AU2019100836A4 - Topical Composition - Google Patents

Abstract

Abstract The present invention relates to a topical aqueous gel composition comprising (i) menthol and/or thymol, and (ii) a viscosity enhancing agent. The composition is used in a method of cleansing or treating or preventing itching and/or inflammation in the gluteal cleft of a subject, the method comprising (i) applying the topical gel composition on toilet paper to the gluteal cleft of the subject, whereby the topical gel composition contacts a contaminant on the gluteal cleft, and (ii) removing at least some of the topical gel composition comprising at least a portion of the contaminant from the gluteal cleft.

Description

TOPICAL COMPOSITION

FIELD

The field of the invention relates to personal care compositions, specifically gel compositions for topical application and which are useful for bodily cleansing and which reduce or prevent itching and inflammation.

BACKGROUND

Wet wipes began to be marketed as a luxury option to toilet paper in around 2005, and many adults now use wet wipes in place of toilet paper. Wet wipes have become more common for use as an alternative to toilet paper, particularly in affluent countries, including the United States, the United Kingdom and Australia. This usage has in some instances been encouraged by manufacturers who have labelled some wet wipe brands as “flushable”. However, wet wipes, including those labelled as “flushable” have been known to clog internal plumbing, septic systems and public sewer systems. The tendency for fat and wet wipes to cling together encourages the growth of the problematic obstructions in sewers known as ‘fatbergs’.

Diseases of the perianal area are manifested by a variety of symptoms, including anal itching, burning, pain, swelling, discharge, bleeding and tenderness. The prevalence of pruritis ani and other perianal diseases is currently unknown, but it is expected in total that these conditions are relatively common, affecting more than 2% of the population. Research studies suggest that pruritis ani is associated physiologic alterations of the perianal skin, the spinal cord, and the brain. Altered signaling between these systems appears to be a major factor in the enhancement and perpetuation of these conditions. Other perianal disorders, such as perianal Crohn's disease, prior radiation therapy and eczema result from altered activity of the intrinsic immune system. Local noxious stimuli in the perianal region result in negative sensory input to the brain. In this manner, the development of perianal conditions produces characteristic symptoms. Stressful or painful experiences may worsen the severity of perianal diseases as well as the perception of symptoms.

Hemorrhoids occur when normal venous structures in the anal canal and external portion of the anus become enlarged and engorged with blood. Symptoms include anal and perianal pain, pressure, bleeding, prolapse, soiling and difficulty evacuating stool contents. Treatments include ingestion of fiber, stool softeners, oral analgesics and local anesthetics. If these treatments are unsuccessful, invasive procedures including infrared coagulation, hemorrhoidal banding and surgical hemorrhoidecomy are used. There are a several disadvantages of currently available topical therapies.

2019100836 29 Jul 2019

Treatment of pruritis ani and other perianal disease initially involves dietary alteration such as the elimination of caffeine containing foods, tomatoes and hot peppers. Limitation of perfumed soaps and avoidance of excessive chafing of the perianal skin may also be beneficial. Over-the counter topical creams and ointments may provide benefit as well. A study of the topical application of capsaicin has suggested that this agent may reduce symptoms. Additional drugs are used to treat perianal diseases. These have potential disadvantages. For example, local anesthetics may produce itching, skin irritation or may have limited or no efficacy. Topical corticosteroid creams and ointments such as hydrocortisone can cause atrophy or thinning of the skin, striae or stretch marks. In addition, skin bruising or tearing with minimal pressure, the development of telangiectasias or abnormal blood vessels of the skin, susceptibility to bacterial skin infections, fungal skin infections and allergic reactions to the cream or ointment vehicle may occur with topical steroid treatment. Topically applied steroids may also be absorbed from the skin and into the bloodstream. This can cause high blood pressure, elevated blood sugar, fluid retention, osteoporosis, psychiatric effects such as depression, and a large number of other side effects

Thus, there remains a need for compositions to replace or reduce the use of wet wipes for cleansing of the gluteal cleft, and for compositions to reduce, alleviate or prevent perianal conditions such as pruritis ani.

