Abstract:
Embodiments of the present invention relate to medical devices and treatments for chronic venous insufficiency, open ulceration and related medical conditions, and more particularly to a device and treatment incorporating negative pressure compression to the foot and lower leg or other appendage of a patient.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims the priority benefit of U.S. Provisional Application No. 61/325,179, entitled AMBULATORY NEGATIVE PRESSURE THERAPEUTICAL COMPRESSION DEVICE and filed on Apr. 16, 2010, which is incorporated herein by reference in its entirety. 
     
    
     STATEMENT REGARDING FEDERALLY-SPONSORED RESEARCH OR DEVELOPMENT 
       [0002]    Embodiments of the present invention were made with U.S. Government support, and the U.S. Government may have certain rights in the invention. The U.S. Government&#39;s rights in the invention are provided for by the terms of contract numbers 9R44AG026244-02 and 5R44AG026244-03, sponsored by the National Institute of Health. 
     
    
     TECHNICAL FIELD 
       [0003]    Embodiments of the present invention relate to medical devices and treatments for venous hypertension, valvular incompetence, leg swelling and open ulceration. 
       BACKGROUND 
       [0004]    Chronic venous insufficiency (CVI) is a significant and growing medical problem. The pathophysicologic basis of CVI is venous hypertension in the lower extremities. The calf muscle pump works by contracting around veins in order to force blood in the veins into motion. One-way valves within the deep venous system allow blood to flow only proximally out of the legs. Failure of these valves leads to increased venous hypertension in the superficial system, thereby decreasing calf-muscle pump efficiency. Increasing venous distension can promote increasing valvular incompetence, leading to symptoms such as leg swelling and aching, discoloring of the skin, activity intolerance, and finally open ulceration. 
         [0005]    Increased venous pressure results in extravasation of fluid, serum proteins, blood cells into the subcutaneous tissue, eventually leading to pigmentation changes and ulceration. The high prevalence and resulting costs of venous pathology, such as health care costs, missed work, and reduced quality of life constitute a heavy burden on society. Approximately 5 million Americans exhibit some evidence of CVI and, depending on estimates, between 500,000 and 600,000 individuals has or will develop venous leg ulcers, causing recurrent hospitalization, high health care costs, and disability. Others estimate that the number of individuals that develop venous leg ulcers may be as high as one million. Fifty percent of venous ulcers may be present for 7-9 months. Between 8 and 34% of the ulcers may be present for more than 5 years, and 67%-75% of patients have recurring problems. An estimated two million work days are lost each year in the United States. The medical costs of treatment and indirect costs associated with disease can be significant. 
       SUMMARY 
       [0006]    Embodiments of the present invention provide therapy and prevention for chronic venous insufficiency, edema, chronic wounds, deep vein thrombosis, varicose veins and/or other medical problems originating from poor venous circulation by assisting the return of interstitial fluid from the limbs to the heart and lungs thereby adding nutrients and oxygen to the blood. This refreshed fluid is carried by the circulatory system to the limbs and heals unhealthy cells. 
         [0007]    According to embodiments of the present invention, a vacuum is applied through air channels or tubes to a single or multiple chambers in a fabricated flexible sock using an electro-mechanical pump. The fabricated flexible sock is worn on any limb and includes any flexible, fluid impermeable material. An outside of the sock material is exposed to the atmosphere and the inside of the material is exposed to the skin, according to embodiments of the present invention. Single or multiple bands and/or seals are applied to the outside and/or inside of the flexible fluid impermeable material, and the bands and/or seals apply circumferential pressure to provide one or multiple vacuum tight chambers, according to embodiments of the present invention. Control of the application of the vacuum is accomplished by one or multiple check valves in series, with vacuum taps between the valves that allow the electro-mechanical pump to provide various pressures, which may include single or multiple gradient pressures, according to embodiments of the present invention. 
         [0008]    In an alternative embodiment, application and control of the vacuum is accomplished by the use of one or more electro-magnetic pneumatic valves connected to a vacuum source by way of one or more pneumatic channels. The pneumatic valves are connected electrically to a programmable logic controller or other electronic or mechanical control device that is capable of providing constant or intermittent flow and/or singular or sequential flow for controlled vacuum time durations for a chamber or multiple chambers at constant values of vacuum. 
         [0009]    A device for providing compressive forces in contiguous chamber locations on a patient&#39;s lower leg may include:
       an elastic flexible air impermeable material formed in the shape of a sock with multiple chambers that form an air tight seal on the lower leg of the body;   seals are incorporated in the sock that provide separate air tight chambers; and/or   an electro-mechanical controlled vacuum source that is pneumatically coupled to multiple chambers in the sock.       
 
