DESC:

COMPLETE SPECIFICATION

Title of Document:

DIAGNOSTIC BANDAGE FOR VENOM DETECTION

The Field of Invention:
The present invention relates to a smart adhesive bandage to be applied onto the skin of the bite victim, particularly an adhesive bandage with a substrate pad, where venom specific component/s will be added for the qualitative and quantitative detection of envenomation status.

Background of the Invention:
Bite envenoming is a potentially life-threatening disease caused by toxins in the bite of a venomous species. Out of the 2500-3000 species of snakes worldwide, about 500 are venomous, combined with a huge number of other venomous species distributed world-wide, the danger faced by human kind is immense. Based on their morphological characteristics including arrangement of scales, dentition, osteology, myology, sensory organs etc., these venomous species are categorized into families. The major families of venomous snake species are Atractaspididae, Elapidae, Hydrophidae and Viperidae. The main families in the Indian subcontinent are: Elapidae which includes Spectacled cobra, King cobra, Common Krait, etc., Viperidae which includes Russell's viper, Pit viper, Saw-scaled viper, etc., and Hydrophidae (the sea snakes). Of the 52 venomous species in India, majority of bites and consequent mortality is attributable to "Big four" species viz. Naja naja (Spectacled cobra), Daboia russelii (Russell's viper), Bungarus caeruleus (Common Krait) and Echis carinatus (Saw-scaled viper). Bite envenomation remains a public health concern in many countries especially India. Populations in these regions experience high morbidity and mortality because of poor access to health services, which are often suboptimal, and, in some instances, a scarcity of polyvalent antivenom, which is the only specific treatment. A large number of victims survive with permanent physical sequelae due to local tissue necrosis and, no doubt, psychological sequelae. Because most bite victims are young, the economic impact of their disability is considerable. Worldwide more than 5 million bites are reported per year, with 2% leading to severe sequelae.

India had the largest number of reported venomous bites and deaths. India has the highest number of deaths due to venomous bites in the world, around 1.2 million venomous bite deaths (representing an average of 58,000 per year) from 2000 to 2019 with nearly half of the victims aged 30-39 and over a quarter being children under 15. The states with largest number of bite cases include Bihar, Jharkhand, Madhya Pradesh, Odisha, Uttar Pradesh, Rajasthan, Gujarat and Telangana. In 2017, venomous bite was recognized by World Health Organization as a neglected tropical disease. Snake venom is the most complex of all poisons, is a mixture of enzymatic and non-enzymatic compounds as well as other non-toxic proteins including carbohydrates and metals.

Antivenom (or antivenin or antivenene) is a biological product used in the treatment of venomous bites or stings. Antivenom is created by milking venom from the desired snake, spider or insect. The venom is then detoxified and injected into a horse, sheep, goat or cat. The subject animal will undergo an immune response to the venom, producing antibodies against the venom's active molecule which can then be harvested from the animal's blood and used to treat envenomation. Antivenoms can be classified into monovalent (when they are effective against a given species' venom) or polyvalent (when they are effective against a range of species, or several different species at the same time). Conventional clinical practice is to administer polyvalent anti- venom usually of horse origin at the time of hospitalization of the victim against Big Four venomous species. This often causes severe anaphylaxis reaction in the victim, (seen in up to 30% of the recipients worldwide) demanding secondary treatment. Acute pulmonary edemas, cerebellar ataxia and uveitis (an immunological complication) are some of the complications following polyvalent anti- venom.

One of the major problems of the envenomation is the lack of early specific detection platforms Time is critically important for detection. Currently, we don’t have any qualitative and quantitative detection diagnostics, we are still depending on symptomatic strategy and non-specific biochemical tests. It may cause delay in giving polyvalent anti-venom to victims. Because of non-specific diagnostics, we are still following the polyvalent treatment strategy to treat the bite patients.

