GB2537658A

GB2537658A - Galactose polymer gel dressing for treatment of skin and deeper tissue structures capable of delivering remedial agents,

Info

Publication number: GB2537658A
Application number: GB1506858.8A
Authority: GB
Inventors: John Newton Christopher; Cantwell Evelyna; Cantwell Jack; Jane Newton Sarah
Original assignee: Individual
Current assignee: Individual
Priority date: 2015-04-22
Filing date: 2015-04-22
Publication date: 2016-10-26
Also published as: GB201506858D0

Abstract

The present invention relates to a system for the repair of bodily damaged tissues with a galactose polymer gel dressing in a mechanically supported and unsupported form. The polymer material may be agarose and is used for the treatment of skin wounds and wounds to sub-dermal structures and skin conditions of cosmetic relevance and those related to inflammatory states such as diabetes. In particular, the galactose polymer gel may be used for the transdermal delivery of remedial agents such as oxygen, and may be used in conjunction with calcium peroxide, ascorbic acid and lactic acid. Remedial agents may be delivered out of the polymer gel matrix by passive diffusion or by an active means such as the use of the technique of iontophoresis. Remedial agents of cosmetic and medical utility can also be combined with the galactose polymer gel by delivery from an external reservoir source such as a syringe which is connected to the galactose polymer gel by interfacing with a suitable galactose polymer gel-encasement structure such as an outer sleeve, glove or plastic enclosure.

Description

The present invention relates to an aid applied to the skin for the treatment of bodily tissues, and as a means of trans-dermal delivery of agents with cosmetic and medicinal importance that may be active within the skin or that may penetrate to, and be active in, deeper bodily tissues.

Damaged bodily tissues resulting from a skin condition or in the form of a wound may require curative, therapeutic or analgesic treatment. A major factor associated with tissue damage is that bacteria and other pathogens are able to bypass the protective barrier provided by the skin and infect the tissues beneath. An infection of this nature can pose a serious risk to health and cause major complications during therapy.

Conventional dressings are a rather crude option for treatment of damaged tissue. The present invention seeks to improve the treatment of damaged bodily tissue by positioning a certain galactose polymer gel in a supported form intimately with the damaged bodily tissue.

Therefore viewed from one aspect the present invention provides an aid for treatment of damaged bodily tissue and for administering substances trans-dermally comprising: A unit of substantially pure, cross-linked galactose polymer gel in a supported and non-supported form placed such that a portion of the proximal surface of the unit is in intimate contact with the damaged bodily tissue or at a skin site deemed suitable for trans-dermal delivery of agents contained within the galactose polymer gel matrix or from an external reservoir such that they may act locally for cosmetic and medical purposes or that may penetrate to deeper tissue structures.

The galactose polymer gel advantageously undergoes no substantial binding to damaged bodily tissue and therefore the unit is straightforward to position on and remove from the bodily tissue. By not causing trauma to the bodily tissue when it is removed, the galactose polymer gel is comfortable for the subject to use and does not interfere with healing. Moreover the galactose polymer gel advantageously feels cool when placed on the bodily tissue thereby easing pain or irritation and improving patent comfort.

Preferably the galactose polymer gel is supported on a mechanical support (or matrix). In this embodiment and from now on in this description of the current invention, the mechanically supported form of the galactose polymer gel is referred to as, 'the unit of galactose polymer gel'. The mechanical support may be a mesh, backing or coating adapted so that a portion of the proximal surface of the unit of galactose polymer gel is intimate with the damaged bodily tissue. The mechanical support may be rigid, semi-rigid or flexible. The mechanical support may be comprised of a synthetic or natural material. The mechanical support may be a fabric (eg a woven fabric such as cotton).

In a most preferable embodiment of this invention the unit of galactose polymer gel may comprise a three-layer system, where the first component comprises a woven fabric, bonded to a thin plastic surface forming the galactose polymer gel support. This component is first manufactured as a unit of various widths and lengths constructed as a continuous roll of up to 20cm wide (or greater) and up to 10m or greater in length. The synthetic or natural fibre roll, of which an example is the Fortuna Contour bandage material is bonded using a process requiring heating such that the fabric is firmly attached to a thin plastic surface that will form the outer backing or distal surface of the unit of galactose polymer gel. It is onto this backing material that the molten (50-75°C, but at least 5°C above the gelling temperature of the galactose polymer gel) galactose polymer gel is poured. Once the galactose polymer gel is solidified, the unit of galactose polymer gel may be cut to the appropriate size and used for the various manifestation of this invention described within the text and associated diagrams on the following pages of this description. Figure la shows the unit of galactose polymer gel constructed in the way described in this paragraph.

In addition to the above, a further preferred embodiment of this invention is to use the unit of galactose polymer gel in a form that does not have the bonded gel support with the plastic backing. Instead, the galactose polymer gel is cast onto the fabric backing that has not been bonded to a thin plastic surface. In this way the unit of galactose polymer gel is semi-supported by the internal fabric. If the fabric has a degree of stretch, then the unit of polymer gel can be formed easily around various parts of the body, for example, around the hand or around the fingers, as in the case of burns. This embodiment of the unit of galactose polymer gel is indicated in Figure lb. The galactose polymer used to make the unit of galactose polymer gel in whichever of the two forms described above may be a heterogeneous polysaccharide. Preferably, the galactose polymer is hydrophilic. Preferably, the galactose polymer gel is hydrated. The galactose polymer may be capable of absorbing water and therefore may be swellable. Typically, the galactose polymer gel has a high gel strength (eg 1500g/cm2 or more). Typically, the galactose polymer gel is highly cross-linked.

Preferably the galactose polymer gel comprises a portion of an aqueous medium. Particularly preferable, the unit of galactose polymer gel and galactose polymer gel has a major proportion of an aqueous medium. The aqueous medium in the most basic embodiment of this invention may be a pH-buffered solution, saline or water. The unit of galactose polymer gel or the galactose polymer gel in a mechanically unsupported form most preferably may comprise at least 90 wt% water, especially preferable, at least 98wt% or more water prior to the addition of agents with remedial activity.

Preferably, the galactose polymer is an agar derivative. An especially preferred galactose polymer is agarose. Agarose is advantageous in that it has a high purity, a high gelling tendency and it can be highly hydrated so as to exhibit a tendency not to bind to damaged bodily tissue, whilst feeling soothingly cool. Agarose is also particularly advantageous in that it has higher gel strength than agar, due to the removal of lower molecular components. Agarose is a product derived from agar by purification.

In a preferred embodiment, the damaged bodily tissue is skin-damaged bodily tissue. For example, the skin-damaged bodily tissue may be characterised by broken, sensitized, blemished or exfoliated skin. In particular, the skin damage may be associated with the diabetic condition, where the inflammatory process prevents the normal wound healing process. Preferably, the unit of galactose polymer gel is positionable dermally, such that a portion of the proximal surface is in intimate contact with the skin-damaged bodily tissue. The skin-damaged bodily tissue may also be characterised by a wound (eg a wound inflicted surgically, on exposure to fire or in combat) or by symptoms of a skin condition, disorder or illness (rash, irritation, ulcer or blemish).

Typically the unit of galactose polymer gel or galactose polymer gel is positionable such that a portion of the proximal surface is close to or in contact with the damaged bodily tissues.

In yet a further preferred embodiment, the unit of galactose polymer is positioned at a bodily site that is considered optimal for the trans-dermal delivery of an agent or agents from within the unit of galactose polymer gel, such that maximum trans-dermal transfer will take place. In addition, the trans-dermal delivery of the agent held within the unit of galactose polymer gel (or held within the galactose polymer gel in unsupported form) that may have cosmecutical, nutraceutical and pharmaceutical properties and be directed to a cosmetic or a medical purpose and may be delivered out of the unit of galactose polymer gel (or galactose polymer gel) into the skin and thence into deeper bodily layers by passive diffusion from the unit of galactose polymer gel (or galactose polymer gel) by a passive process, such as gradient diffusion, or by an active process, such as iontophoresis. For maximal delivery of a substance in this way, the skin should first be prepared by using an exfoliating agent.

The unit of galactose polymer gel in either of the supported forms indicated above (see Figures la and lb) or in an unsupported form may be used as a dressing and it may adopt any convenient shape and size. Preferably, the shape of the unit of the galactose polymer gel or galactose polymer gel will conform substantially to the shape of a part or of the whole of a bodily part. A particularly preferable shape of the unit of galactose polymer gel is that of a roll of material that may comprise a sheet of the unit of galactose polymer gel of up to 1m in length and up to 15 cm in width. Using a roll of this material, most bodily parts may be covered by wrapping the unit of galactose polymer gel around the damaged bodily part and then securing it in place.

The unit of galactose polymer gel, most preferably in the plastic-backed, supported form, but certainly preferably in the supported form, may be used as a dressing or transdermal patch of variable size and thickness. The dressing or transdermal patch may be used as part of a two component system where an outer covering is placed over the unit of galactose polymer gel or galactose polymer gel or it may be used as a component of multi-part (eg multi-layer) system and this may include an outer protective covering to secure the dressing or patch in place on the skin. A two or more component system of which the unit of galactose polymer gel or galactose polymer gel is the proximal component (with respect to the skin) may be designed as a means to remove wound exudate or to supply liquid medications and/or a gas, such as oxygen.