         [0013]    Various embodiments on the invention may also employ one or more of the following configurations: the disposable elastic flexible material covers the limb; the material is air impermeable; the chambers form an air tight seal from one another and from the atmosphere while worn on the limb; the air tight seals are disks of thin elastic material wherein the outside diameter of the disks are the size of the inside diameter of the sock; the disk has a hole at its center of a diameter that interfaces with the limb when worn on the limb and the circumference of the disks are bonded to the inside of the sock; the air tight seals are bands of elastic material that are circumferentially located on the outside of the sock and held in place by an elastic material pocket bonded circumferentially to the sock or band loops made of elastic material to hold the bands in place; flexible tubing, air channels or direct mating with the controller providing fluid communication between the vacuum source and the one or more chambers in the sock; and/or the controlled vacuum source is directly mated with the sock and held in place with a strap, belt, or loop and hook band, or located on the thigh by way of a belt, strap or loop and hook band or located at the waist with belt clip, strap or loop and hook band; the power source is mated with the sock and held in place with a strap, belt, or loop and hook band, or located on the thigh by way of a belt, strap or loop and hook band or located at the waist with belt clip, strap or loop and hook band. 
         [0014]    Other configurations that may be employed in various embodiments include: the power source and controlled vacuum source are separate and connected by a flexible electrical power cord; the sock, controlled vacuum source and power source are separate components allowing for disposal or reuse of the individual components; the sock, controlled vacuum source and power source are a single component; the sock is configured to cover a patient&#39;s limb with an open end allowing for insertion of a limb and a closed end portion; three seals, the first seal placed at the opening of the sock, the second seal placed mid-way between the first and third seal and the third seal placed at the ankle or wrist; the controlled vacuum source is in fluid communication with all chambers; the sock is one of a plurality of socks of multiple sizes with corresponding multiple sizes of sealing disks within, with holes at the centers of the disks, to provide a fit that seals but does not restrict blood flow for thin-walled superficial veins; the sock is one of a plurality of socks of multiple sizes with corresponding multiple sizes of elastic bands outside of the garment to provide a fit that seals but does not restrict blood flow for thin-walled superficial veins for a majority of patients; the sock opening includes a diameter to allow easy fit over the heel to ankle circumference when the leg to foot angle is 120 degrees or greater for a majority of patients; and/or the air channels, if used instead of flexible tubing, are constructed by creating an air space by ultrasonically welding elastic air impermeable flexible material to the surface of the sock in a pattern that allows three separate channels that have vents from the chamber to the air channel and from the air channel to ports on the sock that connect to the controlled vacuum source. 
         [0015]    Furthermore, in some embodiments, each channel may have contained therein a spring, spiral wrap, or tube to prevent collapse of the air channel when sub-atmospheric pressure is induced. 
         [0016]    In another embodiment, the controller produces constant and consistent multiple sub-atmospheric pressures to multiple chambers in the garment, and has one or more of the following features or characteristics:
       said controller has multiple ball or magnetic check valves arranged in series;   a vacuum source pulls air through the valves which are closed until the pressure exceeds the release pressure rating of the valve;   all ball or magnetic check valves in the series are rated at the same pressure release value and the gradient pressure drop between the valves is the same as the value of the valve;   the valve value is chosen based on the target gradient pressure;   the absolute pressure drop between the valves is dependent on air flow and the adjusted sub-atmospheric pressure at the vacuum source;   a vacuum tap is provided between each valve which has a fluid connection to a chamber in the sock;   the sock includes one or more, for example three, different chambers with each of the three chambers having a different compression value than the other, with, for example, the highest compression at the ankle, medium compression at the mid-calf and lowest compression at the upper-calf;   all pressures can be lowered by adjusting the pin valve thereby leaking atmospheric pressure into the vacuum line which will lower the compression in all chambers and lower the gradient pressures in between chambers;   the voltage from a rechargeable power source is made constant over the discharge cycle by way of a step up/step down switching DC-DC converter which maintains pump speed regardless of battery voltage over time; and/or   all chambers of the sock keep constant and consistent compression over a day&#39;s use.       
 
         [0027]    In some embodiments of the present invention, the controller provides constant compression to multiple sock chambers as a sequentially applied step function with programmable durations, and may include one or more of the following features or characteristics:
       the controller includes a re-chargeable battery, step up/step down switching DC-DC converter, micro-controller, rotary or reciprocating pump, pneumatic miniature solenoid valves and pin valve;   the micro-controller or micro-programmable controller manages the operation of the normally closed electrical pneumatic switches that are in fluid communication with the chambers in the sock by opening and closing the valves on predetermined time durations and chamber location cycles;   the vacuum pump runs at a constant revolution per minute rate that is controlled by the adjustable output voltage of the Step-up/Step-down switching DC-DC converter providing a constant singular sub-atmospheric pressure at the pump; the pressure in the chambers of the sock can be set manually by adjusting the pin valve to a desired value;   the pump side of the electrical pneumatic switch array is ported to the pump and the sock chamber side of the electrical pneumatic switch array ports directly to the sock male ports or through tubing for remote mounting of the controller on the thigh or waist;   a removable battery charger is provided to recharge the battery pack after a day&#39;s use;   the controller provides a dynamic sequential controlled “milking” device. In the first period, only the ankle chamber has an applied singular vacuum, which may be, for example, a 5 second duration, in the second period, both the ankle and mid-calf chambers have vacuum which may have a duration of 5 seconds and in the third period the ankle, mid-calf and upper-calf have vacuum, which may have a duration of 5 seconds, in the fourth period, which may, for example, be 20 seconds long, all chambers are returned to atmospheric pressure and the blood in the leg or extremity is allowed to refill with fresh blood to revitalize the tissue. At the end of the fourth period the same cycle is repeated.       
 
