WO2022113072A1 - Topical compositions comprising proton pump inhibitors (ppis) for the treatment of skin disorders - Google Patents

Topical compositions comprising proton pump inhibitors (ppis) for the treatment of skin disorders Download PDF

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Publication number
WO2022113072A1
WO2022113072A1 PCT/IL2021/051399 IL2021051399W WO2022113072A1 WO 2022113072 A1 WO2022113072 A1 WO 2022113072A1 IL 2021051399 W IL2021051399 W IL 2021051399W WO 2022113072 A1 WO2022113072 A1 WO 2022113072A1
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Prior art keywords
ppi
topical composition
another embodiment
dermatitis
skin
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PCT/IL2021/051399
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French (fr)
Inventor
Moshe Arkin
Ori NOV
Galina GEITSAN
Hila HAKAK DJERBI
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Sol-Gel Technologies Ltd.
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Publication of WO2022113072A1 publication Critical patent/WO2022113072A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders

Definitions

  • This invention in some embodiments thereof, relates to a topical composition comprising a proton pump inhibitor (PPI) or pharmaceutically acceptable salt thereof for use in the treatment of skin disorders and/or inflammatory disorders.
  • PPI proton pump inhibitor
  • Topical medicaments are commonly treated with systemic and/or topical medicaments.
  • Topical medicaments while not always available, have the advantage of avoiding systemic side-effects.
  • topical skin disorder treatments are sometimes accompanied by undesirable side-effects, especially at high doses.
  • PPIs prevent proton pump H+, K+-ATPase from functioning thereby reducing the acidity in the stomach (Dig Dis Sci. 2009;54(ll):2312-7).
  • Topical Esomeprazole a PPI, was found to attenuate dermal inflammation and fibrosis caused by radiation (Radiat. Res. 192, 000-000 (2019).
  • the present disclosure provides a topical composition comprising a proton pump inhibitor for treating skin disorders, skin inflammatory disorders and/or non-cancer therapy induced skin disorders.
  • This invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non cancer therapy induced skin disorder.
  • PPI proton pump inhibitor
  • This invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non cancer therapy induced skin inflammatory disorder.
  • PPI proton pump inhibitor
  • composition is useful for the treatment, prevention or alleviation of a skin disorder selected from dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster.
  • a skin disorder selected from dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster.
  • a topical composition comprising a proton pump inhibitor and methods of treatment useful for the treatment, prevention and amelioration of a skin disorder selected from dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster.
  • a skin disorder selected from dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster.
  • the topical composition provided herein for the use in the treatment, prevention and amelioration of a skin disorder selected from dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster comprises between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
  • PPI proton pump inhibitor
  • non-cancer therapy induced skin disorder refers to a skin disorders which is not induced for example by radiation.
  • this invention is directed to uses, methods and regimens for the treatment, prevention or alleviation of a skin disorder selected from dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster, which is not caused/induced by for example radiation.
  • a skin disorder selected from dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster, which is not caused/induced by for example radiation.
  • the PPIs reduce inflammatory response and attenuate skin inflammatory conditions (including dermatitis) by activating AhR.
  • the skin disorders treated by the compositions of this disclosure are selected from psoriasis (selected from plaque psoriasis, flexural/inverse psoriasis, scalp psoriasis, sebopsoriasis and genital psoriasis); dermatitis (also known as eczema) selected from atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis; acne selected from acne vulgaris, papulopustular acne and nodular acne; rosacea selected from erythematotelangiectatic rosacea, papulopustular rosacea, rhinophyma rosacea and ocular rosacea; prurigo nodularis; granuloma annulare; urticaria; hidradenitis suppurativa; lichen planus
  • the skin disorders treated by the compositions of this disclosure are not induced by cancer therapy.
  • the skin disorders treated by the compositions of this disclosure are not induced by for example radiation.
  • Psoriasis is an autoimmune disease, characterized by typically red, scaly patches of skin. There are five main types of psoriasis: plaque, guttate, flexural/inverse, pustular, and erythrodermic. Psoriasis vulgaris is the most common form of psoriasis.
  • Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from androgen-induced increased sebum production, altered keratinization, inflammation, and bacterial colonisation of hair follicles on the face, neck, chest, and back by Propionibacterium acnes (P. acnes). Although early colonisation with P. acnes and family history might have important roles in the disease, exactly what triggers acne and how treatment affects the course of the disease remains unclear (Williams H.C. et ah, The Lancet, Vol.379. Jan 2012, pp. 361-372). [0019] There is no ideal treatment for acne. Good quality evidence on comparative effectiveness of common topical and systemic acne therapies is scarce.
  • Topical therapies including benzoyl peroxide, retinoids, and antibiotics when used in combination usually improve control of mild to moderate acne, but suffer from side-effects. Treatment with combined oral contraceptives can help women with acne. Patients with more severe inflammatory acne usually need oral antibiotics combined with topical benzoyl peroxide to decrease antibiotic-resistant organisms.
  • Oral isotretinoin is the most effective therapy and is used early in severe disease, but its use is limited by teratogenicity and other side-effects.
  • composition of this invention allows using lower amounts of active agents and therefore results in reduced side-effects, due to the additive and/or synergistic effects.
  • Rosacea is a chronic skin disease that affects more than 16 million Americans. The cause of rosacea is still unknown. However, research has allowed doctors to find ways to treat the condition by minimizing its symptoms (Cynthia Cobb, Healthline May 21, 2018).
  • Each subtype has its own set of symptoms. It is possible to have more than one subtype of rosacea at a time.
  • Rosacea typical symptom is small, red, pus-filled bumps on the skin that are present during flare-ups. Typically, rosacea affects only skin on the nose, cheeks, and forehead.
  • Flare-ups often occur in cycles. This means that one will experience symptoms for weeks or months at a time, the symptoms will go away, and then return.
  • Subtype one known as erythematotelangiectatic rosacea (ETR) is associated with facial redness, flushing, and visible blood vessels.
