdermal delivery device disclosed herein. Including. Administration of dissolved gas and / or therapeutic agent treats a disease-related condition and is therefore a therapeutically effective amount. The material can be a vapor, liquid, foam, liquid aerosol, emulsion, gel, sol, or other material that can be supersaturated with an amount of dissolved gas. In some aspects of this embodiment, the dissolved gas is a carbon dioxide molecule. In another aspect of this embodiment, the dissolved gas is a carbon dioxide molecule that also serves as a therapeutic agent.

  Aspects herein disclose, in part, a method of treating an individual's disease. In some embodiments, a method of treating a disease disclosed herein comprises a composition comprising a substance comprising a therapeutically effective amount of a dissolved gas using a transdermal delivery device as disclosed herein. Administering an article to an individual suffering from a disease, wherein administration of the composition relieves symptoms associated with the disease. The administration of gas treats symptoms related to the disease. The substance can be a vapor, liquid, foam, liquid aerosol, emulsion, gel, sol or other substance that can be supersaturated with an amount of dissolved gas. In certain aspects of this embodiment, a composition comprising a substance that includes a therapeutically effective amount of a dissolved gas does not have another therapeutic agent. In another aspect of this embodiment, the dissolved gas is a carbon dioxide molecule. In yet another aspect of this embodiment, the dissolved gas is a carbon dioxide molecule that also serves as a therapeutic agent.

  In another aspect, a method of treating a disease disclosed herein uses a transdermal delivery device as disclosed herein to treat a therapeutically effective amount of dissolved gas and a therapeutically effective Administering a composition comprising a substance comprising an amount of another therapeutic agent to an individual suffering from a disease, the administration of the composition relieves symptoms associated with the disease. The administration of a gas and / or therapeutic agent treats a condition associated with a disease and is therefore a therapeutically effective amount. The substance can be a vapor, liquid, foam, liquid aerosol, emulsion, gel, sol or other substance that can be supersaturated with an amount of dissolved gas. In some aspects of this embodiment, the dissolved gas is a carbon dioxide molecule. In another aspect of this embodiment, the dissolved gas is a carbon dioxide molecule that also serves as a therapeutic agent.

  As used herein, the term “treatment” relieves or eliminates a cosmetic or medical symptom associated with a disease in an individual, or delays the progression of a cosmetic or medical symptom associated with a disease in an individual, or Means to prevent. For example, the term “treatment” is associated with, for example, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or at least 100%, disease It can mean relieving symptoms. The effectiveness of the therapeutic agents disclosed herein in treating a disease can be determined by observing one or more cosmetic, medical symptoms, and / or physiological indicators associated with the disease. . Improvements in disease can also be indicated by a reduced need for combination therapy. A person skilled in the art knows the appropriate symptoms or indicators associated with a particular disease, and the individual is a candidate for treatment with a therapeutic agent by using the transdermal delivery device disclosed herein. You will know how to decide.

  Embodiments herein provide for administering, in part, a therapeutically effective amount of a therapeutic agent disclosed herein. As used herein, the term “therapeutically effective amount” is synonymous with “therapeutically effective dose” and refers to the therapeutic agent disclosed herein that is necessary to obtain the desired therapeutic effect. Means the minimum dose and includes the dose required to relieve symptoms associated with the disease.

  In aspects of this embodiment, the therapeutically effective amount of a therapeutic agent disclosed herein is, for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, Relieve disease-related symptoms by at least 70%, at least 80%, at least 90%, or at least 100%. In other aspects of this embodiment, a therapeutically effective amount of a therapeutic disclosed herein is, for example, up to 10%, up to 20%, up to 30%, up to 40%, up to Relieve symptoms associated with the disease by 50%, up to 60%, up to 70%, up to 80%, up to 90%, or up to 100%. In yet another aspect of this embodiment, the therapeutically effective amount of a therapeutic agent disclosed herein is, for example, from about 10% to about 100%, from about 10% to about 90%, from about 10% to about 80%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 20% to about 100%, about 20% to about 90% About 20% to about 80%, about 20% to about 20%, about 20% to about 60%, about 20% to about 50%, about 20% to about 40%, about 30% to about 100%, about 30% to about 90%, about 30% to about 80%, about 30% to about 70%, about 30% to about 60%, or about 30% to about 50% relieve disease-related symptoms. In yet another aspect of this embodiment, the therapeutically effective amount of a therapeutic agent disclosed herein is, for example, at least 1 week, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least The dosage is sufficient to relieve symptoms associated with the disease over 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, or at least 12 months.

  The actual therapeutically effective amount of a therapeutic agent administered to an individual disclosed herein includes, but is not limited to, the type of disease, the location of the disease, the cause of the disease, the severity of the disease, Duration of treatment, desired degree of relaxation, desired relaxation period, specific therapeutic agent used, elimination rate of the therapeutic agent used, pharmacology of the therapeutic agent used, the nature of the other composition in the vapor, eg age Can be determined by those skilled in the art by taking into account factors including individual characteristics such as weight, general health, medical history and risk factors, individual response to treatment, or combinations thereof. A therapeutically effective amount of a therapeutic agent disclosed herein is therefore readily determined by one of ordinary skill in the art, taking into account all criteria and using the best judgment of one of ordinary skill in the art for an individual. obtain.

  With respect to carbon dioxide as a therapeutic agent, 600 ppm of dissolved carbon dioxide molecules is the minimum amount necessary to produce a therapeutic effect. This is equivalent to 600 parts carbon dioxide mixed with one million parts water, or about 0.6% carbon dioxide and 99.4% water. In aspects of this embodiment, a therapeutic amount of the dissolved carbon dioxide molecule disclosed in the present disclosure includes, for example, about 600 ppm, about 700 ppm, about 800 ppm, about 900 ppm, about 1000 ppm, about 1500 ppm, It can be about 2000 ppm, about 2500 ppm, about 3000 ppm, about 3500 ppm, about 4000 ppm, about 4500 ppm, about 5000 ppm, about 5500 ppm, or about 6000 ppm. In other aspects of this embodiment, a therapeutic amount of dissolved carbon dioxide molecules disclosed herein for a therapeutically required amount is, for example, at least 600 ppm, at least 700 ppm, at least 800 ppm, at least 900 ppm, at least 1000 ppm, at least It can be 1500 ppm, at least 2000 ppm, at least 2500 ppm, at least 3000 ppm, at least 3500 ppm, at least 4000 ppm, at least 4500 ppm, at least 5000 ppm, at least 5500 ppm, or at least 6000 ppm. In other aspects of this embodiment, the therapeutic amount of the dissolved carbon dioxide molecule disclosed in the presently disclosed amount of therapeutic agent is, for example, between about 600 ppm and about 1000 ppm, between about 600 ppm and about 2000 ppm, Between about 600 pppm to about 3000 ppm, between about 600 ppm to about 4000 ppm, between about 600 ppm to about 5000 ppm, between about 600 ppm to about 6000 ppm, between about 600 ppm to about 10,000 ppm, between about 600 ppm to about 20000 ppm, about 600 ppm To about 30000 ppm, between about 600 ppm to about 40000 ppm, between about 600 ppm to about 50000 ppm, between about 600 ppm to about 60000 ppm, between about 1000 ppm to about 2000 ppm, between about 1000 pppm to about 3000 ppm, about 1 00 ppm to about 4000 ppm, about 1000 ppm to about 5000 ppm, about 1000 ppm to about 6000 ppm, about 1000 ppm to about 10,000 ppm, about 1000 ppm to about 20000 ppm, about 1000 ppm to about 30000 ppm, about 1000 ppm to It can be between about 40000 ppm, between about 1000 ppm and about 50000 ppm, or between about 1000 ppm and about 60000 ppm.