Preferably in dressing form, the unit of galactose ploymer gel with the plastic backing to the distal surface may be used as a two component system where once placed in position over the damaged bodily surface (or skin for cosmetic purposes or transdermal delivery of substances), it is held in place by the addition of an outer cover that around its periphery has a non-allergenic adhesive. For this purpose, a roll of a non-allergenic adhesive bandage may be used and it may be cut to size to cover the unit of the galactose polymer gel with the integral plastic backing. An example of this preferred arrangement is provided by reference to Figure 2a. This is a preferred embodiment for a minor wound such as a graze but if the wound is more substantial, with a greater degree of wound exudate, a most preferred embodiment of this invention includes an outer covering with an absorptive layer of material that covers the plastic-backed unit of the galactose polymer gel such that there is an overlap (see Figure 2b) of the absorptive layer with respect to the unit of the galactose polymer gel that allows the overlap area of the absorptive (or absorbant) layer to act as a wick to draw wound exudate (blood, extracellular fluid etc) away from the site of the wound. In a particularly preferred embodiment of this invention, the proximal surface (surface in contact with the skin) of the unit of the plastic-backed galactose polymer gel has a contour structure that provides channels for the egress of wound exudate such that it can be wicked by the material of the absorptive layer that overlies the distal surface of the plastic backed unit of galactose polymer gel. An example of this preferred embodiment is shown in Figure 2c.

In yet another preferred embodiment of this two component dressing system, the unit of galactose polymer gel has channels on the proximal surface arranged in a istarbursti pattern (foe example) connected to one central hole through the thickness of the unit of the galactose polymer gel. An example of this pattern is presented in Figure 3. In this embodiment the unit of the galactose polymer gel, with plastic backing, can be used with the second component covering that has an integral port and tap. This connection port can be used for the removal of larger quantities of wound exudate by applying slight negative pressure by the connection of a suitable sized tube and syringe. It can also be used to supply analgesic agents from an external reservoir such as a syringe and also other agents of remedial value.

In addition to liquids, a small volume of a gas can be applied via the port within the outer covering of the unit of galactose polymer gel as described above for liquids. In the most preferred embodiment of this invention such a gas is oxygen. Oxygen gas (02) is a highly efficacious remedial agent and small quantities have been shown to markedly enhance the wound healing process.

In a most preferred embodiment of this invention, a means of producing oxygen gas in situ is described here. For this, the same two-component system as described in the paragraphs above is used, except that now, a means of oxygen gas generation is built into the substantially gas impermeable outer covering for the unit of galactose polymer gel. The principal of the oxygen gas generation is derived from using the compound, calcium peroxide (Ca02) to generate small quantities of oxygen gas. Ca02 is rather insoluble in water but it slowly decomposes to form calcium hydroxide and oxygen (02). In an acidic environment hydrogen peroxide (H202) is formed as a reaction intermediate when Ca02 comes into contact with an aqueous environment. A small increase in acidity of the system in an aqueous environment will therefore increase the rate of reaction to form 02 according to the following equations: Ca02 2H20 Ca(OH)2 +H202 2H202-> 2H20 + 02 In order to generate 02 from within the two-component system using the unit of galactose polymer gel and to allow oxygen to permeate through the unit of the galactose polymer gel and onto the wound (for example), Figure 4 provides an example of a practical system that may be constructed for this purpose. In this case, the unit of the galactose polymer gel is shown in circular form with a Istarburst pattern' of groves radiating from a central hole through the layers of the unit of galactose polymer gel. This embodiment of this invention is shown where the plastic backing is not continuous across the distal surface of the gel (distal with respect to skin). There is an area of the galactose polymer gel that is not covered with the plastic backing. It is this area that makes contact with the top cover at a site where a 'sachet' or enclosure is positioned that contains a small quantity of Ca02 mixed with ascorbic acid. The ratio of ascorbic acid to Ca02 and the absolute percentages of each of the ascorbic acid and Ca02 may be varied over a wide range from 50:50 to 98:1 ascorbic acid: Ca02 and where the overall proportion of both agents together, is varied from 1% to 100% (over a ratio range of 50:50 to 99:1 of ascorbic acid to Ca02). Adding a carrier material that does not react with ascorbic acid, Ca02 or H202, will vary the absolute amount of both ascorbic acid and Ca02 contained within the enclosure.

Ascorbic acid is a week acid and when the top cover is placed over the unit of the galactose polymer gel, contact between the substantially aqueous agarose polymer gel and the small quantity of the Ca02/ascorbic acid dry powder will start the reaction to liberate H202 and 02. As time proceeds, the wick property of the absorptive layer that surrounds the unit of galactose polymer gel, as indicated in Figure 4a, will draw wound exudate towards the Ca02/ascorbic acid mix and maintain the aqueous environment in which 02 is generated and prevent any further dehydration of the unit of the galactose polymer gel. Oxygen generated in this way will pass through the channels in the unit of the galactose polymer gel and it will be dispersed by the starburst pattern (in this example) over the wound area.

In yet a further embodiment of this invention for producing a small amount of 02 gas in situ using the unit of galacose polymer gel and the outer cover that has a central enclosure of Ca02 and ascorbic acid of various thicknesses that may range from a thin layer (that coats the inside of the outer cover) to a sachet of several mm in depth, the absorptive layer area may also be impregnated with Ca02 and ascorbic acid. In this way when wound exudate is absorbed, the reaction will take place in the absorbant layer and 02 gas will be produced.

As an alternative to the production of 02 from an enclosure in the top cover of this two component system, a further embodiment of this invention where oxygen is produced in situ, is where a circular 'tablet' of a mixture of Ca02 and ascorbic acid is placed on the middle of the unit of the galactose polymer gel, prior to the application of the top cover that does not include an enclosure containing Ca02 and ascorbic acid. This embodiment is shown by the example presented in Figure 4b.

Yet a further variation of this embodiment of this invention where oxygen is produced from the two-component system employing the unit of galactose polymer gel is where only Ca02 is included in the sachet (or enclosure or thin layer coating or impregnated absorptive or absorbant layer), in the top cover or within the tablet. In this embodiment, ascorbic acid is dissolved in the unit of the galactose polymer gel. As ascorbic acid has limited stability in an aqueous environment, it can be stabilized by the addition of a small quantity of the compound, glutathione. This particular embodiment for the in situ production of oxygen from the two-component system using the unit of the galactose polymer gel may become a preferred embodiment as ascorbic acid is an antioxidant (and is required for the dermal fibroblast production collagen). Glutathione is an extremely important antioxidant within biological systems, and it will protect ascorbic acid from oxidation (that may be enhanced in the presence of H202) and with the cellular enzyme, glutathione peroxidase, it will also protect skin cells from peroxidation by any H202 that diffuses through the gel to make contact with live cells of the skin before the H202 has degrade in the aqueous environment to form 02.

Along with the addition of ascorbic acid into the galactose polymer gel matrix, a further preferred embodiment of this invention as it relates to the production of oxygen in situ and other embodiments of this invention involving the unit of galactose polymer gel, is the inclusion of lactic acid over a concentration range from 0.2% to 2%. A combination of ascorbic acid and lactic acid has been found to have antimicrobial properties when both are used at concentrations of less than 0.5%. Lactic acid alone has significant antimicrobial activity at concentration from around 1% and ascorbic acid at 0.2 to 0.4% demonstrates synergism with low doses of lactic acid (0.2%). As a means of preventing microbial growth within the unit of galactose polymer gel or galactose polymer gel a further embodiment of this invention is to add a combination of ascorbic acid with lactic acid or to add lactic acid alone at a concentration between 0.2% and 2% and most preferably around 1%.

In a preferred embodiment for the rapid self-application or assisted-application of the unit of galactose polymer gel in the form of a bandage roll without the integral plastic backing, as indicated earlier in this description of the current invention, and which may be applied under emergency conditions (eg in the case of a triage situation under battle field conditions or when emergency services are called to the scene of an accident or where bodily damage has been inflicted by a knife or gunshot wound or by a fire), the unit of galactose polymer gel-bandage-roll can be secured by applying an outer covering of the thin plastic material commonly referred to as plastic wrap, or cling-film.

In a most preferred embodiment that is particularly pertinent to injury induced by blunt force trauma, by a knife or by gunshot, grenade or bomb, a blood stopping agent may be incorporated into the unit of galactose polymer with the plastic backing (see Figure la) when used as a roll dressing or dressing swab to pack out the wound. Here the dressing or pad of the unit of galactose polymer gel can be constructed with a thickness from 5mm to 15mm and this may be used to push into the wound to stop the bleeding. Alternatively, a blood stopping agent may be administered before applying the unit of galactose polymer gel in whichever form is appropriate to the situation.

In a further preferred embodiment of the bandage-roll-form of the unit of galactose polymer gel without the integral plastic backing (as shown in Figure lb), when it is used in the emergency setting, the plastic-wrapped or cling film-wrapped unit of galactose polymer gel can be encased in an outer sleeve or glove composed of a Gortex-type material. In particular, this will provide further protection form the ingress of particulate material and microorganisms to the wound or burn site.

The unit of galactose polymer gel with the integral plastic backing (as shown in Figure la) may also be used in a trauma setting as described above. In this form and due to the plastic backing, the unit of galactose polymer gel is substantially protected by the plastic backing and may be used without an outer plastic covering. The integral plastic backing will not only provide increased mechanical support but it will also protect from the ingress of dust and particulate material and will also substantially reduce the loss of water by evaporation. Both forms of the unit of galactose polymer gel are suitable for traumatic injury under a triage situation.

In addition to the use of the unit of galactose polymer gel that is composed of the galactose polymer gel in the form of an agarose gel and the mechanical support, the galactose polymer gel can be used without the mechanical support when the thickness of the galactose polymer gel is no less than 3-5mm in depth and has a maximum surface area of 25cm2 or when the area of the galactose polymer gel is between 25 cm2 and 100cm2 and has a graded thickness between 5mm and 10mm.