  • ETR erythematotelangiectatic rosacea
  • Subtype two, papulopustular (or acne) rosacea is associated with acne-like breakouts, and often affects middle-aged women.
  • Subtype three known as rhinophyma rosacea, is a rare form associated with thickening of the skin on your nose. It usually affects men and is often accompanied by another subtype of rosacea.
  • Subtype four is known as ocular rosacea, and its symptoms are centered on the eye area.
  • Hidradenitis suppurativa also known as acne inversa, is a long-term chronic skin disease whose present treatment options are often unsatisfactory. HS has a profound effect on patient’s quality of life (QoL). Alavi A. et ah, reviewed QoL aspects of this disease in an article titled “Quality-of-Life Impairment in Patients with Hidradenitis Suppurativa” (Am J Clin Dermatol, 2014, vol. 15.No. 6). The clinical picture of HS includes solitary nodules, diffuse, painful abscesses, malodorous drainage, sinus tract formation and scarring. The exact cause of hidradenitis suppurativa is still unclear, but it is believed that the underlying mechanism involves dysfunction of the apocrine sweat glands or hair follicles.
  • PN is characterized by hyperkeratotic excoriated papulonodular (itchy) lesions that show symmetrical distribution on the extensor surfaces of the body and/or extremities, the numbers of which range from several to hundreds (Akarsu, S. et al. An Bras Dermatol . 2018;93(5):671-9.). It is a rare disease and is one of the most difficult conditions in terms of determining its etiology and treatment among chronic skin diseases.
  • Granuloma annulare is a cutaneous granulomatous disease. It is not caused by an infection and is the most common non-infectious granulomatous disease. The disease is benign and often self-limited. Granuloma annulare usually presents as erythematous plaques or papules arranged in an annular configuration on the upper extremities. Despite being a benign disease, it can be associated with more serious conditions such as HIV or malignancy.
  • Granuloma annulare lesions are approximately distributed as follows:
  • the localized form of granuloma annulare composes 75 percent of cases. Localized granuloma annulare starts as a ring of small, firm, flesh-colored or red papules.
  • the Disseminated or generalized granuloma annulare is similar to the localized variant but is more widespread, having 10 or more lesions.
  • the papules may fuse to form annular lesions on the extremities, trunk, and neck. In contrast to the localized form, these lesions may persist for three to four years or longer.
  • the Subcutaneous granuloma annulare is diagnosed primarily in children two to five years of age.
  • the lesions are asymptomatic, rapidly growing subcutaneous nodules on the extremities, hands, scalp, buttocks, and pretibial and periorbital areas.
  • the Perforating granuloma annulare is rare and occurs most often in children and young adults. It is also more common in women. Perforating granuloma annulare can have localized and generalized forms.
  • the localized form is found on the upper limbs and pelvis, and the generalized form, which is more common, is present on the abdominal area, trunk, and upper and lower limbs.
  • Lichen planus is a T cell-mediated autoimmune disorder, in which inflammatory cells attack an unknown protein within the skin and mucosal keratinocytes.
  • Lichen planus is a condition that can cause swelling and irritation in the skin, hair, nails and mucous membranes.
  • lichen planus On the skin, lichen planus usually appears as purplish, itchy, flat bumps that develop over several weeks. In the mouth, vagina and other areas covered by a mucous membrane, lichen planus forms lacy white patches, sometimes with painful sores.
  • Urticaria also known as hives, is an outbreak of swollen, pale red bumps or plaques (wheals) on the skin that appear suddenly either as a result of the body's reaction to certain allergens, or for unknown reasons.
  • Hives usually cause itching, but may also bum or sting. They can appear anywhere on the body, including the face, lips, tongue, throat, or ears. Hives vary in size, and may join together to form larger areas known as plaques. They can last for hours, or up to one day before fading.
  • Herpes simplex is a viral infection caused by the herpes simplex vims. Infections are categorized based on the part of the body infected. Oral herpes involves the face or mouth. It may result in small blisters in groups often called cold sores or fever blisters or may just cause a sore throat.
  • Herpes Zooster is a viral infection caused by the varicella-zoster vims characterized by a painful skin rash with blisters in a localized area.
  • This invention provides and makes use, in one aspect, of a topical composition comprising between about 0.5% w/w to about 10.0% w/w proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder.
  • the skin disorder is a skin inflammatory disorder.
  • the skin disorder is not induced by cancer therapy.
  • the skin disorder is not induced by for example radiation.
  • the skin disorder is selected from the group consisting of psoriasis (selected from plaque psoriasis, flexural/inverse psoriasis, scalp psoriasis, sebopsoriasis and genital psoriasis); dermatitis (also known as eczema) selected from atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis; acne selected from acne vulgaris, papulopustular acne and nodular acne; rosacea selected from erythematotelangiectatic rosacea, papulopustular rosacea, rhinophyma rosacea and ocular rosacea; prurigo nodularis; granuloma annulare; urticaria; hidradenitis suppurativa; lichen planus; dry
  • the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 0.5 % to about 10.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 0.5 % to about 1.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 1.0 % to about 5.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 5.0 % to about 10 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 1.0 % to about 1.5 % w/w.
  • the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 1.5 % to about 2.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 2.0 % to about 2.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 2.5 % to about 3.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 3.0 % to about 3.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 3.5 % to about 4.0 % w/w.
  • the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 4.0 % to about 4.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 4.5 % to about 5.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 5.0 % to about 5.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 5.5 % to about 6.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 6.0 % to about 6.5 % w/w.
  • the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 6.5 % to about 7.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 7.0 % to about 7.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 7.5 % to about 8.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 8.0 % to about 8.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 8.5 % to about 9.0 % w/w.
  • the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 9.0 % to about 9.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 9.5 % to about 10.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 1.0 % to about 5.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 5.0 % to about 10.0 % w/w.
  • the amount is 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
  • the PPI within the compositions of this invention is at least one compound selected from the group consisting of: omeprazole, lansoprazole, esomeprazole, dexlansoprazole, pantoprazole, rabeprazole and ilaprazole.