SUMMARY

The present disclosure relates to a gel composition comprising aloe vera, menthol and/or thymol that can be used effectively to cleanse the gluteal cleft of a subject. The gel can be formulated with a consistency which allows application of the gel to toilet paper without disintegrating the toilet paper.

Accordingly, in one aspect there is provided a topical aqueous gel composition comprising:

i) menthol and/or thymol, and ii) a viscosity enhancing agent.

In one embodiment, the topical aqueous gel composition further comprises aloe vera.

In one embodiment, the viscosity enhancing agent is a gelling agent.

In one particular embodiment, the viscosity enhancing agent is a carbomer polymer.

In another embodiment, the composition further comprises a base. In one particular embodiment, the base comprises triethanolamine.

2019100836 29 Jul 2019

In another embodiment, the carbomer polymer in the topical gel composition is selected from carbomer 940 and/or carbomer 980.

In yet another embodiment, the composition further comprises zinc oxide nanoparticles.

In one embodiment, the composition comprises about 0.01 mg/ml to about 0.46 mg/ml menthol. In another embodiment, the composition comprises about 0.01 mg/ml to about 0.03 mg/ml menthol. In one particular embodiment, the composition comprises about 0.02 mg/ml menthol.

In another embodiment, the composition comprises about 0.01 mg/ml to about 0.9 mg/ml thymol. In one embodiment, the composition comprises about 0.01 to about 0.03 mg/ml thymol. In one particular embodiment, the composition comprises about 0.02 mg/ml thymol.

In one embodiment, the aloe vera extract is aloe vera juice. As would be understood in the art, the aloe vera juice may be fresh aloe vera juice, or it may be aloe vera juice that is reconstituted from dried aloe vera juice, for example reconstituted from freeze-dried aloe vera juice.

In one embodiment, the composition comprises between 5% to 85% by volume aloe vera juice. In another embodiment, the composition comprises between 10% and 50% by volume aloe vera juice, or between 15% and 40% aloe vera juice, or 20%, 25%, or 30% by volume aloe vera juice. In one particular embodiment, the composition comprises about 20% aloe vera juice. A level of about 5% to 20% aloe vera juice results in a clear gel without discoloration, and with a minimal aloe vera aroma when compared to higher concentrations of aloe vera juice.

In yet another embodiment, the composition further comprises one or more additional agents selected from an anti-pruritic, astringent, analgesic, and/or an antimicrobial agent.

In one embodiment, the gel composition has a consistency sufficient to allow the gel to remain on the surface of toilet paper, whereby the toilet paper does not disintegrate for a period of time in which a subject may cleanse the gluteal cleft with the toilet paper, for example for a period of less than 1 minute, less than 30 seconds or less than 20 seconds.

There is further provide a method of cleansing an area of skin of a subject, the method comprising:

i) applying the topical gel composition as described herein to an area of skin on the subject, whereby the topical gel composition contacts a contaminant on the skin, and ii) removing at least some of the topical gel composition comprising at least a portion of the contaminant from the skin.

2019100836 29 Jul 2019

A method of cleansing the gluteal cleft of a subject, the method comprising:

i) applying the topical gel composition as described herein to the gluteal cleft of the subject, whereby the topical gel composition contacts a contaminant on the gluteal cleft, and ii) removing at least some of the topical gel composition comprising at least a portion of the contaminant from the gluteal cleft.

In one embodiment, step i) of applying the topical gel composition to the gluteal cleft of the subject comprises applying the topical gel composition to toilet paper, and contacting the topical gel composition on the toilet paper to the gluteal cleft of the subject.

There is further provided a method of treating or preventing itching and/or inflammation in the gluteal cleft of a subject, the method comprising:

i) applying the topical gel composition as described herein to the gluteal cleft of the subject, whereby the topical gel composition contacts a contaminant on the gluteal cleft, and ii) removing at least some of the topical gel composition comprising at least a portion of the contaminant from the gluteal clef.