  In some embodiments, the therapeutically effective amount of carbon dioxide molecules increased blood flow. In aspects of this embodiment, the therapeutically effective amount of the carbon dioxide molecule is a blood flow rate, eg, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70. %, At least 80%, at least 90%, or at least 100%. In other aspects of this embodiment, the therapeutically effective amount of carbon dioxide molecules can be used for blood flow, eg, from about 10% to about 100%, from about 20% to about 100%, from about 30% to about 100%, Increase by about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, or about 80% to about 100%.

  In other aspects of this embodiment, the therapeutically effective amount of the carbon dioxide molecule may provide blood flow, eg, about 5 minutes or more, about 15 minutes or more, about 30 minutes or more, about 45 minutes or more, about 60 minutes or more. About 75 minutes or more, about 90 minutes or more, about 105 minutes or more, about 120 minutes or more, about 135 minutes or more, about 150 minutes or more, about 165 minutes or more, about 180 minutes or more, about 195 minutes or more, about 210 minutes or more At least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, over about 225 minutes, or over about 240 minutes, Or increase by at least 100%. In yet another aspect of this embodiment, the therapeutically effective amount of the carbon dioxide molecule provides blood flow, eg, about 5 minutes or more, about 15 minutes or more, about 30 minutes or more, about 45 minutes or more, about 60 minutes. About 75 minutes or more, about 90 minutes or more, about 105 minutes or more, about 120 minutes or more, about 135 minutes or more, about 150 minutes or more, about 165 minutes or more, about 180 minutes or more, about 195 minutes or more, about 210 minutes About 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% over about 225 minutes or more, or about 240 minutes or more To about 100%, about 60% to about 100%, about 70% to about 100%, or about 80% to about 100%.

  In other aspects of this embodiment, the therapeutically effective amount of carbon dioxide molecules can be used for blood flow, for example, from about 5 minutes to about 30 minutes, from about 5 minutes to about 60 minutes, from about 5 minutes to about 90 minutes, About 5 minutes to about 120 minutes, about 5 minutes to about 150 minutes, about 5 minutes to about 180 minutes, about 5 minutes to about 210 minutes, about 5 minutes to about 240 minutes, about 15 minutes to about 30 minutes, about 15 minutes Minutes to about 60 minutes, about 15 minutes to about 90 minutes, about 15 minutes to about 120 minutes, about 15 minutes to about 150 minutes, about 15 minutes to about 180 minutes, about 15 minutes to about 210 minutes, about 15 minutes to About 240 minutes, about 30 minutes to about 60 minutes, about 30 minutes to about 90 minutes, about 30 minutes to about 120 minutes, about 30 minutes to about 150 minutes, about 30 minutes to about 180 minutes, about 30 minutes to about 210 For about 30 minutes to about 240 minutes At least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or increases at least 100%. In yet another aspect of this embodiment, the therapeutically effective amount of carbon dioxide molecules can be used for blood flow, for example from about 5 minutes to about 30 minutes, from about 5 minutes to about 60 minutes, from about 5 minutes to about 90 minutes. About 5 minutes to about 120 minutes, about 5 minutes to about 150 minutes, about 5 minutes to about 180 minutes, about 5 minutes to about 210 minutes, about 5 minutes to about 240 minutes, about 15 minutes to about 30 minutes, about 15 minutes to about 60 minutes, about 15 minutes to about 90 minutes, about 15 minutes to about 120 minutes, about 15 minutes to about 150 minutes, about 15 minutes to about 180 minutes, about 15 minutes to about 210 minutes, about 15 minutes About 240 minutes, about 30 minutes to about 60 minutes, about 30 minutes to about 90 minutes, about 30 minutes to about 120 minutes, about 30 minutes to about 150 minutes, about 30 minutes to about 180 minutes, about 30 minutes to about 210 minutes, or about 30 minutes to about 240 minutes About 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100% About 70% to about 100%, or about 80% to about 100%.

  In another embodiment, a therapeutically effective amount of carbon dioxide molecules reduces blood pressure. In aspects of this embodiment, the therapeutically effective amount of carbon dioxide molecules is blood pressure, eg, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%. Decrease by at least 80%, at least 90%, or at least 100%. In other aspects of this embodiment, the therapeutically effective amount of carbon dioxide molecules can increase blood pressure, eg, about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, or about 80% to about 100%.

  In other aspects of this embodiment, the therapeutically effective amount of the carbon dioxide molecule is a blood pressure, eg, about 5 minutes or more, about 15 minutes or more, about 30 minutes or more, about 45 minutes or more, about 60 minutes or more, About 75 minutes or more, about 90 minutes or more, about 105 minutes or more, about 120 minutes or more, about 135 minutes or more, about 150 minutes or more, about 165 minutes or more, about 180 minutes or more, about 195 minutes or more, about 210 minutes or more, At least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or over about 225 minutes or more, or about 240 minutes or more, or Decrease by at least 100%. In yet another aspect of this embodiment, the therapeutically effective amount of the carbon dioxide molecule provides blood pressure, eg, about 5 minutes or more, about 15 minutes or more, about 30 minutes or more, about 45 minutes or more, about 60 minutes or more. About 75 minutes or more, about 90 minutes or more, about 105 minutes or more, about 120 minutes or more, about 135 minutes or more, about 150 minutes or more, about 165 minutes or more, about 180 minutes or more, about 195 minutes or more, about 210 minutes or more About 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 225 minutes or more, or about 240 minutes or more Decrease by about 100%, about 60% to about 100%, about 70% to about 100%, or about 80% to about 100%.

  In other aspects of this embodiment, the therapeutically effective amount of carbon dioxide molecules is about 5 minutes to about 30 minutes, about 5 minutes to about 60 minutes, about 5 minutes to about 90 minutes, about 5 minutes to about 90 minutes, for example. 5 minutes to about 120 minutes, about 5 minutes to about 150 minutes, about 5 minutes to about 180 minutes, about 5 minutes to about 210 minutes, about 5 minutes to about 240 minutes, about 15 minutes to about 30 minutes, about 15 minutes About 60 minutes, about 15 minutes to about 90 minutes, about 15 minutes to about 120 minutes, about 15 minutes to about 150 minutes, about 15 minutes to about 180 minutes, about 15 minutes to about 210 minutes, about 15 minutes to about 240 minutes, about 30 minutes to about 60 minutes, about 30 minutes to about 90 minutes, about 30 minutes to about 120 minutes, about 30 minutes to about 150 minutes, about 30 minutes to about 180 minutes, about 30 minutes to about 210 minutes Or for about 30 minutes to about 240 minutes, 10% even without, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or by at least 100%. In yet another aspect of this embodiment, the therapeutically effective amount of carbon dioxide molecules is a blood pressure, eg, about 5 minutes to about 30 minutes, about 5 minutes to about 60 minutes, about 5 minutes to about 90 minutes, About 5 minutes to about 120 minutes, about 5 minutes to about 150 minutes, about 5 minutes to about 180 minutes, about 5 minutes to about 210 minutes, about 5 minutes to about 240 minutes, about 15 minutes to about 30 minutes, about 15 minutes Minutes to about 60 minutes, about 15 minutes to about 90 minutes, about 15 minutes to about 120 minutes, about 15 minutes to about 150 minutes, about 15 minutes to about 180 minutes, about 15 minutes to about 210 minutes, about 15 minutes to About 240 minutes, about 30 minutes to about 60 minutes, about 30 minutes to about 90 minutes, about 30 minutes to about 120 minutes, about 30 minutes to about 150 minutes, about 30 minutes to about 180 minutes, about 30 minutes to about 210 Minutes, or about 30 minutes to about 240 minutes About 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, Decrease by about 70% to about 100%, or about 80% to about 100%.

