AU2013202114B2 - Acne treatment - Google Patents

Abstract

The present application relates to a composition comprising pantothenic acid (vitamin B5), or a pharmaceutically acceptable derivative, salt or prodrug thereof; folic acid (vitamin B9); nicotinamide; a source of copper; and a source of zinc. The composition may further include biotin, vitamin A, silicon and/or Vitex angus-castus. The composition can be used in a method for reducing, treating and/or preventing acne and/or related skin disorders. Additionally, the composition can be used in a method for reducing, treating and/or preventing the appearance of acne and/or related skin disorders on the skin.

Description

1 AUSTRALIA Patents Act 1990 STRITECH HOLDINGS PTY LTD COMPLETE SPECIFICATION STANDARD PATENT Invention Title: Acne treatment The following statement is a full description of this invention including the best method of performing it known to us: - 2 Technical Field [01] The present application relates to a composition comprising pantothenic acid, or a pharmaceutically acceptable derivative, salt or prodrug thereof; folic acid; nicotinamide; a source of copper; and a source of zinc. The composition can be used in a method for reducing, treating and/or preventing acne and/or related skin disorders. Additionally, the composition can be used in a method for reducing, treating and/or preventing the appearance of acne and/or related skin disorders on the skin. Background [02] Acne is a common skin condition in which the skin pores become clogged leading to pimples and inflammation, often including infected abscesses. [03] Acne is a condition sometimes suffered during the teenage years due to an interaction of hormones, skin oils and bacteria that live on and in the skin and in the hair. These subcutaneous glands in the skin during puberty become more active and can produce sebum. The development of sebum, being in the form of an excessive oil accumulation can sometimes dry, resulting in flaked skin and bacteria collecting in the skin pores and forming a comedo. The formation of a comedo blocks sebum from flowing from the hair follicles up to the pores, resulting in the formation of blackheads and sometimes whiteheads. Bacteria are then able to grow in the plugged pores and break down some of the fats in the sebum causing further irritation to the skin. [04] Whilst traditionally acne has not been associated with diet, little in the way of positive treatment is known and the appearance of acne which can sometimes lead to deep acne and can result in considerable distress and possible disfigurement in sufferers. [05] The pathogenesis of acne is currently being challenged where diet is being suggested as contributing to a development and retention of acne; in particular, in relation to the fat content of a patient's diet, where the interaction of cholesterol and acetyl-CoA have indicated in some teachings that pantothenic acid may contribute to the treatment of acne. Such a hypothesis is presented in the journal of Orthomolecular Medicine, Volume 12, Number 2, 3 1997, by Lit-Hung Leung, M.D. entitled Pantothenic Acid in the Treatment ofAcne Vulgaris "A Medical Hypothesis ", which is herein incorporated by reference. [06] Current oral acne control products on the market contain very high amounts of pantothenic acid (vitamin B5). The current dosage levels are approximately 2000 times the recommended daily dietary intake of 4 - 6 mg/day. Such high dosages of pantothenic acid can cause serious side effects such as stomach irritation and diarrhoea. No formulations currently exist that contain lower levels of pantothenic acid that also remain effective for acne treatment. Formulating a more effective oral acne control product with a lower dose of pantothenic acid would help acne sufferers control a persistent problem with decreased risk of side effects. [07] Therefore, there is a need and a demand for an improved oral product for the treatment and/or prevention of acne that uses lower amounts of pantothenic acid as an active ingredient and accordingly has reduced risk of side effects. [08] Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification 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. [09] 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.