As will be apparent, preferred features and characteristics of one aspect of the invention are applicable to many other aspects of the invention.

Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

DETAILED DESCRIPTION

General Techniques and Definitions

Unless specifically defined otherwise, all technical and scientific terms used herein shall be taken to have the same meaning as commonly understood by one of ordinary skill in the art.

As used herein, the terms “treating”, “treat” or “treatment” include topically applying a therapeutically effective amount of a composition as defined herein sufficient to reduce or delay the onset or progression of a specified condition, or to reduce or eliminate at least one sign or symptom of a condition.

As used herein, the terms “preventing”, “prevent” or “prevention” include administering or applying a therapeutically effective amount of a composition as described herein sufficient to stop or hinder the development of at least one sign or symptom of a specified condition.

2019100836 29 Jul 2019

Gel composition

The present disclosure relates to a topical gel composition comprising aloe vera extract, menthol and/or thymol that can be used advantageously to cleanse the gluteal cleft of a subject in place of wet wipes, and so avoid the known issues of wet wipes failing to sufficiently disintegrate, thereby causing accumulations of wipes and fat in the sewerage networks known as fatbergs. In addition, the ingredients in the composition have properties including astringent, antibacterial and mildly analgesic properties. The menthol and/or thymol, both of which are aromatic in nature, assist in reducing and/or masking odours, as well as helping to reduce or prevent itching around the anus and in the gluteal cleft.

Aloe vera

The botanical name of Aloe vera is Aloe barbadensis miller. It belongs to Asphodelaceae (Liliaceae) family, and is a shrubby or arborescent, perennial, xerophytic, succulent, pea- green color plant. The plant has triangular, fleshy leaves with serrated edges, yellow tubular flowers and fruits that contain numerous seeds. Each leaf is composed of three layers: 1) An inner clear gel that contains 99% water and rest is made of glucomannans, amino acids, lipids, sterols and vitamins. 2) The middle layer of latex which is the bitter yellow sap and contains anthraquinones and glycosides. 3) The outer thick layer of 15-20 cells called as rind which has protective function and synthesizes carbohydrates and proteins. Inside the rind are vascular bundles responsible for transportation of substances such as water (xylem) and starch (phloem).

Aloe vera has been reported to contain 75 potentially active constituents: vitamins, enzymes, minerals, sugars, lignin, saponins, salicylic acids and amino acids. Some of the phenolic compounds in Aloe vera, include aloin and emodin which act as analgesics, antibacterials and antivirals. Aloe is also reported to contains auxins and gibberellins that help in wound healing and have anti-inflammatory action. Saponins that are the soapy substances form about 3% of the gel and have cleansing and antiseptic properties.

Menthol

Menthol is an organic compound made synthetically or obtained from com mint, peppermint, or other mint oils. It is a waxy, crystalline substance, clear or white in colour, which is solid at room temperature and melts slightly above. The main form of menthol occurring in nature is (-)-menthol, which is assigned the (1R,2S,5R) configuration. Menthol has local anesthetic and counterirritant qualities, and it is widely used to relieve minor throat irritation. Menthol also acts as a weak kappa opioid receptor agonist.

2019100836 29 Jul 2019

Menthol also has antipruritic properties and has been used to reduce itching. Menthol has also been used in many oral hygiene products and bad-breath remedies (to mask or eliminate unpleasant odours), and generally as a food flavour agent.

Thymol

Thymol (also known as 2-isopropyl-5-methylphenol, IPMP) is a natural monoterpene phenol derivative of cymene, Cl OH 140, isomeric with carvacrol, found in oil of thyme, and extracted from Thymus vulgaris (common thyme) and various other kinds of plants as a white crystalline substance of a pleasant aromatic odor and strong antiseptic properties. Thymol also provides the distinctive, strong flavor of the culinary herb thyme, also produced from T. vulgaris.

