Cerumen softening composition

Abstract

The invention relates to a cerumen softening composition. This composition could be used for example as an earwax or cerumen treatment. This cerumen treatment could be a cerumen softening treatment for which the composition could be used. The invention also relates to the use of the cerumen softening composition. In particular the invention relates to a cerumen softening composition wherein the cerumen softening composition comprises dibasic ester.

Description

[0001] CERUMEN SOFTENING COMPOSITION

[0002] The invention relates to an ear treatment composition or cerumen softening composition. This composition could be used for example as an earwax or cerumen treatment. This cerumen treatment could be a cerumen softening treatment for which the composition could be used. The invention also relates to the use of the cerumen softening composition. It further relates to a composition for use in cerumen softening. The composition is very useful as a ear hygiene and an ear care composition.

[0003] Cerumen, commonly known as earwax, is produced in the external auditory canal to protect the ear. However, when cerumen builds up excessively, it can cause impaction, leading to hearing difficulties, discomfort, water retention in the ear canal, and in some cases, pain and infection. The anatomy of the ear requires careful management of such impactions, as improper handling can damage the sensitive structures of the ear. Cerumen impaction is a common condition that affects a significant percentage of the population, due to the use of hearing aids, particularly among the elderly, the use of earplugs and earphones (trapping the cerumen inside the ear canal), dermatological conditions and anatomical variations in the ear canal.

[0004] Cerumen serves as a protective function by trapping dust, microorganisms, and foreign particles, thus preventing infection in the ear canal and damage to the eardrum. Cerumen typically migrates out of the ear canal naturally, propelled by the movement of the jaw during activities like chewing and speaking. However, when this self-cleaning mechanism is disrupted, cerumen can accumulate and lead to impaction. The causes of this disruption may include narrow or tortuous ear canals, excessive production of cerumen, or the insertion of objects like cotton swabs, which inadvertently push cerumen deeper into the ear canal.

[0005] Impaction is clinically defined when cerumen obstructs the external auditory canal and interferes with hearing or causes discomfort. It can lead to a variety of symptoms, including hearing loss, earache, a sensation of fullness, tinnitus, dizziness, and, in severe cases, infections such as otitis externa. It is believed that cerumen impaction is responsible for 10% of hearing impairment cases in older adults, underscoring its significant public health impact.

[0006] Cerumen has lubricating properties that protect the skin of the ear canal and its acidic pH offers antimicrobial benefits. Despite its protective functions, the overproduction, or inadequate clearance of cerumen, can result in the earlier mentioned ear impaction. In these cases, the cerumen builds up,hardens, and obstructs the ear canal, potentially causing the earlier mentioned range of symptoms. Cerumen impaction can affect people of all ages, but it is particularly common in older adults due to the production of drier and harder wax with aging. Moreover, people with narrow or curved ear canals are more susceptible to impaction as the anatomical structure can hinder the movement of cerumen towards the outer ear.

[0007] If cerumen is not cleared for some time, it will form a hard lump in the ear, which is extremely difficult to remove, and it can also damage the eardrum. In addition, if hard cerumen is not removed for a long time, it may affect hearing, or damage the normal function of the ear and affect people's daily lives.

[0008] For this reason, products that soften cerumen prior to the removal of it have appeared on the market. However, the therapeutic effect is not always satisfactory, and the method of use may be inconvenient as well.

[0009] For example, US 2021 / 0177858 Al describes a composition comprising one or more muscarinic antagonist compounds in propylene glycol. However these compounds should be used with care. WO 2011 / 085155 A2 uses a composition comprising any combination or mixture of the compounds selected from the group consisting of limonene, one or more bile salts and sodium bicarbonate. WO 2013 / 065051 Al discloses a composition comprising olive-squalane and additional natural oils.