4 Surnmaiy 19a] n one aspecttere improved a compositin vhen used for the treatment of acne comprising pantorhenic acid a pharmaceuilly acceptable derivative salt o prodrug folic acid: nicotinamide' a source of copper; and a souce of inc. i] In another speo there is provided a composition when usedor the treatment Moacne com prising the b owing Component Amount (weight %) Biotin -, --- 02 - 003 Calcium pantothenate 37 - 45 Folic-acid 0.005 - 0.008 Viamin A acetate 0.05 - 0.08 Silicondioxide 0.70 -0,90 Co-pper gluct .10atf - 020 Nicotinamide 9 - 1 2 Zinc guconate 2.5 --- 3.0 [Pc] In another aspect there is provided a composition when used for the treatment of acne comprising theiolwing ...- iotin 0.03 - 0.05 Calciu-ptothenate 18 - 23 V Folic Acid 0.01 - 0.02 Vite agnus-casius (fruit extract dry concentrate 10:1-- -- ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 0 0 - - 30- in 50% ethanol and 50% ___water _____________ Silicon Dioxide 1 - .5 Copper Gluconate f 0.15 - 0.30 -- conamide 12- 16 Zinc Gluconate - 7 - 8- 9Pd] In another aspect there is provided a composition when used for the treatment of acne comprising the following: Component Amount Biotin 330 -413 p~g Calcium pantothenate 500 -- 600 m , Folic acid 80 -104 pig Vtan A acetate 760 - 180 [t Silicon dioxide 10 - 1 2 rmg Copper gluconate ___ 1 -3 mg& Nictiamde125 -150 mg ___ Zincegluconate 134 - 39 mg [Pc In another aspect there is provided a composition when used for the treatment of acne Biotin 30-43p Calcium pantothenate 1181 -219 mg ____-Folic acid 97-I3 Vitex agnus-castus (fruit9-13an ___ extract dry concentrate 10:101-3m in 50% ethanol and 50% water Silicn dioxide 1 0 - 12 mng Coppr gluconatc 1 - 3 mgt Nicotinamide j 125 -150 mug Zinc gluconate __ 69 -~ 77 mg 0| in one aspect there is provided a composition for the treatment of acne comprising: antotemi acio, o a phanaceutically acceptable derAnve salt or prodrug thereof; foic aid nicotinarnide a source of copper and a source of Zinc. [111 In another aspect there is pro ided a composit1n for the treatment of acne comprising the following: Biotin 0 - 0,03 Calcium pantothenate 37 45 acid 0,05 - 0,008 Vitamin A acetate ,05 -0,08 Silicon dioxide - 0.7 - 0,90 Copper gluconate 0,10-0,20 Nicotinamide 9 - 12 Zinc gluconate 2,5 -3,0 [121 In another aspect there is provided a composition for the treatment of acne comprising the following: omponet Amount (wet%) Biotin 0.03 - 0,05 alic p an-otenat -18 -. 2 Coppe Ain 0.01 - 0.0 -Nie---n-n---de--------12 ---- extrac ryconate __ 7 10: in 0% thaol nd 50 Wa tr a SnDioide 12- 1, Zinecont 7 8 {13] In another aspect there is provided a composition for the treatment of acne comprising the following: $b Com ponent Amount Biotin 330 - 413 pg Calcium pantothenate 50-60m Folic acid 80 -104 pg Vitamin A acetate 760 -1080 pg Silicon dioxide 10 -12 mg Caopperuconate 1-3mg Nicotinamide 125 - 150 m Zinc gluconate 34-39 mg } [1 41 In another aspect there is provided a composition for the treatment of acne comprising the following: Component Amount Biotin 330 - _413 g - Calcium pantothenate 3 13 - k g 2101k acid 9 7

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1 6 g Vitex agnus-castus (fruit extract dry concentrate 1 0:1 0 in 50% ethanol and 50% * Silicon dioxide 10 -12 mrg * Copper gluconate 1 -3 mg Nicotinamide ~--125 -150 mg Zinc gluconate- 6- ---77g [15 In yetanother aspectnthere is provided a method of reducing, treating and/or preventing acne and/or related skin disordersconmprising the administation otfa composition to a subject in need of such treatment [161 In yet another aspect there is provided a method of reducing, treating and/or preventing the appearance of aCne ard or related skin disorders on the skin comprising the administration of a composition to a subject in need of such treatment.

6 [17] In a further aspect there is provided the use of a composition for the manufacture of a medicament for the reduction, treatment and/or prevention of acne and/or related skin disorders. [18] In a further aspect there is provided the use of a composition for the manufacture of a medicament for the reduction, treatment and/or prevention of the appearance of acne and/or related skin disorders on the skin. [19] In yet a further aspect there is provided a composition when used for the reduction, treatment and/or prevention of the appearance of acne and/or related skin disorders on the skin. Description of Embodiments [20] The present application provides an improved composition for the treatment of acne. The composition comprises pantothenic acid, or a pharmaceutically acceptable derivative, salt or prodrug thereof; folic acid; nicotinamide; a source of copper; and a source of zinc. [21] The inventors have surprisingly found that the composition of the present application is effective in the treatment of acne but does not appear to result in the side effects of stomach irritation and diarrhoea which are commonly demonstrated in the use of current acne therapies containing high doses of pantothenic acid. The inventors have found that the combination of components as described in the present composition can be used to deliver a lower dose of pantothenic acid whilst still maintaining efficacy in the treatment of acne. Additionally, the present composition demonstrates good product stability and shelf life. [22] The compositions comprise pantothenic acid, or a pharmaceutically acceptable derivative, salt or prodrug thereof.