  • the PPI consists essentially of one compound of the list described hereinabove.
  • the PPI consists essentially of two compounds of the list described hereinabove.
  • the PPI consists essentially of more than two compounds of the list described hereinabove.
  • the PPI is omeprazole.
  • the PPI is lansoprazole.
  • the PPI is esomeprazole.
  • Non-limiting examples of pharmaceutically acceptable salts of PPI within the compositions of this invention include: chloride, acetate, citrate, lactate, mesylate, nitrate, sulfate, phosphate, diphosphate, tartrate, carbonate and bicarbonate. Each possibility represents a separate embodiment of this invention.
  • the salt is phosphate.
  • composition can be administered using a variety of routes such as topical application or transdermal application.
  • routes such as topical application or transdermal application.
  • the preferred route is the topical route and the preferred formulations are the cream, the gel and the lotion.
  • the composition can be formulated as a cream, a gel, an ointment, an emulsion, a solution, a suspension, an elixir, a lotion, a tincture, a paste, a foam, an aerosol, a spray, a patch, a stick, a transdermal patch, a sebum control product or an applicator syringe.
  • the composition provided herein is an ophthalmic composition, formulated as an ointment, a paste, drops, a solution or a suspension.
  • Sebum control products may include ingredients selected from the group consisting of: azelaic acid, salicylic acid, sulfur, nicotinamide, L-carnitine and combinations thereof. Each possibility represents a separate embodiment of this invention.
  • compositions have chemical stability problems, caused either by interaction of the active agent with the carrier and/or other excipient and/or by interaction of the active agent with, for example, the subject’s skin - in case of topical compositions.
  • PPI or pharmaceutically acceptable salt thereof in the composition is the encapsulation of PPI or pharmaceutically acceptable salt thereof in the composition.
  • the preferred encapsulation method of this invention is detailed in U.S. PatentNo. 9687465 and published U.S. Patent Application No. 2018147165 (to Sol-Gel Technologies), whose contents are enclosed herein in their entirety.
  • PPI or pharmaceutically acceptable salt thereof in the compositions of this invention may be encapsulated as disclosed above.
  • the PPI or pharmaceutically acceptable salt thereof is included in the carrier in an amount sufficient to exert a therapeutically useful effect i.e., treatment, prevention or alleviation of a non-cancer therapy induced skin disorder (or non-cancer therapy induced skin inflammatory disorder) with minimal or no toxicity or other side effects.
  • emollient or lubricating vehicles that help hydrate the skin are more preferred than volatile vehicles, such as ethanol, that dry the skin.
  • suitable bases or vehicles for preparing compositions for use with human skin are petrolatum, petrolatum plus volatile silicones, lanolin, cetostearyl alcohol, cold cream and hydrophilic ointment. Each possibility represents a separate embodiment of this invention.
  • compositions of this invention comprise PPI or pharmaceutically acceptable salt thereof; and a carrier, a solvent, an emollient, a surfactant, an anti-oxidant, a chelating agent, a gelling agent, a wetting agent, a penetration enhancer, a moisturizing agent, a preservative (e.g. imidurea and methylparaben), an anti-oxidant, a buffer or any combination thereof.
  • a penetration enhancer e.g. imidurea and methylparaben
  • the penetration enhancer is selected from the group consisting of dimethylsulfoxide (DMSO), diethylene glycol monoethyl ether (Transcutol), methyl sulfonylmethane (MSM), oleic acid, oleyl alcohol, propylene glycol, dimethyl isosorbide, isopropyl myristate, diethyl sebacate, ethanol, isopropyl alcohol, a polyethylene glycol, hexylene glycol, glycofurol and any combination thereof.
  • DMSO dimethylsulfoxide
  • Transcutol Transcutol
  • MSM methyl sulfonylmethane
  • oleic acid oleyl alcohol
  • propylene glycol dimethyl isosorbide
  • isopropyl myristate diethyl sebacate
  • ethanol isopropyl alcohol
  • a polyethylene glycol hexylene glycol, glycofurol and any combination thereof.
  • the compositions of this invention comprise an emollient.
  • the emollient is selected from the group consisting of castor oil, mineral oil, vegetable oil, soybean oil, shea butter, cocoa butter, paraffin, beeswax, oleic acid, squalene, cetyl alcohol, isopropyl myristate, urea, glycerol, propylene glycol, lactic acid, cetostearyl alcohol, lanoin and any combination thereof.
  • the emollient is cetostearyl alcohol.
  • the emollient is lanoin.
  • compositions of this invention comprise a chelating agent.
  • the chelating agent is selected from the group consisting of EDTA deferoxamine, deferiprone, deferasirox, dimercaptosuccinic acid (succimer) triethylenetetramine (trientine) and any combination thereof. Each possibility represents a separate embodiment of this invention.
  • the compositions of this invention comprise an anti-oxidant.
  • the anti-oxidant is selected from the group consisting of butylated hydroxytoluene (BHT), parabens, propyl gallate, ascorbic acid, flavones, flavanones, flavonols, stilbenoids, gallic acid, cinnamic acid, ellagic acid, salicylic acid, curcumin, eugenol, citric acid, tocopherols and any combination thereof.
  • BHT butylated hydroxytoluene
  • parabens parabens
  • propyl gallate ascorbic acid
  • flavones flavanones
  • flavonols stilbenoids
  • gallic acid cinnamic acid
  • ellagic acid ellagic acid
  • salicylic acid curcumin
  • curcumin eugenol
  • citric acid tocopherols and any combination thereof.
  • the compositions of this invention comprise a solvent.
  • the solvent is selected from the group consisting of propylene glycol, diethylene glycol monoethyl ether (Transcutol), dimethylsulfoxide (DMSO), diethyl sebacate, polyethylene glycol, oleyl alcohol, isosorbide dimethyl ether, ethanol, isopropyl alcohol, isopropyl myristate, oleic acid, hexylene glycol, glycerin, glycofurol and any combination thereof.
  • DMSO dimethylsulfoxide
  • the compositions of this invention comprise a preservative.