In addition to the delivery of oxygen, the unit of galactose polymer gel or galactose polymer gel can deliver remedial agents where the unit of galactose polymer gel or galactose polymer gel is positionable such that a portion of the proximal surface is intimate with the damaged bodily tissue whereby to confine the amount of remedial agent at or in the vicinity of the damaged bodily tissue. An example of this situation and application is where topical treatment of the skin surface is required for eczema, psoriasis or diabetic skin complications, such as the diabetic ulcer or diabetic foot.

In a further preferred embodiment, the unit of galactose polymer gel or galactose polymer gel comprises: an amount of remedial agent or agents, wherein the unit of galactose polymer gel or galactose polymer gel is positionable such that a portion of the proximal surface is intimate with the damaged bodily tissue whereby to deliver the remedial agent transdermally by a mechanism involving passive diffusion such that the remedial agent or agents are distributed deeper into the body and may diffuse via the capillary system of the dermis, such that body structures substantially distal to the point of skin application are exposed to therapeutic concentrations of the remedial agent or agents. In particular, the substances released from the unit of galactose polymer gel or galactose polymer gel may be released in sufficient amount such that they have systemic therapeutic activity.

The remedial agent may be a liquid, a solid (eg a powdered solid that dissolves or is suspended in the galactose polymer gel) an emulsion, a liposomal suspension or a gas. The remedial agent may be a compound or composition (eg a mixture of two or more remedial compounds or a remedial compound together with one or more carriers, diluents or excipients).

The remedial agents released from the unit of galactose polymer gel or galactose polymer gel, fashioned as a bandage-dressing-roll or patch or dressing, may be cosmecutically, nutraceutically or pharmaceutically active. In other words, the remedial agent or agents may be used for cosmetic or medical purposes. The remedial agent or agents may be curative, therapeutic (eg anti-cancer, wound healing, steroidal, antiviral, bactericidal, antiseptic or antibiotic, etc), prophylactic or analgesic. The amount of the remedial agent or agents may be of cosmetically, therapeutically, prophylactically or analgesically effective amounts and these agents may act locally or systemically (may reach a site distant to the place of attachment of the unit of galactose polymer gel or galactose polymer gel).

The remedial agent may be contained or incorporated into the unit of galactose polymer gel or galactose polymer gel. For example, the amount of remedial agent may be dissolved, suspended or absorbed in or on the unit of galactose polymer gel or galactose polymer gel or any component that is associated with the unit of galactose polymer gel or galactose polymer gel.

The remedial agent may be effective for a cosmetic purpose or in the treatment of a skin condition, disorder or illness. The remedial agent may be effective in the treatment of burns, ulceration, diabetic ulcers, exfoliation, bedsores, and wounds of all types and may act to accelerate the wound healing process, particularly in the diabetic condition.

The remedial agent to be contained within in the unit of galactose polymer gel or galactose polymer gel or to be supplied from a external source such as from a reservoir container may be an antibiotic (eg a tetracycline antibiotic) for example for the treatment of acne rosea. The remedial agent may have anti-inflammatory properties of a steroid (eg hydrocortisone) or it may be anti-inflammatory by way of being directed to signal transduction pathways that are involved in inflammation and that are initiated by Advanced Glycation End-products (AGEs), Pathogen Associated Molecular Patterns (PAMPs) or Damage Associated Molecular Patterns (DAMPs) and their signalling pathways such as the MAPkinase (MAPKs), and the AP-1 and NF kappa beta (NFic(3) transcription factors, as well as to the activation of the autophagosomal-lysosomal pathway (often termed autophargy, however, autophargy can refer to the initiation of the process only, and not the complete process involving autophagosome fusion with lysosomes, where full processing of damaged organelles and misfolded proteins etc., is performed), a pathway that decreases the build-up of inflammatory protein aggregates and malfunctioning organelles, such as mitochondria that produce excessive amounts of reactive oxygen species (ROS) that are pro-inflammatory and that also reduces the concentration of p62/SQSTM1 (sequestosome), a protein that acts as an inflammatory intermediate for NFIcr, signalling. The up-regulation of the autophagosomal-lysosomal flux (the rate at which organelles and proteins and protein complexes etc. are completely processed to release for example, low molecular weight components, such as individual amino acids, nucleic acids and components thereof) also decreases the propensity of cells within a tissue to undergo apoptotic cell death. The remedial agent directed to the autophagosomal-lysosomal pathway may be an agent that targets the initiation of autophargy, such as an agent that inhibits the mTORC1 protein kinase complex, or it may be an agent or combination of agents that increase the rate of autophargosomal-lysosomal flux via increasing the protein expression or the activation of down-stream components of the autophagosomal-lysosomal pathway.

In a most preferred embodiment, the remedial agent contained within the unit of galactose polymer gel or galactose polymer gel or supplied from an external reservoir source, will target the rate of autophagosomal-lysosomal flux. In this respect, agents might be directed to increase the overall stress response within cells of the skin and underlying structures or be directed to increasing the amount and activity of specific and rate limiting components of the autophagosomal-lysosomal pathway, such as Atgb and Atg7. These stressing agents may be directed towards the induction of Heat Shock Factor 1 (HSF1) and this might be achieved with agents that transiently increase oxidative stress and activate Stress Activated Map Kinases (SAPKs) such as Jun N-terminal Kinase (JNK) and increase the transcriptional activity of Forkhead Box 0 protein (FoxO) family members.

Modalities such as nutrient deprivation are know to increase cellular stress pathways and to up-regulate the activity of the autophagosomal-lysosomal pathway (or flux through the pathway) and whilst this may be achieved using in vitro cell culture models, this is not so easily achieved in vivo. An exception is under pathological conditions such diabetes and other inflammatory conditions where cells of the skin and other tissues are under metabolic and oxidative stress. Inflammation and associated apoptotic cell death, collectively termed here as Inflammatosis', and the process of autophagosomal-lysosomal transport (an alternative term for autophagosomal-lysosomal flux) are mutually exclusive, and whilst an area of skin such as a diabetic ulcer is a site of cellular stress, this stress results in inflammatosis. In this situation, treatment modalities must therefore be sought to channel this stress to the up-regulation of autophagosomal-lysosomal flux and away from inflammatosis. Remedial agents that can be included in the unit of galactose polymer gel can be those agents that re-direct stress-induced inflammatosis to stress-induced up-regulation of the autophagosomal-lysosomal flux.

One of the embodiments of this invention for increasing cellular stress within skin cells for the treatment of cosmetic conditions utilizes a non-specific stress response as a trigger factor for the up-regulation of the autophagosomal-lysosmal flux within the epidermis and dermis of the skin. In part, such a preferred embodiments of this invention has already been described for the delivery of oxygen from the two-component system as indicated in Figure 4. Here oxygen is delivered to the skin via the acidification of the aqueous reaction involving Ca02. A corollary of the use of acidic conditions within the unit of galactose polymer gel is the fact that reducing the pH of a cellular system is perceived by cells as a stress and in some cellular systems, this can induce an up-regulation of the autophagosomal-lysosomal flux. For some cellular systems, such as cancerous growths, this is a mechanism by which the tumour cells survive a hypoxic environment. Indeed, it is now being shown that for an existing tumour system, blockade of autophagosomal-lysosomal flux results in cell death and evidence is now accumulating that the autophagosomal-lysosomal flux is a target for tumour therapy (to be returned to in the following pages of this description).

So to continue from the above with respect to a cosmetic intervention, a most preferred embodiment for certain cosmetic skin treatments such as skin lightening, the removal of brown spots and also for tattoo lightening, is the induction of cellular stress that in turn, will up-regulate autophagosomal-lysosomal flux. As a non-specific means of inducing stress, skin cell pH can be reduced by the application of the unit of galctose polymer gel that has been acidified by the addition of lactic add and or ascorbic acid. Additional ways of inducing a non-specific cellular stress are to transdermally provide from within the matrix of the unit of galactose polymer gel, substances that induce oxidant generation within skin. Alternatively, substances may be delivered by passive diffusion from within the matrix of the unit of galactose polymer gel that directly up-regulate components of the autophagosomal-lysosomal pathway, such as those that increase autophagosome initiation by blocking the insulin-PI3K-PKB/Akt-mTORC1 axis or by increasing the interaction of Beclin1 with PI3K type III or that increase the protein concentration and activity of autophagosome elongation factors such as Atgb and Atg7. For some of these targets, this might be achieved by incorporating within the unit of galactose polymer gel or the galactose polymer gel, agents that activate Stress Activated Map Kinases (SAPKs) such as JNK activators, HSF1 activators and factors that increase the nuclear and cytosolic translocation of FoxO family members.

Whilst cellular stress is a trigger for inflammatosis and/or autophargy (and an increase in the autophagososmal-lysosomal flux), whether autophargy or inflammatosis is the outcome of this stress will depend on cellular circumstances. In the case of a cosmetic treatment, a stressing agent may be used as a first line of treatment, but where cosmetic and medical conditions differ, is that for a medical condition, such as the diabetic ulcer, it is already a stressed environment and therefore the environment does not require further cellular stress. However, both a cosmetic indication and a medical indication (where the latter involves inflammatosis in particular) both require similar initial treatment to ensure that the induced or inherent stressing events (cosmetic indication and medical indication, respectively) are directed towards autophargy and the increase in the autophagosomal-lysosomal flux. So under situations that are linked to inflammatosis such as diabetes, cellular signalling factors such as JNK, HSF1 and FoxO are active due to the presence of stressing molecules such as AGEs, PAMPS and DAMPs. However, under these conditions, the transcriptional activity of the FoxO protein, in particular, is directed to promoting further inflammatosis. This situation, in large part, may depend on the acetylation status of the FoxO protein within the nucleus of the cell. If the FoxO protein is acetylated, this will tend to drive the transcription of genes coding for further inflammatory factors such Tumour Necrosis Factor alpha (TNFa) and proapoptotic genes such as Bim.