Our invention is an early ease to use detection platform, where even a layman can also apply and detect the venom’s presence using the innovative design. By adding species specific substrates, in the innovative adhesive bandage, we can detect the species responsible for the bite. This will help to identify various species’ bite including, but not limited to , snakes, spiders, scorpions, centipedes etc.
Figures Explained
Figure 1: Outer/Upper View of the adhesive bandage of different shapes
Fig: 1.a : Outer/Upper View of the adhesive bandage in circular shape
Fig: 1.b: Outer/Upper View of the adhesive bandage in Rectangular shape
Fig: 1.c: Outer/Upper View of the adhesive bandage in square shape.
Figure 2: Inner View of the adhesive bandage of different shapes
Fig: 2.a : Inner View of the adhesive bandage in circular shape
Fig: 2.b: Inner View of the adhesive bandage in Rectangular shape
Fig: 2.c: Inner View of the adhesive bandage in square shape.
Figure.3: Sequence of Incorporation of various pads/layers
1. Backing Layer- The outer layer
2. Intermediate Layer- holds the absorbent pad to the backing layer
3. Absorbent pad- Enabling the absorption of the components from the bite site
4. Substrate pad- The layer on which the venom substrates and colouring agents are placed. This is the area on which the venom components from the bite site combines with the venom substrates to produce resultant products which in turn reacts with the colouring agents to make possible the detection of presence of venom as well as the species which is responsible for the envenomation.

5. Detection Layer- The layer on which the results colours are exhibited.
6. Covering Layer- An outer layer facing the skin which protects the wound surface from the direct interaction of materials in the bandage. This layer is made out of Less hygroscopic material. The porosity of the Covering pad is curated to 100 to 300 microns (micrometers) to avoid clots, clumps of platelets and cells which is essential to remove the unwanted components to reach the Substrate pad other than the venom components.
Fig.4: Cross section of the adhesive bandage
Fig .5 : Substrate pad
1. Substrate pad responsible for venom substrate interaction
2. A single micelle packed with coloring dyes or venom enzyme substrate, covered by phospholipid bilayer
3. Outer phospholipid bilayer which is critically important for a micelle formation
4. Phospholipid bilayer
DETAILED DESCRIPTION OF THE INVENTION
An adhesive smart diagnostic bandage for venom detection comprising a backing layer, with specific perforations and coated with a skin friendly adhesive at its inner surface, followed by an intermediate layer and an absorbent pad. Substrate pad is critically important to this invention, where venom specific substrate/s against venom component/s and coloring reagents/dyes will be placed on the outer surface of the absorbent pad facing skin which is placed on absorbent pad. The substrate pad will be covered with a detection pad, where coloration can be noted/detected. It will be then shielded by a covering pad, where it protects the wound surface with direct interaction of materials in the bandages. The detection and covering pad’s film porosity will be specific and well-designed for the movement of biological samples to the bandage from the bite-victim (Fig.3 and Fig.4), be it a human or animal.
This invention relates to adhesive smart bandage to be applied on the bite site of the victim which is essentially used for the early detection of envenomation. Adhesive bandages, the term being used herein to designate not only the elongated strips (Fig.1.a and Fig.1.b), but also the round “spots” (Fig.2.a and Fig.2.b) and the relatively square "patches (Fig.3.a and Fig.3.b)," are formed of a backing sheet which may be coated on one side with an adhesive and having a dressing pad secured to the adhesive, leaving exposed areas of adhesive on both ends of the dressing. The endwise adhesive tabs generally constitute the major area of exposed adhesive. However, even in the case of the elongated strips appreciable areas of exposed adhesive often appear at the sides of the dressing, although the latter are generally smaller, relatively speaking, than the areas of adhesive exposed at the ends of the dressing. The side wise exposed adhesive areas are proportionately larger in the case of the round "spots” and the square "patch" dressing, in which case they are usually as large as the endwise adhesive areas. Accordingly, the present invention is directed to the "spot" and "patch" dressings as well as the elongated strip adhesive bandages for qualitative detection of envenomation.
Bandages according to the present invention include a backing layer having a first Surface facing away from the skin and a second Surface, opposite the first
Surface, and facing the skin. The backing layer may have various shapes, e.g. rectangular, square, oval, circular, ovoid, oblong, etc. The shape of the bandage is defined by the shape of the backing layer. The backing layer may be thin, highly flexible or deformable, water-impervious, and clear or opaque. In general, the backing layer's thickness should fall within the range of 0.03 to 0.15 millimetres to achieve the forming and flexing characteristics desired.
A polyethylene film may be used as the backing layer, and particularly effective results may be achieved with stretchable, elastomeric films formed of polyurethane, which has the further advantage of gas (including water vapour) transmissibility. It is to be understood, however, that other flexible, water insoluble polymeric films known in the art may be used. Furthermore, the backing layer may be formed from closed cell polymeric foam, particularly one with an integral skin covering the side facing away from the skin of the user. Foam layers formed of polyurethane or polyethylene are suitable, while other polymeric foams having similar properties may be used. In addition, the backing layer may be made from other polyolefins, vinyl polyethylene acetate, textile non-woven fabrics, rubber, or other materials known in the bandage art. The backing layer may be impermeable to liquid, but permeable to gas, which allows the wound and the skin to which the bandage of the present invention is adhered to breathe. In one embodiment, the backing layer may have pores of such a size that will allow only the passage of gases, which have molecules of extremely small size. Perforations may be circular in area and have a range of diameters, such as from about 0.05 to about 0.1 millimetres. However, the backing layer may be totally impermeable to gases, when necessary.