  • the preservative is selected from the group consisting of benzoic acid, methylparaben, , imidurea, chlorocresol, Phenoxyethanol, propyl paraben, benzalkonium chloride, benzyl alcohol, imidazolidinyl urea, sodium benzoate, sorbic acid, thimerosal sorbic acid, sodium sorbate, sodium sulfite, ethanol, and any combination thereof.
  • the preservative is imidurea and methylparaben. Each possibility represents a separate embodiment of this invention.
  • the compositions of this invention comprise a buffer.
  • the buffer is selected from the group consisting of citric acid, phosphoric acid, acetic acid, tartaric acid, glutamic acid, aspartic acid, malic acid, succinic acid, fumaric acid, salt thereof, and any combination thereof.
  • the compositions of this invention comprise a gelling agent.
  • the gelling agent is selected from the group consisting of carbomer homopolymer type A (Carbopol®981, Carbopol®980), Sepineo P600, Natrosol hydroxy ethylcellulose, starch, pectin, gelatin, agar, alginic acid and salts thereof, Carbomer® 934, carboxymethylcellulose, hydroxypropylmethylcellulose and any combination thereof.
  • carbomer homopolymer type A Carbopol®981, Carbopol®980
  • Sepineo P600 Natrosol hydroxy ethylcellulose
  • starch starch
  • pectin hydroxy ethylcellulose
  • gelatin agar
  • alginic acid and salts thereof Carbomer® 934
  • carboxymethylcellulose hydroxypropylmethylcellulose and any combination thereof.
  • the compositions of this invention comprise a surfactant.
  • the surfactant is selected from the group consisting of carbomer copolymer type B (Pemulen®TR-l), sorbitan monooleate (Span80), polysorbate 80 (Tween 80), polysorbate 20, polysorbate 60 (Tween 60), sodium dodecyl sulfate, cetearyl alcohol, dioctyl sodium sulfosuccinate, glyceryl oleate, glyceryl stearate, poloxamers and any combination thereof.
  • carbomer copolymer type B Pemulen®TR-l
  • Span80 sorbitan monooleate
  • Polysorbate 80 Teween 80
  • polysorbate 20 polysorbate 60
  • sodium dodecyl sulfate cetearyl alcohol
  • dioctyl sodium sulfosuccinate glyceryl oleate
  • glyceryl stearate polox
  • the compositions of this invention comprise a wetting agent.
  • the wetting agent is selected from the group consisting of PEG 400, glycerin, poloxamers, sorbitan monooleate (Span80), polysorbate 80 (Tween 80), polysorbate 20, polysorbate 60 (Tween 60), benzalkonium chloride, sodium dodecyl sulfate and any combination thereof.
  • the wetting agent is selected from the group consisting of PEG 400, glycerin, poloxamers, sorbitan monooleate (Span80), polysorbate 80 (Tween 80), polysorbate 20, polysorbate 60 (Tween 60), benzalkonium chloride, sodium dodecyl sulfate and any combination thereof.
  • the compositions of this invention comprise a moisturizing agent.
  • the moisturizing agent is selected from the group consisting of lanolin, cetostearyl alcohol, hyaluronic acid or its salt, pyrrolidone, glycerin, diglycerin, polyglycerin, a polyol such as propylene glycol, hexylene glycol, dipropylene glycol and 1,3-butylene glycol, shea butter, hyaluronic acid, dimethicone, petrolatum, stearic acid, proteins, urea, mineral oil and any combination thereof .
  • the moisturizing agent is lanolin.
  • the moisturizing agent is cetostearyl alcohol.
  • compositions provided herein include any such carriers known to those skilled in the art to be suitable for the particular mode of administration.
  • Suitable pharmaceutically and dermatologically acceptable carriers or vehicles for topical application include lotions, creams, foams, solutions, gels, patches, a stick and the like.
  • the carrier or vehicle is either organic in nature or an aqueous emulsion and capable of accommodating the selected active agent(s), which may be micronized, dispersed, suspended or dissolved therein.
  • the vehicle or carrier may include pharmaceutically-acceptable emollients, moisturizers, including lactic acid, ammonium lactate and urea, skin penetration enhancers, coloring agents, fragrances, emulsifiers, thickening agents, vegetable oils, essential oils, zinc oxide and solvents.
  • emollients include lactic acid, ammonium lactate and urea, skin penetration enhancers, coloring agents, fragrances, emulsifiers, thickening agents, vegetable oils, essential oils, zinc oxide and solvents.
  • this invention provides a dosage form comprising a composition as described hereinabove.
  • the dosage form is used in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder (or non-cancer therapy induced skin inflammatory) disorder.
  • the skin disorder is selected from the group consisting of psoriasis (selected from plaque psoriasis, flexural/inverse psoriasis, scalp psoriasis, sebopsoriasis and genital psoriasis); dermatitis (also known as eczema) selected from atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis; acne selected from acne vulgaris, papulopustular acne and nodular acne; rosacea selected from erythematotelangiectatic rosacea, papulopustular rosacea, rhinophyma rosacea and ocular rosacea; prurigo nodularis; granuloma annulare; urticaria; hidradenitis suppurativa; lichen planus; dry
  • compositions or dosage forms of this invention are used in the methods as described hereinbelow and/or are used in the preparation of medicaments that are used in said methods.
  • this invention provides a regimen for the treatment, prevention or alleviation of non-cancer therapy induced skin disorder (or non-cancer therapy induced skin inflammatory disorder), comprising topically applying onto an affected skin area of a subject in need thereof, once a day, twice a day, more than twice a day, weekly, bi-weekly a topical composition which comprises between about 0.5% w/w to about 10.0% w/w proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
  • the skin disorder is a skin inflammatory disorder.
  • the skin disorder is not induced by cancer therapy.
  • the skin disorder is not induced by for example radiation.
  • the skin disorder (or the skin inflammatory disorder) is selected from the group consisting of: dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster.
  • the dermatitis is selected from the group consisting of: atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis.
  • the psoriasis is selected from the group consisting of: plaque (vulgaris), guttate, flexural/inverse, pustular, and erythrodermic.