So a preferred embodiment of this invention for treatment of cosmetic skin conditions, where an increase in the autophagososmal-lysosomal flux is beneficial (eg skin lightening, brown spot removal and tattoo fading), is to include within the unit of galactose polymer gel or the galactose polymer gel, those agents that induce a stress response and also those agents that prevent the deacetylation of the nuclear FoxO proteins. Such agents are Sirtuin 1 (Sirtl) activators. In the preferred embodiment for the treatment of cosmetic skin conditions, a macrophage activator should also be included in the unit of galactose polymer gel or the galactose polymer gel along with stressing agents. In the case of pathologies linked to inflammatosis, such as the diabetic skin ulcer, a macrophage activator should not be included in the first line therapy provided by the application of the unit of galactose polymer gel containing remedial agents, as macrophage activity will already be high in the diabetic condition.

To re-iterate this important concept, a first line treatment for certain cosmetic indications such as skin lightening, brown spot fading and tattoo fading that constitutes a further preferred embodiment of this invention, is to include a stressing agent within the unit of the galactose polymer gel together with agents than ensure that this stress is directed towards the up-regulation of the autophagosomallysosomal pathway and to combine these with an activator of the phagocytic activity of macrophages, of dendritic cells and of dermal fibroblasts.

To re-iterate this important concept with respect to treatment for diabetic skin complications such as ulcers and other skin conditions involving inflammation, such as psoriasis, a preferred embodiment of this invention is to incorporate within the unit of galactose polymer gel, an agent or agents that maintain the deacetylation status of nuclear FoxO proteins. Those agents that activate a stress response, as in the case of the first line treatment of a cosmetic indication, are not included in the unit of galactose polymer gel. In the case of FoxO deacetylation, agents can be selected from those known to that maintain Sirt1 activity and to maintaining the supply of the nicotinamide adenenine dinucleotide cofactor (NAD+). As an example, such agents may be resveratrol and nicotinamide respectively. In respect of the latter, care must be taken to avoid a concentration that is inhibitory towards Sirt1. Other strategies to increase Sirt1 activation are those that induce or mimic nutrient deprivation. In this respect, nutrient deprivation not only suppresses NADH concentrations and hence increases NAD+ concentrations (and activates Sirt1), it also raises the AMP/ATP ratio. Such an increase in AMP/ATP ratio activates the AMPkinase and this in-turn relieves inhibition on the initial stages in the activation of autophagosomallysososomal pathway (eg AMPkinase blocks mTORC1 activation; mTORC1 activity inhibits autophagosome initiation). An example of compounds that may be used in this respect is the pharmaceutical agent, metformin and nutraceutical agent, berberine.

Whilst the pathway that blocks cellular entry into autophagosomal-lysososomal pathway, namely, the insulin-PI3K-PKB/Akt-mTORC1 pathway, is not be as active in the diabetic state (due to a poorly functioning insulin receptor), entry into the autophagosomal-lysososomal pathway may be diminished by the propensity of skin cells in diabetes to undergo apoptosis. So as indicated above, within the unit of galactose polymer gel, or galactose polymer gel, Sirt1 activators that prevent FoxO from inducing pro-apoptotic genes must be incorporated. However, in addition to blocking the pro-apoptotic and pro-inflammatory role of nuclear-located FoxO, continuous FoxO residency within the nucleus is not optimal for maintaining the flux through the autophagosomal-lysosomal pathway. In the cases of pathologies linked to inflammatosis, following a period of relief from Fox() directed inflammation and apoptosis by the application of Sirt1 activators (during which time pro-survival genes that include those involved in autophargy will be transcribed), to maximize the flux through the autophagosomal-lysososomal pathway, an induced transition of FoxO from the nucleus to the cytoplasm is necessary to allow the FoxO proteins to interact with proteins like Atg7 (particularly when cytosolic FoxO is in an acetylated form) to increase the autophagosomal-lysosomal flux. This rationale is also correct for the treatment of cosmetic indications where an increase in the autophagosomallysososmal flux is desired.

So to achieve the aim as stated at the end of the last paragraph for sites such as ulcerated skin and also for skin sites that require cosmetic attention, after a period of several hours (at least 2 hours but not more than 5 hours) exposure to activators of Sirt1 (without or with stressing agents, medical v. cosmetic usage, respectively), it will be necessary to replace the unit of galactose polymer gel or galactose polymer gel with those agents that now also reduce cell signalling in response to cellular stress. These agents added to the unit of the galactose polymer gel are those that inhibit SAPKs. Examples of such agents are the herbal JNK inhibitors, curcumin (extracted from turmeric), salicortin (extracted from Polulus balsamifera) and tenuifoliside A (extracted from Polygala tenuifolia). Alternatively, pharmacologically-derived JNK inhibitors may be used. By reducing JNK activation, the phosphorylation of FoxO, that acts as a nuclear localization signal, will be diminished, allowing both the serum and glucocorticoid kinase (SGK) and the PI3K-PKB/Akt to induce phosphorylation of FoxO at another site within the FoxO molecule and this provides a nuclear to cytosolic translocation signal. Once FoxO proteins are in the cytoplasm of the cell, they can interact with Atg7 and increase the phagorphore membrane elongation step of autophargy. In order to prevent the loss of Fox() once it is in the cytoplasm, a most preferred embodiment of this invention will include within the unit of galactose polymer gel or galactose polymer gel, a compound or compounds that maintain the acetylation status of cytosolic FoxO and also block proteosomal degradation of cytosolic FoxO. Therefore in addition to JNK inhibitors, a most preferred embodiment of this invention will be to include a compound or compounds that specifically inhibit Sirt2 (eg AK-7) within the unit of galactose polymer gel or galactose polymer gel along with proteosome inhibitors like the polyphenol, epigallocatechin gallate (EGCG), a compound derived from green tea. Also, whilst low doses of nicotinamide activate Sirt1 by providing substrate for the formation of NAD+, high doses of nicotinamide inhibit both Sirt 1 and Sirt2. Whilst it is desirable to maintain the activity of Sirt1, if JNK activity is reduced by the presence of inhibitory compounds, Fox() will take-up a cytosolic location (under the influence of SGK and PI3KJAkt-induced phosphorylation) and now the addition of an inhibitor of both Sirt1 and Sirt2 (eg high dose nicotinamide) will not be as problematic as the concentration of nuclear FoxO will be low and it can no longer take part in inflammatosis. So at the expense of inhibiting Sirt1, a preferred embodiment of this invention is to include along with JNK inhibitors and proteosome inhibitors within the unit of the galactose polymer gel or galactose polymer gel, an amount of nicotinamide that inhibits Sirt2 and therefore will maintain cytosolic FoxO in an acetylated form.

Whilst FoxO proteins are important for the control of cell proliferation, antioxidant protein expression, the production of pro-inflammatory molecules like TNFa, apoptosis and autophagosomal-lysosomal flux, the Transcription Factor EB (TFEB) has been found to control the expression of numerous intermediates in the autophagosomal-lysosomal pathway. In order to increase the expression of these intermediates, a most preferred embodiment of this invention for the treatment of inflammatory skin conditions, like diabetic ulcers and for cosmetic purposes would be to include a compound that activates TFEB. In this respect, the often-used excipient compound, 2-hydroxypropyl-I3-cyclodextrin, is a most preferred addition to make to the unit of the galactose polymer gel. This compound should be present during both phases of treatment; during the Sirti activation step (in addition to the cellular stress and macrophage activation for the cosmetic embodiment) and then in the second stage of the treatment process, along with inhibitors of JNK, proteosome inhibitors and Sirt2 inhibitors (the second step components are common to both inflammatory skin complication, such as in diabetes, and for a cosmetic embodiment of this invention).

For the purpose of treating skin conditions such as ulcers, where there may be a varying degree of wound exudate, the unit of galactose polymer gel with the plastic backing should be used in the form as demonstrated in Figure 2c. This is the form that allows wound exudate to be 'wicked-away' by the absorbant layer incorporated into the outer cover. Also, in addition to the various remedial substances addressed to reducing inflammation and cell death as outlined above, it would be highly beneficial to incorporate these remedial agents along with the delivery of oxygen using the arrangement of the unit of galactose polymer gel as shown in Figure 4.

In a further preferred embodiment of this invention, remedial agents delivered from the unit of galactose polymer gel or galactose polymer gel, have anti-tumour (anticancer) properties. These agents may be delivered from the gel by passive diffusion or under the influence of an electrical potential, by using the technique of iontophoresis using a preferred embodiment as outlined in Figure 5 (and further described below). The concentration range of the remedial agent within the gel may be selected to have an effect restricted to the vicinity of the tumour site, as in the case of a skin tumour type, such as a melanoma. The concentration range of the remedial agent to be delivered from the gel may also be selected to have an effect on a tumour somewhat distant from the site of application to the skin. An example of this is delivery of a remedial agent to a breast cancer, where the unit of galactose polymer gel or galactose polymer gel is affixed to the skin surface of the breast such that the remedial agent can be delivered to the breast tumour located within the subcutaneous tissues of the breast.

In a most preferred embodiment, the unit of galactose polymer gel or galactose polymer gel may be used for the treatment of skin cancers or cancers deeper within the body by delivery out of the unit of galactose polymer gel-or galactose polymer gel-matrix, a remedial agent (compound) that is targeted to mitochondria of the cell by way of the remedial agent having a positively charged head group attached to an aliphatic side chain (of between 6 to 16 carbon units) with or without a functional head group, that is diametrically opposed to the positively charged head group. In a preferred embodiment, this compound is a triphenylphosphonium (TPP) derivative (see Figure 6 for the structure), where the aliphatic side has a carbon-to-carbon number of between 5 and 16 and most preferably, between 10 and 12 and that terminates in a methy group (eg dodecytriphenylphosphonium bromide) (see Figure 6). In a further preferred embodiment, the compound to be delivered from the unit of galactose polymer gel or galactose polymer gel belongs to a class of compound called a Mitocan, of which methyl-to hexadecyl-triphenyphosphonium bromide series of compounds constitute the prototype compounds of this category of mitochondria! targeting agents. These mitochondrial-targeted remedial agents intercalate within the inner mitochondrial membrane phospholipids and disrupt the mitochondrial membrane potential (Atji,n) allowing the release of inner mitochondria! matrix components that can activate the apoptotic cell death pathway.

