WO2021078896A1

WO2021078896A1 - Apparatus for administering a topical agent

Info

Publication number: WO2021078896A1
Application number: PCT/EP2020/079815
Authority: WO
Inventors: Chetan MORJARIA
Original assignee: Morjaria Chetan
Priority date: 2019-10-22
Filing date: 2020-10-22
Publication date: 2021-04-29
Also published as: GB2590174A8; GB2590174A; GB202016787D0

Abstract

Apparatus for placement over a tooth of a patient to dispense a local aesthetic to a focused area. The apparatus comprises an elastomeric polymer mould having an inner section for receiving topical agent to be administered to a patient in a focused area and an outer section, surrounding the inner section. The outer being made from an impermeable material and acting as a barrier to prevent the agent from spreading from the inner section to and beyond the outer section thereby ensuring that the agent is administered to the patient in only the focused area.

Description

APPARATUS FOR ADMINISTERING A TOPICAL AGENT

Field of invention

The present invention relates to apparatus for administering a topical agent.

Background to the invention

The administration of topical agents in the mouth is challenging due to the uniqueness of the oral environment.

The presence of saliva causes active agents to be washed away from their target site. Furthermore, the saliva transports such agents to other areas of the oral cavity, where sensory and special sensory (taste) receptors may be affected.

This tends to have a negative impact on the patient experience and often reduces the effectiveness and the duration of activity of the active ingredients.

Moreover, the oral structures of each individual are unique in their anatomy. This presents a challenge in creating an all in one application apparatus, which is further complicated by the mobile nature of some oral structures and differences in their surface characteristics.

Furthermore, in relation to teeth, it can be difficult for active ingredients to penetrate through the dental hard tissues (especially enamel) and to reach an inflamed dental pulp, for example, thus liming effectiveness. These challenges reduce the ability of the patient to self-medicate where it might have been otherwise appropriate for them to do so.

US2005260544 A1 discloses a device for delivering an oral healthcare substance to the teeth, gingival and/or mucosal tissues. The device of the main embodiment is a device is a wax based material with a barrier layer if the form of a fabric coating forming an impermeable membrane. The device is used primarily for tooth whitening and can be placed over multiple teeth. The applicant has found that dental waxes are suitable for the present invention. Dental waxes are heat sensitive and, as the mouth is inherently warm, they may deform in an unpredictable way causing discomfort or variation on tooth exposures to outside temperatures. Moreover, wax materials does not benefit from the ability of the user to apply light masticatory forces as the softness of the wax can lead to teeth cutting into the structure.

The present invention seeks to provide apparatus and a method of administering active agents to a target site within the mouth, for example, to provide pain relief whilst waiting for dental treatment.

Use of the apparatus is painless and does not involve for example, an injection to the gums.

The present invention also seeks to provide apparatus for administering a topical agent in a focused area of a patient and providing a barrier around that area to prevent the topical agent from extending past the boundary to other areas of the patient beyond the focused area.

The topical agent may be an anesthetic.

Statements of invention

According to a first aspect there is provided, apparatus for placement over a tooth of a patient to dispense a topical agent to a focused area, the apparatus comprising a elastomeric polymer mould having a first section for receiving topical agent to be administered to a patient in a focused area and a second section, surrounding the first section, the outer being made from an impermeable material and acting as a barrier to prevent the agent from spreading from the first section and beyond the second section thereby ensuring that the agent is administered to the patient in only the focused area.

Preferably the topical agent is or includes an anesthetic.

Preferably the mould is made from rubber polymer. Alternatively the mould is made from a silicone polymer.

Preferably the second section includes an impermeable coating or layer. Preferably the second section has means to adhere the section to at least one tooth of a patient to form an outer boundary around the tooth or teeth.

Preferably the first section includes means to release the agent onto the area within the confines of the first section. In the majority of cases, but not all, the area requiring treatment will be a dental cavity.