  • the rosacea is selected from the group consisting of: erythematotelangiectatic rosacea (ETR), papulopustular (or acne) rosacea, rhinophyma and ocular rosacea.
  • ETR erythematotelangiectatic rosacea
  • papulopustular (or acne) rosacea rhinophyma
  • ocular rosacea ocular rosacea
  • the effective amount is a therapeutically effective amount of the PPI or pharmaceutically acceptable salt thereof, namely an amount which will treat, prevent or alleviate a non-cancer therapy induced skin disorder (or non-cancer therapy induced skin inflammatory disorder).
  • the frequency of administration (of compositions or dosage forms) can be determined empirically.
  • Exemplary frequencies of the administration are once daily, twice daily, weekly, bi weekly or monthly. Typical administration frequencies of the compositions of this invention are once daily and twice daily. Each possibility represents a separate embodiment of this invention.
  • Dosage frequencies can be gradually decreased over time and maintained at a steady dose suitable for long-term - six months, 1 year, 5 years, 10 years or more, up to lifelong administration to control the symptoms of non-cancer therapy induced topical skin disease, disorder or condition.
  • dosage administration can begin at from once a day, to two times a week, to once a week, to once every two weeks or less frequent than once every two weeks.
  • Each possibility represents a separate embodiment of this invention.
  • this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced skin disorder, wherein the method comprises administering to a subject in need thereof, a topical composition or the dosage form as described herein.
  • this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof, a topical composition or the dosage form as described herein.
  • this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced skin disorder (or non-cancer therapy induced skin inflammatory disorder), wherein the method comprises administering to a subject in need thereof, a topical composition comprising between 0.5% w/w to about 10.0% w/w PPI or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  • this invention provides a method of treatment, prevention or alleviation of a skin disorder, wherein the method comprises administering to a subject in need thereof, a topical composition comprising between 0.5% w/w to about 10.0% w/w PPI or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein the skin disorder is not induced by cancer therapy, or was not induced by radiation.
  • this invention provides a method of treatment, prevention or alleviation of a skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof, a topical composition comprising between 0.5% w/w to about 10.0% w/w PPI or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein the skin disorder is not induced by cancer therapy, or was not induced by radiation.
  • this invention provides a method of treatment, prevention or alleviation of a skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof, a topical composition comprising between 0.5% w/w to about 10.0% w/w PPI or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein the skin disorder is selected from the group consisting of psoriasis (selected from plaque psoriasis, flexural/inverse psoriasis, scalp psoriasis, sebopsoriasis and genital psoriasis); dermatitis (also known as eczema) selected from atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis; acne selected from acne vulgaris, papulopustular acne and nodular acne; rosacea selected from erythe
  • the skin disorders being treated by the composition of this invention is selected from the group consisting of: dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster.
  • the dermatitis is selected from the group consisting of: atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis.
  • the psoriasis is selected from the group consisting of: plaque (vulgaris), guttate, flexural/inverse, pustular, and erythrodermic.
  • the rosacea is selected from the group consisting of: erythematotelangiectatic rosacea (ETR), papulopustular (or acne) rosacea, rhinophyma and ocular rosacea.
  • ETR erythematotelangiectatic rosacea
  • papulopustular (or acne) rosacea rhinophyma and ocular rosacea.
  • the effective amount is a therapeutically effective amount of the PPI or pharmaceutically acceptable salt thereof, namely an amount which will treat, prevent or alleviate a skin disorder, or skin inflammatory disorder.
  • Dosage frequencies can be gradually decreased over time and maintained at a steady dose suitable for long-term - six months, 1 year, 5 years, 10 years or more, up to lifelong administration to control the symptoms of the non-cancer therapy induced topical skin disease, disorder or condition.
  • dosage administration can begin at from once a day, to two times a week, to once a week, to once every two weeks or less frequent than once every two weeks.
  • this invention provides a kit comprising the compositions or dosage forms as described hereinabove.
  • the kit further comprises instructions for administration.
  • compositions provided herein can be packaged as articles of manufacture containing packaging material, a composition provided herein, and a label that indicates that the composition is for treating a non-cancer therapy induced topical skin disease, disorder or condition, and is formulated for e.g. topical delivery.
  • packaging materials for use in packaging pharmaceutical products are well known to those of skill in the art.
  • Examples of pharmaceutical packaging materials include, but are not limited to bottles, tubes, containers, application syringes or dual chamber application syringes and any packaging material suitable for the selected formulation and intended mode of administration and treatment. Each possibility represents a separate embodiment of this invention.
  • this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder.
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI.
  • the topical composition comprises between about 1 % w/w to about 5% w/w PPI.
  • the topical composition comprises 1 % w/w PPI.
  • the topical composition comprises 5 % w/w PPI.
  • the topical composition comprises between about 5 % w/w to about 10 % w/w PPI.
  • the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
  • this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin inflammatory disorder.
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI.
  • the topical composition comprises between about 1 % w/w to about 5% w/w PPI.
  • the topical composition comprises 1 % w/w PPI.
  • the topical composition comprises 5 % w/w PPI.
  • the topical composition comprises between about 5 % w/w to about 10 % w/w PPI.
  • the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
  • this invention provides a topical composition
  • a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder, wherein the PPI is selected from the group consisting of: omeprazole, lansoprazole, esomeprazole, dexlansoprazole, pantoprazole, rabeprazole and ilaprazole.
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI.
  • the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
  • this invention provides a topical composition
  • a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin inflammatory disorder, wherein the PPI is selected from the group consisting of: omeprazole, lansoprazole, esomeprazole, dexlansoprazole, pantoprazole, rabeprazole and ilaprazole.
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI.
  • the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
  • this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder, wherein the skin disorder is selected form the group consisting of: dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster.
  • PPI proton pump inhibitor
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI.
  • the dermatitis is selected from the group consisting of: atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis.
  • the psoriasis is selected from the group consisting of: plaque (vulgaris), guttate, flexural/inverse, pustular, and erythrodermic.