  In other aspects of this embodiment, the therapeutically effective amount of the carbon dioxide molecule provides blood pressure, eg, about 4 hours or more, about 6 hours or more, about 8 hours or more, about 10 hours or more, about 12 hours or more, At least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or over about 18 hours or more, or about 24 hours or more, or Decrease by at least 100%. In yet another aspect of this embodiment, the therapeutically effective amount of the carbon dioxide molecule increases blood pressure, eg, about 4 hours or more, about 6 hours or more, about 8 hours or more, about 10 hours or more, about 12 hours or more. About 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 18 hours or more, or about 24 hours or more Decrease by about 100%, about 60% to about 100%, about 70% to about 100%, or about 80% to about 100%.

  Aspects of the specification disclose, in part, disease. Diseases include defects, defects, diseases and / or disorders that are sought to be alleviated by the individual suffering from the disease. In another aspect, the disease is an impairment, defect, disease and / or disorder associated with low blood flow and oxygen delivery that is sought to be mitigated by the individual suffering from the disease. )including. Diseases include, but are not limited to treating ischemia, hypertension, cardiovascular disorders, diabetic diseases, trauma, chronic inflammation, arthritis, migraine, cellulite disease, facial pallor, cosmetic disorders . In certain embodiments, the present specification discloses the use of a substance comprising a supersaturated amount of dissolved gas to treat a disease. Therefore, transdermal delivery devices are useful for cosmetic applications, medical applications and veterinary applications. The individual is generally a mammal and the term includes humans.

  Proper flow of oxygen-rich blood in the microcirculation is important for proper body function. For example, better blood flow is important for maintaining cardiovascular health. A dramatic increase in the incidence of heart disease in recent years (more than one in three Americans suffers from diseases that endanger this life), leading to the development of problems related to restricted blood flow. ing. The rapidly increasing obesity rate exacerbates this problem. In addition to the most important issues with bad blood flow, such as heart attacks and strokes, bad blood flow can cause edema, kidney damage, brain function, memory loss, sexual function, muscle movement, limb ischemia, injured trauma, It can also potentially lead to diseases such as diabetic ulcers and strokes. Proper flow of oxygen-rich blood in the microcirculation is also important in removing toxins from the body while completely improving overall skin health. The additional effects of increased oxygen include reducing stress and reducing obesity, cellulite, wrinkles, and scars.

  The body needs oxygen for metabolism, but low oxygen levels may not normally promote breathing. However, carbon dioxide can be one of the mediators of local self-regulation of blood supply. When the level of carbon dioxide is high, the capillaries expand and a greater amount of blood flow can flow into the tissue. Thus, in certain aspects herein, the devices disclosed herein are extracorporeal devices that function by transdermal delivery of carbon dioxide molecules into the bloodstream through the pores of the skin and sweat glands. Carbon dioxide molecular water vapor dissolved in supersaturation readily mixes in wet sweat pores and sweat glands that quickly lead to microcirculation. By the Bohr effect (migration of the oxygen dissociation curve), carbon dioxide initiates a gas exchange equilibrium process at the level of microvessels that facilitates the release of oxygen when blood cells exchange carbon dioxide and water, and For example, reducing the pH of blood in areas with lower perfusion levels of oxygen, such as areas with low blood flow. When red blood cells sense local oxygen demand, the increased oxygen molecules trigger the dissociation of vasodilators from these blood cells, consistent with local blood flow demand. This dissociation dilates the blood vessel and greatly improves the circulation and blood flow of oxygen-rich blood to that area. Increased blood flow results in better oxidized cells and tissues, thereby providing nutrient support and waste detoxification for many body processes. Hence, carbon dioxide molecules are the signal that ultimately directs the body to increase blood flow and oxygen levels in areas where demand is highest.

  The average density of sweat pores varies greatly depending on the individual and body part. The palmer surfaces, ie palms and fingers, and the sole surfaces, ie the soles of the feet and toes, have, on average, 2700 skin pattern skin surface pores per square inch. This compares to about 400 holes per square inch for other parts of the body's skin surface. The total number of sweat pores distributed throughout the body has been estimated to be 1.6 million to 4 million. Although the circulatory system distributes oxygen-rich red blood cells almost instantly throughout the body, human palms, fingers, toes and soles have more than seven times more pores than any part of the body, so these The area is ideal for performing the treatment disclosed herein.

  In certain embodiments, the route of administration is a transdermal route. In aspects of this embodiment, the therapeutic agents disclosed herein are delivered transdermally to an individual's finger, toe, palm of the hand, or sole of the foot. In another aspect of this embodiment, the therapeutic agent disclosed herein is delivered transdermally to the skin surface of the individual. In yet another aspect of this embodiment, the therapeutic agent disclosed herein is delivered transdermally to the skin surface of the individual around the disease.

  In certain embodiments, a method of treating ischemia uses a transdermal delivery device disclosed herein to treat a composition comprising a substance comprising a therapeutically effective amount of a dissolved gas with an ischemic disorder. Administering to the individual, the administration of the composition alleviates symptoms associated with ischemia. Ischemia is a restriction of blood supply with resulting tissue damage or dysfunction, generally due to intravascular factors. Ischemia is a characteristic of cerebrovascular disorders that rupture sensitively to heart disease, transient cerebral ischemic attacks, and inappropriate blood supply. For example, ischemia in the brain tissue due to stroke or head injury causes a linked process called ischemic waterfall, which is ultimately caused by proteolytic enzymes, reactive oxygen species, and other harmful chemical damage Can be killed. Ischemia is particularly widespread in diabetic and obese patients, whose poor blood flow often leads to inadequate oxygen supply to lower limb tissues, often causing cutaneous ulcers and unhealed trauma. Better blood flow can help these traumas heal and protect many potentially lost legs. There are various types of ischemia organized by organs that experience ischemic stroke, including but not limited to cardiac ischemia, intestinal ischemia, cerebral ischemia, lower limb ischemia and skin ischemia . Pain is a common symptom associated with ischemia, but it does not always occur. Cerebral ischemia can cause cognitive, sensory or motor problems. Heart attacks and intestinal ischemia can cause nausea and vomiting. Peripheral ischemia can cause paleness, bluish discoloration or darkening of the skin on the nose, ears, fingers, toes or other surface areas. The treatments disclosed herein can improve blood circulation and oxygen-rich blood delivery to ischemic tissue, thereby treating ischemia.

  In one aspect of this embodiment, a method of treating ischemia uses a transdermal delivery disclosed herein to comprise a composition comprising a substance comprising a therapeutically effective amount of a dissolved carbon dioxide molecule, Administering to an individual suffering from ischemia, wherein administration of the composition relieves symptoms associated with ischemia.

  In another aspect, a method of treating hypertension uses a transdermal delivery device disclosed herein to treat a composition comprising a substance comprising a therapeutically effective amount of a dissolved gas with a hypertension. Administering to the individual, wherein administration of the composition alleviates symptoms associated with hypertension. Hypertension is a chronic condition in which the blood pressure in the arteries increases, requiring the heart to move more violently than normal to circulate blood through the blood vessels. Normal blood pressure is 120/80 mmHg or less. Hypertension is said to be present when blood pressure continuously exceeds 140/90 mmHg. Hypertension includes, but is not limited to, stage I hypertension, stage II hypertension, and systolic hypertension. Symptoms of hypertension include, but are not limited to, headache, dizziness, blurred vision, nausea and vomiting, chest pain, shortness of breath, heart attack, heart failure, heart attack, or transient ischemic attack ( TIA), renal failure, ocular disorders with progressive visual loss, peripheral arterial disease causing leg pain (crawling) during walking, aneurysms, and any combination thereof. The treatments disclosed herein may improve blood circulation and oxygen-rich blood delivery to the body, thereby lowering blood pressure and treating hypertension.