Preferably the apparatus is formed as a monolayer having a thickness that is sufficient to prevent seepage of the agent away from the focused area.

Brief description of drawings One embodiment of the invention will now be described, by way of example only, with reference to the figures in which:

Figure 1 is a schematic plan view of apparatus constructed in accordance with the invention; and

Figure 2 is a side view of the apparatus of figure 1. Detailed description of preferred embodiments of the invention

An embodiment of the invention specifically used for oral pain will now be described.

The apparatus, or agent dispenser, takes the form of a elastomeric polymer mould that is located in the mouth of the patient and extends over and around a tooth or teeth of the patient that require dental treatment. The apparatus is formed from an elastomeric polymer material in a gum or gum-like form. The gum-like structure allows for manipulation of the mould using light forces applied by the user’s fingers. During compression, the mould does not undergo a permanent deformation. The mould is held against the tooth by weak mechanical retention rather than stronger adherence which can cause problems by sticking to the tooth leaving debris is frustrating and difficult to remove.

The apparatus does not adhere to the tooth or soft tissues such as the gum or mucosal tissue, and is preferably hydrophobic.

The figures provide a schematic illustration for the purposes of understanding the invention. To this end, the figures show the mould 2 to be square or rectangular.

The mould 2 is formed from an elastomeric polymer and is intended to be moulded around a tooth or teeth of a patient during use. The mould could alternatively be a silicone or rubber mould.

Silicon polymers are known in dentistry but have never been used for placement onto a tooth long term. Some polymers are used in the profession as agents for taking moulds but are not used to expel active ingredients on a targeted area of the tooth. Silicon and rubber polymers have, until being considered for use with the present invention, only been used for placement in the mouth to take moulds of teeth rather than dispensing any active ingredient onto them. Other than that, oral strips have generally been made as dissolvable ones.

The applicant has found that the majority of teeth which need application of active ingredients (except whitening), are back teeth. Through extensive research the applicant has identified an optimum range of thickness to provide the best effect. The applicant has subsequently been able to prevent seepage into unwanted areas, which otherwise would happen with elastomeric polymers.

The shape of the mould 2 prior to use is inconsequential but size and dimensions is dictated by the need for the mould 2 to be placeable within the mouth and around the area of the tooth or teeth requiring treatment.

Typically, the mould 2 has a thickness of approximately 1 to 3 mm, which is thicker than the use of a polymeric film, like that shown in the prior art, which is typically 0.2 to 0.3 mm thick. The polymer mould 2 is formed with an inner section 4 and an outer section 6. As can be seen in the figures the outer section 6 completely surrounds the inner section 4.

A topical agent 8 is located only within the inner section 4 of the mould 2 and the active ingredients are held in the inner section by mechanical retention. For the purpose of the description the agent 8 will be referred to as an anesthetic.

Anaesthetic agents are not generally considered for use on the dental hard tissues because generally the hard tissues are impenetrable and anaesthetics are short acting. Usually local anaesthetics are injected so that they can bathe the nerve and anesthetise the area supplied by the nerve.

If applied to enamel, anaesthetics do not penetrate the crystal structure at all. If applied to a cavity where dentine is exposed, the dentine itself acts as a physical barrier, and though dentine has tubules, there is an outflow of dentinal fluid from these tubules which reduce the ability of agents travelling down them. This is the reason why, if someone is in pain, the dentist has to drill through the dentine, to access into the nerve chamber and work directly on the nerve tissue.

The applicant has appreciated that this procedure would be a lot less painful if the dentist could just apply anaesthetic to the cavity to treat a throbbing nerve pain.

Some penetration of agents does occur, but studies have shown that, as the agent penetrates, the concentration of the agent reduces dramatically per millimetre of dentine. So not only are many anaesthetics not long acting, they would not penetrate very far and would probably escape into the mouth as well. Hence they would not normally be considered for use.

The current invention overcomes the side effects of using aesthetic gel in the mouth providing a targeted approach which prevents seepage into the oral cavity and maximising the dosage of active agent to the specific site.