In a preferred embodiment, as positively charged compounds, these Mitocans, of which Mitoquinone (MitoQ), MitaTempo! and MitoE are members, can be delivered out of the unit of galactose polymer gel-or galactose polymer gel-matrix by a trans-dermal route using the technique of iontophoresis (see Figure 5 for an example of this embodiment), where the Mitocan is contained within the gel matrix and is driven across the skin and sub-dermal tissues, by pulsed positive potential (electric field potential driving charge carriers through the skin) supplied by an iontophoresis unit.

Unlike treatment of conditions that involve excessive and ongoing inflammation (eg diabetic wounds and psoriasis), where up-regulation of autophagosomal-lysosomal flux is of benefit (whilst cancer initiation does indeed involve an element of inflammation) for the treatment of an established cancer tumour mass, inhibition of autophagosomal-lysosomal flux is beneficial, as it is now recognized that the tumour cells activate the autophagosomal-lysosomal pathway as a means of survival under stressed conditions such as hypoxia and lowered cellular pH. In a most preferred embodiment of this invention, delivery of a Mitocan by a transdermal route can be achieved by iontophoresis from the unit of galactose polymer gel or galactose polymer gel that is placed over the site of a melanoma for example, or where the tumour is situated in a subcutaneous position, such as a breast tumour and delivery of a Mitocan-type molecule can be combined with the delivery of an agent or agents that block the autophagosomal-lysosomal flux. Such an agent that blocks autophagosomal-lysosomal flux might be hydroxychloroquine for example or it may be an agent that maintains the nuclear location of the Fokhead Box 0 (FoxO) protein family member (Fox01 or FoxO3) and prevents the cytosolic activation of the phagophore elongation activator, Atg7, from increasing the rate of autophagosomallysosomal flux. In respect of the latter, a remedial agent may be incorporated in to the unit of galactose polymer gel-or galactose polymer gel that blocks, or reduces the activation of the PKB/Akt pathway; a pathway that is activated by insulin and growth factor pathways and is often found to be over-activated in cancerous tumours. In this way phosphorylation of FoxO proteins on amino-acid residues of the FoxO protein that activates a nuclear to cytosolic translocation of the FoxO protein will be prevented or reduced and this will decrease the autophagosomal-lysosomal flux. Such an agent that blocks the activation of PKB/Akt might be combined with a high dose of nicotinamide to block Sirt1 and the deacetylation of FoxO proteins; the rational here is that FoxO will remain in an acetylated form within the nucleus of the cancer cell where it can drive apoptosis.

A further pathway of considerable clinical significance that can re-direct the effect of the Mitocan (and other anti-cancer therapies) away from inducing apoptosis to that which induces autophargy (and hence is a means by which tumour cells escape the effect of therapy) is the pathway activated by the interaction of glucocorticoids with the glucocorticoid receptor (GR). Many tumour cells types express the GR and glucocorticoids are produced within the body and are often administered at high doses to reduce inflammation around the tumour site (especially in regard to tumours within the confines of the head-brain tumours in particular). A mitocan such as hexadecyltriphenlyphosphonium bromide when administered to cells can be shown to induce apoptotic cell death (see Figure 7b) and when the synthetic glucocorticoid, dexamethasone is co-administered, apoptotic cell death is blocked and this is replaced by the appearance of cells with a number of autophargic vacuoles (see Figure 7c). By blocking the activation of the GR by dexametahasone, the antiglucocorticoid RU 486 can be shown to re-instate apoptotic cell death for cells exposed to the mitocan (Figure 7d). These observations highlight the necessity of combining within the unit of the galactose polymer gel not only the mitocan, but also a compound that blocks the transcriptional activity of the GR, such as the antiglucocorticoid, RU 486. The GR has been shown to be phosphorylated by a number of kinases and JNK activation has been shown to be one of these; activation of JNK in several cell types reduce the transcriptional activation of the GR. A partial blockade of the transactivation function of the GR might also be induced by the activation of JNK and substances that increase JNK activity might be included in the unit of galactose polymer gel along with a mitocan.

Whist the embodiment of this invention presented in the last paragraph above has focussed on the role of the GR in modulating sensitivity of tumour cells in terms of cell death induced by substances delivered from the unit of galactose polymer gel or galactose polymer gel, a corollary of these experimental findings presented here in Figure 7 is that 1), activation of the GR when cells are exposed to a mitocan-type substance may be a suitable modality of treatment under circumstances that relate to a cosmetic therapy (as GR activation and mitocan exposure up-regulates the formation of autophargic vacuoles and presumably also the autophagosomallysosomal flux) and 2), any cellular circumstance that may ameliorate the effect of a SAPK like JNK, to inactivate the GR (and hence may increase the activity of the GR), may block the effectiveness of the tumour therapy. For example, studies show that another kinase, namely protein kinase A (PKA) is able to phosphorylate the GR and this overrides the inactivation of the GR by JNK-induced phosphorylation. As PKA is responsive to the cellular level of cyclicAMP (cAMP), then any stimulus that increases cAMP will have a tendency to maintain the activity of the GR. The GR is not only involved in blocking cell death by apoptosis, it is also a factor that increases the activity of the SGK that induces the phosphorylation of FoxO proteins to induce a nuclear to cytosolic translocation and potentially, the up-regulation of the phagophore elongation activity of Atg7 (by cytosolic FoxO interacting with Atg7). So whilst agents such as caffeine, that block cAMP phosphodiesterase activity, will increase cAMP concentrations, and these may be beneficial in combination with cellular stressing agents in the up-regulation of the autophagosomal-lysosomal flux for certain cosmetic applications (eg skin lightening, brown spot lightening and tattoo lightening) it may be wise to avoid caffeine-containing substances during cancer therapy. Based on this reasoning, a further preferred embodiment of the unit of galactose polymer gel or galactose polymer gel for the up-regulation of the autophagosomal-lysosomal flux for both cosmetic and medical purposes is to include an amount of caffeine within the galactose polymer matrix that maintains the transcriptional activation of the GR under situations of cellular stress when SAPKs like JNK are active.

In a further most preferred embodiment of the current invention, compounds such as the charged molecule, MitoQ as described above, and also non-charged and non-polar molecules can be delivered from with the unit of galactose polymer gel-and galactose polymer gel-matrix by the technique of iontophoresis. MitoQ was originally designed to provide the ubiquinone moiety of the MitoQ such that it is positioned within the inner mitochondria! and can function to enhance the electron transport function of the mitochondrial inner membrane. In this way, using lower doses than would be used for cancer therapy (doses that do not reduce the Dye,,,) MitoQ and similar compounds may have efficacy for the treatment of neurological degenerative conditions such as Alzheimer's and Parkinson's disease. These agents may be delivered via patches of the unit of galactose polymer gel or galactose polymer gel applied to the neck either in a passive mode (by transdermal diffusion), or by iontophoresis and in particular they may be applied at the side of the neck over the vertebral and common carotid arteries. These patches may also be used to deliver remedial agents that will reduce inflammation such as those referred to earlier in this invention (and mentioned above for Alzheimer's and Parkinson's disease sufferers) that are targeted to enhancing autophagosomal-lysosomal flux. Conditions that are related to inflammation of the arteries and the vasculature in general (vasculitis), such as Giant Cell Arteritis (GCA), may also be treated in this way.

In a preferred embodiment of the present invention, the unit of galactose polymer gel or galactose polymer gel can be fashioned as circular, square or oblong patches that form one of the electrodes of the small iontophoresis unit (as indicated in Figure 5). The unit may be constructed such that the patches of the unit of galactose polymer gel or galactose polymer gel containing the substance to be provided by a transdermal route can be placed into the iontophoresis electrode cassette unit prior to attachment to a skin site. In this way, patches can be stored under the appropriate conditions prior to use (eg stored at 4-8°C).

The iontophoresis unit may be used to provide remedial agents of cosmetic and medical benefit and the patches of the unit of galactose polymer gel or galactose polymer gel may be used to deliver from a portable and disposable iontophoresis unit (such as exemplified in Figure 5), an amount of MitoQ that may be beneficial to the brain after stroke or after cardiac arrest. The disposable iontophoresis unit may be applied to an area of skin where the maximum transdermal delivery, in the shortest period of time, of the essential inner mitochondria! membrane component ubiquinone (as MitoQ), can be achieved. Skin body sites suggested for this purpose as indicated above are on the side of the neck to allow entry via the vertebral and common carotid arteries in the case of stroke, and directly over the heart, in the case of cardiac arrest.

In a further preferred embodiment, the unit of galactose polymer gel or galactose polymer gel may be used for the delivery of minerals (eg magnesium, selenium, zinc, molybdenum) and vitamins (eg vitamin D, vitamin C and vitamins, B1, B2, B3, B5, B6, B7, B9 and B12). In a most preferred embodiment, the unit of galactose polymer gel or galactose polymer gel may be used for the delivery of high doses of methylcobalamin (a form of vitamin B12) and 5-methyl-tetrahydrofolate (a form of vitamin B9 or folic acid). These doses may be of such an amount that they act locally or they are of sufficient quantity to act at a site distant from the site of application and therefore they act systemically. These remedial agents may be administered from within the unit of galactose polymer gel or galactose polymer gel by a passive means or by an active means, using the technique of iontophoresis.