7 [23] With respect to pantothenic acid, the term "pharmaceutically acceptable derivative" may include any pharmaceutically acceptable salt, hydrate, solvate, or prodrug, or any other compound which upon administration to a subject, is capable of providing (directly or indirectly) a compound of pantothenic acid or an active metabolite or residue thereof. [24] As used herein the term "salt" includes base addition, acid addition and quaternary salts. Suitable pharmaceutically acceptable salts include, but are not limited to, salts of pharmaceutically acceptable inorganic acids such as hydrochloric, sulphuric, phosphoric, nitric, carbonic, boric, sulfamic, and hydrobromic acids, or salts of pharmaceutically acceptable organic acids such as acetic, propionic, butyric, tartaric, maleic, hydroxymaleic, fumaric, malic, citric, lactic, mucic, gluconic, benzoic, succinic, oxalic, phenylacetic, methanesulphonic, toluenesulphonic, benzenesulphonic, salicylic, sulphanilic, aspartic, glutamic, edetic, stearic, palmitic, oleic, lauric, pantothenic, tannic, ascorbic and valeric acids. [25] Base salts include, but are not limited to, those formed with pharmaceutically acceptable cations, such as sodium, potassium, lithium, calcium, magnesium, zinc, ammonium, alkylammonium such as salts formed from triethylamine, alkoxyammonium such as those formed with ethanolamine and salts formed from ethylenediamine, choline or amino acids such as arginine, lysine or histidine. [26] Basic nitrogen-containing groups may be quarternised with such agents as lower alkyl halide, such as methyl, ethyl, propyl, and butyl chlorides, bromides and iodides; dialkyl sulfates like dimethyl and diethyl sulfate, and others. [27] General information on types of pharmaceutically acceptable salts and their formation is known to those skilled in the art and is as described in general texts such as "Handbook of Pharmaceutical salts" P.H.Stahl, C.G.Wermuth, 1st edition, 2002, Wiley-VCH. [28] The term "solvate" is used herein to describe a molecular complex comprising the compound and a stoichiometric amount of one or more pharmaceutically acceptable solvent molecules, for example, ethanol. The term "hydrate" is employed when said solvent is water. [29] The term "prodrug", is used herein to describe derivatives of compounds which may have little or no pharmacological activity themselves but which, when administered into or 8 onto the body, are converted into compounds having the desired activity, for example, by hydrolytic cleavage. Further information on the use of prodrugs may be found in "Pro-drugs as Novel Delivery Systems", Vol. 14, ACS Symposium Series (T. Higuchi and W. Stella) and Bioreversible Carriers in Drug Design, Pergamon Press, 1987 (ed. E. B. Roche, American Pharmaceutical Association). [30] Prodrugs can, for example, be produced by replacing appropriate functionalities present in a compound with certain moieties known to those skilled in the art as 'pro moieties' as described, for example, in "Design of Prodrugs" by H. Bundgaard (Elsevier, 1985). For example, compounds having free amino, amido, hydroxy or carboxylic groups can be converted into prodrugs. [31] Prodrugs include compounds wherein an amino acid residue, or a polypeptide chain of two or more (eg, two, three or four) amino acid residues which are covalently joined to free amino, hydroxy and carboxylic acid groups. Prodrugs also include compounds wherein carbonates, carbamates, amides and alkyl esters are covalently bonded to amino, hydroxy and carboxylic acid groups. Prodrugs also include phosphate derivatives (such as acids, salts of acids, or esters) joined through a phosphorus oxygen bond to a free hydroxyl group. [32] Examples of pantothenic acid, a pharmaceutically acceptable derivative, salt or prodrug thereof, suitable for use in the present compositions include, but are not limited to, pantothenic acid, calcium pantothenate and pantothenol. In a specific embodiment, the pantothenic acid, a pharmaceutically acceptable derivative, salt or prodrug thereof, is calcium pantothenate. [33] The compositions can comprise the pantothenic acid, or a pharmaceutically acceptable derivative, salt or prodrug thereof, in an amount sufficient to provide an amount of pantothenic acid of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48, 49 and 50% by weight of the composition, or a range comprising any of two of those integers. In one embodiment, the compositions comprise an amount of pantothenic acid of from about 1% to about 50% by weight of the composition. In another embodiment, the compositions comprise an amount of pantothenic acid of from about 30% to about 45% by weight of the 9 composition. In yet another embodiment, the compositions comprise an amount of pantothenic acid of from about 10% to about 30% by weight of the composition. [34] The compositions can comprise the pantothenic acid, or a pharmaceutically acceptable derivative, salt or prodrug thereof, in an amount sufficient to provide an amount of pantothenic acid of 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250,260,270,280,290,300,310,320,330,340,350,360,370,380,390,400,410,420,430, 440,450,460,470,480,490,500,510,520,530,540,550,560,570,580,590,600,610,620, 630, 640, 650, 660, 670, 680, 690 and 700 mg, or a range comprising any of two of those integers. In one embodiment, the compositions comprise an amount of pantothenic acid of from about 100 mg to about 700 mg. In another embodiment, the compositions comprise an amount of pantothenic acid of from about 100 mg to about 250 mg. In yet another embodiment, the compositions comprise an amount of pantothenic acid of from about 350 mg to about 700 mg. [35] The compositions comprise folic acid. Folic acid is also known as folate, vitamin M, vitamin B 9 , vitamin Bc (or folacin), pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid. [36] The compositions can comprise folic acid in an amount of 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.015, 0.02, 0.025, 0.03, 0.035, 0.04, 0.045, 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, 0.095 and 0.1% by weight of the composition, or a range comprising any of two of those integers. In one embodiment, the compositions comprise folic acid in an amount of from about 0.00 1% to about 0. 1% by weight of the composition. In another embodiment, the compositions comprise folic acid in an amount of from about 0.001% to about 0.02% by weight of the composition. [37] The compositions can comprise folic acid in an amount of 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145 and 150 pg, or a range comprising any of two of those integers. In one embodiment, the compositions comprise folic acid in an amount of from about 50 pg to about 150 pg. In another embodiment, the compositions comprise folic acid in an amount of from about 60 pg to about 120 pg. In yet another embodiment, the compositions comprise folic acid in an amount of from about 70 pg to about 150 pg.