Bandages of the present invention comprise an absorbent pad associated with the backing layer. The absorbent pad is affixed either directly or indirectly to the backing layer so that it will not become separated from the backing layer during normal use. Association may be accomplished by applying an adhesive layer between the second surface of the backing layer and first surface of the absorbent pad, thereby adhesively bonding the absorbent pad directly to the backing layer. The absorbent pad also may be associated with an intermediate layer, which in turn is associated with the backing layer, thus indirectly associating the absorbent pad to the backing layer via the intermediate layer.
The absorbent pad includes a first surface facing the second Surface of the backing layer, and that has a first Surface area, and a second Surface opposite the first Surface and facing the skin, and that has a second Surface area. The absorbent pad used in bandages of the present invention may have various shapes, e.g. rectangular, Square, oval, circular, ovoid, oblong, etc., and is sized to cover less area than the backing layer so that, in use, the adhesive layer on the backing layer is in contact with the user's skin, but preferably does not contact the wound surface. The absorbent pad may be a fibrous matrix comprising materials selected from the group consisting of threads, yarns, nets, laces, felts and nonwovens. The basis weight of the materials selected as the absorbent pad in bandages of the present invention may be any of those used conventionally to make absorbent pads for bandages utilized in applications similar to those of the present invention.
Followed by absorbent pad, we have Substrate pad, which is the most important design component, where the venom specific substrates, will be incorporated and