[0010] Products on the market include, for example, A. Vogel Oordruppels Oorsmeer. This composition incorporates a Calendula extract. Alpine Hygiene spray Oorverzorging uses only olive oil, while A.Vogel Oorspray Oorpijn comprises, amongst other components, olive oil. Calendula officinalis, vitamin E and garlic oil.

[0011] However, all the compositions of the prior art have some disadvantages with respect to the softening of the cerumen, the safety of use, or the harshness of the used components. The softening, or dissolving of cerumen prior to removal of it is usually performed with compositions comprising oils, carbamide peroxide or hydrogen peroxide. These solutions can be applied as ear drops to break down the waxy cerumen. But some of these products cause ear irritation as an unwanted side effect and do not contain the desired dissolving properties. Therefore, there is a need for a product that has a significant therapeutic effect, prevents the excess formation of cerumen and is also easy to use. Further it is preferred to have an ear treatment composition or cerumen softening composition that comprises natural ingredients (so without the use of peroxides or surfactants), that have no side-effects and are safe to use over longer periods of time as a temporary or precautionary measure. Further, thecomposition should be gentle and soft to the skin, not irritating and not cause an allergic reaction. On top of that a composition is desired that needs no preservatives as it is not susceptible to microbial decay. The composition should also have a favourable smell to encourage the patient to use it.

[0012] The current invention relates to solve these problems of the prior art and provides an cerumen softening composition comprising a dibasic ester. It also provides a composition for use in cerumen softening. The use of dibasic ester, which acts as a solvent, dissolving the other components of the composition, breaks down the key components of cerumen in a very effective manner. Dibasic ester for this purpose is understood as a mixture of three esters, namely dimethyl glutarate (IUPAC name dimethyl pentanedioate), which helps in dissolving cerumen, dimethyl adipate (IUPAC name dimethyl hexanedioate), which enhances formula stability, and dimethyl succinate (IUPAC name dimethyl butanedioate), which is a mild dissolving agent. The use of dibasic ester in the cerumen softening composition effectively softens and dissolves the cerumen present, aiding in the natural expulsion of cerumen without the need for any mechanical interventions. By including dibasic ester as a solvent, the softening effect is enhanced and the cerumen is dissolved, providing a better solution for cerumen impaction than the compositions of the prior art. The composition of the invention is a non-invasive, topical otic composition that improves the health of the ear and ear canal.

[0013] A suitable and commercially available source of dibasic esters could be obtained from OQEMA, AachenerStr. 258, D-41061 Monchengladbach, Germany. Their product Imsol R-LVP, article number 833736, has proven to give very good results in the tests.

[0014] Dibasic esters are clear, colourless liquids having a mild and agreeable fruity odour, making it pleasant for a patient to use. They are readily soluble in alcohols, ketones, ethers, and many hydrocarbons, but are only slightly soluble in water. Dibasic esters are biodegradable, which means it can be considered a safer alternative to many hydrocarbon-based solvents and can therefore be seen as an environmentally friendly product. Further, dibasic esters are highly effective solvents for lipophilic compounds such as long-chain fatty acids and cholesterol, due to their unique molecular structure. The combination of ester functional groups and alkyl chains allows for both dipole-dipole interactions and hydrophobic interactions, enabling efficient solubilisation. Impacted earwax has a denser composition with elevated levels of long-chain fatty acids and cholesterol. The inventors found that by effectively dissolving these lipophilic components, dibasic esters help soften and breakdown impactedcerumen, facilitating easier removal.

[0015] Preferably, the cerumen softening composition further comprises one or more oils, preferably vegetable oils. More preferably, the one or more vegetable oils comprise Vitis vinifera seed oil and / or Brassica campestris seed oil. The main advantage is that these vegetable oils are low-viscosity oils, which possess softening properties, but also make sure that a good contact surface with the cerumen is obtained when used. This makes them highly effective for gentle cerumen removal and maintaining ear hygiene. Vitis vinifera seed oil, also known as grape seed oil, acts as a natural emollient to soften and soothen the skin and soften the cerumen. Brassica campestris seed oil, also known as rapeseed oil, acts as a natural lubricant and cleanser. The low-viscosity oils lubricate and soften the cerumen, promoting a natural and healthy expulsion.