Thymol is part of a naturally occurring class of compounds known as biocides, with strong antimicrobial attributes. Numerous studies have demonstrated the antimicrobial effects of thymol, ranging from inducing antibiotic susceptibility in drugresistant pathogens to powerful antioxidant properties. Thymol has been shown to be an effective fungicide, particularly against fluconazole-resistant strains. This is especially relevant to Candida infections. Thymol has antimicrobial activity because of its phenolic structure, and has shown antibacterial activity against bacterial strains including Aeromonas hy dr ophila and Staphylococcus aureus. Though the exact mechanism is unknown, some evidence suggests thymol effects at least some of its biocidal properties by membrane disruption.

The antifungal nature of thymol is due to its ability to alter the hyphal morphology and cause hyphal aggregates, resulting in reduced hyphal diameters and lyses of the hyphal wall. Additionally, thymol is lipophilic, enabling it to interact with the cell membrane of fungus cells, altering cell membrane permeability permitting the loss of macromolecules.

Gel

To obtain a suitable consistency of the topical gel composition, any of a number of commercially available gelling agents may be used. Such gelling agents are well known in the art. Suitable gelling agents include Carbopol, hydroxypropyl cellulose, hydroxy ethylcellulose, or other cellulosic ethers, other polymeric gelling agents such as xanthan gum, guar gum, and the like, fatty alcohols, fatty acids and their alkali salts and mixtures thereof, as well as inorganic gelling agents.

In one embodiment, the gelling agent is Carbopol 980. The Carbopol 980 is typically added to an aqueous solution and stirred slowly to allow the polymer to swell. Swelling may take place for more than 20 minutes up to around 1 to 2 hours. The addition

2019100836 29 Jul 2019 of Carbopol to aqueous solutions typically results in a low pH and incomplete swelling of the polymer. To achieve complete swelling of the polymer, a base is added to the solution in order to increase the pH to around 6-6.5. A suitable base that is commonly used in the production of cosmetics and personal care compositions is triethanolamine. The pH of the resultant gel, being around pH of 6-6.5, is suitable for a topical gel composition.

Preservatives

Typically, to extend shelf-life of the topical gel composition, the composition will comprise a preservative. Preservatives may be, for example benzoic acid, benzyl alcohol, phenoxyethanol, methylparaben, propylparaben. In one embodiment, the preservative is Germall Plus. Liquid Germall Plus is a synergistic combination of Germall II preservative (Diazolidinyl Urea) and Iodopropynyl Butylcarbamate (IPBC) in propylene glycol. Germall Plus is a highly effective, broad spectrum preservative for emulsions and aqueous formulations. It can be incorporated into a variety of leave-on and rinse-off cosmetic and personal care formulations for broad preservation.

Therapeutic methods

The present disclosure is based on the finding that that a topical aqueous gel composition comprising menthol and/or thymol can be used for cleansing the skin. In one embodiment, the composition is suitable for cleansing the gluteal cleft and/or anus, such as after defecation, to remove sweat and/or lint from clothing.

Regular use of the composition may help in the treatment or prevention of certain skin disorders such as puritis ani, an itching condition in the gluteal cleft. Without wishing to be bound by theory, it is believed that the gentle cleansing action of a topical gel composition combined with the mildly antipuritis properties of menthol, thymol and/or aloe vera reduce skin itching.

The topical aqueous gel composition is also suitable for general cleansing of the skin. The gel can be conveniently carried in a container for use in any situation. For example, the gel may be used by carers for the cleansing of skin of both the elderly and infants and help to reduce skin irritation such as nappy rash.

The invention is hereinafter described by way of the following non-limiting Examples and with reference to the accompanying figures.

