WO2023194712A1

WO2023194712A1 - Medicinal patch

Info

Publication number: WO2023194712A1
Application number: PCT/GB2023/050886
Authority: WO
Inventors: Michael Brett SMITH
Original assignee: Smith Michael Brett
Priority date: 2022-04-03
Filing date: 2023-04-03
Publication date: 2023-10-12
Also published as: GB202204852D0

Abstract

A medicinal patch comprises a base (4) on which microneedles (1) are mounted, the microneedles (1) being formed from frozen medicine, such as a vaccine. The medicine may be safely preserved in a frozen state until it thaws on implantation into the skin. The base (4) of the patch may be formed from a biodegradable bio-polymer strengthened with graphene. Each microneedle (1) may be mounted on a pedestal (3) on the base and may be bonded to graphene oxide flakes (2) protruding from the pedestal (3). The patch may be manufactured by applying the liquid medicine into evacuations (6) in the surface of a cooled roller (5) to form frozen cones (8), then marrying the roller with the base (4) of the patch, whereby the pedestals (3) contact the frozen cones of medicine and become attached, via the base of each cone (8) freezing onto a respective pedestal (3).

Description

TITLE

Medicinal patch

DESCRIPTION

Technical field

The invention relates to the delivery of medical substances into the body of a patient by applying a patch to the skin of a patient. The medical substance may be a vaccine. The patient may be human or animal.

Background of the invention

The world has been and still is under the influence of COVID-19, a virus that has cost millions of lives and trillions of dollars. By far the single biggest factor in the healing of economies and rebuilding of tourism and travel is the control or elimination of COVID-19. The only way this can occur is through successful and ongoing mass vaccination, which requires a low cost and highly scalable vaccination method and delivery apparatus in order to be accessible by all people on the planet. To eradicate COVID-19, the relevant vaccine must be delivered soon after a mutation or new strain is detected and to most of the population.

COVID-19 vaccines have been developed and widely administered using both conventional and novel (mRNA) technologies. Such vaccines need to be kept cold before use to maintain their safety and effectiveness so they are typically transported and stored in a frozen state. When ready for use, they must be thawed under controlled conditions, while maintaining a low temperature, then each dose must be attached to a syringe for delivery into the muscle of a patient. These steps must be carried out by medically trained personnel, which limits the ease with which the vaccines can be distributed.

It is known to deliver certain medicinal substances into the body using an array of microneedles provided on a patch. The patch may be applied to the skin of patient to penetrate the outer layer (stratum corneum) of the skin and deliver the substance to the underlying tissue. The patch may be applied by the patient themselves or administered by a non-medical professional such as a teacher or office manager. The use of a patch may be more acceptable to people who have a fear of needles; and the length of the microneedles may be such that they penetrate the stratum corneum without reaching the nervous layer in the skin, and thereby avoid triggering pain signals.

In some cases, known microneedles are hollow, providing a channel through which the substance may be delivered in liquid form. In other cases, the microneedles are solid and the substance may be coated on their surface. It is also known to mould such microneedles from a soluble carrier material such as a sugar which incorporates the medicinal substance so that, when the patch is removed, the microneedles remain embedded in the skin and the medicinal substance is released as the carrier material dissolves in the interstitial fluid of the patient.

There is very little prior art in the direction of patch-based vaccine delivery, and especially those that use microneedles.

Summary of the invention

The invention involves the utilisation of a graphene strengthened base patch onto which graphene oxide pedestals are formed and on top which the frozen vaccine spikes are mounted. A patch according to the invention may comprise hundreds of such microneedles in the form of “micro-icicles”, which are frozen vaccine that when pressed on the arm or other skin area of a patient, will become embedded in the dermal layer and then thaw to the deliver the vaccine below the skin.

The invention also provides a novel process of combining the base patch and the frozen vaccine.

More generally, the invention provides a medicinal patch as defined in claim 1.

The invention further provides a method of forming a medicinal patch as defined in claim 9. It also provides a method of delivering a medicine to a patient as defined in claim 15.

The dependent claims define features of the invention that are preferred but not essential.

It should be noted that this invention provides additional benefits that are unique to this form of vaccine delivery which include:

1. As the vaccine stays frozen for the life of the patch until administered, the integrity of the vaccine is ensured. Shipping the patches around the world does involve the use of containers or crates that are able to maintain a below freezing temperature (as is the case for existing vaccines). The temperature for freezing can vary from -10 to -80°C without negative influence on the patch.

2. Since all the vaccine is infused into the patient at just below the surface of the skin, there is no waste of vaccine and thus total costs can be reduced and the delivered dose can be precisely known and calibrated. It should be noted that in syringe-based vaccine delivery, a small amount of vaccine is wasted with every patient as a small amount of vaccine is expelled before administration to ensure there are no air bubbles and there remains vaccine inside the needle and the syringe after administration.