         [0034]    While multiple embodiments are disclosed, still other embodiments of the present invention will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the invention. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0035]      FIG. 1  is a perspective view of an ambulatory negative pressure therapeutical compression device assembly on a human leg, according to embodiments of the present invention. 
           [0036]      FIG. 2  is a perspective view of an arrangement of diaphragm vacuum seals, according to embodiments of the present invention. 
           [0037]      FIG. 3  is a perspective view of an alternative arrangement of elastic band seals, according to embodiments of the present invention. 
           [0038]      FIG. 4  is a sectional representation of a mechanism for securing one or more bands to the flexible sock taken along the line A-A of  FIG. 3 , according to embodiments of the present invention. 
           [0039]      FIG. 5  is a perspective view of a flexible sock, before evacuation, on a human leg, demonstrating its looseness to allow easy application in consideration of the heel to ankle circumference and foot angle relative to the tibia, according to embodiments of the present invention. 
           [0040]      FIG. 6  is a perspective view of the flexible sock of  FIG. 5 , after evacuation, on a human leg, demonstrating evacuation of air from the sock, according to embodiments of the present invention. 
           [0041]      FIG. 7  is a perspective view of air channels that allow evacuation of the chamber or chambers of the sock; such channels may incorporate springs, tubes and/or spiral wrap, according to embodiments of the present invention. 
           [0042]      FIG. 8  is a sectional view of a single air channel taken along line B-B of  FIG. 7 , illustrating a construction technique, according to embodiments of the present invention. 
           [0043]      FIG. 9  is a perspective view of a control module illustrating a mounting technique of the controller to the flexible sock, according to embodiments of the present invention. 
           [0044]      FIG. 10  is a schematic of a controller utilizing a ball or magnetic check valve design, according to embodiments of the present invention. 
           [0045]      FIG. 11  illustrates a graph of vacuum pressure verses time for the ball or magnetic check valve controller of  FIG. 10 , according to embodiments of the present invention. 
           [0046]      FIG. 12  is a schematic of an alternative embodiment of a controller that manages user definable timing and the application of sub-atmospheric pressure to single or multiple chambers by sequence, progression or intermittence, according to embodiments of the present invention. 
           [0047]      FIG. 13  is a graph of illustrating sequential application of vacuum to multiple chambers over time, according to embodiments of the present invention. 
           [0048]      FIGS. 14A-B  illustrate a system for delivering drugs according to embodiments of the present invention. 
           [0049]      FIGS. 15A-C  illustrate a vacuum device and a port of a sock according to embodiments of the present invention. 
           [0050]      FIG. 16  illustrates an ultrasonic transducer and a port of a sock according to embodiments of the present invention. 
           [0051]      FIG. 17  illustrates a dual layer sock according to embodiments of the present invention. 
           [0052]      FIG. 18  illustrates a sock with positive pressure seals according to embodiments of the present invention. 
           [0053]      FIG. 19A  illustrates a top view of a sock with balloon seals according to embodiments of the present invention. 
           [0054]      FIG. 19B  illustrates a sectional view taken along the line A-A of  FIG. 19A . 
           [0055]      FIG. 19C  is a side view of the sock of  FIG. 19A . 
           [0056]      FIGS. 20A-B  illustrate a thermal device and a port of a sock according to embodiments of the present invention. 
           [0057]      FIGS. 21A-B  illustrate a controller configured to introduce ozone or nitric oxide into a sock through a port according to embodiments of the present invention. 
           [0058]      FIGS. 22A-C  illustrate a drug delivery system and a port of a sock according to embodiments of the present invention. 
           [0059]      FIGS. 23A-C  illustrate socks employing helical pressure chambers according to embodiments of the present invention. 
           [0060]      FIG. 24  illustrates a cross sectional view of an inner layer and an outer layer of a sock according to embodiments of the present invention. 
           [0061]      FIG. 25  illustrates a cross sectional view of an upper portion of a sock according to embodiments of the present invention. 
       