Furthermore, for the purpose of this description the area of treatment will be referred to as a cavity. Although this is most likely to be the case, it is understood that the area of treatment could relate to any aspect of the tooth. In place, the inner section 4 is compressed against the cavity and releases the active ingredients of the topical anesthetic 8 directly onto the cavity area. The outer layer 6 absorbs any active ingredient which does not go into the tooth after compression.

The outer section 6 of the polymer mould 2 is impermeable, or has an impermeable layer or coating, such that the outer section 6 acts as a peripheral barrier to contain the anesthetic 8 over the cavity within the boundary of the mould 2. The mould 2 may be formed as a monolayer having a thickness, or areas of thickness, sufficient to prevent seepage of the anesthetic 8 away from the focused area.

The outer section 6 prevents anesthetic 8 from seeping from the inner section 4 and beyond the outer section 6 into the oral cavity.

The outer section 6 also provides adhesion to the tooth thereby forming a seal further containing the anesthetic 8 to the treated area. To this end the outer section may have a medical-grade non-permanent adhesive layer to assist adhesion to the tooth or teeth to retain the apparatus against the tooth or teeth and keep the inner section 4 over the area required the anesthetic 8 whilst the patient is waiting for treatment.

In some cases the rubber material chosen may have sufficient natural adhesion properties.

The apparatus can be simply peeled off the tooth to allow a dentist to begin treatment. This also allows for medicated and non-medicated areas to be clearly demarcated, which is important in order to target the medicines and to avoid medicine being administered in incorrect places which could have the potential of causing undesirable side effects.

The polymer stays in situ and moulds around the tooth or teeth of the patient providing a comfortable without affecting speech or taste.

Additional anesthetic for increased pain relief can be expelled by gently pressing on the inner section 4 which acts as a dispenser for the anesthetic.

It is appreciated that the dispenser may be formed of other rubbers or other materials that are considered suitable for use in the mouth of a person. Different molecular weights of the same polymers may also be used to take advantage of the different properties that result.

The apparatus may include further compounds to be expelled for tooth whitening and/or cleaning, or preventing tooth decay. They may contain may other ingredients, for example without limitation, softeners or flavorings. Other such compounds may be provided within the inner section 4 instead or in addition to the topical anesthetic.

Alternatively or in addition, the apparatus could hold or contain other compounds such as, for example without limitation, surfactants or adhesive agents and/or other health benefiting compounds such as mineralizing agents. The components are held by physical and or chemical retention, and are released either on mechanical pressure or by chemical release, from the inner layer area.

In a further embodiment, for use for treatment of pain in other patient areas, the apparatus may have a simpler form as a strip of material having inner and outer sections as described. The apparatus has means to retain the anesthetic within the confines of the inner section and prevent it from extending beyond the outer section and into the oral cavity.

The outer section is impermeable and may have, for example, raised edges that act as a barrier to anesthetic flowing onto the outer section such that the anesthetic is contained within the inner section and so is only applied to the patient in the focused area requiring treatment. As the inner section is raised slightly above the focused area (due to the outer area having raised edges), the amount of anesthetic can be controlled by the patient simply pressing on the back surface of inner section (the surface facing outwardly from the patient) to apply further anesthetic to the focused area.

In an alternative embodiment the outer later is formed from a different rubber to the inner layer to provide the effective barrier to the anesthetic or topical agent. In addition, or alternatively, the outer layer could have a different thickness to the inner layer which thickness being sufficient to absorb the active ingredient before it can enter the mouth. Whilst the apparatus described has two layers, it may have more than two. Alternatively the apparatus may be formed as a monolayer or single layer structure with or without an impermeable membrane.