In addition to delivery of remedial agents from within the unit of galactose polymer gel-matrix or galactose polymer gel-matrix as described above for the conditions relating to trauma, inflammation, cancer, neurodegeneration, stroke and cardiac arrest and for the delivery of minerals and nutrients, remedial agents may be provided from an external source and therefore can be considered replenishible (ie in use, the amount of remedial agent is replenished without changing the unit of galactose polymer gel). For example, the amount of a remedial agent may be a replenishable gas or a replenishable liquid. Preferred, is a repleinshible gas and most preferably it is 02 gas. The gas may be replenished by flow-through that causes liquid debris from the damaged bodily tissue to be entrained and removed as to advantageously promote wound healing. A preferred embodiment of this invention is the unit of the galactose polymer gel with the outer cover in which a suitable port is located for the connection of the external reservoir as described in Figure 3b. In order to allow some flow through of gas, a modification to the embodiment shown in Figure 3b is the inclusion in the outer cover of a suitable vent to allow the egress of gas as shown now in Figure 8.

Preferably, the current invention comprises a remote source of remedial agent (eg a remedial agent repository or remedial agent-generating apparatus) adapted to replenish the amount of remedial agent. Preferable the remedial agent-generating apparatus is connected directly or indirectly to the unit of galactose polymer gel. Preferably the remedial agent-generating apparatus is a remedial agent flow-generating apparatus. The amount of remedial agent may be replenished continuously or periodically (eg in variable pulses or on-demand).

In a preferred embodiment the unit of galactose polymer gel or galactose polymer gel may be affixed to a damaged body and this site to which the unit of galactose polymer gel or galactose polymer gel has been secured (eg the lower portion of a limb or legs and trunk of body) may then be encased in a plastic enclosure that may be sealed against a surface of the body such that a semi-air tight seal is formed. Into this plastic enclosure and via a suitable delivery tube with a tap, a remedial agent such 02 gas may be delivered. This embodiment is outlined in Figure 9.

Preferably the unit of galactose polymer gel or galactose polymer gel is adapted to facilitate distribution of the amount of remedial agent on or around the proximal surface of the unit of galactose polymer gel. For example, the proximal surface may be non-uniform (eg textured). The proximal surface may have one or more channels, tracks, undulations or holes. Preferably the unit of galactose polymer gel or galactose polymer gel comprises one or more channels. Preferably the one or more channels are in the form of a network of channels or holes. The channels or holes or undulations may usefully provide a flow path towards and away from the bodily tissue (ie irrigation for gas or liquid). This is especially advantageous for 02 gas which otherwise cannot penetrate the unit of galactose polymer gel to any great extent.

In a most preferred embodiment when 02 gas is to be combined with the unit of galactose polymer gel, the skin or bodily site to be treated in this way may first be treated with a aqueous cream containing the compound MitoQ, a form of Coenzyme Q1c, (or ubiquinone) that is attached to a mitochondria! targeting sequence as described above (see Mitocan). Alternatively, MitoQ may be incorporated into the unit of galactose polymer gel or galactose polymer gel such that the compound is delivered to the bodily part by a transdermal route, either passively, or under the influence of an electrical potential using the technique of iontophoresis. In particular, the concentration of MitoQ that will be incorporated into the gel matrix will be considerably lower than the concentration that will be used for delivery to a cancerous tumour.

Figure legends Figure 1 (a): The unit of galactose polymer gel with waterproof backing (or membrane) shown here in dressing-roll form. The gel is formed as a roll that may be up to lm or more in length and up to 15 cm or greater in width but preferably around between about 20mm and 100mm wide with a thickness from 3 to 10 mm or more. Figure 1 (b): The unit of galactose polymer gel without the waterproof backing or membrane. Details otherwise the same as Figure 1 (a).

Figure 2: Three embodiments of the two-component system for the unit of galactose polymer gel. The first, Figure 2a exemplifies the most basic form where the unit of galactose polymer gel with the waterproof backing or membrane has an outer cover placed over it such that it is firmly attached to the skin or wound area by the outer adhesive area of the outer cover. Figure 2 b shows the embodiment of the unit of galactose polymer gel with the waterproof backing or membrane where the outer cover has an absorbant layer such that it is able to absorb wound exudate. Figure 2c shows the embodiments of the unit of galactose polymer gel as in Figure 2b but where the unit of galactose polymer gel with the waterproof backing or membrane has channels in its proximal surface to allow wound exudate to flow more freely to be absorbed by the absorbant layer of the outer cover. The unit of galactose polymer gel is shown in Figure 2c in two forms, a circular form with channels in a starburst' patter that radiate from the centre of the galactose polymer gel and in a square or oblong form.

Figure 3 (a): This is an example of the embodiment of the unit of the galactose polymer gel where it is formed with a starburst pattern on its proximal side where the groves radiate from a central hole throughout the thickness of the unit of galactose polymer gel with the waterproof backing or membrane.

Figure 3 (b): The embodiment of the unit of galactose polymer gel as shown in Figure 3 (a) when used in combination with an outer cover of essentially similar design to the one shown in Figure 2 b and c but where now a central port and tap is included in the outer cover as shown. This arrangement allows the connection of an external reservoir to deliver remedial agents or to remove a larger amount of wound exudate by applying slight negative pressure.

Figure 4 (a): This is a similar embodiment of two component system of the unit of galactose polymer gel as shown in Figures 2b and 2c and Figure 3b except that around the central hole in the unit of the galactose polymer gel there is margin of several mm or more that is not covered by the waterproof backing or membrane. It is this area of exposed galactose gel that makes contact with a sachet or enclosure or thin layer on the underside of the top cover that contains an amount of calcium peroxide (Ca02) and ascorbic acid, when the this outer cover is brought down over the unit of galactose polymer gel to affix the unit of galactose polymer gel to the body site. On contact with the aqueous medium within the exposed galactose polymer gel, the Ca02 will react in the aqueous environment under the acidic conditions supplied by the ascorbic acid, and oxygen (02) gas will be produced. This gas will filter through the hole within the unit of galactose polymer gel and be dispersed to the underlying body site by the groves or channels in the proximal surface of the unit of galactose polymer gel.

Figure 4 (b): This figure shows a similar embodiment as exemplified in Figure 4 (a), except that the sachet of Ca02 and ascorbic acid is not included. Here a tablet containing a mixture of Ca02 and ascorbic acid is placed centrally over the hole through the unit of galactose polymer gel and the top cover is brought down to secure the unit of galactose polymer gel to the body site.

For both the embodiments of Figure 4 (a and b), the sachet or enclosure or thin layer or the tablet may be constructed to only contain Ca02. In these embodiments of this two-component system (with the aim of delivering a small amount of oxygen to the skin site), the ascorbic acid may be contained within the unit of galactose polymer gel along with the antioxidant compound, glutathione.

Figure 5: An example of an iontophoresis unit that may be applied to different areas of skin for the active delivery of remedial agents and particularly, for the delivery of agents with a marked polarity or charge, such as the Mitocans described in the various paragraphs of the description to this document. Although molecules with a net overall charge, whether this is positive of negative, are transferred most efficiently by iontophoresis, molecules that are uncharged or neutral can also be carried by coupled flow with a charge carried by a molecule that is added to the galactose polymer as an excipient or carrier. This molecule is added to one or other of the galactose gel pads that are placed in the iontophoresis unit.

Figure 6: An example of one of the positively charged prototype molecules that belongs to a chemical class now termed, Mitocan' and that may be used for the treatment of cancerous tissues and that may be delivered by an iontophoresis unit as exemplified in Figure 5. This particular molecule is decyl-triphenylphosphonium bromide (decylTPP). An agent that belongs to this class but that has an aliphatic side chain of 16 carbons (instead of the 10 carbons as shown here) has been used for experiments on tumour vascular endothelial cells, some of the results from which are presented in Figure 7 to follow.

Figure 7: The effect of hexadecylTPP (5 x10-6Molar (M)) on tumour-derived vascular endothelial cells in the absence and presence of the synthetic glucocorticoid receptor agonist, Dexamethasone (1 x10-7M) (Dex) and the synthetic glucocorticoid receptor antagoinist, RU486 (1 x10-5M). Cells were observed by normal light microscopy using Image Modulation Contrast optics following 48h exposure to compounds.

Figure 7b shows that hexadecylTPP induces the appearance of apoptotic vascular endothelial cells, and this effect is blocked by Dex (Figure 7c) and re-instated by the presence of both Dex and RU486 (Figure 7d). Evidence of apoptosis for cells exposed to a combination of both hexadecylTPP and Dex is absent; instead of apoptotic morphology, these cells now show numerous autophargic vacuoles.

Figure 8: An example of an embodiment of this invention where the two component system of the unit of galactose polymer gel as described in Figure 3b, now has a vent in the outer cover that allows the egress of 02 (for example) to prevent overpressure of the outer cover that is placed over the unit of galactose polymer gel. In this way, the atmosphere within the wound (for example) will assume near 100% partial pressure (or concentration) of 02 gas.