3. Because the vaccine is placed just below the surface of the skin, if the patient should have an allergic reaction to it, the skin forms a blister and the vaccine may easily be expelled through the surface, whereas a vaccine injected into deep muscle could cause a more serious problem.

4. The dose is proportional to the area of the patch so can easily be varied.

5. It should be especially noted that a major and substantial benefit of this form of delivery is the speed at which the vaccine can be administered. The time to administer a single dose is reduced from 10 minutes (including preparation) down to typically 5-15 seconds. 6. The patch can be made fully recyclable or biodegradable. When disposed of after use, it will readily dissolve in salinated water or desalinated water or in a composting process, making it very eco-friendly. The patch material can biodegrade in just a few weeks to leave inert carbon and carbohydrate/cellulose base material. It therefore avoids the problem of medical waste that is associated with the use of syringes.

7. The invention is highly scalable, due to the patch base material being very low- cost and produced in the same industrial processes as plastic injection moulding and polymer extrusion. The patch can be produced relatively cheaply and supplied to the market using existing technology such as freezer cases and storage.

Although the invention was created for use with the COVID vaccine, the aforementioned benefits can be obtained by using the same technology to deliver other vaccines and other medicines where the intravenous medical substance can be frozen before use. An example of this is insulin.

When directional terms such as “upper” or “top” are used in this specification, these directions refer to patches that are orientated as shown in Figure 1. It will be understood that patches according to the invention may be manufactured, stored, transported and used in any orientation.

The drawings

Figure 1 is a schematic vertical cross-section through a patch according to one embodiment of the invention.

Figure 2 is a schematic plan view of the patch of Figure 1.

Figure 3 is a schematic vertical cross-section through a roller used in a manufacturing process according to the invention.

Figures 1 and 2 show a patch for delivery of a vaccine or other medicine. Multiple vaccine spikes or microneedles 1 are provided in an array over the surface area of the patch. Each microneedle 1 is formed from frozen vaccine, with a sharp tip. The vaccine may be a conventional composition, comprising an active ingredient with other additives to maintain its effectiveness, stability, pH, etc., all typically provided in aqueous solution. Therefore the freezing point of the vaccine may be at or slightly below 0°C, such that the microneedles formed from it will quickly thaw when implanted into the skin of a patient, the outer layer of skin being at a temperature between normal body temperature (37°C) and the ambient temperature in the location where the vaccine is being administered. In ideal conditions, the ambient temperature may be optimized to ensure that the vaccine spike thaws quickly when implanted into the skin but not before.

The base 4 of the patch is formed from a flexible sheet material, which may be a bio-polymer such as a cellulose. Functionalised graphene may be added to the material of the base 4 for strength. The functional groups added to the graphene may be selected to bond chemically with the material of the base.

Pedestals 3 protrude at intervals from the upper surface of the patch and are raised above the surface of the patch. The pedestals 3 may be formed by depositing graphene oxide on the base. The graphene oxide bonds to the functionalised graphene in the base. It is preferably in the form of microscopic flakes or platelets, which protrude from the top of each pedestal 3. The protruding flakes 2 act like mountain ridges, creating a large and irregular surface area for the vaccine spikes 1 to bond to, chemically and/or mechanically. Graphene oxide bonds strongly to ice. Each microneedle or vaccine spike 1 is formed on a respective pedestal 3. The pedestals 3 help to ensure that when the patch is pressed against the skin of a patient, the microneedles 1 are fully inserted below the surface of the skin. However, in alternative embodiments (not illustrated), the pedestals 3 could be omitted so that the graphene oxide flakes 2 are deposited directly on the base 4 and the microneedles are mounted directly on the base. In still other embodiments, the pedestals 3 could be formed of materials other than graphene oxide, including being formed integrally with the based from the same material. The top surface of each pedestal 3 could be moulded with regular or irregular projections to increase its surface area and enhance bonding with the vaccine spikes 1. Figure 3 schematically illustrates a process by which a patch according to the invention may be formed. A roller 5 is provided with an array of very small conical evacuations 6 over its outer surface. The roller 5 is cooled to below the freezing point of the vaccine and is rotated past a supply 7 of the vaccine in liquid form, which is applied to fill each of the evacuations 6 of the roller 5. The vaccine freezes in the evacuations 6 to form vaccine cones 8, owing to the sub-zero temperature of the roller 5 itself.

As the roller 5 rotates, it is married up with the synchronously travelling base 4 of the patch, whereby the patch pedestals 3 contact the vaccine cones 8 and become attached via the process of rapid thawing of the base of the cone 8 and then refreezing onto the pedestal 3 which is attached to the base 4. Further rotation of the roller 5 and translation of the base 4 causes the cones 8 to separate from the evacuations 6 in the roller and continue as microneedles 1 mounted on the pedestals 3 of the patch. The frozen conical shaped vaccine forms 1 remain fastened or frozen to the patch if sub-zero temperatures are maintained or for as long as it takes to administer the patch to a patient.