  In one aspect of this embodiment, a method of treating hypertension comprises using a transdermal delivery device disclosed herein to comprise a composition comprising a substance comprising a therapeutically effective amount of dissolved carbon dioxide molecules. Administering to an individual suffering from hypertension, administration of the composition relieves symptoms associated with hypertension.

  In aspects of this embodiment, administration of the composition results in blood pressure, eg, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, Reduce by at least 90%, or at least 100%. In other aspects of this embodiment, administration of the composition improves blood pressure, eg, from about 10% to about 100%, from about 20% to about 100%, from about 30% to about 100%, from about 40% to about 100. %, About 50% to about 100%, about 60% to about 100%, about 70% to about 100%, or about 80% to about 100%.

  In other aspects of this embodiment, the administration of the composition comprises blood pressure, eg, about 5 minutes or more, about 15 minutes or more, about 30 minutes or more, about 45 minutes or more, about 60 minutes or more, about 75 minutes or more, About 90 minutes or more, about 105 minutes or more, about 120 minutes or more, about 135 minutes or more, about 150 minutes or more, about 165 minutes or more, about 180 minutes or more, about 195 minutes or more, about 210 minutes or more, about 225 minutes or more, Or at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 100% decrease over about 240 minutes or more Let In yet another aspect of this embodiment, administration of the composition improves blood pressure, eg, about 5 minutes or more, about 15 minutes or more, about 30 minutes or more, about 45 minutes or more, about 60 minutes or more, about 75 minutes or more. About 90 minutes or more, about 105 minutes or more, about 120 minutes or more, about 135 minutes or more, about 150 minutes or more, about 165 minutes or more, about 180 minutes or more, about 195 minutes or more, about 210 minutes or more, about 225 minutes or more Or about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 240 minutes or more 60% to about 100%, about 70% to about 100%, or about 80% to about 100%.

  In other aspects of this embodiment, the administration of the composition improves blood pressure, eg, from about 5 minutes to about 30 minutes, from about 5 minutes to about 60 minutes, from about 5 minutes to about 90 minutes, from about 5 minutes to about 120 minutes. Minutes, about 5 minutes to about 150 minutes, about 5 minutes to about 180 minutes, about 5 minutes to about 210 minutes, about 5 minutes to about 240 minutes, about 15 minutes to about 30 minutes, about 15 minutes to about 60 minutes, About 15 minutes to about 90 minutes, about 15 minutes to about 120 minutes, about 15 minutes to about 150 minutes, about 15 minutes to about 180 minutes, about 15 minutes to about 210 minutes, about 15 minutes to about 240 minutes, about 30 minutes Minutes to about 60 minutes, about 30 minutes to about 90 minutes, about 30 minutes to about 120 minutes, about 30 minutes to about 150 minutes, about 30 minutes to about 180 minutes, about 30 minutes to about 210 minutes, or about 30 minutes At least 10% over a period of time to about 240 minutes, Even without 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or by at least 100%. In yet another aspect of this embodiment, administration of the composition comprises administering blood pressure, eg, from about 5 minutes to about 30 minutes, from about 5 minutes to about 60 minutes, from about 5 minutes to about 90 minutes, from about 5 minutes to about 120 minutes, about 5 minutes to about 150 minutes, about 5 minutes to about 180 minutes, about 5 minutes to about 210 minutes, about 5 minutes to about 240 minutes, about 15 minutes to about 30 minutes, about 15 minutes to about 60 minutes About 15 minutes to about 90 minutes, about 15 minutes to about 120 minutes, about 15 minutes to about 150 minutes, about 15 minutes to about 180 minutes, about 15 minutes to about 210 minutes, about 15 minutes to about 240 minutes, about 30 minutes to about 60 minutes, about 30 minutes to about 90 minutes, about 30 minutes to about 120 minutes, about 30 minutes to about 150 minutes, about 30 minutes to about 180 minutes, about 30 minutes to about 210 minutes, or about About 10% to about about 30 minutes to about 240 minutes 00%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100% Or about 80% to about 100%.

  In other aspects of this embodiment, the administration of the composition comprises blood pressure, eg, about 4 hours or more, about 6 hours or more, about 8 hours or more, about 10 hours or more, about 12 hours or more, about 18 hours or more, Or a decrease of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 100% over about 24 hours or more Let In yet another aspect of this embodiment, administration of the composition provides blood pressure, eg, about 4 hours or more, about 6 hours or more, about 8 hours or more, about 10 hours or more, about 12 hours or more, about 18 hours or more. Or about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 24 hours or more 60% to about 100%, about 70% to about 100%, or about 80% to about 100%.

  In yet another aspect, a method of treating a cardiovascular disease comprises using a transdermal delivery device disclosed herein to provide a composition comprising a substance comprising a therapeutically effective amount of dissolved gas. Administering to the individual suffering from the disease, administration of the composition relieves symptoms associated with cardiovascular disease. Cardiovascular disease is any of many specific diseases that affect the heart itself and / or the vascular system, particularly the veins and arteries that connect to the heart. There are over 60 types of cardiovascular disease, including but not limited to diabetic heart disease, arteritis, phlebitis, vascular inflammation such as vasculitis, arteriosclerosis, stenosis, peripheral arterial disease Arterial occlusive diseases such as aneurysm, embolism, dissection, pseudoaneurysm, vascular malformation, vascular nevus, thrombosis, venous thrombosis, varicose veins, and stroke. Symptoms of cardiovascular disease affecting the heart include, but are not limited to: chest pain or chest discomfort (angina), one or both arms, left shoulder, neck, jaw or back pain, shortness of breath, Includes dizziness, palpitation, nausea, abnormal heartbeat, and great fatigue. Symptoms of cardiovascular disease affecting the brain include, but are not limited to, sudden numbness or weakness of the face, arms or legs, particularly sudden turbidity or speech difficulty or speech comprehension, one eye or Includes sudden visual disturbances in both eyes, sudden dizziness, difficulty walking, or balance or coordination impairment, sudden headache without harbinger. Symptoms of cardiovascular disorders affecting the legs, pelvis and / or arms include but are not limited to painful lameness, pain, or muscle spasms, especially the coldness or numbness felt on the feet or toes at night including. The treatments disclosed herein can improve blood circulation and oxygen-rich blood delivery to the body, thereby treating cardiovascular disease.

  In one aspect of this embodiment, a method of treating a cardiovascular disease comprises a composition comprising a therapeutically effective amount of dissolved carbon dioxide molecules using a transdermal delivery device disclosed herein. Is administered to an individual suffering from cardiovascular disease, and administration of the composition relieves symptoms associated with cardiovascular disease.

  In yet another aspect, a method of treating a diabetic disease comprises using a transdermal delivery device as disclosed herein to comprise a composition comprising a substance comprising a therapeutically effective amount of dissolved gas, Administering to an individual suffering from a diabetic disease, administration of the composition relieves symptoms associated with the diabetic disease. Diabetic diseases are a group of metabolic diseases in which human blood sugar levels increase because the body does not produce enough insulin or the cells do not respond to the insulin produced. Diabetic diseases include but are not limited to type I diabetes, type II diabetes and gestational diabetes. Symptoms of diabetic disease include, but are not limited to, increased hunger, unexplained weight loss, frequent urination, hyperglycemia, coma, slow healing of trauma, and persistent trauma. The treatments disclosed herein may improve blood circulation and oxygen-rich blood delivery to the body, thereby treating diabetic diseases.

  In one aspect of this embodiment, a method of treating a diabetic disease comprises a composition comprising a therapeutically effective amount of a dissolved carbon dioxide molecule using a transdermal delivery device disclosed herein. Is administered to an individual suffering from a diabetic disease, the administration of the composition relieving symptoms associated with the diabetic disease.