    
    
       [0062]    While the invention is amenable to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and are described in detail below. The intention, however, is not to limit the invention to the particular embodiments described. On the contrary, the invention is intended to cover all modifications, equivalents, and alternatives falling within the scope of the invention as defined by the appended claims. 
       DETAILED DESCRIPTION 
       [0063]    While the etiology and pathophysicology of CVI and resulting venous ulcers are well established, there has not been satisfactory progress in the treatment of this problem. Compression of the foot and lower leg may be beneficial in the treatment of CVI. It is believed that the application of external pressure to the calf muscles raises the interstitial pressure, forcing blood into the deep venous system, decreasing the superficial venous pressure and improving venous return, leading to a reduction in superficial hypertension. This allows ulcers to heal. Gradient pressure may be achieved using a “Jobst® stocking”, for example, a compressive sock (related to compression bandages and hosiery) that is worn around the foot and lower leg. Compression techniques have been used in a number of different treatment regimes, achieving a reasonable degree of success when combined with good patient compliance. Unfortunately, compression has not proven efficacious in poorly compliant patients, who universally have a high rate of ulcer persistence or recurrence. Several factors contribute to poor patient compliance. Often patients do not have enough strength or mobility to pull on compression stockings. Attempts have been made to overcome these difficulties, such as by use of a zippered back (Jobst®), or leggings with a series of interlocking bands fastened with hoop and loop fasteners (CircAid®). However, even these improvements have not been successful in solving the problem of poor compliance. 
         [0064]    Such compression socks may be ineffective in patients with massive edema or obesity, as the socks lose their elasticity over time. By the end of the day, edema often returns along with the symptoms. As a result of the loss of elasticity, these socks must be replaced frequently—generally every three or four months. 
         [0065]    Embodiments of the present invention incorporate negative pressure, dynamic gradient compression, comfort, ease of application and/or total ambulatory freedom. 
         [0066]    Inflatable socks may be used to apply compression to the foot and lower leg in a non-ambulatory setting. Such devices often do not allow patients to be ambulatory while under therapy or for periods of time that will provide successful therapies. Sequential inflatable compression devices are used to “milk” fluid in the legs proximally. These devices can be bulky and interfere with normal gait and/or ambulation. These inflatable devices sometimes include multiple compressed air bladders with intermittent “dead spaces” between bladders that attenuate the values of the therapy, and these bladders can be susceptible to puncture or tearing. 
         [0067]    Embodiments of the present invention are capable of applying gradient pressure (multiple chambers with differing pressure values) and/or dynamic sequential/synchronous compression (control of each of multiple separate chamber actuation by compression, order and time) in an ambulatory patient in the treatment of CVI, wound healing and other similar or related conditions. 
         [0068]    With reference to  FIG. 1 , a flexible garment  102  may be used in accordance with embodiments of the invention. The flexible garment  102  may be configured like a sock for use on a subject&#39;s leg or may be configured for use with other appendages. The flexible garment  102  may be formed of a flexible air impermeable material. Seals  104  are used to create an air space between the inside of the flexible garment and the subject&#39;s leg or other appendage.  FIG. 1  also illustrates a mobile power source  106  that may be secured to the waist, thigh or lower leg using a band  108 . The mobile power source  106  is connected to a controller  110  through a power cable  112 . The controller  110  may be secured to the flexible garment  102  by a band  114 , and may be configured to control pressure within the flexible garment through one or more air channels  116 . The air channels  116  may include one or more valves, and the bands  108 ,  114  may be a belt clip, strap, elastic band, or other attachment mechanisms. The controller  110  may be mechanical or electronic in nature and may control a rotary or reciprocating pneumatic vacuum pump. Air is drawn from a chamber or chambers within the flexible garment by way of the pump, through air channels  116 , to the atmosphere, creating one or more sub-atmospheric pressure conditions within the flexible garment  102 . 
         [0069]    According to embodiments of the invention, a flexible air impermeable disposable sock  200  with one or multiple chambers  202 , as illustrated in  FIG. 2 , is created by flexible air impermeable disks  204  with holes  206  at the center of a diameter to cause minor deflection of the material when applied around the leg, or other appendage, thereby applying an air tight seal. At the same time, the seals provided by the disks  204  are not tight enough to restrict the emptying of the thin-walled superficial veins. Other embodiments use socks  200  and disks  204  of varying sizes in order to create air tight seals while allowing thin-walled superficial veins to empty. In some embodiments, the disks are ultrasonically bound, or otherwise adhered to, the flexible sock material, as shown at location  208 . 