The roller may be made of a metal or alloy such as stainless steel or titanium. It may comprise a graphene coating making it non-stick, which assists removal of the microneedles 1 from the evacuations 6. The described process lends itself to continuous manufacture of the patches. The patches could be formed as a continuous strip, as illustrated, and then cut into units of the desired size. Alternatively, a series of separate units could be mounted on a substrate (not shown) and fed through the apparatus. The base 4 of the patch is flexible so does not necessarily need to follow a straight path through the manufacturing apparatus. In particular, the path could be made to curve about or away from the circumference of the roller, in order to manage the rate of separation of the microneedles 1 from the evacuations 6. The invention does not exclude some reciprocating movement of the base 4, first to compress each pedestal 3 against the base of the vaccine cone 8 in the roller, then to withdraw it with the cone 8 attached. The relative temperatures of the roller 5 and the pedestals 3, as well as the degree of pressure applied, may be carefully controlled to enhance the thawing and refreezing process that adheres the vaccine cones 8 to the patch. It should be emphasized that the drawings are purely schematic. They do not necessarily represent the shape, proportions, spacing or number of microneedles in a practical patch according to the invention. A practical patch is likely to comprise hundreds of microneedles, depending on the dose of vaccine to be delivered.

The length of the microneedles may be determined by the desired depth of penetration into the skin. It may be from a few tens of microns up to 1 ,5mm.

The width of the microneedles may be determined by balancing various factors. For example, narrower needles may cause less pain and may thaw more quickly when they enter the skin, thereby making administration of the patch faster. On other hand, broader needles may be more robust against possible mechanical damage during manufacture and transport or deployment, for example when pressing the microneedles through the tough outer layer (stratum corneum) of the skin. Broader needles may also be more robust against or possible changes in temperature, for example immediately before application to the skin when administering the patch in hot climates. Typical widths will be in the range tens to hundreds of microns. The microneedles may have a non-circular cross-section - for example, elliptical or angular - which may enhance penetration into the skin.

Although described in relation to some embodiments of the invention as conical, the microneedles need not be in the form of pure geometric cones but may also be cylindrical, as seen in Figure 1, and are typically provided with a conical or pointed tip, having a small radius to enhance penetration of the needle into the skin.

The spacing of the microneedles on the patch may depend on the desired dose per unit area of the patch and also on the ease of withdrawing them from the evacuations in the roller during manufacture. It is not essential that the microneedle array forms a rectangular grid as seen in Figure 2; it could adopt other patterns such as a triangular grid or a more irregular pattern.

Claims

1. A medicinal patch comprising a base 4 on which microneedles 1 are mounted, the microneedles 1 being formed from frozen medicine.

2. A patch according to claim 1, wherein the base 4 is formed from a bio-polymer.

3. A patch according to claim 2, wherein the base 4 is strengthened with graphene.

4. A patch according to any preceding claim, wherein the base 4 comprises an array of pedestals 3, each microneedle 1 being mounted on top of a pedestal 3.

5. A patch according to claim 4, wherein the pedestals 3 are formed from graphene oxide.

6. A patch according to claim 5, comprising graphene oxide flakes 2 that protrude from the pedestals 3, wherein the microneedles 1 adhere to the graphene oxide flakes 2.

7. A patch according to any preceding claim, wherein the medicine is a vaccine.

8. A patch according to any preceding claim, wherein the medicine is insulin.

9. A method of forming a medicinal patch, comprising the steps of: providing a roller 5, which comprises conical evacuations 6 in a surface of the roller 5, the evacuations 6 being filled with cones 8 of a frozen medicine; providing a base 4, which comprises an array of pedestals 3 corresponding to the evacuations of the roller 5; marrying the roller 5 with the base 4 of the patch and rotating the roller 5, whereby the pedestals 3 contact the frozen cones 8 of medicine and become attached, via the base of each cone 8 freezing onto a respective pedestal 3.

10. A method according to claim 9, wherein the step of providing a roller 5, which comprises evacuations 6 filled with cones of a frozen medicine, comprises: cooling the roller 5 to below the freezing point of the medicine; and applying the medicine as a liquid to fill the evacuations 6 of the roller 5, whereby the medicine freezes in the evacuations 6.

11. A method according to claim 9 or claim 10, wherein the roller 5 comprises a non-stick graphene coating.

12. A method according to any of claims 9 to 11, wherein the base 4 is formed from a bio-polymer strengthened with graphene.

13. A method according to claim 12, wherein the pedestals 3 are formed from graphene oxide.

14. A method according to any of claims 9 to 13, wherein the medicine is a vaccine.

15. A method of delivering a medicine to a patient comprising: providing a medicinal patch, which comprises a base 4 on which microneedles 1 formed from frozen medicine are mounted; and pressing the patch against the skin of a patient.

16. A method according to claim 15, wherein the temperature of the skin causes the frozen microneedles 1 to thaw and detach from the pedestals.

17. A method according to claim 15 or claim 16, wherein the medicine is a vaccine.

18. A method according to claim 15 or claim 16, wherein the medicine is insulin.