  In another aspect, a method of treating trauma suffers from trauma using a composition comprising a substance that includes a therapeutically effective amount of dissolved gas using the transdermal delivery device disclosed herein. Administering to the individual, the administration of the composition relieves symptoms associated with trauma. Delivery of oxygen, nutrients and other substances is necessary to build the necessary physiological functions in the area and promote wound healing. The treatments disclosed herein may improve blood circulation and oxygen-rich blood delivery to the trauma area to promote healing, thereby treating the trauma.

  In one aspect of this embodiment, a method of treating trauma uses a transdermal delivery device disclosed herein to comprise a composition comprising a substance that includes a therapeutically effective amount of dissolved carbon dioxide molecules. Administering to an individual suffering from trauma, and administration of the composition relieves symptoms associated with trauma.

  In another aspect, a method of treating chronic inflammation uses a transdermal delivery device as disclosed herein to treat a composition comprising a substance comprising a therapeutically effective amount of a dissolved gas with chronic inflammation. Administration to an individual suffering from, the administration of the composition relieves symptoms associated with chronic inflammation. In general, inflammation not only initiates the healing process for injured tissue, but also functions as a defense mechanism by the organ to remove harmful stimuli. This acute neurogenic inflammation forms the first line of defense by preserving tissue integrity and by contributing to tissue recovery. In fact, in the absence of acute neurological inflammation, trauma and infection will never heal and progressive destruction of tissue will jeopardize tissue survival. However, severe or long-term noxious stimuli lead to a chronic inflammatory response that induces injury rather than mediating repair. This inflammation is involved in the pathophysiology of a wide range of unrelated diseases that underlie a wide range of human diseases. Non-limiting examples of diseases that exhibit inflammation as a symptom include, but are not limited to, acne, acid reflux / heartburn, Alzheimer's disease, appendicitis, arteritis, arthritis, asthma, allergy, allergic rhinitis, atherosclerosis Disease, autoimmune disease, balanitis, blepharitis, bronchiolitis, bronchitis, bullous pemphigoid, bursitis, cancer, carditis, celiac disease, cellulitis, cervicitis, cholangitis, cholecystitis , Chorioamnionitis, chronic obstructive pulmonary disease (COPD), cirrhosis, colitis, conjunctivitis, cystitis, normal cold, lacrimal inflammation, dementia, dermatitis, dermatomyositis, eczema, emphysema, encephalitis, endocarditis Endometritis, enteritis, enterocolitis, epicondylitis, epididymis, fasciitis, connective tissue inflammation, gastritis, gastroenteritis, gingivitis, glomerulonephritis, glossitis, heart disease , Hepatitis, sweat gland pus , Hypertension, ileitis, inflammatory skin disease, inflammatory neuropathy, insulin resistance, interstitial cystitis, iritis, ischemic heart disease, keratitis, keratoconjunctivitis, laryngitis, mastitis, mastoid process Inflammation, meningitis, metabolic syndrome (syndrome X), migraine, osteomyelitis, myocarditis, myositis, nephritis, obesity, umbilitis, ovitis, testitis, osteochondritis, osteopenia, osteoporosis, bone Inflammation, otitis, pancreatitis, Parkinson's disease, parotitis, pelvic inflammation, pemphigus vulgaris, pericarditis, peritonitis, pharyngitis, phlebitis, pleurisy, pneumonia, proctitis, prostatitis, psoriasis, pulpitis, Pyelonephritis, portal vein, rheumatic fever, rhinitis, tubitis, salivary glanditis, sinusitis, convulsive colon, stomatitis, synovitis, tendonitis, tendonopathy, tendon synovitis, thrombophlebitis, tonsils Inflammation, dermatitis, tumors, urethritis, uveitis, vaginitis, vasculitis and vulvitis. Common symptoms of chronic inflammation include, but are not limited to, fatigue, pain, asthma, tissue swelling, while other symptoms are specific to certain types of chronic inflammation and are known to those skilled in the art ing. The treatments disclosed herein may improve blood circulation and oxygen-rich blood delivery to the inflamed area, thereby treating chronic inflammation.

  In one aspect of this embodiment, a method of treating chronic inflammation comprises using a transdermal delivery device disclosed herein to comprise a composition comprising a substance comprising a therapeutically effective amount of dissolved carbon dioxide molecules. Administering to an individual suffering from chronic inflammation, and administration of the composition relieves symptoms associated with chronic inflammation.

  In yet another aspect, a method of treating arthritis uses a transdermal delivery device as disclosed herein to treat a composition comprising a substance comprising a therapeutically effective amount of a dissolved gas with arthritis. Administering to the affected individual, the administration of the composition relieves symptoms associated with arthritis. Arthritis includes a group of more than 100 diseases including damage to the joints of the body due to inflammation of the synovium, including but not limited to osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing arthritis Spondyloarthropathy, reactive arthritis (Reiter syndrome), psoriatic arthritis, enteropathic arthritis related to inflammatory bowel disease, Whipple and Behcet's disease, septic arthritis, gout (gouty arthritis, crystalline synovium) Inflammation, also known as metabolic arthritis), pseudogout (calcium pyrophosphate) and Still's disease. Arthritis can affect a single joint (monoarthritis), 2-4 joints (oligoarthritis) or more than 5 joints (polyarthritis), either in autoimmune or non-autoimmune diseases possible. Symptoms of arthritis include, but are not limited to, joint pain, joint swelling, joint stiffness, chills, fever, joint tenderness, joint redness and loss of appetite. The treatment disclosed herein may improve blood circulation and oxygen-rich blood delivery to the joint pain area, thereby treating joint pain.

  In one aspect of this embodiment, a method of treating joint pain comprises using a transdermal delivery device disclosed herein to comprise a composition comprising a substance that includes a therapeutically effective amount of dissolved carbon dioxide molecules. Administering to an individual suffering from joint pain, the administration of the composition relieving symptoms associated with joint pain.

  In yet another aspect, a method of treating migraine includes using a transdermal delivery device as disclosed herein, a composition comprising a substance comprising a therapeutically effective amount of a dissolved gas, Administering to an individual suffering from headache, the administration of the composition relieves symptoms associated with migraine. Migraine is a chronic neurological disease characterized by moderate to severe headaches and nausea. Migraine is without exception migraine without aura, migraine with aura, menstrual migraine, migraine equivalent, complex migraine, retinal migraine, abdominal migraine or mixed migraine (tension migration). Symptoms of migraine include, but are not limited to, throbbing pain on one side of the head, nausea, vomiting, diarrhea, facial pallor, cold hands, cold feet, photosensitivity and hypersensitivity. The treatments disclosed herein may improve blood circulation and oxygen-rich blood delivery to areas of the brain, thereby treating migraine.

  In one aspect of this embodiment, a method of treating migraine comprises using a transdermal delivery device disclosed herein, a composition comprising a substance that includes a therapeutically effective amount of dissolved carbon dioxide molecules. Administering to an individual suffering from migraine, wherein administration of the composition relieves symptoms associated with migraine.

  In another aspect, a method of treating cellulite disease comprises using a transdermal delivery device as disclosed herein to comprise a composition comprising a substance comprising a therapeutically effective amount of dissolved gas, cellulite disease. And administering the composition to relieve symptoms associated with cellulite disease. Cellulite is subcutaneous fat located directly below the top layer of the skin. Cellulite occurs when adipocytes become too large relative to the natural fiber compartments that support the skin, causing these compartments to swell and form a non-uniform layer of subcutaneous fat. The treatments disclosed herein may improve blood circulation and oxygen-rich blood delivery to cellulite areas, thereby treating cellulite disease.