10 [38] The compositions comprise nicotinamide. Nicotinamide is also known as niacinamide and nicotinic acid amide and is the amide of nicotinic acid (vitamin B3 / niacin). [39] The compositions can comprise nicotinamide in an amount of 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5 and 20% by weight of the composition, or a range comprising any of two of those integers. In one embodiment, the compositions comprise nicotinamide in an amount of from about 5% to about 20% by weight of the composition. In another embodiment, the compositions comprise nicotinamide in an amount of from about 8% to about 18% by weight of the composition. [40] The compositions can comprise nicotinamide in an amount of 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195 and 200 mg, or a range comprising any of two of those integers. In one embodiment, the compositions comprise nicotinamide in an amount of from about 50 mg to about 200 mg. In another embodiment, the compositions comprise nicotinamide in an amount of from about 110 mg to about 160 mg. [41] The compositions comprise a source of copper. Examples of suitable sources of copper include, but are not limited to, copper gluconate, copper sulphate, copper acetate and copper citrate. In one embodiment the source of copper is copper gluconate. [42] The compositions can comprise copper in an amount of 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.015, 0.02, 0.025, 0.03, 0.035, 0.04, 0.045 and 0.05% by weight of the composition, or a range comprising any of two of those integers. In one embodiment, the compositions comprise copper in an amount of from about 0.001% to about 0.05% by weight of the composition. In another embodiment, the compositions comprise copper in an amount of from about 0.005% to about 0.03% by weight of the composition. [43] The compositions can comprise copper in an amount of 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, 295 and 300 pg or a range comprising any of two of those integers. In one embodiment, the compositions comprise copper in an amount of from about 200 pg to about 300 pg. In another embodiment, the compositions comprise copper in an amount of about 225 pg to 275 pg.

11 [44] The compositions comprise a source of zinc. Examples of suitable sources of zinc include, but are not limited to, zinc gluconate, zinc sulphate, zinc acetate and zinc citrate. In one embodiment the source of zinc is zinc gluconate. [45] The compositions can comprise zinc in an amount of 0.05, 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40, 0.45, 0.50, 0.55, 0.60, 0.65, 0.70, 0.75, 0.80, 0.85, 0.90, 0.95, 1.0, 1.05, 1.10, 1.15, 1.20, 1.25, 1.30, 1.35, 1.40, 1.45, 1.50, 1.55, 1.60, 1.65, 1.70, 1.75, 1.80, 1.85, 1.90, 1.95 and 2.0% by weight of the composition, or a range comprising any of two of those integers. In one embodiment, the compositions comprise zinc in an amount of from about 0.05% to about 2% by weight of the composition. In another embodiment, the compositions comprise zinc in an amount of from about 0. 1% to about 1.50% by weight of the composition. [46] The compositions can comprise zinc in an amount of from about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5 and 20 mg or a range comprising any of two of those integers. In one embodiment, the compositions comprise zinc in an amount of from about 1 mg to about 20 mg. In another embodiment, the compositions comprise zinc in an amount of from about 5 mg to about 15 mg. [47] In one aspect, the compositions comprise biotin. Biotin is also known as vitamin H or coenzyme R. The compositions may comprise biotin in an amount of 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.015, 0.02, 0.025, 0.03, 0.035, 0.04, 0.045, 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, 0.095 and 0.1% by weight of the composition, or a range comprising any of two of those integers. In one embodiment, the compositions comprise biotin in an amount of from about 0.00 1% to about 0. 1% by weight of the composition. In another embodiment, the compositions comprise biotin in an amount of from about 0.01% to about 0.05% by weight of the composition. [48] The compositions may comprise biotin in an amount of 200, 210, 220, 230, 240, 250, 260,270,280,290,300,310,320,330,340,350,360,370,380,390,400,410,420,430,440, 450, 460, 470, 480, 490, and 500 pg or a range comprising any of two of those integers. In one embodiment, the compositions comprise biotin in an amount of from about 200 pg to about 500 pg. In another embodiment, the compositions comprise biotin in an amount of from about 300 pg to about 450 pg.

