AU2013100016A4 - Composition For Alleviating The Symptoms Of Mastitis - Google Patents

Abstract

The invention relates to a topical medicinal composition for alleviating the symptoms of mastitis, the composition comprising (i) 0.5 to 95 wt% of an active comprising extract of a mentha species, optionally including a further naturally occurring active, (ii) 0.1 to 20 wt% dermal penetration vehicle, and (iii) adjuvants. Typically the further naturally occurring active is chosen from mentha species and Brassica olerancea and combinations thereof, and the major proportion of the composition is naturally derived. It is particularly preferred that the medicinal composition is used to treat a human suffering from mastitis by topical application to the affected breast at least once per day.

Description

PI/00/002 Regulation 3.2B AUSTRALIA Patents Act 1990 ORIGINAL COMPLETE SPECIFICATION INNOVATION PATENT Innovation Title: COMPOSITION FOR ALLEVIATING THE SYMPTOMS OF MASTITIS The following statement is a full description of this innovation, including the best method of performing it known to the Applicant: 2 COMPOSITION FOR ALLEVIATING THE SYMPTOMS OF MASTITIS FIELD OF INVENTION [0001] The present invention relates to the field of compositions based on natural substances. [0002] In one form, the invention relates to a composition and method for alleviating symptoms comprising the use of extracts of mentha species. [0003] In one particular aspect the present invention is suitable for use for alleviating the symptoms of mastitis. [0004] Furthermore it is to be understood that the present invention is not limited to particular compositions or composition delivery systems which may vary. BACKGROUND ART [0005] It is to be appreciated that any discussion of documents, devices, acts or knowledge in this specification is included to explain the context of the present invention. Further, the discussion throughout this specification comes about due to the realisation of the inventor and/or the identification of certain related art problems by the inventor. Moreover, any discussion of material such as documents, devices, acts or knowledge in this specification is included to explain the context of the invention in terms of the inventor's knowledge and experience and, accordingly, any such discussion should not be taken as an admission that any of the material forms part of the prior art base or the common general knowledge in the relevant art in Australia, or elsewhere, on or before the priority date of the disclosure and claims herein. [0006] Mastitis occurs in a wide range of domestic animals a well as humans. In particular it is a major concern in the livestock industry because mastitis affected cows, sheep or goats produce milk of a lower yield and quality. Reducing mastitis is an issue of animal comfort and good animal husbandry.

3 [0007] Mastitis is the most common disease in dairy cattle and the most costly. As a result a large range of treatments have been tried including long-acting antibiotics, vaccinations and topical products. While these have some effectiveness they can be impractical or difficult to apply and may not provide rapid relief. Most reduce the severity of the condition and do not prevent new infection. [0008] In humans mastitis initially causes breast engorgement, tenderness, localised inflammation and elevated body temperature. If left untreated, the breast becomes painful, and fever and flu-like symptoms develop. Breast infection due to bacteria (usually staphylococcus) may also occur. In extreme cases, breast abscesses develop. Home remedies for managing mastitis include application of fresh cabbage leaves to the affected breast. [0009] Mastitis is routinely treated by massage to increase blood circulation, expression of milk to loosen any plugged milk ducts, and the application of warmth to stimulate the local immune response. Pharmaceutical treatment typically includes analgesics - particularly acetaminophen or ibuprofen - to counter pain and tenderness. If necessary, antibiotics are administered to counter any bacterial infection. [0010] A well known home remedy for mastitis involves placing fresh cabbage leaves over the affected breast, either by wearing them inside a bra or nursing shirt, or laying the leaves over the breast during rest. US patent application 2008/0160115 describes a pad suitable for holding cabbage leaves or cabbage extracts against a woman's breast. US patent application 2007/0207197 discloses a topical composition for reducing symptoms of breast engorgement, mastitis, galactorrhea and other disorders, the composition comprising cabbage extract (preferably derived from Brassica olerances capitata) combined with a base cream having liposomes. [0011] According to US patent application 2004/0258778, constant exposure to cabbage leaves or their extracts is inadvisable because it may inhibit milk supply. The application teaches and discloses a topical composition for encouraging cessation of lactation, or reduction of breast engorgement, the composition comprising greater than wt% cabbage leaf extract.