  In one aspect of this embodiment, a method of treating cellulite disease comprises using a transdermal delivery device disclosed herein to comprise a composition comprising a substance comprising a therapeutically effective amount of dissolved carbon dioxide molecules. Administering to an individual suffering from cellulite disease, the administration of the composition relieves symptoms associated with cellulite disease.

  In yet another aspect, a method of treating pallor comprises using a transdermal delivery device as disclosed herein to prepare a composition comprising a substance comprising a therapeutically effective amount of dissolved gas. Administering to an individual suffering from a symptom, administration of the composition relieves symptoms associated with pallor. Whitening occurs when there is a reduced amount of oxygen hemoglobin in the skin or mucous membrane. It depends on the factors and can happen suddenly or gradually. Whitening can be caused by illness, mental shock or stress, stimulant use, lack of sun bathing, anemia or inheritance. The pallor is more clearly seen on the face and palm. The treatments disclosed herein may improve blood circulation to the skin and delivery of oxygen rich blood, thereby treating pallor.

  In one aspect of this embodiment, a method of treating pallor comprises using a transdermal delivery device disclosed herein, a composition comprising a substance that includes a therapeutically effective amount of dissolved carbon dioxide molecules. Administering to an individual suffering from pallor, wherein the administration of the composition alleviates symptoms associated with pallor.

  In yet another aspect, a method of treating a cosmetic disorder comprises using a transdermal delivery device as disclosed herein to prepare a composition comprising a substance comprising a therapeutically effective amount of a dissolved gas. Administering to the individual suffering from the disorder, the administration of the composition relieves symptoms associated with the cosmetic disorder. Beauty is the maintenance, repair or besting of the beauty of the body. As used herein, the term “cosmetic disorder” refers to a skin condition that has unwanted or undesirable characteristics that prevent it from being beautiful in the body. Skin is the body's largest tissue and the first line of defense against illness, chemicals, sunlight and other environmental factors. Increasing oxygen supply and blood flow across the skin surface provides a stronger and more resilient barrier to combat these environmental invaders. Cosmetic disorders include, but are not limited to, skin conditions, defects or imperfections. The location may include any body part where the skin is present, including but not limited to the body including the face, neck, upper limbs, lower limbs, hands, shoulders, back, abdomen, buttocks, thighs, calves including calves. , Feet, genital area, or any other body part, region or area. Non-limiting examples of cosmetic disorders include skin folds, skin wrinkles, skin wrinkles, skin texture, or other dimensions, shapes or contour defects or defects in the skin. including. Skin folds, skin wrinkles, and / or skin wrinkles include, but are not limited to, wrinkles, gnalar lines, lines around the mouth (Peripheral line) and / or a marionette line. The treatments disclosed herein may improve blood circulation and oxygen-rich blood delivery to areas containing cosmetic disorders, thereby treating cosmetic disorders.

  In one aspect of this embodiment, a method of treating a cosmetic disorder comprises using a transdermal delivery device disclosed herein to comprise a composition comprising a substance comprising a therapeutically effective amount of dissolved carbon dioxide molecules. Administering to an individual suffering from a cosmetic disorder, the administration of the composition relieving symptoms associated with the cosmetic disorder.

  In yet another aspect, a method of treating a fungus comprises using a transdermal delivery device as disclosed herein to produce a composition comprising a substance comprising a therapeutically effective amount of a dissolved gas. Administering to the affected individual, the administration of the composition relieves symptoms associated with the fungus. In some embodiments, carbon dioxide can be used as a therapeutic gas. Fungi can be located inside or on the body. Using the delivery devices described herein, the location of nails, toes, fingers, pubic areas, etc. can be treated. Fungi can be anaerobic organisms that can survive only in a hypoxic environment. Thus, treatment with a therapeutic gas can lead to improved oxygen-rich microcirculation that can kill fungi and / or treat illnesses and related symptoms. In certain embodiments, the treatments disclosed herein may improve blood circulation to the skin and delivery of oxygen rich blood, thereby treating fungi.

  The following non-limiting examples are provided for illustrative purposes only to facilitate a more complete understanding of each aspect discussed herein. These examples should not be construed as limiting any aspect described herein, which is a device, composition, or method for treating a disease disclosed herein. And anything related to use.

Example 1 Measurement of Blood Flow An experiment was conducted that showed that the use of the device disclosed herein can improve blood flow in an individual. Treatment was provided by having the individual insert the left thumb into the delivery outlet where the end of the device disclosed herein is open to create a seal. The finger will be “soaked” for 5 minutes in a vapor containing supersaturated dissolved carbon dioxide molecules from a can that supplies high purity medical carbon dioxide. Nine individuals were tested.

  Using the SensiLase® system (a device that has passed the review of the US Food and Drug Administration) to measure tissue tissue in the distal artery by measuring skin tissue perfusion pressure (SPP) and volume pulse wave recording (PVR). Perfusion was evaluated. SPP is a pressure measurement in mmHg that uses laser Doppler to assess local blood perfusion in capillaries and measures reactive hyperemia reflecting microcirculation related to blood flow in the distal artery. . PVR is a plethysmographic measurement that evaluates changes in arterial blood flow. The change in blood flow (CBF) in the capillaries is calculated by measuring the change in the numerical value of SPP per hour. For this experiment, the CBF value for all post-treatment measurements was calculated by dividing the post-treatment SPP value by the pre-treatment SPP value. SPP measurements were performed at the following six time points on the right toe of the individual. 1) 5 minutes before treatment (before treatment), 2) 5 minutes after treatment, 3) 30 minutes after treatment, 4) 60 minutes after treatment, 5) 120 minutes after treatment, and 6) 240 minutes after treatment.

  Experimental results show that administration of carbon dioxide molecules increases blood flow in all individuals tested at several points during the measured period (Table 1). Seven of the 9 individuals tested showed that capillary blood flow increased by about 25% relative to baseline, and 4 of these showed an increase of about 35% or more in capillary blood flow. (Table 1). In addition, 6 out of 9 patients showed a continuous increase in blood flow in the capillaries over the course of the 240 minute study.

Example 2 Measurement of Blood Pressure An experiment was conducted that showed that use of the device disclosed herein can reduce high blood pressure in an individual. To perform this experiment, individuals in the experiment described in Example 1 were then measured for blood pressure. Measurements of both diastolic and systolic blood pressure of the upper arm were performed on the individual's upper right arm at the following six time points. 1) 5 minutes before treatment (before treatment), 2) 5 minutes after treatment, 3) 30 minutes after treatment, 4) 60 minutes after treatment, 5) 120 minutes after treatment, and 6) 240 minutes after treatment.

  The experimental results showed that the administration of carbon dioxide molecules reduced blood pressure in all individuals tested at several points during the measured period (Table 2). Seven of the 9 individuals tested showed reduced diastolic and systolic blood pressure over the course of the 240 minute study.

  To conclude, although aspects herein are emphasized by reference to specific embodiments, those skilled in the art will appreciate that these disclosed aspects are merely illustrative of the nature of the subject matter disclosed herein. It will be appreciated that those skilled in the art will readily understand that this is only the case. Therefore, it is to be understood that the disclosed subject matter is not limited in any way to the specific methods, procedures, and / or reagents disclosed herein. Accordingly, various modifications or variations of the disclosed subject matter or alternative arrangements can be made in accordance with the teachings herein without departing from the spirit of the invention. Finally, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the invention which is defined only by the claims. Therefore, the present invention is not limited to what has been previously shown and described in detail.