         [0070]    In the embodiment illustrated in  FIGS. 3 and 4 , a flexible air impermeable disposable sock  300  includes one or multiple chambers  302 , defined by elastic bands  304  that are secured in pockets  306 , as illustrated in  FIG. 4 . The pockets may be attached to the sock  300  by ultrasonic welding  308  or through other attachment methods. The sock  300  is configured to fit snugly when applied to a human appendage. In another embodiment, the elastic bands  304  are secured in pockets that include a window through which the elastic bands  304  may be adjusted by way of a hook and loop fabric. 
         [0071]    In some embodiment, the sock is oversized in order to easily fit over the ankle-to-heel circumference, which for some subjects may be larger than the circumference of the calf even with the foot minimally extended (e.g., with the foot extended approximately 120 degrees). 
         [0072]      FIGS. 5 and 6  illustrate a sock  400  before and after evacuation of the air according to embodiments of the invention. Although not depicted, a sock  200  with seals  204 , as illustrated in  FIG. 2 , may similarly be slightly oversized to fit over a patient&#39;s ankle-to-heel circumference. Ease of application and production of air tight seals is a significant problem with existing devices. 
         [0073]      FIGS. 7 and 8  illustrate a system  500  that extracts air from the chambers  502  of a sock  503  through air channels  504  by way of a vacuum generated by an electromechanical pump, according to embodiments of the present invention. An air channel  504  may be provided or fabricated by the use of a small diameter flexible plastic tube  506  with or without an air impermeable flexible material enclosure  508 . As shown in  FIG. 8 , the air channel  504  may be formed by a spiral wrap  510  encased in a flexible air impermeable material  508 . In other embodiments, the air channel  504  may be formed by a spring encased in a flexible air impermeable material  508 . Multiple air channels  504  may be ultrasonically welded  514  to the sock  503  or otherwise adhered to the sock  503  forming separate and independent air channels  504 . Male chamber ports  512  may be provided on the sock to connect with the air channels  504  to form air tight seals and allow easy access to the female ports on the controller. The spiral wrap  510  or spring provide internal support to the air channel pocket  516  while under sub-atmospheric pressure to prevent collapse of the air channel  504 , according to embodiments of the present invention. 
         [0074]    As shown in  FIG. 9 , a controller  518  can interface directly with the sock upon insertion of the male ports  512  on the sock  503  into the female ports  520  on the controller  518 , according to embodiments of the present invention. The controller  518  may also include a belt loop  522 . 
         [0075]      FIG. 10  illustrates an exemplary schematic of the controller  518 . The controller  518  provides multiple sub-atmospheric consistent pressures simply and effectively to multiple chambers in the sock, according to embodiments of the present invention. A DC voltage from power source  602  (e.g., a battery), which is recharged from a removable battery charger  604 , is synthesized by an adjustable step-up/step down switching DC-DC converter  606  to provide a constant voltage to the pump  608  (e.g. 5 Volts DC). In existing devices, the rotational speed of the pump decreases as available voltage decreases, which in turn reduces the pressure that the pump provides. Existing devices, including fabric compression devices (e.g., Jobst®, CircAid® and the like), lose compression during use. The DC to DC converter provides an adjustable constant voltage supply over the use of the device providing a constant pressure and therefore consistent therapy, according to embodiments of the present invention. This is a substantial advancement over existing technologies which do not provide constant pressure therapy, resulting in reduced efficacy and costly replacement of devices. 
         [0076]    As air is drawn through the device illustrated in  FIG. 10  it passes through multiple ball or magnetic check valves  610  that are arranged in series, according to embodiments of the present invention. Each ball or magnetic check valve  610  releases air pressure at a certain air pressure level that is determined by the amount of force a spring exerts on a ball or magnet  612  set in an internal seal  614 , according to embodiments of the present invention. The ball or magnetic check valves  610  are configured based on a target gradient pressure selected by the designer. If the ball or magnetic check valves  610  have the same value, then the gradient pressure drop between valves will be the same. The absolute pressure drop between any two valves is also dependent on air flow and adjusted air pressure input. Taps  616 ,  618 ,  620  are provided between each valve (V 3 , V 2 , and V 1 ) to produce gradient sub-atmospheric values P 3 , P 2  and P 1 . The sub-atmospheric value of the pressure gradients P 2  and P 1  can be expressed as:
       P 3 =Manually Adjusted Pump Pressure   V=Release Pressure of the Ball or magnetic check valve       
 