12 [49] In one aspect, the compositions comprise a form of vitamin A. Examples of forms of vitamin A suitable for use in the compositions include, but are not limited to, vitamin A acetate, retinol, retinoic acid, retinyl acetate, retinyl palmitate and beta-carotene. In one embodiment, the form of vitamin A is Vitamin A acetate. [50] The compositions may comprise a form of vitamin A in an amount of 0.001, 0.002, 0.003, 0.004, 0.004, 0.005, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.015, 0.02, 0.025, 0.03, 0.035, 0.04, 0.045, 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, 0.095, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45 and 0.5% by weight of the composition, or a range comprising any of two of those integers. In one embodiment, the compositions comprise a form of vitamin A in an amount of from about 0.0010% to about 0.50% by weight of the composition. In another embodiment, the compositions comprise a form of vitamin A in an amount of from about 0.010% to about 0.10% by weight of the composition. [51] The compositions may comprise a form of vitaminA in an amount of 50, 60, 70, 80, 90,100,110,120,130,140,150,160,170,180,190,200,210,220,230,240,250,275,300, 325,350,375,400,425,450,475,500,525,550,575,600,625,650,675,700,725,750,775, 800, 825, 850, 875, 900, 925, 950, 975, 1000, 1025, 1050, 1075, 1110, 1125, 1150, 1175 and 1200 pg or a range comprising any of two of those integers. In one embodiment, the compositions comprise a form of vitamin A in an amount of from about 50 pg to about 1200 pg. In another embodiment, the compositions comprise a form of vitamin A in an amount of from about 700 pg to about 1100 pg. [52] In one aspect, the compositions comprise silicon. Examples of forms of silicon suitable for use in the compositions include, but are not limited to, silicon dioxide, orthosilicic acid and choline-stabilized orthosilicic acid. In one embodiment, the form of silicon is silicon dioxide. [53] The compositions may comprise silicon in an amount of 0.01, 0.015, 0.02, 0.025, 0.03, 0.035, 0.04, 0.045, 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, 0.095, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 and 2% by weight of the composition, or a range comprising any of two of those integers. In one embodiment, the compositions comprise silicon in an amount of from about 0.01% to about 2% by weight of 13 the composition. In another embodiment, the compositions comprise silicon in an amount of from about 0.5% to about 1.5% by weight of the composition. [54] The compositions may comprise silicon in an amount of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 and 50 mg or a range comprising any of two of those integers. In one embodiment, the compositions comprise silicon in an amount of from about 1 mg to about 50 mg. In another embodiment, the compositions comprise silicon in an amount of from about 1 mg to about 10 mg. [55] In one aspect, the compositions comprise Vitex angus-castus. Vitex agnus-castus (VAC, Chasteberry) is a supplement derived from the berries of the chaste tree. Examples of suitable forms of Vitex agnus-castus include, but are not limited to, a dry fruit extract and a fruit extract dry concentrate 10:1 in 50% ethanol and 50% water. In one embodiment, the Vitex agnus-castus is a fruit extract dry concentrate 10:1 in 50% ethanol and 50% water. In a further embodiment, the Vitex agnus-castus fruit extract dry concentrate comprises 1.5 mg of Vitex agnus-castus. [56] The compositions may comprise Vitex angus-castus in an amount of 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9 and 5.0 % by weight of the composition, or a range comprising any of two of those integers. In one embodiment, the compositions comprise silicon in an amount of from about 0.01% to about 5% by weight of the composition. In another embodiment, the compositions comprise Vitex angus-castus in an amount of from about 0.05% to about 1% by weight of the composition. [57] The compositions may comprise Vitex angus-castus in an amount of 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 and 100 mg or a range comprising any of two of those integers. In one embodiment, the compositions comprise Vitex angus-castus in an amount of from about 0.1 mg to about 100 mg. In another embodiment, the compositions comprise Vitex angus-castus in an amount of from about 1 mg to about 10 mg.