  • the rosacea is selected from the group consisting of: erythematotelangiectatic rosacea (ETR), papulopustular (or acne) rosacea, rhinophyma and ocular rosacea.
  • the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
  • this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin inflammatory disorder, wherein the skin inflammatory disorder is selected form the group consisting of: dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster.
  • PPI proton pump inhibitor
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI.
  • the dermatitis is selected from the group consisting of atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis.
  • the psoriasis is selected from the group consisting of: plaque (vulgaris), guttate, flexural/inverse, pustular, and erythrodermic.
  • the rosacea is selected from the group consisting of: erythematotelangiectatic rosacea (ETR), papulopustular (or acne) rosacea, rhinophyma and ocular rosacea.
  • the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
  • this invention provides a topical composition
  • a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder, wherein the composition is formulated as a cream, a gel, an ointment, an emulsion, a solution, a suspension, an elixir, a lotion, a tincture, a paste, a foam, an aerosol, a spray, a patch, a stick, a transdermal patch or an applicator syringe.
  • PPI proton pump inhibitor
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
  • this invention provides a topical composition
  • a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin inflammatory disorder, wherein the composition is formulated as a cream, a gel, an ointment, an emulsion, a solution, a suspension, an elixir, a lotion, a tincture, a paste, a foam, an aerosol, a spray, a patch, a stick, a transdermal patch or an applicator syringe.
  • PPI proton pump inhibitor
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
  • this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder, wherein the topical composition is an ophthalmic composition.
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI.
  • the topical composition comprises 1 % w/w PPI.
  • the topical composition comprises 5 % w/w PPI.
  • the topical composition comprises between about 5 % w/w to about 10 % w/w PPI.
  • the ophthalmic composition is formulated as an ointment, a paste, a gel, a cream, drops, a solution or a suspension.
  • the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
  • this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin inflammatory disorder, wherein the topical composition is an ophthalmic composition.
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI.
  • the topical composition comprises between about 1 % w/w to about 5% w/w PPI.
  • the topical composition comprises between about 5 % w/w to about 10 % w/w PPI.
  • the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the ophthalmic composition is formulated as an ointment, a paste, a gel, a cream, drops, a solution or a suspension. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
  • this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
  • a topical composition comprising between about 0.5 % w/w to about 1% w/w PPI.
  • the topical composition comprises between about 1 % w/w to about 5% w/w PPI.
  • the topical composition comprises between about 5 % w/w to about 10 % w/w PPI.
  • the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
  • this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
  • a topical composition comprising between about 0.5 % w/w to about 1% w/w PPI.
  • the topical composition comprises between about 1 % w/w to about 5% w/w PPI.
  • the topical composition comprises between about 5 % w/w to about 10 % w/w PPI.
  • the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
  • this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the PPI is selected from the group consisting of: omeprazole, lansoprazole, esomeprazole, dexlansoprazole, pantoprazole, rabeprazole and ilaprazole.
  • PPI proton pump inhibitor
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
  • this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the PPI is selected from the group consisting of: omeprazole, lansoprazole, esomeprazole, dexlansoprazole, pantoprazole, rabeprazole and ilaprazole.
  • PPI proton pump inhibitor
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
  • this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the skin disorder is selected form the group consisting of: dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster.
  • PPI proton pump inhibitor
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI.
  • the dermatitis is selected from the group consisting of: atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis.
  • the psoriasis is selected from the group consisting of: plaque (vulgaris), guttate, flexural/inverse, pustular, and erythrodermic.
  • the rosacea is selected from the group consisting of: erythematotelangiectatic rosacea (ETR), papulopustular (or acne) rosacea, rhinophyma and ocular rosacea.
  • the PPI is encapsulated.
  • the PPI is not encapsulated.
  • the administration is once daily, twice daily, weekly, bi-weekly or monthly.
  • this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the skin inflammatory disorder is selected form the group consisting of: dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster.
  • PPI proton pump inhibitor
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI.
  • the dermatitis is selected from the group consisting of: atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis.
  • the psoriasis is selected from the group consisting of: plaque (vulgaris), guttate, flexural/inverse, pustular, and erythrodermic.
  • the rosacea is selected from the group consisting of: erythematotelangiectatic rosacea (ETR), papulopustular (or acne) rosacea, rhinophyma and ocular rosacea.
  • the PPI is encapsulated.
  • the PPI is not encapsulated.
  • the administration is once daily, twice daily, weekly, bi-weekly or monthly.
  • this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the composition is formulated as a cream, a gel, an ointment, an emulsion, a solution, a suspension, an elixir, a lotion, a tincture, a paste, a foam, an aerosol, a spray, a patch, a stick, a transdermal patch or an applicator syringe.
  • PPI proton pump inhibitor
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPL In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPL In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
  • this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the composition is formulated as a cream, a gel, an ointment, an emulsion, a solution, a suspension, an elixir, a lotion, a tincture, a paste, a foam, an aerosol, a spray, a patch, a stick, a transdermal patch or an applicator syringe.
  • PPI proton pump inhibitor
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPL In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPL In another embodiments, the topical composition comprises 1 % w/w PPL In another embodiments, the topical composition comprises 5 % w/w PPL In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPL In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi weekly or monthly.
  • this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the topical composition is an ophthalmic composition.
  • a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the topical composition is an ophthalmic composition.
  • PPI proton pump inhibitor
  • the topical composition comprises between about 0.5 % w/w to about 1% w/w PPL In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPL In another embodiments, the topical composition comprises 1 % w/w PPL In another embodiments, the topical composition comprises 5 % w/w PPL In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPL In another embodiment, the ophthalmic composition is formulated as an ointment, a paste, a gel, a cream, drops, a solution or a suspension. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
  • this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the topical composition is an ophthalmic composition.
  • a topical composition comprises between about 0.5 % w/w to about 1% w/w PPI.
  • the topical composition comprises between about 1 % w/w to about 5% w/w PPI.