4 [0012] Furthermore, in one controlled post-partum study the effectiveness of cabbage leaf extract was found to be no more effective than that of a placebo in treating breast engorgement in lactating women. (Roberts et al, J.Hum.Lact. 1998 14:231) [0013] US patent application 2007/0207197 discloses a topical composition for reducing symptoms of breast engorgement, mastitis, galactorrhea and other disorders, the composition comprising cabbage extract (preferably derived from Brassica olerances capitata) combined with a base cream having liposomes. [0014] Other formulations relying on natural substances are well known. For example, US patent 5,061,491 discloses a medicinal agent for the treatment of mastitis in animals and humans which includes a decoction of a mixture of medicinal herbs. However the formulation additionally includes ammonia and has an elevated pH which is not features generally associated with skin treatments. SUMMARY OF INVENTION [0015] An object of the present invention is to provide an improved composition for alleviating the symptoms of mastitis in a human subject. [0016] A further object of the present invention is to alleviate at least one disadvantage associated with the related art. [0017] It is an object of the embodiments described herein to overcome or alleviate at least one of the above noted drawbacks of related art systems or to at least provide a useful alternative to related art systems. [0018] In a first aspect of embodiments described herein there is provided a topical medicinal composition for alleviating the symptoms of mastitis, the composition comprising: - 0.5 to 95 wt% of an active comprising an extract of a mentha species, optionally a further naturally occurring active, 5 - 0.1 to 20 wt% dermal penetration vehicle, and - adjuvants. [0019] Preferably the active comprising an extract of a mentha species is present from 30 to 90 wt%, more preferably 35 to 85 wt%. [0020] The term 'alleviating the symptoms' as used herein is intended refer to reduction in severity or frequency of symptoms, or elimination, prevention or improvement of symptoms of mastitis. [0021] The term 'topical application' where used herein is intended to refer to mean application to the dermis of the skin in a specific area, in this case, the breast. Topical administration provides a local effect, and subsequent transdermal penetration may provide a local systemic effect. [0022] The composition includes all galenic forms conventionally used for applying a topical composition to the skin, such as for example, milk, cream, gel, lotion, ointment, solution, paste, plaster or patch. Topical delivery is particularly preferred because it is a convenient and provides good control over blood concentration of the active. It also avoids problems inherent in other dosage forms such as gastrointestinal irritation by oral dosages. [0023] Preferably the compositions are suitable for organic certification or include a predominance of naturally derived materials. Where used herein the term 'naturally derived' is intended to refer to naturally occurring materials such as plants and minerals and materials which are prepared from plants and minerals (in contradistinction to materials that are synthesised in a laboratory). [0024] Actives: Mentha (commonly known as Mint) is a genus of flowering plants of the lamiaceae (mint) family. Typically the mentha extract of the present invention is in the form of an oil, solution or suspension and may comprise one compound (such as menthol or menthone), or more commonly a complex mixture of compounds.