  Several aspects of the invention are described herein, including the best mode known to the inventors for carrying out the invention. Of course, variations on these described embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventor expects those skilled in the art to make such modifications as appropriate, and the inventor intends the invention to be practiced differently from what is specifically described herein. doing. Accordingly, this invention includes all modifications and equivalents of the subject matter referenced in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described aspects in all possible variations thereof is intended to be encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

  Alternative aspects, elements or groups of steps of the invention shall not be construed as limiting. Each group of components may be referred to and claimed individually or in any combination with other groups of components disclosed herein. For convenience and / or patentability reasons, it is anticipated that one or more members of a group may be included in or removed from the group. When any such inclusion or deletion occurs, the specification shall be deemed to include the amended group and therefore shall satisfy the description requirements of all Markush groups used in the appended claims.

  Unless otherwise stated, features, items, quantities, parameters, properties, terms, etc. used in the specification and claims shall be understood to be modified in all examples by the term “about”. To do. As used herein, the term “about” means that a feature, item, quantity, parameter, property or term is plus or minus 10% of the numerical value of the described feature, item, quantity, parameter, property or term. It is meant to appropriately encompass the range within. Therefore, unless indicated to the contrary, the numerical parameters set forth in this specification and the appended claims are approximations that may vary. At least, and unless you intend to limit the application of the doctrine of equivalents to the claim categories, each numerical representation will at least take into account the number of significant figures listed and apply normal rounding techniques Should be interpreted. Although the numerical ranges and numerical values defining the broad scope of the present invention are approximations, the numerical ranges and numerical values defined in the specific examples are described as accurate as possible. Any numerical range or numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. The description of a numerical range of numerical values herein is intended only to serve as a convenient way to individually reference each separate numerical value falling within the range. Unless otherwise stated herein, each individual value of a numerical range is intended to be included herein as if it were individually described herein.

  The terms “a”, “an”, “the” and like indicators used in the context to describe the present invention (particularly in the context of the following claims) are indicated herein or otherwise defined by the context. Unless otherwise stated, shall be construed to protect both the singular and plural. The methods described herein may be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples or exemplary languages (e.g., examples) described herein are merely intended to better illustrate the invention and, unless claimed, are within the scope of the invention. It does not bring a limitation. No language in the specification should be construed as indicating any non-claimed element as necessary in the practice of the invention.

  The specific aspects disclosed herein can be further limited in the claims using language or essentially consisting of language. The transition term “consisting of” when used in a claim, whether at the time of filing or added by amendment, excludes any element, step or component not specified in the claim. The transition term “consisting essentially of” limits the scope of the claims to a particular material or step and does not significantly affect the basic and novel features. The claimed aspects of the invention are described either explicitly or silently and enable the specification.

  All patents, patent publications and other publications referenced and identified herein describe and disclose configurations and procedures described in such publications that can be used, for example, in connection with the present invention. All of which are hereby incorporated by reference herein individually and explicitly. These publications are provided solely for their disclosure prior to the filing date of the present application. Nothing in this respect should be construed as an acknowledgment that the inventor has no right to predecessor such disclosure for any other reason, or for any other reason. is there. All statements regarding dates or interpretation of the contents of these documents are not to be construed as based on information available to the applicant, the accuracy of the dates or any approval of the contents of these documents.

All patents, patent publications and other publications referenced and identified herein describe and disclose configurations and procedures described in such publications that can be used, for example, in connection with the present invention. All of which are hereby incorporated by reference herein individually and explicitly. These publications are provided solely for their disclosure prior to the filing date of the present application. Nothing in this respect should be construed as an acknowledgment that the inventor has no right to predecessor such disclosure for any other reason, or for any other reason. is there. All statements regarding dates or interpretation of the contents of these documents are not to be construed as based on information available to the applicant, the accuracy of the dates or any approval of the contents of these documents.
(Appendix)
(Appendix 1)
a) a housing,
i) an outer body shell comprising a fluid chamber assembly access cover removably engaged with the outer body shell;
ii) an internal compartment including a delivery outlet having an open end and a steam generating assembly compartment;
iii) a cartridge holding container comprising an outer cover shell and an inner cartridge compartment capable of holding a compressed gas cartridge;
A housing including
b) a steam generation assembly comprising:
i) a fluid chamber assembly comprising a fluid container and a removable fluid container cap;
ii) a permeation valve configured to reduce the pressure of the gas removed from the compressed gas cartridge and delivered to the fluid chamber assembly;
A steam generation assembly comprising:
With
The cartridge holding container is removably engaged with the outer body shell;
The outer shell defines the inner compartment;
The vapor generating assembly section is disposed between a delivery outlet having an open end and the cartridge holding container;
The steam generating assembly is generally contained within the steam generating assembly compartment;
A transdermal delivery device characterized by the above.
(Appendix 2)
The device further comprises an adjustment switch assembly;
The transdermal delivery device according to Supplementary Note 1, wherein the device is a transdermal delivery device.
(Appendix 3)
The adjustment switch assembly is a mechanical switch or an electronic switch;
The transdermal delivery device according to Supplementary Note 2, wherein
(Appendix 4)
The device further comprises a compressed gas cartridge;
The transdermal delivery device according to any one of appendices 1 to 3, characterized in that:
(Appendix 5)
The compressed gas cartridge is a 16 g compressed gas cartridge;
The transdermal delivery device according to Supplementary Note 4, wherein
(Appendix 6)
The compressed gas cartridge comprises carbon dioxide;
The transdermal delivery device according to appendix 4 or 5, characterized by the above.
(Appendix 7)
The permeation valve is set to reduce the pressure of the gas to less than 40 psi;
The transdermal delivery device according to any one of appendices 1 to 6, wherein the device is a transdermal delivery device.
(Appendix 8)
The permeation valve comprises a permeable member selected from rubbers, corks, woven materials, porous polymer materials, dense sintered metal materials and combinations thereof;
8. The transdermal delivery device according to any one of appendices 1 to 7, wherein
(Appendix 9)
A cylinder containing pressurized carbon dioxide;
A permeation valve configured to reduce the pressure of the pressurized carbon dioxide;
A chamber configured to form a therapeutic vapor by supersaturating the liquid in the chamber with carbon dioxide;
A treatment chamber configured to carry said therapeutic vapor to an individual;
A transdermal delivery device comprising:
(Appendix 10)
A method of transdermally administering a therapeutically effective amount of dissolved carbon dioxide molecules to an individual, comprising:
Said method comprises
Administering to the individual a composition comprising a vapor comprising supersaturated amounts of dissolved carbon dioxide molecules using the transdermal delivery device of any one of appendices 1-9.
Method.
(Appendix 11)
A method of transdermally administering a therapeutically effective amount of a therapeutic agent to an individual comprising:
Said method comprises
Administering to the individual a composition comprising a supersaturated amount of dissolved carbon dioxide molecules and a vapor comprising a therapeutic agent using the transdermal delivery device of any one of appendices 1-9.
Method.
(Appendix 12)
The amount of carbon dioxide molecules dissolved is at least 600 ppm,
The method according to appendix 10 or 11, characterized in that:
(Appendix 13)
Said administration increases blood flow,
The method according to any one of appendices 10 to 12, characterized in that:
(Appendix 14)
Said administration increases blood flow by at least 10%;
The method according to appendix 13, characterized by:
(Appendix 15)
The administration increases blood flow by about 10% to about 100%;
The method according to appendix 13, characterized by:
(Appendix 16)
Increased blood flow for at least 5 minutes,
The method according to any one of appendices 13 to 15, characterized in that:
(Appendix 17)
The increased blood flow is from about 5 minutes to about 240 minutes,
The method according to any one of appendices 13 to 15, characterized in that:
(Appendix 18)
Said administration reduces blood pressure;
The method according to any one of appendices 9 to 17, characterized in that:
(Appendix 19)
Said administration reduces blood pressure by at least 10%;
The method according to appendix 18, characterized by:
(Appendix 20)
Said administration reduces blood pressure by about 10% to about 100%;
The method according to appendix 18, characterized by:
(Appendix 21)
A state in which the blood pressure has decreased is at least 5 minutes,
The method according to any one of appendices 18 to 20, characterized in that:
(Appendix 22)
The state in which the blood pressure has decreased is about 4 hours to about 24 hours.
The method according to any one of appendices 18 to 21, characterized in that:
(Appendix 23)
A method of treating a disease in an individual comprising
The method
A composition comprising a substance containing a therapeutically effective amount of dissolved carbon dioxide molecules is administered to the individual suffering from a disease using the transdermal delivery device according to any one of appendices 1 to 9. Including steps,
Administration of the composition relieves symptoms associated with the disease;
A method characterized by that.
(Appendix 24)
The disease is ischemia, hypertension, heart disease, diabetic disease, trauma, chronic inflammation, arthritis, migraine, cellulite disease, pallor, or cosmetic disorder,
24. The method according to appendix 23, wherein:
(Appendix 25)
The amount of carbon dioxide molecules dissolved is at least 600 ppm,
25. The method according to appendix 23 or 24, wherein
(Appendix 26)
Said administration increases blood flow ,
26. The method according to any one of appendices 23 to 25, wherein
(Appendix 27)
Said administration increases blood flow by at least 10%;
27. The method according to appendix 26, wherein:
(Appendix 28)
The administration increases blood flow by about 10% to about 100%;
27. The method according to appendix 26, wherein:
(Appendix 29)
Increased blood flow for at least 5 minutes,
29. The method according to any one of appendices 26 to 28, wherein
(Appendix 30)
The increased blood flow is from about 5 minutes to about 240 minutes,
29. The method according to any one of appendices 26 to 28, wherein
(Appendix 31)
Said administration reduces blood pressure;
31. The method according to any one of appendices 23 to 30, characterized in that:
(Appendix 32)
Said administration reduces blood pressure by at least 10%;
The method according to supplementary note 31, characterized by:
(Appendix 33)
Said administration reduces blood pressure by about 10% to about 100%;
The method according to supplementary note 31, characterized by:
(Appendix 34)
A state in which the blood pressure has decreased is at least 5 minutes,
34. The method according to any one of appendices 31 to 33, wherein
(Appendix 35)
The state in which the blood pressure has decreased is about 4 hours to about 24 hours.
34. The method according to any one of appendices 31 to 33, wherein

