WO2013144895A1

WO2013144895A1 - Otic pharmaceutical composition

Info

Publication number: WO2013144895A1
Application number: PCT/IB2013/052483
Authority: WO
Inventors: Jacobus TERBLANCHE
Original assignee: Terblanche Jacobus
Priority date: 2012-03-28
Filing date: 2013-03-28
Publication date: 2013-10-03

Abstract

An otic pharmaceutical composition is disclosed. The composition comprises a ceruminolytic agent, acetic acid and a water soluble carrier and is intended for topical use in the ear canal. In preferred embodiments of the invention the ceruminolytic agent is carbamide peroxide or hydrogen peroxide and the carrier is water or glycerin.

Description

OTIC PHARMACEUTICAL COMPOSITION

FIELD OF THE INVENTION This invention relates to a pharmaceutical composition and, more specifically, to an otic fluid preparation for the removal of excess cerumen from an ear canal.

BACKGROUND TO THE INVENTION

Cerumen blockage of the ear, also known as wax build-up, is the obstruction of the ear canal with a natural material called cerumen, commonly known as ear wax. Cerumen blockage is common among adults and children alike and many people experience the discomfort of having a blocked up ear sometime during their lifetime.

The ear canal is lined with hair follicles and glands that secrete the wax-like cerumen. Cerumen acts as a protective layer for trapping dust, bacteria and other microorganisms from entering deeper into the ear canal and forms a layer that also protects the skin of the ear canal from becoming irritated or inflamed when liquids such as water enter the ear canal.

After the cerumen is secreted, it typically makes its way towards the external opening of the ear, where it falls out, or is removed by cleansing the ear. In some individuals, the cerumen producing glands secrete an excessive amount of cerumen. The excess cerumen may then harden in the ear canal to form a cerumen plug, which in turn may cause the ear canal to become blocked. This blockage can cause an uncomfortable sensation or a feeling of fullness in the ear canal.

To alleviate the discomfort, people experiencing these symptoms often introduce objects such as cotton buds into their ear canals in an attempt to clear out the excess cerumen. Rather than remove the cerumen, the introduction of foreign objects into the ear canal often has the effect of pushing the cerumen plug blocking the ear canal deeper into the ear canal, thereby worsening the symptoms and blockage. The uncomfortable sensation consequently worsens and the blockage can also cause the individual to experience additional symptoms such as strange jingling, ringing or buzzing noises in the ear (tinnitus), earache or even partial hearing loss.

Cerumen blockage is often disregarded as not being serious and is often treated without consulting a medical physician or other healthcare professional. One way of treating an ear blocked up by cerumen, is by softening the cerumen by using liquids such as mineral oils, baby oil or commercial pharmaceutical products of the type sold in pharmacies. A problem generally associated with current pharmaceutical products is that they are oil-based, whilst cerumen is a water soluble substance. Another disadvantage of current pharmaceutical products used for the removal of excessive cerumen is their lack of antibacterial or antifungal properties. Cerumen can also be removed from the ear canal by a method known as irrigation. This method involves the use of a syringe to gently direct a small stream of water against the ear canal wall next to a plug of excessive cerumen in an attempt to loosen and remove it. Problems associated with this method are that it must typically be repeated frequently in order to be effective and also the fact that it can cause dizziness, vertigo, external ear canal injury or even infection.

SUMMARY OF THE INVENTION In accordance with this invention there is provided a pharmaceutical composition for topical use in an ear canal, the composition comprising a ceruminolytic agent, acetic acid and a water soluble carrier. Further features of the invention provide for the ceruminolytic agent to be selected from carbamide peroxide and hydrogen peroxide and for the carrier to be selected from water and glycerin.

Still further features of the invention provide for the pharmaceutical composition to include 1 % to 7% (w/v) carbamide peroxide or hydrogen peroxide, 0.5% to 3% (w/v) acetic acid and water or glycerin as carrier; and preferably for the pharmaceutical composition to include 1 .5% (w/v) hydrogen peroxide, 1 % (w/v) acetic acid and water as carrier.

Even further features of the invention provide for the pharmaceutical composition to include a local anaesthetic; and for the local anaesthetic to be selected from benzocaine, antipyrine and pramoxine.

Yet further features of the invention provide for the pharmaceutical composition to include one or more drying agents, one or more preservatives and one or more surfactants; for the drying agent to be selected from isopropyl alcohol and anhydrous glycerin; for the preservative to be selected from thiomersal, parabens, sulphites, oxyquinoline sulphate and benzalkonium chloride; and for the surfactant to be thonzonium bromide.

Even further features of the invention provide for the pharmaceutical composition to have a pH of between 2,5 and 4.5, preferably between 2.5 and 3, and more preferably 2.86.

DETAILED DESCRIPTION OF THE INVENTION

A pharmaceutical composition for topical use in an ear canal is described herein. The composition comprises a ceruminolytic agent, acetic acid and a water-soluble carrier. The applicant has surprisingly observed that a composition comprising a ceruminolytic agent, acetic acid and a water-soluble carrier as set out in this specification exhibits a synergistic effect. A ceruminolytic agent dissolves or loosens cerumen to allow for the removal thereof from the ear canal. The pharmaceutical composition of this invention contains either carbamide peroxide or hydrogen peroxide as ceruminolytic agent. Carbamide peroxide releases hydrogen peroxide, which serves as a source of nascent oxygen when coming into contact with catalase. Hydrogen peroxide thus mechanically softens and loosens excessive cerumen in the ear canal, making it easier to remove. Bubbling occurs when the carbamide peroxide or hydrogen peroxide enters the ear canal. This bubbling loosens the cerumen and helps move it out of the ear canal in the direction of the external opening of the ear.