         [0000]    
       
      
       P 
       2 
       =P 
       3 
       −V  
      
     
         [0000]    
       
      
       P 
       1 
       =P 
       2 
       −V  
      
       
         
           
             For example: 
             Required Gradient Pressure: 12 mmHg 
             V 3 , V 2 , V/=12 mmHg 
             P 3  is adjusted to 40 mmHg 
           
         
       
     
         [0000]        P   2   =P   3   −V= 40−12=28 mmHg
 
         [0000]        P   1   =P   2   −V= 28−12=16 mmHg
 
         [0000]    The highest vacuum is created at the junction of the pump  608 , pin valve  622 , and ankle tap P 3    620 , according to embodiments of the present invention. The tap  620  (P 3 ) is fluidically connected to the ankle section of the sock, according to embodiments of the present invention. The level of the vacuum at P 3  may be adjusted by way of the pin valve  622  at any constant voltage. By allowing a controlled amount of leakage from atmosphere pressure, through the pin valve, into the junction between the pump and V 3 , the vacuum can be adjusted to any lesser value. The pressures at P 2  and P 1  may be determined with the formulas presented above. 
         [0083]      FIG. 11  illustrates a graph of pressure versus time, for the ankle, mid-calf and upper calf chambers for the controller illustrated in  FIG. 10 , according to embodiments of the present invention. In this example, the sub-atmospheric pressure values remain at a constant 40 mmHg, 28 mmHg and 15 mmHg regardless of the drain down of the battery. Based on the disclosure provided herein, one of ordinary skill in the art will recognize that other pressure values and/or numbers of pressure zones may be used. 
         [0084]      FIG. 12  illustrates a schematic of another controller  800 , which employs a different approach to vacuum control and application, according to embodiments of the present invention. Vacuum may be applied as a step or progressive function, singularly or sequentially, constantly or intermittently, with programmable time periods for each chamber. A DC voltage from power source  818  (e.g. a battery) is synthesized by an adjustable step-up/step-down switching DC-DC converter  819  to provide a constant voltage to the rotary or reciprocating pump (e.g. 5 Volts DC). Without component  819 , the rotational speed of the pump decreases as available voltage is reduced, which in turn reduces the pressure that the pump  820  provides. Existing devices, including fabric compression devices (e.g. Jobst®, CircAid®, and the like) lose compression during use. The DC to DC converter provides an adjustable constant voltage supply over the daily use of the device, thus providing a constant pressure and therefore consistent therapy. Existing technologies often do not provide constant pressure therapy, resulting in reduced efficacy and costly replacement. 
         [0085]    A micro-controller or micro-programmable controller  821  manages the operation of the normally closed electrical pneumatic switches  822  to actuate on predetermined time and chamber location cycles, according to embodiments of the present invention. Pump  820  runs at a constant or substantially constant revolution per minute rate that is controlled by the adjustable output voltage of the step-up/step-down switching DC-DC converter  819  providing a substantially constant singular sub-atmospheric pressure that is set manually by the controlled voltage and by adjusting the pin valve  823  to a desired value, according to embodiments of the present invention. One side of the electrical pneumatic switch array  822  is ported to the pump, and the other side of the electrical pneumatic switch array  822  ports directly to the sock male ports or indirectly through tubing for remote mounting (e.g. mounting to a calf or waist), according to embodiments of the present invention. A removable battery charger  824  is provided to recharge the battery pack after a day&#39;s use, according to embodiments of the present invention. 
         [0086]      FIG. 13  illustrates a graph of a control cycle demonstrating a dynamic sequential control of a “milking” device. In the first period  902 , which may be 5 seconds long for example, only the ankle chamber has an applied vacuum, for example 30 mmHg. In the second period  904 , which may be 5 seconds in duration for example, both the ankle and mid-calf chambers experience vacuum, and in the third period  906  the ankle, mid-calf and upper-calf are under vacuum for a duration of, for example, five seconds. In the fourth period  908 , which may, for example, be 20 seconds long, all chambers are returned to atmospheric pressure and the blood in the leg or extremity is allowed to refill with fresh blood to revitalize the tissue. At the end of the fourth period  908  the same cycle begins, according to embodiments of the present invention. 
         [0087]    In an alternative cycle, during the first period, which may be 5 seconds long for example, only the ankle chamber has an applied vacuum, for example 30 mmHg. In the second period, which may be 5 seconds in duration for example, only the mid-calf chambers experiences vacuum. In the third period, only the upper-calf is placed under vacuum for a duration of, for example, five seconds. In the fourth period, which may, for example, be 20 seconds long, all chambers are placed at atmospheric pressure and the blood in the leg or extremity is allowed to refill with fresh blood to revitalize the tissue. In other embodiments, the fourth period may be omitted and the cycle may begin again. 
         [0088]      FIGS. 14A-B  illustrate a sock  1402  having a port  1404 . In some embodiments, the port  1404  comprises a patch that is placed over a hole formed in the sock  1402 . In other embodiments, the sock  1402  includes a port  1404  for each chamber. The ports  1404  may have a seal that enables the chambers to maintain their pressure level. In addition, the ports and seals may be configured to permit various devices, for example tubes, needles, catheters, and/or electro-magnetic devices, to access the interior of the sock  1402  while maintaining the pressure level within the chambers. 