The active ingredient may include, without limitation, one or more of, appearance and structural changes to teeth, whitening, stain bleaching, stain removal, plaque removal, tartar removal, cavity prevention and treatment, inflamed and/or bleeding gums, mucosal wounds, lesions, ulcers, aphthous ulcers, cold sores, tooth abscesses, tooth and/or gum pain, tooth sensitivity (e.g. to temperature changes), toothache and the elimination of mouth malodour resulting from the conditions above and other causes such as microbial proliferation.

A mould of the present invention is simple and easy to manufacture, which in turn gives the advantage of being cheap to manufacture and supply high need populations in poorer communities.

A suitable anaesthetic to be dispensed using the apparatus will now be described.

Dental or oral pain can be the bane of people’s lives. Toothache can override any enjoyment of day to day activities and often leaves the sufferer in agony or distress for long periods of time, until they are able to receive the required dental treatment.

There is significant scope for the development of agents to aid in the management of pain. Topical agents would be beneficial for superficial lesions on skin, the musculoskeletal system, joints or mucosa membranes as well as sources of pain within the oral cavity or musculoskeletal system. For example, dental or oral pain has a reported incidence of up to 70% in some countries. It has a significant impact on quality of life, where toothache can override any enjoyment of day to day activities and often leaves the sufferer debilitated and in agony for long periods of time. The prevalence is increased in lower socioeconomic groups where barriers to access to healthcare professionals worsen the problem.

Whilst topical anaesthetics are available over the counter, they provide limited pain relieving effects for the oral/dental tissues. They are firstly, limited in terms of duration of activity. Secondly, they may lack the ability to reach the source of the noxious stimulus at an effective concentration for pain relief due to the inability to penetrate through tissues effectively. Some analgesic agents are also not generally administered for topical administration because they can lead to serious complications such as mouth ulceration. Whilst there are also concerns about dosages and concentrations of certain other anesthetics due to concerns of systemic absorption. Current orally ingested analgesics are limited in their effectiveness for pain relief and can take up to 30 minutes to take effect. Indeed, as a result of their ineffectiveness, a large number of hospital admissions are due to overdose, 38% of paracetamol overdose cases in the UK for example, are due to dental pain.

The present invention seeks to provide a topical anesthetic for inter alia application to a tooth which is causing toothache or to the oral mucosa. The anesthetic can be applied to the problem tooth or teeth or to the site of pain on skin generally and is rapidly absorbed to dull or numb the skin and hence the pain in the area without causing adverse side effects.

In particular the present invention seeks to provide an anesthetic consisting of a combination of active agents, the combination of which provides a therapeutic or synergistic effect of enhanced anesthesia.

The invention provides a topical anesthetic consisting of a combination of a conventional drug and a herbal derivative.

Reference to conventional drug is intended to include a pharmaceutical drug, a compound used as a medicinal drug, or an allopathic drug.

The conventional drug may be a voltage dependent sodium or calcium channel blocker or other local anesthetic agents. The conventional drug component may consist of a single agent or multiple agents, and may be derived synthetically or naturally or by any other means. Preferably the conventional drug is benzocaine or lignocaine.

Benzocaine is well known short acting topical anaesthetic, usually used in the dental profession as a numbing gel prior to injecting children or by general anaesthetists/gastroenterologists. It has been used for mouth ulcers or numbing gels for toothache and baby teething but has been found to be generally inadequate for such purposes because the active numbing time and the extent of the area numbed is limited. Over application, which may for example be caused by repeated use over a short period of time, can result in significant systemic absorption leading to life threatening adverse effects.

The herbal derivative may be from the terpenes, terpenoids, phenylpropanoids, vanilloids or natural phenol classes, either in their pure or natural form (for example as part of an essential oil or herb). The examples given are intended to include sub classes, variants and derivatives. The herbal derivative may consist of a single agent or multiple agents, and may be derived synthetically or naturally or by any other means.

Preferably the herbal derivative is Eugenol. The herbal derivative could be an alternative phenyl proponoid.