  • the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the ophthalmic composition is formulated as an ointment, a paste, a gel, a cream, drops, a solution or a suspension. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
  • treating includes curing a condition, treating a condition, preventing a condition, treating symptoms of a condition, curing symptoms of a condition, ameliorating symptoms of a condition, treating effects of a condition, ameliorating effects of a condition, and preventing results of a condition.
  • inflammatory skin conditions As used herein, the terms “inflammatory skin conditions”, “inflammatory skin disorders”, “inflammatory skin diseases” and “inflammatory cutaneous conditions” are any medical conditions affecting the integumentary system and are used interchangeably.
  • a "pharmaceutical composition” refers to a composition comprising one or more active ingredients with other components such as pharmaceutically acceptable ingredients or excipients.
  • the purpose of a pharmaceutical composition is to facilitate administration of an active ingredient to a subject.
  • compositions, method formulation may include additional ingredients, steps and/or parts, but only if the additional ingredients, steps and/or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure.
  • method refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.
  • Pantoprazole Topical Compositions Preparation of 4 developed formulations of Pantoprazole (PPZ) ointment 1% and 5% for preliminary short term stability study were prepared.
  • Table 1 1% PPZ in Lanolin matrix * PPZ 17% suspension is in mineral oil/cyclometicone 5 (in a ratio of 17:43:40) was prepared using Dyno mill.
  • PPZ 17% suspension is in mineral oil/cyclometicone 5 (in a ratio of 17:43:40) was prepared using Dyno mill.
  • Preparation procedure for all Formulations 1-4.
  • Pantoprazole (PPZ) ointments at 1% w/w or 5% w/w is stable for at least 2 months at 25 °C, as no phase separation was observed and no degradation.

Abstract

This invention, in some embodiments thereof, relates to a topical composition comprising a proton pump inhibitor (PPI) or pharmaceutically acceptable salt thereof for use in the treatment of skin disorders and/or inflammatory disorders.

Description

TOPICAL COMPOSITIONS COMPRISING PROTON PUMP INHIBITORS (PPIS) FOR
THE TREATMENT OF SKIN DISORDERS
FIELD OF THE INVENTION [001] This invention, in some embodiments thereof, relates to a topical composition comprising a proton pump inhibitor (PPI) or pharmaceutically acceptable salt thereof for use in the treatment of skin disorders and/or inflammatory disorders.
BACKGROUND OF THE INVENTION [002] Skin disorders (also known as skin conditions) vary greatly in symptoms and in severity.
They are commonly treated with systemic and/or topical medicaments. Topical medicaments, while not always available, have the advantage of avoiding systemic side-effects. On the other hand, topical skin disorder treatments are sometimes accompanied by undesirable side-effects, especially at high doses. [003] PPIs prevent proton pump H+, K+-ATPase from functioning thereby reducing the acidity in the stomach (Dig Dis Sci. 2009;54(ll):2312-7). Topical Esomeprazole, a PPI, was found to attenuate dermal inflammation and fibrosis caused by radiation (Radiat. Res. 192, 000-000 (2019). For other dermatitis, it was reported that exfoliative dermatitis was shown after lansoprazole, esomeprazole and omeprazole systemic treatment (Exp Ther Med. 2016 Feb; 11(2): 543-546). In addition, it was also described that Cutaneous adverse reactions to PPIs range from minor drug rashes to a severe, life-threatening reaction. Individuals with a history of adverse drug reaction have an increased risk of cutaneous reaction to PPIs or photoallergic dermatitis (Current Opinion in Allergy and Clinical Immunology.2012; 12(4)348; Current Treatment Options in Allergy.2015;2(2)110). [004] PPIs surprisingly and unlike previous reports reduce inflammatory response and attenuate skin inflammatory conditions including dermatitis which is not caused by radiation. [005] The present disclosure provides a topical composition comprising a proton pump inhibitor for treating skin disorders, skin inflammatory disorders and/or non-cancer therapy induced skin disorders. SUMMARY OF THE INVENTION
[006] This invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non cancer therapy induced skin disorder.
[007] This invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non cancer therapy induced skin inflammatory disorder.
[008] The above composition is useful for the treatment, prevention or alleviation of a skin disorder selected from dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster.
DETAILED DESCRIPTION OF THE INVENTION
[009] Provided herein is a topical composition comprising a proton pump inhibitor and methods of treatment useful for the treatment, prevention and amelioration of a skin disorder selected from dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster. [0010] The topical composition provided herein for the use in the treatment, prevention and amelioration of a skin disorder selected from dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster comprises between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
[0011] Provided herein is a topical composition comprising between about 0.5% w/w to about 10.0% w/w proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non cancer therapy induced skin disorder or non-cancer therapy induced skin inflammatory disorder. [0012] “non-cancer therapy induced skin disorder” refers to a skin disorders which is not induced for example by radiation. Thus, this invention is directed to uses, methods and regimens for the treatment, prevention or alleviation of a skin disorder selected from dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster, which is not caused/induced by for example radiation.
[0013] Without being bound to any theory, the PPIs reduce inflammatory response and attenuate skin inflammatory conditions (including dermatitis) by activating AhR.
SKIN DISORDERS TREATED WITH THE COMPOSITION OF THIS DISCLOSURE
[0014] The skin disorders treated by the compositions of this disclosure are selected from psoriasis (selected from plaque psoriasis, flexural/inverse psoriasis, scalp psoriasis, sebopsoriasis and genital psoriasis); dermatitis (also known as eczema) selected from atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis; acne selected from acne vulgaris, papulopustular acne and nodular acne; rosacea selected from erythematotelangiectatic rosacea, papulopustular rosacea, rhinophyma rosacea and ocular rosacea; prurigo nodularis; granuloma annulare; urticaria; hidradenitis suppurativa; lichen planus; dry skin; herpes simplex and herpes zoster.
[0015] The skin disorders treated by the compositions of this disclosure are not induced by cancer therapy. The skin disorders treated by the compositions of this disclosure are not induced by for example radiation. PSORIASIS
[0016] Psoriasis is an autoimmune disease, characterized by typically red, scaly patches of skin. There are five main types of psoriasis: plaque, guttate, flexural/inverse, pustular, and erythrodermic. Psoriasis vulgaris is the most common form of psoriasis.