         [0089]    In some embodiments, the port  1404  is a universal port configured to receive a variety of devices, such as the devices shown in  FIGS. 14A-B , and may be placed over a wound  1406 . One device that may be used with the port  1404  is a pump  1408 . The pump  1408  is operated by a control  1410 , and accesses a reservoir  1412  that includes, for example, medicine. The pump  1408  is attached to a tubing  1414  that couples with the port  1404 . The pump  1408  may send medicine from the reservoir  1412  through the tubing  1414  and the port  1404  to the wound  1406 . In other embodiments, the tubing  1414  includes a catheter  1416  configured to deliver medicine through the port  1404  to the wound  1406 . 
         [0090]    In some embodiments, the port  1404  is not placed directly over the wound  1406  but is instead placed on the chamber in which the wound is located. In such cases, the port  1404  permits connection of the tubing  1414  to the sock  1402  at a standard location, such that the port  1404  is located on each chamber without regard to the location of the wound. Separate tubing (not shown) may be connected to the other end (e.g. the inside) of the port  1404  on the inside of the sock  1402 , and then extended between the port  1404  and the actual wound location, and may be coupled with or placed adjacent to the wound and/or the wound dressing on the inside of the sock  1402 . In this manner, the ports  1404  may be located on the sock  1402  based on convenience of external attachment (e.g. aligned on the same side of the sock), and then during the application of each particular sock  1402 , internal tubing may be employed to extend the suction, medicine delivery, ozone delivery and/or other wound treatment or therapy delivery systems from the location of the port  1402  to the location of the wound. 
         [0091]    As shown in  FIGS. 15A-C , a vacuum device  1500  configured to couple to a sock  1502  having a port  1504 , such as a universal port, according to embodiments of the present invention. The port  1504  may be located on the sock  1502  so as to be over a wound  1506 . The vacuum device  1500  may include a pump  1508 , a controller  1510 , a reservoir  1512 , and a tubing  1514 . The tubing  1514  may be configured to couple with and form an air-tight seal with the port  1504 . The pump  1508  is activated by the controller  1510  and creates a vacuum in the tubing  1514 , which pulls matter from the wound  1506  inside the sock  1502  up through the tubing  1514  and into the reservoir  1512 . Such a configuration could be useful, for example, in draining the wound  1506  without removing the sock  1502 . 
         [0092]      FIG. 16  illustrates a sock  1602  having a port  1604 , which may be a universal port, placed over a wound  1606 . In some embodiments, an ultrasonic transducer  1608 , operated by a controller  1610  and powered by a power source  1612 , may be placed over the port  1604 . In other embodiments, the ultrasonic transducer  1608  couples with the port  1604  for direct access to the wound  1606 . When activated, the ultrasonic transducer  1608  may send energy  1614  into and/or through a wound  1606  to promote healing, for example. 
         [0093]      FIG. 17  illustrates a dual layer sock  1702  that includes an inner sock  1704  and an outer sock  1706 . In some embodiments, a negative pressure is applied to the inner sock  1704  and a positive pressure is applied to the outer sock  1706 . In other embodiments, the negative pressure is applied to the outer sock  1706  and the positive pressure is applied to the inner sock  1704 . 
         [0094]    As shown in  FIG. 18 , a sock  1802  includes one or more chambers  1804  in which negative pressure is applied, according to embodiments of the present invention. The sock  1802  also includes one or more seals  1806  in which positive pressure is applied. In other embodiments, the chambers  1804  receive a positive pressure and the seals  1806  receive a negative pressure. The seals  1806  may themselves be independent chambers, which may be supplied with positive pressure in order to seal around the subject&#39;s limb and hinder or prevent fluid flow between the various chambers formed by the sock  1802  and the patient&#39;s limb, according to embodiments of the present invention. 
         [0095]      FIGS. 19A-C  illustrate a sock  1900  according to various embodiments of the present invention. The sock  1900  includes a plurality of positive pressure seals  1902 ,  1904 ,  1906 . The pressure seals  1902 ,  1904 ,  1906  may be of varying sizes to match the varying diameters of a patient&#39;s lower leg. In some embodiments, the pressure seals  1902 ,  1904 ,  1906  may operate independent of each other, applying positive pressure to distinct parts of a patient&#39;s lower leg in many different patterns. For example, the pressure seals  1902 ,  1904 ,  1906  may inflate sequentially. A negative pressure may be applied within the sock  1900  and/or within the chambers formed while the positive pressure seals  1902 ,  1904 , and  1906  (which may themselves be independent chambers) are activated, according to embodiments of the present invention. 
         [0096]      FIGS. 20A-B  illustrate a sock  2002  having a port  2004 , which may be a universal port, placed over a wound  2006 . In some embodiments, a thermal device  2008  is placed over the port  2004 , while in other embodiment the thermal device  2008  couples with the port  2004  to directly access the wound  2006 . In some embodiments, the thermal device  2008  includes heating coils  2010  placed on a lower surface  2012  of the thermal device  2008 . When activated, the thermal device  2008  transmits energy to the wound  2006  to promote healing, for example. 
         [0097]      FIGS. 21A-B  illustrate a sock  2102  incorporating a port  2104 , for example a universal port, through which a gas may be introduced into the sock  2102 . In some embodiments, the port  2104  is placed over a wound  2106 . A gas source  2108  may be coupled to a control valve  2110  by a first tubing  2112 . The control valve  2110  may be operated by a controller  2114 , and may be coupled to the port  2104  by a second tubing  2116 . The controller  2110  may selectively introduce a gas from the gas source  2108  into the sock  2102 , for application onto the wound  2106 , for example. In other embodiments, the controller  2114  may introduce enough gas to inflate the sock  2102 , as shown in  FIG. 21B . In some embodiments, the gas may be ozone or nitric oxide. 