placed in the layer as polymerization or intermediate linking process. It will contain substrates and reagents responsible for detection. The basic principle behind the step is that when the venom specifically reacts with the substrate, either the reaction outputs, products, by-products, interactive outputs, etc. based color reaction and other recognition parameters are responsible for identification. The substrate pad is indigenously designed in such a way that when the venom components reacts the specific substrate, it will produce a color reaction so that even a layman can also understand or interpret the bite result. They can easily identify it as a venomous or non-venomous bite.
Venom proteins commonly seen in major venomous species like phospholipases, three finger toxins, metalloproteases, serine proteases, L-amino acid oxidase, acetyl choline, Hyaluronidases, serine peptidases, metalloproteinases etc. will be detected by incorporating venom protein specific substrates on substrate pad, and the products and the by-products will be specifically identified by setting up the reagents or materials, that can potentially develop or scale up the coloration reaction as part of visual identification. For example, for the detection of venom Phospholipase, one of the major venom proteins in venomous families (Elapidae and Viperidae), will be detected using our innovative smart adhesive bandage platform (Fig. 4). For example, the substrate of the phospholipase, phospholipids will be incorporated into the substrate pad in a specific design. The phospholipids will be converted into a micelle structure using controlled micelle formation condition and the high molecular weight hydrophilic dyes/coloring molecules will be trapped in the micelle structure. This will be arranged/incorporated in the substrate pad. When somebody bitten with a venomous species, places the bandage in the bite site, the fluid including blood will be taken by the bandage,
and when it reaches the substrate pad, it reacts with the micelles, whose outer layer made up of phospholipids and dissolves or digests it and thereby releasing the coloring reagents/dyes to the detection pads. It will be then eventually detected visually after spotting the color reactive dots, responsible or evidence for envenomation. Non-envenomation won’t show any color, which means we can detect or differentiate a venomous or non-venomous bite using this simple adhesive bandage. In addition to the snake venom proteins, this type of model can also be applicable for the detection of all venomous species detection like scorpion, spiders, cone snails, etc. which are medically significant and their venom specific substrates can be added/incorporated in the substrate pad for identification process.
The substrate pad followed by a detection layer, where the color reaction can be easily captured/visualized in the layer. It is less hygroscopic in nature made up of polymers and the porosity is designed in such a way that the reactants, substrate, by products, etc. won’t reach the bite wound site. Finally, the covering layer is considered as an integral component of the second surface of the detection layer. The covering layer comprises the network of inter connecting channels recessed in the skin-facing Surface. The covering layer provides additional protection to the wound and, where the absorbent pad is fibrous, prevents fibres from Sticking
to the wound or obscuring the channels. The covering layer is permeable to exudates to allow passage of the exudates from the wound to the absorbent pad. Thus, the covering layer may include perforations with less hygroscopic materials.
The exposed areas of adhesive bandages, at opposite end portions of backing with adhesive regions and opposite exposed area of covering layer will be then covered by protective labels/cover/strips or peel off strips, which is made up of completely non-hygroscopic polymers. This is essentially important for protection of the highly sensitive substrate pad from external contamination.

,CLAIMS:
CLAIMS
We Claim:-
1. The present invention relates to a smart adhesive bandage to be applied onto the skin of the bite victim, human or animal, with a substrate pad attached, where venom specific (substrate/s) component/s will be added for the qualitative and quantitative detection of envenomation status with regard to the presence of venom and identification of the species which is responsible for the envenomation.
A. As claimed in claim 1: this novel innovative bandage can be made in any desired shapes and size.
B. As claimed in claim 1: this novel innovative bandage is made up of 6 layers, The Backing Layer (Fig 3.1) with specific perforations and coated with a skin friendly adhesive at its inner surface, followed by an intermediate layer (Fig 3.2) and an absorbent pad (Fig 3.3). The intermediate layer which in turn is associated with the backing layer, thus indirectly associating the absorbent pad to the backing layer. The Substrate pad (Fig3.4), which is placed in between the absorbent and detection layer, is critically important to this invention, where venom specific substrate/s against venom component/s and coloring reagents/dyes will be placed on the outer surface of the absorbent pad facing skin which is placed on absorbent pad. The substrate pad will be covered with a detection pad (fig3.5), where coloration of venom particles can be noted/detected. It will be then shielded by a covering pad (fig 3.6), where it protects the wound surface with direct interaction of materials in the bandages. The detection and covering pad’s film porosity will be specific and well-designed for the movement of biological samples to the bandage from the bite-site of the victim (Fig.3 and Fig.4).

2. An innovative Substrate pad is included in the innovation which is coated with multiple specific venom substrates which will react with the venom components, the resultant products will react with the coloring agents by which detection is made possible as to the presence of venom and the species which is responsible for the envenomation.
3. The backing layer's thickness should fall within the range of 0.03 to 0.15 millimeters to achieve the forming and flexing characteristics desired. Perforations may be circular in area and have a range of diameters, such as from about 0.05 to about 0.1 millimetres
4. The porosity of the Covering pad is curated to 100 to 300 microns (micrometers) to avoid clots, clumps of platelets and cells which is essential to remove the unwanted components to reach the Substrate pad other than the venom components.