Figure 9: This figure provides an example of an embodiment of this invention where the unit of galactose polymer gel in the dressing-roll, waterproof backing -(or membrane) form or the form without the waterproof backing, is used for wrapping around a large wound site such as a limb as shown in the upper diagram or the torso in the lower diagram. This area is then enclosed in a semi-gas tight plastic enclosure that is sealed between the top of the outer enclosure and a skin surface such as the thigh or the upper chest as shown in the diagram here. A gas, but preferably 02, can then be fed into the outer plastic enclosure through a suitably positioned input port (with tap) such that the partial pressure (or concentration) of 02 within the plastic enclosure reaches almost 100%. For this embodiment of the invention involving the unit of galactose polymer gel, the proximal surface of the unit of galactose polymer gel should be formed with ridges or undulations to allow the ingress of 02 to the skin and tissue site that is under treatment. In addition to the use of 02 gas in this embodiment, the unit of the galactose polymer gel may be constructed such that it contains other agents with remedial value that have been described through the pages of the description of this document

Claims

Claims: 1. A system for the repair of bodily damaged tissues based on a substantially pure, cross-linked galactose polymer gel in a form that is supported by a mechanical support or matrix that is a mesh or waterproof backing or membrane or coating or a combination of mesh and waterproof backing that is rigid, semi-rigid or flexible and which may be a fabric such as cotton and as a unit, is applied to a bodily surface, particularly a skin-bodily surface.
2. A system for the repair of skin-damaged bodily tissue where the cross-linked galactose polymer as in claim 1 is agarose and the galactose polymer gel is formed on a mechanical support, as in claim 1.
3. A system as in claims 1 and 2 where the agarose polymer is formed as a gel around a mechanical support by suspending the agarose polymer in purified water, a pH-buffered solution or saline and heating until the polymer dissolves, then cooling to temperature of at least 5°C above the gelling point and then pouring over the mechanical support or allowing the mechanical support to be laid on the molten agarose and then allowing the molten agarose to cool to allow the formation of the gel with an internal mechanical support. Henceforth, the mechanically supported form of the galactose polymer gel is known as the unit of galactose polymer gel.
4. A procedure as outlined in claim 3 where the galactose polymer gel is formed in the absence of a mechanical support; this embodiment is henceforth know as the galactose polymer gel.
5. The unit of galactose polymer gel or galactose polymer gel as described in claims 1 to 4 above, constructed as a roll of dressing, a slap of dressing (of any shape), a cast or transdermal patch, as a single component or part of a multi-layer system that is designed to remove wound exudate, or to supply a remedial agent of cosmetic or medial benefit and which may be provide by a reservoir external to the unit of galactose polymer gel or galactose polymer gel when part of a multi-layer system or may be provided from within the polymer gel matrix or within a system that comprises the unit of galactose polymer gel or galactose polymer gel and another component or several components.
6. The unit of galactose polymer gel or the galactose polymer gel as in claim 5, that is used for the treatment of skin-damaged bodily tissue caused by accidental and traumatic injury or by surgery or used for the treatment of skin-damaged bodily tissue that results from a skin condition related to inflammation or to cancer or for the remediation of a cosmetic indication such as skin colour lightening, focal skin pigmentation removal (brown spots) or for the removal of tattoos.
7. The unit of galactose polymer gel or galactose polymer gel as in claim 6 and that encompasses claims 1 to 5, that contains within the unit of galactose polymer gel or galactose polymer gel, remedial agents that have cosmecutical, nutraceutical or pharmaceutical properties that are directed to enhancing health or are specifically directed to a cosmetic or medical purposes or cellular mechanisms that benefits the overall heath of the human body or that of any other mammalian species for which the application of the unit of galactose polymer gel or galactose polymer gel is deemed to be suitable.
8. The unit of galactose polymer gel that may or may not have included in the gel matrix a remedial agent or agents as in claim 7, where the unit of galactose polymer gel is formed as a continuous dressing-roll during the manufacturing process by a methodology that is encompassed in claim 3 but that is prepared for practical use as a dressing-roll.
9. As in claim 8 where the dressing-roll-form of the unit of galactose polymer gel or a dressing slab of the unit of galactose polymer gel (or galactose polymer gel) is use for emergency purposes and is either self-administered or administered by a member of an emergency service and where traumatic skin damage and/or deeper, sub-dermal damaged, has been caused accidently by blunt force trauma or non-accidentally by a knife attack or by a bullet, a grenade or bomb and where the dressing is combined with a blood stopping agent either applied prior to the dressing application or by application from within the unit of galactose polymer gel matrix or galactose polymer gel matrix.
10. As in claim 9 where the dressing roll-form of the unit of galactose polymer gel is administered and secured in place by a mechanical clip system or is wrapped with a plastic wrap or cling film and where both systems of securing are protected by an outer Gortex-type-material-cover that will provide protection from the ingress of particulate material and microorganisms to the wound.
11. Where the same procedure as described in claims 9 and 10 is applied in the case of a burn. In particular, for a burn to the hand, the fingers may be kept from fusing together by winding a narrow dressing-roll (2 cm in width for example) of the unit of galactose polymer gel (without the waterproof backing or membrane) between the fingers such that the fingers are completely separated by the unit of galactose polymer gel. The whole hand can then be wrapped in the unit of galactose polymer gel of greater width (without or with a waterproof backing) that may be secured as in claim 10 and where a Gortex-type covering in the form of an extended mitten (without thumb position) can be secured to a portion of the arm that is not burnt. If the arm is burnt, the unit of galactose polymer gel can be wound around the area until all the burn area is covered. After securing the unit of galactose polymer gel as described in claim 10, the hand and arm may then be covered by the Gortex protective covering for the reasons given in claim 10.
12. Given the high water content within the unit of galactose polymer gel, a degree of dehydration of the gel in an uncovered form (and to a lesser extent in the covered form) cannot be avoided. This property gives rise to a significant cooling effect and this provides comfort to the recipient of the unit of the galactose polymer gel.
13. The unit of galactose polymer gel and galactose polymer does not adhere to damaged bodily tissue and in a basic form, without the addition of any remedial agent, it is highly hypoallergenic.
14. The unit of galactose polymer gel, as described in the claims above (although an unsupported form can be used in some situations), may be constructed to conform to any anatomical portion of the body and in particular, the unit of galactose polymer gel in a form without the waterproof backing, can be constructed within a mould that conforms to the shape of the top of the head and the cast of the unit of galactose polymer gel that is formed, can be used for treatment of wounds and burns to the scalp. The unit of galactose polymer gel can contain pain relief agents and other remedial substances as suggested in claim 7.
15. By using a similar procedure as described in claim 14, the unit of galactose polymer gel can be cast in a mould to treat burns and other types of skin damage to the face or indeed any other portion of the head or body.
16. The galactose polymer gel can be used to provide mechanical support to the stump of amputated limbs and in so doing, provide considerable pain relief by acting as a shock absorbing substance between the stump and the prosthetic limb. In this situation, the galactose polymer gel may contain an analgesic agent for pain relief. For this purpose, the concentration of agarose used to construct the galactose polymer gel must be increased to increase the mechanical strength of the galactose polymer gel formed.
17. Particularly for accidental damage to skin surfaces and damaged to sub-skin structures caused by knife injury or bullet, grenade or bomb, an analgesic agent can be included in the unit of galactose polymer gel constructed with particular reference to claims 5, and 9 and that when combined with the cooling effect of the unit of galactose polymer gel, will provide a degree of pain relief.
18. The unit of the galactose polymer gel or galactose polymer gel, as indicated in the relevant claims, but in particular claim 5, may be used for the treatment of minor bruises or abrasions and be formed in a variety of sizes over which an outer plastic-type covering can be placed that is designed to protect the wound and reduce evaporation of the water contained within the unit of galactose gel or galactose polymer gel and by way of the presence of a hypo-allergenic adhesive around the perimeter of the outer covering, provides a means of attachment of the unit of galactose polymer gel or galactose polymer gel to the skin surface.
19. The unit of galactose polymer gel as in claim 18 and the relevant claims preceding that can be used as a multiple component system for minor wounds and abrasions, for wounds inflicted by surgery or by trauma (accidental or otherwise inflicted) and that forms part of a two-component system as indicated in claim 18 (or multi-component system), where wound exudate can be removed and remedial and pain relief agents can be applied in liquid or gas form from an external reservoir connected to the two component system via a suitable connection port with a tap.
20. As for claims 18 and 19 but where in addition, remedial agent and pain relief agents are included in the matrix of the galactose polymer gel as indicated in claim 7.
21. The unit of galactose polymer gel as described in the relevant claims above but particularly claims 7, 18 and 19, that can be used as a means of transferring across the skin, cosmecutically, nutraceutically and pharmaceutically active agents and the amount of agent transferred may be cosmetically, therapeutically, prophylactically or analgesically (medically) effective locally or systemically.
22. As claim 21 and to allow the most effective transfer by a transdermal route, the skin should be prepared before application of the unit of galactose polymer gel or galactose polymer gel using by an exfoliating agent in liquid or solid form.
23. Where remedial agents, as indicated in claim 21 and in the relevant claims above, are contained within the unit of galactose polymer gel or are produced from a two or more component system as claims 18 and 19 of which the unit of galactose polymer gel is the proximal component with respect to a body surface.
24. As per claims 22 and 23 and with reference to preceding claims, the remedial agents transferred by a transdermal route may be for the enhancement of wound healing, the reduction of inflammation, the reduction of apoptotic and necrotic cell death (inflammation and cell death collectively referred to as, cinflammatosis'), for cancer therapy, for the treatment neurodegeneration, for vasculitis, for treatment of stroke, and for treating cardiac arrest/insufficiency.
25. As per claims 22 and 23 and with reference to preceding claims, where in particular, oxygen gas (02) is produced from within a two (or more) component system where the waterproof-backed unit of galactose polymer gel is the proximal component to the body surface.
26. As per claim 25, where built into the top cover of a two-component system and activated by means of the top cover or outer cover component coming into intimate contact with the unit of galactose polymer gel, is a means of 02 gas generation.
27. As per claim 26 where 02 gas is formed from within the two-component system where the unit of galactose polymer gel is used in conjunction with the compounds, calcium peroxide (Ca02), ascorbic acid and lactic acid.
28. As per claim 27 where Ca02 and ascorbic acid are held within a sachet or enclosure or layer associated with the top outer cover of a two component system and where on application of this two component system to a body site, this sachet or enclosure or layer is brought into contact with the aqueous galactose polymer gel of the unit of galactose polymer gel with a result that 02 gas is formed and this gas is delivered via a vertical channel through the unit of galactose polymer gel to be distributed by channels in the proximal surface of the unit of galactose polymer gel to the body surface for remedial purposes.
29. As in claim 28 where the outer cover of the two-component system for producing 02 gas does not have a sachet or enclosure or layer of Ca02 and ascorbic acid. Instead, Ca02 and ascorbic acid are contained within a tablet that is placed over the vertical channel (or hole) in the centre of the unit of galactose polymer gel that is positioned on the skin body surface and where this is fixed in place by an outer cover as described for the two component system in 28.
30. As 28 and 29 where only Ca02 is contained in the sachet, enclosure, layer or tablet and ascorbic acid is provided in the unit of galactose polymer gel along with an amount of glutathione to prevent the oxidation of ascorbic acid and to prevent any hydrogen peroxide formed in the reaction between Ca02 and water from damaging the skin and sub-dermal structures.
31. To use the ascorbic acid that is contained within the unit of galactose polymer gel as an antimicrobial agent along with lactic acid for the purpose of preserving the unit of galactose polymer gel and galactose polymer gel from microbial contamination when in storage or when applied to a body surface.
32. To combine lactic acid with the unit of galactose polymer gel or galactose polymer gel at a concentration of 2% or less to prevent microbial growth within the unit of galactose polymer gel or galactose polymer gel and during its deployment, in any embodiment of this invention, on a skin body surface.
33. With respect to claim 24, for inflammation, remedial agents may be incorporated into the unit of galactose polymer gel or galactose polymer gel that target and block signal transduction pathways activated by any pro-inflammatory factors. In particular, compounds that up-regulate the initiation of autophargy and increase the rate of autophagosomal-lysosomal flux may be included in the unit of galactose polymer gel. These agents may be nutraceutically or pharmaceutically derived and be directed to up-regulating the rate of autophagosomal-lysosomal flux and in so doing, to decreasing inflammation and apoptotic cell death (inflammatosis).
34. As claim 24 but where the agents contained within the unit of galactose polymer matrix or galactose polymer gel matrix for the purpose of transdermal delivery, target cellular stress pathways in general and those pathways that increase the expression and activation of components within the autophagosomal-lysosomal pathway in particular.
35. Of particular relevance to cosmetic indication such as skin lightening, brown removal and tattoo removal, a general stressing modality is provided by the unit of galactose polymer gel by including an agent that reduces the pH of the skin and by providing agents that activate stress-activated protein kinases (SAPKs) and that also activate macrophages and other phagocytic cells within the skin. In this respect, lactic acid or ascorbic acid or both will be included within the unit of galactose polymer gel and these compounds will be combined with other stressing agents and those that will activate phagocytic cellular activity.
36. For skin conditions, for example diabetic ulcers and psoriasis, where inflammatosis is up-regulated, the addition of a further stressing agent within the unit of the galactose polymer gel is not required. In these conditions the outcome of the inherent stress must be re-directed, and for this purpose, agents that activate Sirtuin 1 (Sirt-I), when added to the unit of galactose polymer gel, will redirect the stress to those pathways that lower cellular stress and facilitate the increase in the concentration of components of the autophagosomal-lysosomal pathway and that allow an increase in autophagosomal-lysosomal flux.
37. The agents outlined in claims 35 and 36 are combined for cosmetic indications such that stress is appropriated directed to pathways that up-regulate the autophagosomal-lysosomal function and phagocytic cellular activity.
38. After a period of skin exposure to the unit of galactose polymer gel (at least 2 hours but not more than 5 hours) according to claims 35, 36 and 37, the unit of galactose polymer gel containing remedial agents should be exchanged for the unit of polymer gel containing remedial agents that block the stress response. For this purpose, the unit of galactose polymer gel will contain agents that allow the further up-regulation of the autophagosomal-lysosomal flux and in particular, those agents that maintain the cytosolic location and protein concentration of the Forkhead Box 0 proteins (FoxO) and that increase the transcriptional activity of the Transcription Factor EB (TFEB).
39. Agents can be delivered from within the matrix of the unit of the galactose polymer gel according to claim 24 and claims therein, that target cancerous tumours of the skin and deeper structures by means of passive diffusion or by an active process, such as iontophoresis with a portable and disposable iontophoresis unit, where these agents are contained within the unit of galactose polymer gel or galactose polymer gel formed as suitably shaped rectangular or square or circular slabs/pads of the unit of the galactose polymer gel or galactose polymer gel and so that these can be loaded into the ionotophoresis unit.
40. As claim 39, where remedial agents that are transferred from the unit of galactose polymer gel or galactose polymer gel have a structure of a positively charged head group with an aliphatic side chain of between 5 and 16 carbons and where the side chain is substantially or completely composed of saturated bonds and where the side chain terminates in a methyl group or a functional group with the aim that the overall compound targets mitochondria within tumour cells.
41. As claim 40 where the molecule is a triphenlylphosphonium salt such as hexadecyl-triphenylphosphonium bromide or it is a compound that belongs to the growing class of compound named, Mitocan(s).
42. As in 41, where in addition to a mitocan, included within the matrix of the unit of galactose polymer gel or galactose polymer gel is a compound or compounds that blocks the autophagososmal-lysosomal flux by direct inhibition of components of the pathway or that block pathways that protect cells from apoptotic death and that reciprocally enhance the autophagosomal-lysosomal flux.
43. The inclusion of agents within the matrix of the unit of galactose polymer gel or galactose polymer gel that are cosmetically and medically active based on a corollary of the cancer therapies of claim 42 and claims therein, where the activity of the glucocorticoid receptor (GR) is maintained by the inclusion, along with components as per claim 38, of components that increase cellular signalling by increasing the cellular concentration of cyclic AMP (cAMP). These should be applied to the skin surface during the second phase treatment with the unit of galactose polymer gel or galactose polymer gel as per claim 38.