14 [58] Further optional excipients may also be included in the compositions. Such optional excipients include, but are not limited to, antiadherents, binders, coatings, disintegrants, fillers, flavours, colours, lubricants, glidants, sorbents, preservatives and sweeteners. Examples of binders include, but are not limited to, sugars (such as mono- and disaccharides, polysaccharides, and their derivatives including starches, cellulose such as microcrystalline cellulose and cellulose ethers such as hydroxypropyl cellulose), sugar alcohols (such as xylitol, sorbitol and maltitol), proteins (such as gelatin) and polymers (such as PVP, crospovidone, polyethylene glycols and polypropyleneglycols). Examples of coatings include, but are not limited to, cellulose ethers (such as hydroxypropoyl methyl cellulose), synthetic polymers, shellac, gelatin, polysaccharides and coating systems available under the tradename Opadry*. Examples of disintegrants include, but are not limited to, starches (such as sodium starch glycolate), and cross-linked polymers, (such as crospovidone and croscarmellose sodium). Examples of fillers include, but are not limited to, fats and oils, calcium phosphate, dibasic calcium phosphate, lactose, sucrose, glucose, mannitol, sorbitol, calcium carbonate and magnesium stearate. Examples of lubricants include, but are not limited to, talc, silica, fats (such as vegetable stearin, magnesium stearate and stearic acid). Examples of glidants include, but are not limited to, silica, talc, and magnesium carbonate. Examples of sorbents include, but are not limited to, fatty acids, waxes, shellac, plastics, and plant fibers. Examples of preservatives include, but are not limited to, antioxidants, the amino acids cysteine and methionine, citric acid and sodium citrate, and parabens (such as methyl paraben and propyl paraben). In one embodiment, the optional excipients include, but are not limited to, calcium phosphate, calcium hydrogen phosphate, microcrystalline cellulose, crospovidone, magnesium stearate and Opadry* coatings. [59] In one aspect, the compositions comprising pantothenic acid, or a pharmaceutically acceptable derivative, salt or prodrug thereof; folic acid; nicotinamide; a source of copper; and a source of zinc are in a dosage form selected from the group consisting of, but not limited to, a tablet, caplet, capsule, gel cap, pellet and granule. In one embodiment, the dosage form is a caplet. In a specific embodiment, the caplet weighs from about 900 mg to about 1100 mg. In another embodiment, the dosage form is a tablet. In a specific embodiment, the tablet weighs from about 1200 mg to about 1500 mg. In another embodiment, the dosage form is a coated caplet or a coated tablet. In yet another embodiment, the dosage form is an oral dosage form.

15 [60] In one aspect, the compositions comprising pantothenic acid, or a pharmaceutically acceptable derivative, salt or prodrug thereof; folic acid; nicotinamide; a source of copper; and a source of zinc are used in a method for reducing, treating and/or preventing acne and/or related skin disorders. Acne related skin disorders includes other follicular disorders and acne like skin conditions which would be known to a skilled person. [61] The method for reducing, treating and/or preventing acne and/or related skin disorders comprises the administration of a composition to a subject in need of such treatment. In one embodiment, the method for reducing, treating and/or preventing acne and/or related skin disorders on the skin comprises administration of the composition to the subject orally. In another embodiment, administration of the composition provides to the subject pantothenic acid in an amount of between about 2.5 g and about 3.5 g per day. In a specific embodiment, administration of the composition provides to the subject pantothenic acid in an amount of about 3 g per day. In a further embodiment, administration of the composition provides to the subject pantothenic acid in an amount of between about 400 mg and about 600 mg per day. In a specific embodiment, administration of the composition provides to the subject pantothenic acid in an amount of about 500 mg per day. [62] The compositions may be used in a method relating to the following types of acne: acne vulgaris (common acne, including blackheads and whiteheads), cystic acne, nodulocystic acne, acne excorie6, acne fulminans, infantile acne (acne in babies), acne in pregnancy, acne due to medicines, adult acne, acne scarring, chloracne, comedonal acne and pyoderma faciale. Acne related skin disorders include skin conditions that appear similar to acne. Such skin conditions include, but are not limited to, acne keloidalis nuchae (acne cheloidalis), acne necrotica (scalp folliculitis), acne urticata (itchy spots), comedone naevus, cysts, disseminate and recurrent infundibulofolliculitis , folliculitis, gram negative folliculitis, hidradenitis suppurativa, hot tub (spa pool) folliculitis, keratosis pilaris, lichen spinulosus, miliaria (sweat rash), neonatal cephalic pustulosis, oil folliculitis, perioral dermatitis (muzzle rash), pityrosporum folliculitis, pseudofolliculitis barbae, pustular tinea, rosacea, sebaceous, hyperplasia, solar (senile) comedones, seborrhoea (oily skin), staphylococcal folliculitis, steatocystoma multiplex, steroid acne, steroid rosacea and trichostasis spinulosa. [63] In another aspect, the compositions comprising pantothenic acid, or a pharmaceutically acceptable derivative, salt or prodrug thereof; folic acid; nicotinamide; a source of copper; 16 and a source of zinc are used in a method for reducing, treating and/or preventing the appearance of acne and/or related skin disorders on the skin. [64] The method for reducing, treating and/or preventing the appearance of acne and/or related skin disorders on the skin comprises the administration of a composition to a subject in need of such treatment. In one embodiment, the method for reducing, treating and/or preventing the appearance of acne and/or related skin disorders on the skin comprises administration of the composition to the subject orally. In another embodiment, administration of the composition provides to the subject pantothenic acid in an amount of between about 2.5 g and about 3.5 g per day. In a specific embodiment, administration of the composition provides to the subject pantothenic acid in an amount of about 3 g per day. In a further embodiment, administration of the composition provides to the subject pantothenic acid in an amount of between about 400 mg and about 600 mg per day. In a specific embodiment, administration of the composition provides to the subject pantothenic acid in an amount of about 500 mg per day. [65] In one aspect, the composition comprising pantothenic acid, or a pharmaceutically acceptable derivative, salt or prodrug thereof; folic acid; nicotinamide; a source of copper; and a source of zinc are used for the manufacture of a medicament for the reduction, treatment and/or prevention of acne and/or related skin disorders. [66] In another aspect, the composition comprising pantothenic acid, or a pharmaceutically acceptable derivative, salt or prodrug thereof; folic acid; nicotinamide; a source of copper; and a source of zinc are used for the manufacture of a medicament for the reduction, treatment and/or prevention of the appearance of acne and/or related skin disorders on the skin. Examples [67] Tables 1 to 4 provide example compositions comprising pantothenic acid, or a pharmaceutically acceptable derivative, salt or prodrug thereof; folic acid; nicotinamide; a source of copper; and a source of zinc.