[0016] Preferably, the cerumen softening composition further comprises squalane. Squalane is an organic compound also known as 2,6,10,15,19,23-Hexamethyltetracosane. Squalane is a natural substance and safe to use. The squalane component aids the softening of the cerumen. By combining low-viscosity oils (grapeseed oil and rapeseed oil) with squalane and dibasic esters, the cerumen is even further softened and dissolved in a very effective manner. The dibasic ester component acts as a solvent, breaking down the key components of cerumen, while the oils lubricate and soften the cerumen, promoting natural expulsion. Squalane acts as a natural moisturiser and enhances the penetration of the composition to the cerumen. Squalane was introduced as an emollient in the 1950’s. In the unsaturated form, called squalene, this substance is produced in human sebum. Squalane has a low acute toxicity and is not a significant human skin irritant or sensitiser.

[0017] Preferably the cerumen softening composition further comprises an antioxidant, preferably a-tocopheryl acetate. a-Tocopheryl acetate, also known as Vitamin E, acts as an antioxidant in the composition and also protects the skin. It is a natural component as well.

[0018] In an embodiment, the cerumen softening composition comprises - 50 to 70 weight-%, preferably 60 to 65 weight-%, more preferably 62 to 63 weight-%, most preferably 62,5 weight-% Vitis vinifera seed oil,

[0019] - 10 to 30 weight-%, preferably 15 to 25 weight-%, more preferably 18 to 22 weight-%, most preferably 20 weight-% Brassica campestris seed oil,

[0020] - 8 to 16 weight-%, preferably 10 to 12 weight-%, more preferably 11 ,5 to 12,5 weight-%, most preferably 12 weight-% squalane,

[0021] - 2,5 to 7,5 weight-%, preferably 4 to 6 weight-%, more preferably 4,5 to 5,5 weight-%, most preferably 5 weight-% dibasic ester,- 0,25 to 0,75 weight-%, preferably 0,4 to 0,6 weight-%, more preferably 0,45 to 0,55 weight-%, most preferably 0,5 weight-% a-tocopheryl acetate.

[0022] The used components are safe, biodegradable, non-carcinogenic and non-corrosive, making it suitable for long-term ear care. When applying the composition, the effect is immediate, making it a quick and practical solution to soften and remove cerumen buildup within a few days. Further benefits are that it is very gentle to the skin. Also the combination of the ingredients leads to a mild and pleasant odour. Unlike some other cerumen treatments that may have strong or unpleasant odours, making it a nasty experience to use for the patient, this combination of ingredients produces a mild, fruity scent derived from its natural oils and esters, making the application more pleasant for the user. The combination of both solvents and oils, provides a more effective treatment for cerumen impaction than the solutions of the prior art.

[0023] In an embodiment, the dibasic ester composition comprises

[0024] - 60 to 80 weight-%, preferably 70 to 80 weight-%, more preferably 77 weight-% Dimethyl Glutarate,

[0025] - 15 to 35 weight-%, preferably 20 to 27 weight-%, more preferably 22 weight-% Dimethyl Adipate,

[0026] - 0,5 to 1 ,5 weight-%, preferably 0,75 to 1 ,5 weight-%, most preferably 1 weight-% Dimethyl Succinate. These amounts have proven in the test to be very effective as ear treatment composition, especially when used as a cerumen softening composition and / or a cerumen dissolving composition.

[0027] The invention is also related to the use of the cerumen softening composition according to the invention.