6 [0025] The substances that give the mints their characteristic aromas and flavors include menthol which imparts the main aroma to peppermint, menthone which contributes to the aroma of peppermint and pennyroyal, pulegone which imparts the main aroma of Pennyroyal and R-carvone which imparts the main aroma to spearmint. In one embodiment of the composition of the present invention the menthe extract has the aroma reduced by removal of the menthol, menthone, pufegone or R-carvone as appropriate. [0026] While it has previously been known to use peppermint for a range of gastro intestinal disorders (particularly colic in infants, flatulence, diarrhea, indigestion, nausea and vomiting), respiratory disorders (particularly congestion, coughs, bronchitis and inflammation of the oral mucosa, throat, anorexia, morning sickness, irritable bowl syndrome, Crohn's disease, ulcerative colitis, gallbladder and biliary tract disorders, liver complaints, gas and intestinal cramps) and neurological disorders (particularly neuralgia, myalgia, headaches and migraines) it has not hitherto been used as the principal active for injury or disorders such as mastitis in humans. [0027] More than two dozen species belong to the Mentha family. In a particularly preferred embodiment of the composition of the present invention the menthe species is chosen from the group comprising Mentha aquatic (watermint), Mentha arvensis (corn mint, wild mint, Japanese peppermint, field mint), Mentha asiatica (Asian mint), Mentha australis (Australian mint), Mentha Canadensis, Mentha cervina (Hart's pennyroyal) Mentha citrate (Bergamot mint), Mentha crispate (wrinkled leaf mint), Mentha cunninghamii, Mentha dahurica (Dahurian thyme) , Mentha diemenica (slender mint) Mentha gattefossei, Mentha grandiflora, Mentha haplocalys, Mentha japonica, Mentha kopetdaghensis, Mentha laxiflora (forest mint), Mentha longifolia (horse mint), Mentha piperita (peppermint), Mentha pulegium (pennyroyal), Mentha requienii (Corsican mint), Mentha sachalinensis (garden mint), Mentha satureioides (native pennyroyal) Mentha spicata (spearmint), Mentha suaveolens (apple mint), Mentha vagans (gray mint), and hybrids and combinations thereof. [0028] In a particularly preferred embodiment, the mentha species is chosen from the group comprising peppermint oil, dementholised peppermint oil and spearmint oil.

7 [0029] Optionally the mentha extract of the composition is combined with an active such as a dermal stimulant which may additionally act as a counter irritant. The active is preferably plant derived, such as from a culinary plant, such as a vegetable or a herb which may be used in any convenient form such as extracts, concentrates, juices or pulps. Preferably the active is a dermal stimulant and may additionally act as a counter irritant. [0030] Further active: In a preferred embodiment the menthe species is combined with a further active chosen from the group comprising cabbage extract, alfalfa, ginger, chamomile, raspberry leaf, capsicum, clove, rosemary, tea, coffee, aloe, celery, calendula and combinations thereof. [0031] In a particularly preferred embodiment the further active is chosen from cabbage leaf extract. At least a hundred different cabbage types exist, and although the composition of the present invention can include any of a wide variety of cabbages, cabbages of the type Brassica olerancea are particularly preferred. Preferably the composition includes cabbage as a juice, extract or pulp. [0032] In a second aspect of embodiments described herein there is provided a topical medicinal composition for alleviating the symptoms of mastitis, the composition comprising; - 0.5 to 50 wt%, of an active comprising an extract of a mentha species, and 0.5 to 90 wt% of cabbage extract, - 0.1 to 20 wt% dermal penetration vehicle, and - adjuvants. [0033] Preferably the mentha species is present at 1 to 5 wt% and the cabbage extract is present at 80 to 90 wt%. [0034] Dermal Penetration Vehicle: To have the desired effect when applied topically, an active must adequately penetrate the skin and be delivered to an 8 appropriate locus in the breast. However, the three principal layers of the skin - the stratum corneum, epidermis and papillary dermis - each have quite different structures and each pose quite different challenges for transport of an active. [0035] Where used herein the term dermall penetration vehicle' refers to carrier materials suitable as a transdermal or topical composition. Carrier materials useful herein include any such materials known in the art which are non-toxic and do not interact with other components of the composition in a deleterious manner. [0036] In the composition of the present invention, typically the dermal penetration vehicle is chosen from the group comprising lemon oil, citrus oils (oranges, grapefruit, citrus, eucalyptus oil, limonene, linalool, cinnamon oil, eugenia oil, galangal oil, cajeput oil, cardamom oil, melissa oil, myrtle oil, niaouli oil, wintergreen oil, methyl salicylate, volatile oils, mint oils, menthol, ethanol, alcohols, propylene glycol, fatty acids, fatty alcohols, terpenes fatty acid esters, and pyrrolidine derivatives, cyclodextrins, chitosan derivatives, solvent substances, dimethyl-sulfoxide (DMSO), urea, sodium lauryl sulphate, surfactant substances, squalene, cineole, ethyl acetate, glycofurol, lauric acid, mineral oil, linoleic acid, myristic acid, oleic acid, Isopropyl myristate, polycarbophil, polyoxyethylene alkyl ethers, (including cetomacrogol 1000, polyoxyl 6 cetostearyl ether, polyoxyl 20 cetostearyl ether, polyoxyl 25 cetostearyl ether, polyoxyl 2 cetyl ether, polyoxyl 10 cetyl ether, polyoxyl 20 cetyl ether, polyoxyl 4 lauryl ether, polyoxyl 9 lauryl ether, polyoxyl 23 lauryl ether, polyoxyl 2 oleyl ether, polyoxyl 10 oleyl ether, polyoxyl 20 oleyl ether, polyoxyl 2 stearyl ether, polyoxyl 10 stearyl ether, polyoxyl 21 stearyl ether, polyoxyl 100 stearyl ether) dimethylacetamide salicylates, quaternary ammonium compounds, medium chain fatty acids, medium chain glycerides, calcium binding agents, EDTA, azone, saponins, amines, amides, hydrocarbons, phospholipids, co-solvents such as benzyl alcohol, glycols, alkanones, polyols or combinations thereof. [0037] Penetration of the dermis can be optimized biochemically by pH adjustment or adjustment of osmotic differential. In particular, the composition may include pharmaceutically acceptable anionic, cationic or amphoteric substances, particularly pharmaceutically acceptable inorganic or organic bases.