43a Although a mitocan is directed to tumour treatment (and at lower doses to supporting mitochondria) function -see claim 44 below), it may be used as a stressing agent in certain cosmetic therapies where skin cells are protected from the apoptosis-inducing effects of the mitocan by including within the unit of galactose polymer gel and galactose polymer gel, those agents that block the induction of apoptosis and that up-regulate the autophagosomal-lysosomal pathway.
44. The delivery by iontophoresis out of the matrix of the unit of galactose polymer gel or galactose polymer gel of agents that belong to the mitocan compound class (MitoQ for example), that are beneficial to neurodegenerative conditions such as Alzheimer's and Parkinson's disease. The concentration of these agents will be chosen to support mitochondrial function and not to collapse the mitochondrial membrane potential (Ay 1 the latter a purpose expressed in the claims above when referring to cancer therapy.
45. As in claim 44 where the iontophoresis unit is applied to the neck over the vertebral and common carotid arteries where in addition to the indications of claim 44, the use of the iontophoresis unit is for the treatment of vasculitis, such as Giant Cell Arteritis.
46. As 45 where the delivery of agents from the unit of galactose polymer gel is by passive diffusion using a two component system comprising the unit of galactose polymer gel with an outer cover to affix the unit of galactose polymer gel to the skin as per a previous claims and where other agents are included in the unit of galactose polymer gel that target and reduce imflammatosis within the vasculature and nervous tissue structures by the up-regulation of the autophagosomal-lysosomal flux.
47. To deliver from the unit of the galactose polymer gel, using iontophoresis or by passive diffusion with a two-component system as in claim 46, essential vitamins and minerals, at suitable sites on the body, such as the neck.
48. Where a compound belonging to the class named mitocan such as MitoQ is delivered from the iontophoresis unit, as per claims 44 and 45, at such a dose that it is beneficial to the brain of very recent stroke sufferers and those individuals who have undergone a cardiac arrest or are suffering from cardiac insufficiency, where in the case of heart complications, the iontophoresis is placed directly over the heart.
49. To use the unit of galactose polymer gel with a circular hole through the thickness of the unit of galactose polymer gel and where the proximal surface has channels, and is used in a two component system, where the outer cover that can absorb wound exudate, can be connected to an external reservoir via a port in the outer cover and via a vent in the top cover, allows the flow through of 02 gas (from an external source) within the enclosure around the unit of galactose polymer gel such that the body site is expose to nearly 100% 02 gas for the purposes of wound remediation.
50. An embodiment of the unit of galactose polymer gel where as opposed to a discrete dressing component as described by claim 49, the unit of galactose polymer gel is used as a dressing (bandage)-roll with channels and furrows on the proximal surface (adjacent to a skin body site) and that can be wrapped around a damaged body structure such as a limb or torso and where the bandaged site can be encased by a plastic chamber into which 02 gas is passed through a suitable connection port (with tap) to achieve a concentration approaching 100% for the purposes of wound remediation.
51. Where other remedial agents are added to the unit of galactose polymer gel that along with the claims of 49 and 50, enhance the wound healing process by blocking inflammatosis and that up-regulate the autophagosomal-lysosomal flux and/or that enhance 02 gas utilization by passively transferring a compound such as MitoQ from within the matrix of the unit of galactose polymer gel.
52. As in claim 49 and 50 where prior to the application of the unit of galactose polymer gel and the outer cover or plastic enclosure, remedial agents are applied to the skin via a suitable topical cream. These agents might be those that target and up-regulate the autophagosomal-lysosomal flux and reduce inflammatosis and/or those that provide for the enhanced utilization of oxygen, such as MitoQ, and/or those that generally increase cellular wellbeing by the transdermal provision of vitamins and other nutrients and minerals such as magnesium.