[0028] Preferably, the cerumen softening composition is applied to the ear, for example to the cerumen, by means of a liquid spray. Applying it In this manner creates a fine mist, ensuring superior contact with the ear, for example the cerumen for more effective softening and removal of the cerumen without the need for deep insertion. This application is very convenient for the patient. The spray ensures precise dosing and minimal mess. The composition is designed to be applied directly on, for example, the cerumen into the ear canal using a spray, offering a simple solution for cerumen build-up without the need for other mechanical interventions.

[0029] Preferably, and alternatively to the application by means of a liquid spray, the cerumen softening composition is applied to the ear, for example to the cerumen, by means of liquid drops to the ear canal. The big advantage of using it in the form of drops is that the application mode is very gentle and convenient for the patient to soften and dissolve hardened cerumen, making iteasier to flush out. Applying it as drops makes sure that it is a targeted but gentle application, directly onto the cerumen.

[0030] The invention will hereinafter be further elucidated with reference to an exemplary embodiment according to the invention that is not limiting as to the appended claims.

[0031] Table 1 shows the composition of the experimental cerumen softening composition with the dibasic esters.

[0032] Table 2 shows the composition of dibasic esters in individual components in a most preferred embodiment.

[0033] Table 3 shows the Visual Grading Scale for the presence of cerumen (average cerumen grade).

[0034] Table 1. Composition of the experimental cerumen softening

[0035] composition with the dibasic esters.

[0036] Component (INCI name) weight-%

[0037] Vitis vinifera seed oil 62,5

[0038] Brassica campestris seed oil 20

[0039] Squalane 12

[0040] Dibasic esters 5

[0041]

[0042] Tocopheryl Acetate 0,5

[0043] Table 2. Composition of dibasic esters in individual

[0044] components in a most preferred embodiment.

[0045] Dibasic ester (INCI name) weight-%

[0046] Dimethyl Glutarate 77

[0047] Dimethyl Adipate 22

[0048]

[0049] Dimethyl Succinate 1

[0050] Table 3. Visual Grading Scale for the presence of cerumen

[0051] Visual Grading Scale for the presence of cerumen

[0052] 0 No cerumen visible

[0053] 1 Minimal cerumen; <10% of the ear canal is occluded

[0054] 2 Small amount of cerumen; 10-20% of the ear canal is occluded

[0055] 3 Mild cerumen accumulation; 20-30% of the ear canal is occluded

[0056] 4 Moderate cerumen accumulation; 30-40% of the ear canal is occluded

[0057]

[0058] 5 Noticeable cerumen accumulation; 40-50% of the ear canal is occluded6 Significant cerumen accumulation; 50-60% of the ear canal is occluded 7 Extensive cerumen accumulation; 60-70% of the ear canal is occluded 8 Severe cerumen accumulation; 70-80% of the ear canal is occluded

[0059]

[0060] 9 Complete or near-complete occlusion; >80% of the ear canal is occluded

[0061] Experimental

[0062] The study performed was an open-label, single-centre clinical evaluation of the composition of the invention, for the treatment of cerumen impaction. Seven subjects, aged 30 to 63, experiencing symptoms of cerumen impaction, participated in the trial. The formula was applied as a topical spray, twice daily, for a duration of 6 days. The subjects underwent daily assessments of the cerumen quantity using a validated Visual Grading Scale, along with evaluations of symptoms such as itching, fullness, hearing loss, pain, and dizziness using an other Visual Grading Scale scale.

[0063] The composition comprising dibasic esters demonstrated an excellent safety profile, with no adverse events reported. The subjects did not experience redness, irritation, sensitisation, burning, or any other negative reactions in the ear canal during the treatment period.

[0064] The study's primary goal was the reduction in cerumen quantity, which showed significant improvement. 7 out of 8 participants experienced a marked decrease in cerumen levels, with an average reduction of 5,5 points on the Visual Grading Scale, see Table 3. In total 9 subjects enrolled, 1 subject was lost in the follow-up, leaving 8 participants that completed the whole test.