17 [68] Table 1: Example Composition 1. Component Amount (weight %) Amount (pg/mg) Biotin 0.025 330 pg Calcium pantothenate 37 500 mg Folic acid 0.006 80 pg Vitamin A acetate 0.057 765 pg Silicon dioxide 0.8 10.7 mg Copper gluconate 0.13 1.8 mg Nicotinamide 9.3 125 mg Zinc gluconate 2.6 34.9 mg [69] Table 2: Example Composition 2. Component Amount (weight %) Amount (pg/mg) Biotin 0.03 330 pg Calcium pantothenate 18.8 181.8 mg Folic Acid 0.01 97 pg Vitex agnus-castus (fruit extract dry concentrate 10:1 in 0.15 1.5 mg 50% ethanol and 50% water Silicon Dioxide 1.1 10.7 mg Copper Gluconate 0.19 1.8 mg Nicotinamide 12.9 125 mg Zinc Gluconate 7.2 69.8 mg [70] Table 3: Example Composition 3. Component Amount (weight %) Amount (pg/mg) Biotin 0.03 412.5 pg Calcium pantothenate 45 600 mg Folic acid 0.0077 103.2 pg Vitamin A acetate 0.08 1071 pg Silicon dioxide 0.85 11.4 mg Copper gluconate 0.13 1.8 mg Nicotinamide 11.2 150 mg Zinc gluconate 2.8 38.2 mg 18 Table 4: Example Composition 4. Component Amount (weight %) Amount (pg/mg) Biotin 0.04 412.5 pg Calcium pantothenate 22.6 218.2 mg Folic acid 0.014 135.6 pg Vitex agnus-castus (fruit extract dry concentrate 10:1 in 0.16 1.5 mg 50% ethanol and 50% water Silicon dioxide 1.18 11.4 mg Copper gluconate 0.19 1.8 mg Nicotinamide 15.5 150 mg Zinc gluconate 7.93 76.7 mg [71] The following provide examples of the use of compositions in methods for treating acne. [72] Example 1: A subject suffering from cystic acne was administered Example composition 1, according to the regime of 2 dosages, three times a day to deliver an amount of pantothenic acid of about 3 g per day. The subject observed that their acne lessened significantly. [73] Example 2: A subject suffering from acne was administered Example composition 2, according to the regime of 1 dosage, three times a day to deliver an amount of pantothenic acid of about 500 mg per day. The subject observed a reduction in the appearance of their acne. [74] It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the above-described embodiments, without departing from the broad general scope of the present disclosure. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims (9)