2019100836 29 Jul 2019

EXAMPLES

Example 1. Determining suitable topical gel consistency

Aloe Vera gel was obtained from Aloe Vera Australia (aloeveraustralia.com.au) and dilutions were made with water to 5%, 10% gel, 20% gel, 30% gel, 40% gel, 50% gel, 60% gel, and 70% gel. The gel compositions were tested for suitable consistency by application to toilet paper. The gel was allowed to remain of the surface of the toilet paper for approximately 30 seconds and then a finger was rubbed across the paper to determine whether the paper was in the process of disintegration. Visual signs of wetting were also used as an indicator of whether the gel dilutions were wetting the toilet paper.

At higher dilutions, e.g., 10%-30% gel diluted with water, the composition rapidly wet the toilet paper and initiated paper disintegration, meaning these compositions were unsuitable for use on toilet paper for cleansing the gluteal cleft. The inventor determined that gel compositions comprising approximately 60% or more of the gel could be applied to the toilet paper without significant disintegration or wetting of the paper over a 30 second period. The gel was tested on four different brands of commercially available toilet paper with similar results achieved when the gel was applied to each of the four toilet paper products. This indicates gels of this consistency would have physical properties suitable for use as a topical gel composition for cleansing the gluteal cleft.

The 60% gel preparation was retained as a reference for further experiments to formulate gel compositions using aloe vera juice, carbomer 980 and triethanolamine as the starting ingredients.

Example 2. Formulation of topical gel composition from aloe vera juice A 500 ml batch of gel was prepared with the following ingredients:

500 ml initial formula

150 ml Aloe juice

350 ml water

1.25 g menthol (0.25%) 5 g Carbomer 980 (1%) Approximately 6.75 ml Triethanolamine- added to achieve approximately pH 6.3 1.25 ml Germall Plus preservative (0.25%)

300 ml warm water (between 45° C and 50°C) was added to a beaker. The menthol crystals were added to the water and dissolved by stirring. Once the menthol was dissolved, the carbomer 980 was added slowly to the water:aloe mix and stirred slowly.

2019100836 29 Jul 2019

Once all of the carbomer had been added and dissolved (approximately 1 hour), the Germall plus preservative was added. The pH was adjusted to approximately 6.3 using triethanolamine. The resultant gel mixture was stirred slowly and then dispensed into 3 x 100 ml bottles.

The gel was relatively thick, around the consistency of a hair gel product. A small amount was applied to toilet paper, where it managed to sit for a minute or more with no signs of soaking into the paper. Upon application to the gluteal cleft, the menthol was strong and the consistency of the gel was relatively thick.

The gel composition was further tested for suitable consistency by application to toilet paper. The gel was allowed to remain of the surface of the toilet paper for approximately 30 seconds and then a finger was rubbed across the paper to determine whether the paper was in the process of disintegration. Visual signs of wetting of the paper were also monitored. The gel was of sufficient viscosity to allow it to sit on the surface of the paper for a period of at least 30 seconds without visible signs of wetting or disintegration of the toilet paper.

Example 3. Formulation of topical gel composition with menthol and thymol A revised gel formula comprising a lower concentration of menthol, less aloe vera juice and less carbomer 980, but with the addition of thymol, was prepared according to the following formula:

500 ml Revised formula (less menthol; less carbomer)

100 ml Aloe juice

400 ml water

250 mg menthol (0.05%; 0.5 mg/ml)

400 mg thymol (0.08%; 0.8 mg/ml) g Carbomer 940 (0.6%) Triethanolamine (approximately 4 ml) to achieve pH around 6.3 Germall Plus 1.25 ml (0.25%)

Formulation steps

1. Place 400 ml warm water (approx. 50°C) in beaker

2. Add 100 ml aloe juice

3. Place in warm water bath (approx. 50° C)

4. Add thymol crystals and menthol crystals

5. Stir until dissolved

6. Add carbomer slowly while stirring

2019100836 29 Jul 2019

7. Allow to swell for at least 1 hour with occasional stirring

8. Add Germall plus

9. Add triethanolamine to pH 6.3

The gel was of a suitable consistency for application to toilet paper. Application of the gel to the gluteal cleft resulted in a still slightly strong menthol sensation. The fragrance of the thymol in the composition was also strong.