[0065] A second test included the effect of reductions in discomfort symptoms like Itching, fullness, hearing loss, pain and dizziness. A Visual Analogue Scale (VAS) was used by the subjects to measure the severity of symptoms occurring (0 = no inconvenience, 10 = severe inconvenience), which is the total sum of the severity of symptoms occurring during episodes of cerumen impaction. Further recordings included the number of ears with cerumen impaction, the duration of cerumen impaction and the skin tissue affected.

[0066] The results showed a statistically significant 50% reduction in total symptom scores over six days. VAS scores decreased by an average of 3,875 points during the treatment period.

[0067] Participants rated the product highly in terms of efficacy and ease of application. 87,5% (7 out of 8) objects rated the treatment as "excellent" and 12,5% (1 out of 8) rated the treatment as "good." 87,5% of the objects were satisfied with the spray’s application method and found it user-friendly. Thecerumen softening composition of the invention demonstrated a strong clinical benefit in treating cerumen impaction in a safe and effective manner over the 6-day regimen. It effectively reduced cerumen quantity and alleviated associated symptoms without causing any adverse effects. The product's tolerability and safety were rated as excellent by both the study participants and investigators.

[0068] An in vitro study compared the cerumenolytic performance of various commercially available earwax removal products using a standardised artificial cerumen model. The results demonstrated that formulations containing dibasic ester, specifically a formula containing 5% dibasic ester and a formula containing 24% dibasic ester significantly outperform both dibasic ester free formulations and competing products. The 24% dibasic ester formula achieved complete disintegration of artificial cerumen within 30 minutes, while the 5% dibasic ester also showed strong activity. In contrast, a dibasic ester free version and market alternatives such as olive oil, docusate sodium, glycerol, isotonic solutions, and hydrogen peroxide exhibited only mild or no disintegration.

[0069] A follow-up test confirmed that the formula, containing 5% dibasic ester, after just a 5-minute exposure and subsequent rinsing with lukewarm water, achieved full cerumen disintegration, reinforcing the role of dibasic ester as a key active ingredient. The findings underline that the presence of dibasic ester significantly enhances the efficacy of cerumenolytic agents, providing a faster and more complete removal mechanism compared to dibasic ester-free or conventional formulations. Further, these results demonstrated the composition of the invention as a reliable and effective solution for managing cerumen impaction.

[0070] Although the invention has been discussed in the foregoing with reference to exemplary embodiments of the invention, the invention is not restricted to these particular embodiments which can be varied in many ways without departing from the invention. The discussed exemplary embodiments shall therefore not be used to construe the appended claims strictly in accordance therewith. On the contrary, the embodiments are merely intended to explain the wording of the appended claims, without intent to limit the claims to these exemplary embodiments. The scope of protection of the invention shall therefore be construed in accordance with the appended claims only, wherein a possible ambiguity in the wording of the claims shall be resolved using these exemplary embodiments.

Claims

AMENDED CLAIMSreceived by the International Bureau on 06 July 2026 (06 / 07 / 2026)1. A composition comprising a mixture of dimethyl glutarate, dimethyl adipate and dimethyl succinate for use in cerumen softening treatment.

2. A composition according to claim I , characterised in that the composition further comprises one or more oils, preferably vegetable oils.

3. A composition according to claim I or 2, characterised in that the one or more vegetable oils comprise Vitis vinifera seed oil and / or Brassica campestris seed oil.

4. A composition according to anyone of the previous claims, characterised in that the composition further comprises squalane.

5. A composition according to anyone of the previous claims, characterised in that the composition further comprises an antioxidant, preferably a-tocopheryl acetate.