9 [0038] The term 'effective amount' of dermal penetration vehicle for the present composition is intended to refer to a pharmaceutically acceptable amount that provides the desired skin permeability and desired depth of penetration, rate of administration. [0039] Adjuvants: Typically the adjuvants are those commonly used in cosmetology or dermatology to contribute any other attributes necessary to provide an effective delivery system so that the active reaches the tissue in which the pain or inflammation originate. In particular the adjuvants contribute to formation of a composition that is suitable for topical application, such as for example, milk, cream, gel, lotion, ointment, solution or paste and may be incorporated into a convenient delivery means such as a plaster or patch. [0040] Typically the adjuvants are chosen from the group comprising diluents, solvents, dispersion agents, suspension agents, colouring, flavouring, fragrance, preservatives, emollients, emulsification agents, emulsifiers, oils, rheology modification agents, stabilisers, preservatives, blockers, modifiers, antibacterial agents, anti fungal agents, antioxidants, enzyme cofactors, or other adjuvants considered to be cosmetically acceptable such as those included in The European Commission Cosmetic Ingredient database COSing http://ec.europa.eu/consumers/cosmetics/cosing/. [0041] Adjuvants such as stabilisers, preservatives, anti-microbial and anti-fungal agents may be necessary to prolong the shelf-life of the composition. Compositions according to preferred embodiments may natural preservatives that ensure antimicrobial activity and allow development of compositions having an appropriate and acceptable shelf-Iife. [0042] Suitable naturally occurring stabilisers may include, for example, aloe, artichoke, bilberry, blueberry, buckwheat, carotene, cat's claw, ciderberry, cranberry, curcumin, fennel, ginger, gingko, grape seed, hawthorn, lavender, lemon, lemon balm, licorice, lycopene, marjoram, melissa, mint, olive, oregano, peppermint, perilla, pine bark, pomegranate, rosemary, sage, St Mary's thistle, tea, thyme, turmeric, Vitamin E and witchhazel.