Eugenol is known for its obtundent properties. It is used as a temporary filling in combination with zinc oxide for people with toothache or after root canal therapy. It’s mode of action is still under research although it is generally thought that it targets a number of receptors on the nerve cell. The effects of which are both immediate and delayed in onset time. However in high concentration, eugenol can can be irritant to mucosal membranes and cause cell necrosis.

As a result of the known risks of use of the individual active agents, potential adverse effects are limiting factors in the concentration/amount used of both benzocaine and eugenol independently. However the Applicant has demonstrated through extensive research, development and experimentation, that safe doses of benzocaine and eugenol in combination leads to an enhanced anesthetic affect greater than that seen with the individual agents, without adverse effect. The Applicant has also demonstrated a drug in the same class as benzocaine, lignocaine, also has an enhanced effect when combined with eugenol.

The resultant anesthetic can provide highly localized but very effective anesthetic without the risks that would otherwise be incurred using higher doses of the medications.

The concentration of the Eugenol and/or Benzocaine may depend on the target site and pain experience. An example of an effective concentration of Eugenol reaching the target site would be 1x 10^~4 M, though the concentration in the invention may be higher by up to a factor of 1000 due to dilution as the compound diffuses through various tissues.

An example of an effective concentration of Benzocaine would be 0-20%, or up to 1.42M.

The results of research conducted by the Applicant using a topical anesthetic consisting of a combination of Benzocaine and Eugenol found numbing effects of over 10hrs on average, which is far longer than Benzocaine’s duration of action.

A combination of compounds resulted in a complete blockage of the action potential events which is in contrast to a 30% and 50% reduction in amplitude and 60% and 20% increase in the number of events seen upon exposure to the compounds separately. This indicates at a surprising and very strong synergestic effect upon combination of compounds. Synergy has also been demonstrated with other conventional anesthetic compounds in the same class as benzocaine, for example with lignocaine/lidocaine.

Through extensive tests and research, the Applicant has discovered that this combination can be more effective as analgesics in combination with one another, possibly because they affect different receptors. Furthermore, there may be complimentary action, as there is, for example, both immediate and delayed onset of anti-nociceptive activity in neural cells.

Thus a highly effective anesthetic invention is produced by the use of herbal and conventional drugs, allowing for enhanced anesthetic properties, whilst reducing side effects associated with high concentrations of all components.

Reference to the herbal and conventional drugs described herein is intended to include any equivalent forms or modifications, such as, without limitation, isoforms of those drugs.

The anesthetic can be administered as a spray, a gel or any other appropriate form. The anesthetic may be combined with a rubber or polymer based matrix to form a gum such that the anesthetic is administered through masticatory pressure. Whilst the present description refers primarily to a topical anesthetic for oral pain, it may be applied to a different site or source of pain.

Claims

1. Apparatus for placement over a tooth of a patient to dispense a local aesthetic to a focused area, the apparatus comprising an elastomeric polymer mould having an inner section for receiving topical agent to be administered to a patient in a focused area and an outer section, surrounding the inner section, the outer being made from an impermeable material and acting as a barrier to prevent the agent from spreading from the inner section to and beyond the outer section thereby ensuring that the agent is administered to the patient in only the focused area.

2. Apparatus according to claim 1 , wherein the topical agent includes an aesthetic.

3. Apparatus according to claim 1 or claim 2, wherein the mould is made from rubber polymer.

4. Apparatus according to claim 1 or claim 2, wherein the mould is made from a silicon polymer.

5. Apparatus according to any one of claims 1 to 4, wherein the apparatus is formed as a monolayer having a thickness that is sufficient to prevent seepage of the agent away from the focused area.

6. Apparatus according to any one of claims 1 to 5, wherein the outer section includes an impermeable coating or layer.

7. Apparatus according to any preceding claim, wherein the outer section has means to adhere the section to at least one tooth of a patient to form an outer boundary around the tooth or teeth.

8. Apparatus according to any preceding claim, wherein the inner section includes means to release the agent onto the area within the confines of the inner section.