Experiment 4. Revised gel formulation containing menthol and thymol

In this experiment, the gel was made with 0.2 mg/ml menthol (0.02%) and 0.2 mg/ml thymol (0.02%). The amounts of other ingredients remained the same as in the previous experiment. The method steps were modified slightly. Aloe juice and water were combined with the carbomer 980. The mix was stirred for approximately 20 minutes and then stirred intermittently over a period of around 2 hours. This resulted in more complete dissolving of the carbomer.

The menthol and thymol crystals were then added, and the beaker was placed in a warm water bath (approximately 50°C) to warm the solution and allow for the menthol and thymol crystals to dissolve. The pH of the solution was adjusted to about pH 6.3 and the Germall plus was added. The resultant gel was clear, whereas the gels prepared in the previous experiments had been slightly cloudy. Presumably, this was due to incomplete swelling of the carbomer polymer in the earlier experiments.

The clear gel had excellent consistency. Application of the gel to toilet tissue did not result in breakdown of the paper and the gel remained on the surface of the toilet paper. The gel has a pleasant menthol/thyme fragrance that is not overpowering. The gel is refreshing when used on the gluteal cleft, and not too strong. There is little or no burning sensation from the menthol.

The gel was placed into a 100 ml pump pack container. Operation of the pump results in a nice-looking gel product being applied to toilet paper, showing this method of application would be suitable.

Example 5. Cleansing ability of topical composition

Several volunteers tested the ability of the gel composition to remove fecal contamination from around the anus and in the gluteal cleft following defecation. Volunteers were instructed to use dry toilet paper initially to remove most of the fecal contamination, and then to use a small amount of the gel on toilet paper to cleanse the anus and gluteal cleft. Volunteers found the gel to be particularly effective at removing fecal contamination.

2019100836 29 Jul 2019

Example 6. Disintegrating and flushing of toilet paper containing topical composition

The gel composition was placed on toilet paper, and the toilet paper with gel was agitated in water for 2 minutes to determine how readily it would dissolve. A comparison was made to agitation of toilet paper alone in water for 2 minutes. The inventor determined the gel composition readily dissolved in water, and there was no discernible difference in disintegration of the toilet paper with gel versus toilet paper alone.

Example 7. Viscometer analysis of topical composition

Samples of topical gel composition that had been determined as suitable for application to toilet paper for cleansing the gluteal cleft were subject to rheological analysis at department of Chemical Engineering at the University of Queensland.

It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

All publications discussed and/or referenced herein are incorporated herein in their entirety.

Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim of this application.

Claims (5)

1. 2019100836 29 Jul 2019

   CLAIMS:

   1. A topical aqueous gel composition comprising:

   i) menthol and/or thymol, and ii) a viscosity enhancing agent.
2. 2. The topical aqueous gel composition of claim 1, wherein the composition comprises about 0.01 mg/ml to about 0.46 mg/ml menthol and/or the composition comprises about 0.01 mg/ml to about 0.9 mg/ml thymol.
3. 3. A method of cleansing the gluteal cleft of a subject, the method comprising:

   i) applying the topical gel composition of any of claims 1 to 2 to the gluteal cleft of the subject, whereby the topical gel composition contacts a contaminant on the gluteal cleft, and ii) removing at least some of the topical gel composition comprising at least a portion of the contaminant from the gluteal cleft.
4. 4. The method of claim 3, wherein the step i) of applying the topical gel composition to the gluteal cleft of the subject comprises applying the topical gel composition to toilet paper, and contacting the topical gel composition on the toilet paper to the gluteal cleft of the subject.
5. 5. A method of treating or preventing itching and/or inflammation in the gluteal cleft of a subject, the method comprising:

   i) applying the topical gel composition of any of claims 1 to 2 to the gluteal cleft of the subject, whereby the topical gel composition contacts a contaminant on the gluteal cleft, and ii) removing at least some of the topical gel composition comprising at least a portion of the contaminant from the gluteal cleft.