10 [0043] Suitable naturally occurring anti-microbial agents may include, for example, andrographis, apple, arnica, basil, bearberry, benzoates/benzoic acid, berberis, chamomile, chaste tree, chelidonium, cinnamon, citrus seed, clove, cranberry, eyebright, fennel, feverfew, forsythia, garlic, ginger, hops, hydrastis, lemongrass, licorice, melilotus, myrrh, onion, pau d'arco, peppermint, plums, rosemary, sage, scutellaria, thyme and turmeric. [0044] Suitable naturally occurring anti-fungal agents may include, for example. apple, arnica, cardamom, chaste tree, cheledonium, cinnamon, citrus seed, clove, cranberry, cumin, ginger, nettle, oregano, pau d'arco, peppermint, plums, rowan, sorbates/sorbic acid and tea tree. [0045] The composition may be formulated for any convenient physical conformation suitable for topical application. These include, for example oil-in-water emulsions, water in-oil emulsions, liposomes, including transferosomes, ethosomes and niosomes, and multilamellar vesicles. [0046] Further additives: The composition of the present invention may include additives that have an additional biological effect. For example vitamins such as Vitamin E may be added. [0047] Method: In another aspect of embodiments described herein there is provided a method of alleviating the symptoms of mastitis in a human subject, the method involving the step of applying a therapeutically effective amount of a composition according to the present invention to the breast of the subject at least once per day. [0048] Typically the application would be such that it delivered a therapeutically effective amount of the active for the alleviating of symptoms of mastitis. Where used herein the term 'therapeutically effective amount' is intended to mean a nontoxic but sufficient amount of the active to provide the desired alleviating effect. The amount that is 'effective' will vary from subject to subject and can be determined by one of ordinary skill in the art by routine trial and error.

11 [0049] Typically, topical application of the composition would be accompanied by massage following breastfeeding or expression of milk. The formulation may be applied directly to the skin, rolled or spread or massaged into the skin. Alternatively the composition could be applied under ice packs, heat packs or to medical dressings. It may also be applied to breast pads inserted inside a bra. The breast would typically be rinsed clean prior to breast feeding. [0050] Other aspects and preferred forms are disclosed in the specification and/or defined in the appended claims, forming a part of the description of the invention. [0051] In essence, embodiments of the present invention stem from the realisation that it is possible to successfully incorporate naturally occurring actives, in particular mentha extracts, into a topical application that effectively traverses the dermal barrier. [0052] Advantages provided by the present invention comprise the following: e the compositions of preferred embodiments are predominantly or exclusively formulated from naturally occurring components, and fully acceptable to regulatory authorities such as the Australian Therapeutic Goods Administration; * the compositions are simple to manufacture, providing high margins due to low costs of blending/mixing and packaging of the compositions; and a the compositions are topical and thereby include all the advantages associated with dermal and transdermal application and avoid disadvantages associated with other dosage forms such as oral dosages. [0053] Further scope of applicability of embodiments of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the disclosure herein will become apparent to those skilled in the art from this detailed description.