Claims (35)

a) a housing,
i) an outer body shell comprising a fluid chamber assembly access cover removably engaged with the outer body shell;
ii) an internal compartment including a delivery outlet having an open end and a steam generating assembly compartment;
iii) a cartridge holding container comprising an outer cover shell and an inner cartridge compartment capable of holding a compressed gas cartridge;
A housing including
b) a steam generation assembly comprising:
i) a fluid chamber assembly comprising a fluid container and a removable fluid container cap;
ii) a permeation valve configured to reduce the pressure of the gas removed from the compressed gas cartridge and delivered to the fluid chamber assembly;
A steam generation assembly comprising:
With
The cartridge holding container is removably engaged with the outer body shell;
The outer shell defines the inner compartment;
The vapor generating assembly section is disposed between a delivery outlet having an open end and the cartridge holding container;
The steam generating assembly is generally contained within the steam generating assembly compartment;
A transdermal delivery device characterized by the above. The device further comprises an adjustment switch assembly;
The transdermal delivery device according to claim 1. The adjustment switch assembly is a mechanical switch or an electronic switch;
The transdermal delivery device according to claim 2, wherein: The device further comprises a compressed gas cartridge;
The transdermal delivery device according to any one of claims 1 to 3, wherein the device is a transdermal delivery device. The compressed gas cartridge is a 16 g compressed gas cartridge;
The transdermal delivery device according to claim 4. The compressed gas cartridge comprises carbon dioxide;
The transdermal delivery device according to claim 4 or 5, characterized in that The permeation valve is set to reduce the pressure of the gas to less than 40 psi;
The transdermal delivery device according to any one of claims 1 to 6, wherein the device is a transdermal delivery device. The permeation valve comprises a permeable member selected from rubbers, corks, woven materials, porous polymer materials, dense sintered metal materials and combinations thereof;
The transdermal delivery device according to any one of claims 1 to 7, wherein the device is a transdermal delivery device. A cylinder containing pressurized carbon dioxide;
A permeation valve configured to reduce the pressure of the pressurized carbon dioxide;
A chamber configured to form a therapeutic vapor by supersaturating the liquid in the chamber with carbon dioxide;
A treatment chamber configured to carry said therapeutic vapor to an individual;
A transdermal delivery device comprising: A method of transdermally administering a therapeutically effective amount of dissolved carbon dioxide molecules to an individual, comprising:
The method comprises
Using the transdermal delivery device of any one of claims 1 to 9 to administer to the individual a composition comprising a vapor comprising a supersaturated amount of dissolved carbon dioxide molecules.
Method. A method of transdermally administering a therapeutically effective amount of a therapeutic agent to an individual comprising:
The method comprises
Administering to the individual a composition comprising a supersaturated amount of dissolved carbon dioxide molecules and a vapor containing a therapeutic agent using the transdermal delivery device of any one of claims 1-9.
Method. The amount of carbon dioxide molecules dissolved is at least 600 ppm,
The method according to claim 10 or 11, characterized in that: Said administration increases blood flow,
13. A method according to any one of claims 10 to 12, characterized in that Said administration increases blood flow by at least 10%;
The method according to claim 13. The administration increases blood flow by about 10% to about 100%;
The method according to claim 13. Increased blood flow for at least 5 minutes,
16. A method according to any one of claims 13 to 15, characterized in that The increased blood flow is from about 5 minutes to about 240 minutes,
16. A method according to any one of claims 13 to 15, characterized in that Said administration reduces blood pressure;
18. A method according to any one of claims 9 to 17, characterized in that Said administration reduces blood pressure by at least 10%;
The method according to claim 18, wherein: Said administration reduces blood pressure by about 10% to about 100%;
The method according to claim 18, wherein: A state in which the blood pressure has decreased is at least 5 minutes,
21. A method according to any one of claims 18 to 20, characterized in that The state in which the blood pressure has decreased is about 4 hours to about 24 hours.
The method according to any one of claims 18 to 21, characterized in that: A method of treating a disease in an individual comprising
The method
10. A composition comprising a substance comprising a therapeutically effective amount of dissolved carbon dioxide molecules is administered to the individual suffering from a disease using the transdermal delivery device according to any one of claims 1-9. Including the steps of
Administration of the composition relieves symptoms associated with the disease;
A method characterized by that. The disease is ischemia, hypertension, heart disease, diabetic disease, trauma, chronic inflammation, arthritis, migraine, cellulite disease, pallor, or cosmetic disorder,
24. The method of claim 23. The amount of carbon dioxide molecules dissolved is at least 600 ppm,
25. A method according to claim 23 or 24, wherein: Said administration increases blood flow,
26. A method as claimed in any one of claims 23 to 25. Said administration increases blood flow by at least 10%;
27. A method according to claim 26. The administration increases blood flow by about 10% to about 100%;
27. A method according to claim 26. Increased blood flow for at least 5 minutes,
29. The method according to any one of claims 26 to 28, wherein: The increased blood flow is from about 5 minutes to about 240 minutes,
29. The method according to any one of claims 26 to 28, wherein: Said administration reduces blood pressure;
31. A method according to any one of claims 23 to 30, characterized in that Said administration reduces blood pressure by at least 10%;
32. The method of claim 31, wherein: Said administration reduces blood pressure by about 10% to about 100%;
32. The method of claim 31, wherein: A state in which the blood pressure has decreased is at least 5 minutes,
34. A method according to any one of claims 31 to 33. The state in which the blood pressure has decreased is about 4 hours to about 24 hours.
34. A method according to any one of claims 31 to 33.

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