         [0098]    In other embodiments, for example those shown in  FIGS. 22A-C , a sock  2202  includes a port  2204  placed over a wound  2206 . In some embodiments, a pump  2208  is operated by a controller  2210  to deliver medicine and/or other fluids from reservoir  2212  through a tubing  2214  to the wound  2206 . As shown in  FIG. 22C , the tubing  2214  may include a catheter  2216  to deliver the medicine to the wound  2206 . In some embodiments the catheter  2216  may pierce the port  2204 . 
         [0099]    In yet other embodiments, for example those shown in  FIGS. 23A-C , a sock  2302  may incorporate a pressure chamber  2304  configured as a single helix wrapped substantially around the sock  2302 . In other embodiments, the sock  2302  may incorporate two pressure chambers  2306 ,  2308  configured in a double helix wrapped around the sock  2302 . Alternatively, one or more pressure chambers  2310  may wrap around the sock  2302  and cover substantially the entire sock  2302 . The pressure within the chambers  2310  may be configured to exert decreasing pressure on the sock from a toe portion  2312  to a top portion  2314 . In other embodiments, the pressure chambers may be configured to exert negative pressure on select portions of the sock. In particular, the selected portions of the sock may be chosen in a linear fashion, starting from a toe portion  2312  of the sock  2302  to a top portion  2314  of the sock  2302 . The pressure chambers  2304 ,  2306 ,  2308 ,  2310  may be inflated with positive pressure gas and applied by themselves over a patients limb, and/or may be applied over a negative pressure sock, according to embodiments of the present invention. 
         [0100]    Referring to  FIG. 24 , according to some embodiments, a sock  2400  may include an outer layer  2402  and an inner layer  2404 . The outer layer may be a flexible, air impermeable layer, and the inner layer  2404  may be configured for user comfort and may be formed of a foam, for example. Alternatively, the inner layer  2404  may be formed from a thin strip of a cotton-based material that is wrapped around the patient&#39;s limb, or a cotton inner sock, according to embodiments of the present invention. Inner layer  2404  may be referred to as a “comfort” or low compression layer. Inner layer  2404  may be a separate sock applied prior to application of the negative pressure sock  2402 ; alternatively, inner layer  2404  may be incorporated with outer layer  2402  to form a dual-layer sock. Although two layers are discussed, the sock  2400  may also include one or more additional layers, for example extra “comfort” layers below the outer layer  2402 . Sock  2400  may alternatively include an inner flexible air-impermeable layer, a “comfort” middle layer  2404 , and an outer flexible air-impermeable layer  2402 , to form one or more closed cavities within the sock  2400 , such that the sock  2400  does not rely on the patient&#39;s limb, or an undersock applied to the patient&#39;s limb, to form a portion of each pressure zone chamber, according to embodiments of the present invention. 
         [0101]    Referring to  FIG. 25 , in some embodiments, an outer layer  2502  is formed of a flexible, air impermeable material with one or more disks  2506  attached to the inside surface  2508  of the outer layer  2502 . The disks  2506  may be configured to create air tight chambers  2510  between the outer layer  2502  and the patient&#39;s limb. In situations in which an under-sock, or “comfort” layer, is worn on the patient&#39;s limb below the negative pressure sock, such under-layers may interfere with the proper seal between the pressure zones which would normally be created by the contact of the disks  2506  with the patient&#39;s skin. For example, a cotton sock worn under the negative pressure sock might permit air to flow around the disks  2506  by flowing through the air permeable structure of the cotton sock. To complete the air tight chambers, an inner layer  2512  may incorporate bands  2514  of air impermeable material that are or may be aligned with the disks  2506 . In that arrangement, the disks  2506  of the outer layer  2502  are configured to connect with, press against, and/or otherwise contact the bands  2510  of the inner layer  2512  to create an impermeable seal between chambers. 
         [0102]    A “universal port” as discussed herein is a port which accepts the hardware connections for two or more different wound treatment and/or therapy systems on the same sock. For example, the same port formed on the sock may be used to interface with and/or fluidly couple with two or more external systems at different times, for example the systems shown in  FIGS. 14A-B ,  15 A-C,  16 ,  21 A-B, and  22 A-C. The connecting hardware and/or tubing for each system may be customized in order to interface with the universal port, and the user of a port which is interchangeable among treatment and/or therapy systems mitigates or prevents the need to provide a negative pressure sock with a large number of different ports, thereby minimizing complexity and manufacturing cost, according to embodiments of the present invention. 
         [0103]    As used herein, the term “negative pressure” is used to refer to a pressure which is lower than the pressure outside of the sock, and also refers to a vacuum or near-vacuum condition in which most or all of the air has been evacuated from a chamber, and a suction force applied to the chamber, according to embodiments of the present invention. 
         [0104]    Various modifications and additions can be made to the exemplary embodiments discussed without departing from the scope of the present invention. For example, while the embodiments described above refer to particular features, the scope of this invention also includes embodiments having different combinations of features and embodiments that do not include all of the described features. Accordingly, the scope of the present invention is intended to embrace all such alternatives, modifications, and variations as fall within the scope of the claims, together with all equivalents thereof.