Otitis externa is a common inflammatory condition of the external ear canal, most commonly caused by bacterial or fungal infection. The most characteristic symptoms include erythema and swelling of the ear canal with variable amounts of discharge. If otitis externa is not optimally treated, the infection can become life-threatening, especially in immunocompromised patients.

Otitis media is inflammation of the middle ear and most often caused by blockage of the Eustachian tube. Blockage of the Eustachian tube is usually due to swelling of the mucous membranes in the nasopharynx. Viral and bacterial infections are commonly associated with otitis media due to the presence of excessive fluid in the middle ear.

Bacterial and fungal infections associated with the ear are often caused by Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumonia, Haemophilus influenza, Moraxella catarrhalis, Candida albicans and certain Aspergillus species such as Aspergillus fumigates, while viral infections are often complicated by secondary bacterial infections.

Acetic acid has a bactericidal effect on certain organisms, such as Staphylococcus aureus, Pseudomonas aeruginosa and Candida Albicans. Acetic acid stops the growth of these bacteria and therefore acts as a bacteriostatic agent. Acetic acid can also inhibit the growth of certain bacteria and fungi responsible for causing ear infections, such as certain Aspergillus species. Applicant believes that the hitherto unknown combination of acetic acid and hydrogen peroxide in an otic composition to be antimicrobial and to exhibit anti-fungal and bactericidal/bacteriostatic properties. It is further envisaged that, in the presence of a tympanic membrane perforation, it can penetrate the middle ear to at least partially reduce the infection associated with otitis media.

Cerumen is a mixture of water soluble viscous secretions from the sebaceous glands and less viscous secretions from modified apocrine sweat glands, dead skin and hair. The water-solubility of cerumen makes water a suitable carrier for use in an otic composition as this further facilitates the softening and loosening of excessive cerumen. It should, however, also be appreciated that glycerin or other water-soluble carriers maybe used as a carrier in the composition of the current invention. Glycerin adds moisture and lubrication to the composition, making it easier for the loosened cerumen to exit the ear. Glycerin is also hygroscopic and attracts water that might be trapped in the ear canal.

The pharmaceutical composition of this invention may contain 0.5% to 3% (w/v) acetic acid and 1 % to 7% (w/v) of either carbamide peroxide or hydrogen peroxide together with a carrier, which is preferably water or glycerin. In a preferred embodiment of the invention, the composition contains 1 % (w/v) acetic acid and 1 .5% (w/v) hydrogen peroxide in combination with water as a carrier. The pharmaceutical composition may include one or more local anaesthetics, selected from benzocaine, antipyrine and pramoxine. The inclusion of a local anaesthetic in the composition is beneficial when treating a patient having an ear blocked by excessive cerumen,or treating a patient suffering from a microbial infection such as otitis externa, as the excess cerumen or swelling of the ear canal can cause pressure on the tympanic membrane, causing severe ear ache. It is envisaged by the applicant that the pharmaceutical composition may also include drying agents such as isopropyl alcohol or anhydrous glycerin. It is further envisaged that the pharmaceutical composition may include one or more preservatives such as thiomersal, parabens, sulphites, oxyquinoline sulfate, or benzalkonium chloride and surfactants such as thonzonium bromide.

Most bacteria associated with ear infections experience optimal growth in environments having a pH between about 5 and about 8.5. An acidic environment is bactericidal to some of these bacteria, including Pseudomonas aeruginosa. An acidic environment also suppresses several fungi responsible for causing otitis externa. It is therefore envisaged that the pH of the pharmaceutical composition may be between 2.5 and 4.5. An even more suitable pH of the pharmaceutical composition is believed to be between 2.85 and 2.9. A preferred embodiment of the pharmaceutical composition has a pH of 2.86.

The above description is by way of example only and it should be appreciated that the invention is not limited to the embodiments of the invention described. Numerous variations may be made to the embodiments described without departing from the scope of the invention, particularly with regard to the number and variations of excipients included in the composition. The term "comprising" as used in this specification should be interpreted broadly so as to be inclusive, rather than exclusive.

Claims

CLAIMS:

1 . A pharmaceutical composition for topical use in an ear canal, the composition comprising a ceruminolytic agent, acetic acid and a water soluble carrier.

2. A pharmaceutical composition as claimed in claim 1 , in which the ceruminolytic agent is selected from carbamide peroxide and hydrogen peroxide and the carrier is selected from water and glycerin.

3. A pharmaceutical composition as claimed in claim 2, which contains 1 % to 7% (w/v) carbamide peroxide or hydrogen peroxide, 0.5% to 3% (w/v) acetic acid and water or glycerin as carrier.

A pharmaceutical composition as claimed in claim 2 or claim 3 which contains 1.5% (w/v) hydrogen peroxide, 1 % (w/v) acetic acid and water as carrier.

A pharmaceutical composition as claimed in any one of claims 1 to 4 which includes one or more local anesthetics selected from benzocaine, antipyrine and pramoxine.

A pharmaceutical composition as claimed in any one of claims 1 to 5 which includes one or more drying agents selected from isopropyl alcohol and anhydrous glycerin, one or more preservatives selected from thiomersal, parabens, sulphites, oxyquinoline sulphate and benzalkonium chloride, and one or more surfactants.

7. A pharmaceutical composition as claimed in any one of claims 1 to 6 which has a pH of between 2.5 and 4.5.

8. A pharmaceutical composition as claimed in claim 7 in which the pH is between 2.5 and 3.

9. A pharmaceutical composition as claimed in claim 7 or claim 8 in which the pH is 2.86.