6. A composition according to anyone of the previous claims, characterised in that the composition comprises:- 50 to 70 weight-%, preferably 60 to 65 weight-%, more preferably 62 to 63 weight-%, most preferably 62,5 weight-% Vitis vinifera seed oil, - 10 to 30 weight-%, preferably 15 to 25 weight-%, more preferably 18 to 22 weight-%, most preferably 20 weight-% Brassica campestris seed oil,- 8 to 16 weight-%, preferably 10 to 12 weight-%, more preferably 11 ,5 to 12,5 weight-%, most preferably 12 weight-% squalane,- 2,5 to 7,5 weight-%, preferably 4 to 6 weight-%, more preferably 4,5 to 5,5 weight-%, most preferably 5 weight-% of a mixture of dimethyl glutarate, dimethyl adipate and dimethyl succinate,- 0,25 to 0,75 weight-%, preferably 0,4 to 0,6 weight-%, more preferably 0,45 to 0,55 weight-%, most preferably 0,5 weight-% a-tocopheryl acetate.

7. A composition according to anyone of the previous claims, characterised in that the composition comprises:- 60 to 80 weight-%, preferably 70 to 80 weight-%, most preferably 77 weight-% Dimethyl Glutarate,- 15 to 35 weight-%, preferably 20 to 27 weight-%, most preferably 22 weight-% Dimethyl Adipate,- 0,5 to 1 ,5 weight-%, preferably 0,75 to 1 ,5 weight-%, most preferably 1 weight-% Dimethyl Succinate.

8. Use of the composition of anyone of the claims 1 to 7, characterised in that the composition is applied to the ear canal by means of a liquid spray.

9. Use of the composition of anyone of the claims 1 to 7, characterised in that the composition is applied to the ear canal by means of liquid drops.[0001]Please find a Statement under Article 19(1) with respect to the amendments.[0002]DI and D2[0003]The date on these leaflets is the revision date, not the publication date. The publication of these leaflets is of a later date.[0004]Screenshots (see DI 3) clarify that these internal documents were uploaded only on 22 August 2025 and 20 October 2025, both after the priority date of the patent application. The date is indeed 1 May 2024. But, this is an internally used revision date.[0005]As a medical device manufacturer, NW Pharma must comply with the General Safety and Performance Requirements (GSPR) of the EU MDR (2017 / 745) and with EN 15020417:2021 under its Quality Management System (QMS). The GSPR requirement (y) - see D14a - requires the Instructions For Use (IFU) to state “the date of issue” or, if revised, “the date of issue and identifier of the latest revision”. The “ 1 May 2024” date on the leaflets is exactly this: the regulatory issue / revision date of the IFU text (version control), as shown by the Translation File DI 4b (vl .0, 2024-05-01). It records when the controlled text was last revised, not when the document was made public.[0006]Publication of both product leaflets on the website was carried out after the priority date, in order to comply with regulatory obligations requiring public accessibility.[0007]All actions that could lead to publication of the formulation and / or product are all done after the priority date. DI and D2 were not public before the priority date and are therefore not relevant for novelty and / or inventive step. An accountant's statement (DI 5) is added to evidence this statement.[0008]D3[0009]Regarding D3, this is not an enabling disclosure. The Linkedln post discloses no formulation, not any mixture of dibasic esters, no ingredient names and no quantitative composition. It therefore cannot anticipate a claim requiring a mixture of dibasic esters. The composition could also not have been analysed as no samples were made available. DI 1 shows that the first production took place on 17 April 2025 at Medi-fill in Alkmaar, the Netherlands. This is after the priority date, so no samples could have been given out before that time.[0010]Further to that, at the CPHI in Milan (held between 8 and 10 October 2024), NW Pharma were present solely as visitors, to make contact with potential customers. NW Pharma did not exhibit, had no stand, and did not[0011]display or distribute any product, sample or formulation sheet. See our statement in DI 2.[0012]D4, D5 and D6[0013]D4 relates to a refreshing cosmetic, D5 to a nail polish remover and D6 to wipes for cleaning hands. Therefore these documents are not relevant as to the amended claims.[0014]Clarity - Article 6 PCT[0015]The clarity issue under Article 6 PCT is believed to be removed.

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