1. 2. A composition according to claim 1 wherein the pantothenic acid, or a pharmaceutically acceptable derivative, salt or prodrug thereof, is selected from the group con si sting of pantothenic acid, calcium pantothenate and pan tothenol. 3 A composition according to claim I or 2, wherein the source of copper is selected from the group consisting of copper gluconate. copper sulphate, copper acetate and copper citrate.
2. 4. A composition according to any one of claims I to 3. wherein the source of zinc is selected from the group consisting of zinc gluconate, zinc sulphate. zinc acetate and zinc citrate. 5 A composition according to any one of claims I to 4, wherein the pantothenic acid, or a pharmaceutically acceptable derivative, salt or prodrug there, is present in an amount suficiont to provide an amount of pantothenic acid of from about 1% to about 50% by weight of the composition.
3. 6. A composition according to claim 5, wherein the amount of pantothenic acid is from about 30% to about 45%, by weight of the composition.
4. 7. A composition according to claim 5, wherein the amount of pantothenic acid is from about 10% to about 30% by weight of the composition, S. A composition according to anyone of plains ,to7ompnsia one or moreof the flowing 20 folic acid present in an amount of from about 0.001% to about 0.1% b weight of the composition; icotinamide present in an amount of from about 5%o about 20% by weight of the composition; coppe preseIt in an moun of fom aout 0001% to about 00 by eigof the composition and zinc present in an amount of from about 0.05' to abot 2% by eghtofthe composition.
5. 9. A compostn accoding to any one of caims I to 4. xherein the pantothen acid or a pharmaceutially aceptable deivative, sat or prodrug thereof, is present in an amount sufient to pride an amount of pantothenic acid of from about 100 Mg to about00 Mg.
6. 10. A compositin according to Mai 9, wheein he amount of pantoheic aid is from about 100 mg to about 250 mg, 1 L A composion according to clain 9, wherein the amount of pantothenic acid is from about g to about 70, mg A composition according to any one of claims 9 to 11 comprising any one or nore of the tolowing: folic acid present in an amount of fronm about 50 ggto about 150 pg; rncotnamide present in an amount of fron about 50 mg i about 200 ing; copper present in an amount of nom about 200 pg o about 300 g and zinc present in an atmountaf from about 1 mI to about 20 ng A composition according to any one of claims !to 12 further comprising any one or more of the following: biotin; a form of Vtamin A; a sourcedo silicon; and Viex angus-cstus. 14, A composition according to claim 13, wherein the vitamin A is present as Vitamin A acetate
7. 15. A composition according to claim 13 or claim 14, wherein the source of silicon is silicon dioxide.
8. 16. A composition when used for the treatment of acne comprising the following: Comp onent Amount weight% Biotin_______0.02 - 0.03 Calciumrpantothenate 37 - 45 Folic acid 0,005 - 0.008 Vitamin A actate 0.05 - 0.08 Silicon dioxide 0.70 --0.90 Copper gluconate 0.10- 0.20 Nicotinamide 9 - 1____2 Zinc gluconate | ___ 2.5 - 3,0 1. A compositon when vised for the treatment of acne comprising the following: Conwponent |. __Amount (weight %)__ Biotin . __ 0.03 - 0.05 _ Calciurn pantothenate ___ 18 -23 ____Folic Acid 0.01 - 0.02 extract dry concentrate 10:1 05-03 in 50% ethanol and 50% ________ water _____________________ Silicon Dioxide 1 -1.5 Copper Gunae0.15 -0.30 Nicotinamiide |12-- 16 Zinc G.ilucona.e |____ j ___- 7 --- 8- 1 1 8. A omposition when used for the treatment of acne comprising the following: Component Amount Bdiotin 330 -- 41 3 pg Calcium pantothenate 500 -600nmg ________Folic acid 80 - 104 pg Vitamin A acetate 760 - 1080 pg Silicon dioxide 10 - 12 mg Coppergluconate 1 - __3 mg Nico-inmid--2 -
9. 150. m -- i--------a------- 2 - -5 ----- g--- ......... 22 Zinc gluconate 34 -39 mg 19 A composition whenused for the treatmeiof acnecmpising the folowin: Component Amount Biotin 330 -413 pg Calcium pantothenate 181 -219 mg Folic acid 97 - 136 pg Vitex agnus-castus (fruit extract dry concentrate 10:1 in 50% ethanol and 50%. water Silicon dioxide 10- 12 mg Copper gluconate - - 3 mg Nicotinamide 125 -- 150m Zine'L gjluconlate 69-77 20. A composition according to any one of cAiMs 1 to 19, wherein the composition is a dosage form selected from the group consisting of a tablet. caplet. capsule. gel cap. pellet and granule. 21. A composition according to claim 20, wherein the dosage form is a caplet and wherein the caplet weighs from about 900 mg to about 1100 mg. 22. A composition according to claim 20, wherein the dosage form is a tablet and wherein the tablet weighs from about 1200 mg to about 1500 mg. 23. A method of reducing, treating and/or preventing acne and/or related skin disorders comprising the administration o a composition according to any one of claims I to 22, to a subject i need of such tretmem. 24. A method of reducing, treating and/or preventing the appearance of acne and/or related skin disorders on the skin comprising the administration of a composition according to any one of clainsI to 22 to a subject in need of such treatment. 25. A method according to claim 23 or claim 24. wherein administration provides to the subject pantothenic acid in an amount of between about 2,5 g and about 3.5 g per day. 26. A method according to claim 23 or 24, wherein administration provides to the subject pantothenic acid in an amount of between about 400 mg and about 600 mtg per day, 27, The us of a composition according to any one of claims I to 22, for the manufacture of a medicament for the reduction, treatment and/or prevention of acne and/or related skin disorders. 28 The use of a composition a rdig to any one claims I to 22. for theanufacture of a medieame for the reducdon, eatment m /an prevenion ofthe appease of acne and/or related skin disrders on the skin, 29. A composition according to any one of claims I to 22, when used for the reduction treatment and/or prevention of acne and/or related skin disorders. 30. A Composition according to any one of claims I to 22 dhen used for the redaon, treatment and/or preventon of the appearance of acne and/or related sin orders on the Akin