12 DETAILED DESCRIPTION [0054] The present invention will be further described and exemplified with reference to the following preferred compositions. [0055] Example 1: A composition according to the present invention was prepared using the following formulation: Table 1: Component Proportion Active Peppermint oil (or dementholised peppermint oil) 35 wt% Dermal Penetration Vehicle (as an emulsion) Lemon oil 0.5 wt% Eucalyptus oil 2 wt% Polysorbate 20 7 wt% Adjuvants Water To 100 wt% Salt 0.1 wt% Preservative 0.8 wt% Almond oil emollient 1.0 wt % Emulsifying wax 5 wt % [0056] The composition was prepared by combining the abovementioned amounts of wax phase ingredients, (peppermint oil, lemon oil, eucalyptus oil, almond oil and emulsifying wax) in a suitable heat resistant vessel and melting at 70 to 800C. This was carefully done a well ventilated space due to the irritating nature of peppermint oil fumes. [0057] In a separate heat resistant vessel, the aforementioned amounts of water and salt were combined and heated to 70 to 800C. [0058] The hot salt water was gradually introduced into the melted oils with rapid stirring to induce homogenisation. Once all the salt water had been added and 13 homogenised with the melted oils, the homogeneous combination was cooled with intermittent stirring. Once the blend cooled to below 40 0 C, the preservative was stirred in. Finally the cooled emulsion was apportioned into clean packaging materials. [0059] Example 2: A further composition according to the present invention was prepared using the following formulation: Table 2: Component Proportion Active Cabbage leaf juice 85 wt% Mint oil 2 wt% Dermal Penetration Vehicle Methyl salicylate (oil of wintergreen) 0.1 wt% Polysorbate 80 (as surfactant) 2 wt% Adjuvants Water To 100 wt% Sepigel 305 1.5 wt% Preservative 0.8 wt% [0060] The composition was prepared by solubilising the oils (peppermint oil and wintergreen oil) in the surfactant. [0061] The cabbage leaf juice was then filtered to exclude particulates and microbial contaminants. The Sepigel 305, preservative, additional water and solubilised oils where then added to the cabbage juice and stirred until homogeneous. The resultant composition was encapsulated in clean packaging materials. [0062] Example 3: A further composition according to the present invention was prepared using the following formulation which uses a cold emulsifier and jojoba oil, which has a lipid profile similar to human skin and thus provides a more nourishing emollient: 14 Table 3: Component Proportion Active Dementholised peppermint oil 35 wt% Dermal Penetration Vehicle Ethanol 20 wt% Adjuvants Aracel 2121 (as emulsifier) 5.5 wt% Jojoba Oil (emollient) 35 wt% Preservative 0.8 wt% [0063] Aracel 2121 is incorporated into a mixture of peppermint and jojoba oils. The remaining combined ingredients are then added with mixing sufficient to form a uniform emulsion. The composition was then stored in clean packaging. [0064] While this invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modification(s). This application is intended to cover any variations uses or adaptations of the invention following in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains and as may be applied to the essential features hereinbefore set forth. [0065] As the present invention may be embodied in several forms without departing from the spirit of the essential characteristics of the invention, it should be understood that the above described embodiments are not to limit the present invention unless otherwise specified, but rather should be construed broadly within the spirit and scope of the invention as defined in the appended claims. The described embodiments are to be considered in all respects as illustrative only and not restrictive. [0066] Various modifications and equivalent arrangements are intended to be included within the spirit and scope of the invention and appended claims. Therefore, 15 the specific embodiments are to be understood to be illustrative of the many ways in which the principles of the present invention may be practiced. [0067] "Comprises/comprising" and "includes/including" when used in this specification is taken to specify the presence of stated features, integers, steps or components but does not preclude the presence or addition of one or more other features, integers, steps, components or groups thereof. Thus, unless the context clearly requires otherwise, throughout the description and the claims, the words 'comprise', 'comprising', 'includes', 'including' and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of "including, but not limited to".

Claims (5)

1. A topical medicinal composition for alleviating the symptoms of mastitis, the composition comprising: - 0.5 to 95 wt% of an active comprising an extract of a mentha species, optionally including a further naturally occurring active, - 0.1 to 20 wt% dermal penetration vehicle, and - adjuvants.

2. A medicinal composition according to claim 1 wherein the further naturally occurring active is a cabbage extract, and wherein the major proportion of the composition is naturally derived.

3. The medicinal composition according to claim 1 or claim 2 when used to alleviate the symptoms of mastitis, wherein the extract of a mentha species is chosen from the group comprising spearmint, peppermint, mint, dementholised peppermint oil or combinations thereof.

4. A method of alleviating the symptoms of a breast disorder in a subject, the method involving the step of applying a therapeutically effective amount of the composition of any one of claim 1 or claim 2 to the affected breast of the subject at least once per day.

5. A method of manufacturing a medicinal composition according to claim 1 or claim 2 comprising the steps of: (i) isolating an extract of a mentha species, (ii) combining the extract of a mentha species with a dermal penetration vehicle and adjuvants.