[0017] Though a number of psoriasis treatments are available, most treatments bring about symptom alleviation or remission rather than complete cure.
ACNE
[0018] Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from androgen-induced increased sebum production, altered keratinization, inflammation, and bacterial colonisation of hair follicles on the face, neck, chest, and back by Propionibacterium acnes (P. acnes). Although early colonisation with P. acnes and family history might have important roles in the disease, exactly what triggers acne and how treatment affects the course of the disease remains unclear (Williams H.C. et ah, The Lancet, Vol.379. Jan 2012, pp. 361-372). [0019] There is no ideal treatment for acne. Good quality evidence on comparative effectiveness of common topical and systemic acne therapies is scarce. Topical therapies including benzoyl peroxide, retinoids, and antibiotics when used in combination usually improve control of mild to moderate acne, but suffer from side-effects. Treatment with combined oral contraceptives can help women with acne. Patients with more severe inflammatory acne usually need oral antibiotics combined with topical benzoyl peroxide to decrease antibiotic-resistant organisms.
[0020] Oral isotretinoin is the most effective therapy and is used early in severe disease, but its use is limited by teratogenicity and other side-effects.
[0021 ] The treatment of acne with the composition of this invention allows using lower amounts of active agents and therefore results in reduced side-effects, due to the additive and/or synergistic effects.
ROSACEA (ACNE ROSACEA)
[0022] Rosacea is a chronic skin disease that affects more than 16 million Americans. The cause of rosacea is still unknown. However, research has allowed doctors to find ways to treat the condition by minimizing its symptoms (Cynthia Cobb, Healthline May 21, 2018).
[0023] There are four subtypes of rosacea. Each subtype has its own set of symptoms. It is possible to have more than one subtype of rosacea at a time.
[0024] Rosacea’s typical symptom is small, red, pus-filled bumps on the skin that are present during flare-ups. Typically, rosacea affects only skin on the nose, cheeks, and forehead.
[0025] Flare-ups often occur in cycles. This means that one will experience symptoms for weeks or months at a time, the symptoms will go away, and then return.
[0026] The four types of rosacea are:
[0027] Subtype one, known as erythematotelangiectatic rosacea (ETR), is associated with facial redness, flushing, and visible blood vessels.
[0028] Subtype two, papulopustular (or acne) rosacea, is associated with acne-like breakouts, and often affects middle-aged women.
[0029] Subtype three, known as rhinophyma rosacea, is a rare form associated with thickening of the skin on your nose. It usually affects men and is often accompanied by another subtype of rosacea.
[0030] Subtype four is known as ocular rosacea, and its symptoms are centered on the eye area. HIDRADENITIS SUPPURATIVA
[0031] Hidradenitis suppurativa (HS), also known as acne inversa, is a long-term chronic skin disease whose present treatment options are often unsatisfactory. HS has a profound effect on patient’s quality of life (QoL). Alavi A. et ah, reviewed QoL aspects of this disease in an article titled “Quality-of-Life Impairment in Patients with Hidradenitis Suppurativa” (Am J Clin Dermatol, 2014, vol. 15.No. 6). The clinical picture of HS includes solitary nodules, diffuse, painful abscesses, malodorous drainage, sinus tract formation and scarring. The exact cause of hidradenitis suppurativa is still unclear, but it is believed that the underlying mechanism involves dysfunction of the apocrine sweat glands or hair follicles.
[0032] There is no cure for HS, but treatments with drugs selected from oral antibiotics, corticosteroid injections, antiandrogen therapy with high dosages of cyproterone acetate and ethynyl estradiol, TNF inhibitors like adalimumab and immunosuppressive drugs have been attempted.
PRURIGO NODULARIS (PN)
[0033] PN is characterized by hyperkeratotic excoriated papulonodular (itchy) lesions that show symmetrical distribution on the extensor surfaces of the body and/or extremities, the numbers of which range from several to hundreds (Akarsu, S. et al. An Bras Dermatol . 2018;93(5):671-9.). It is a rare disease and is one of the most difficult conditions in terms of determining its etiology and treatment among chronic skin diseases.
GRANULOMA ANNULARE (GA)
[0034] Granuloma annulare (GA) is a cutaneous granulomatous disease. It is not caused by an infection and is the most common non-infectious granulomatous disease. The disease is benign and often self-limited. Granuloma annulare usually presents as erythematous plaques or papules arranged in an annular configuration on the upper extremities. Despite being a benign disease, it can be associated with more serious conditions such as HIV or malignancy.
[0035] Although numerous theories have been proposed to explain the cause of granuloma annulare, the pathogenesis of this cutaneous disease remains unclear. It has been reported to follow trauma, malignancy, viral infections (including human immunodeficiency virus [HIV], Epstein- Barr virus, and herpes zoster), insect bites, and tuberculosis skin tests. [Smith MD, Downie JB, DiCostanzo D. Granuloma annulare. Int J Dermatol . 1997; 36: 326-33; Prendiville JS. Chapter 44. Granuloma Annulare. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K. eds. Fitzpatrick's Dermatology in General Medicine, 8e New York, NY: McGraw-Hill; 2012. Samlaska CP, Sandberg GD, Maggio KL, et al. Generalized perforating granuloma annulare, J Am Acad Dermatol 1992; 27: 319-322]
[0036] Granuloma annulare lesions are approximately distributed as follows:
60% isolated to the hands and arms; 20% on the legs and feet; 7% on both upper and lower extremities and 5% on the trunk plus other areas.
The four main clinical variants of granuloma annulare are:
Localized; Disseminated; Subcutaneous; and Perforating.
[0037] The localized form of granuloma annulare composes 75 percent of cases. Localized granuloma annulare starts as a ring of small, firm, flesh-colored or red papules.
[0038] Most cases of localized granuloma annulare are diagnosed in patients before 30 years of age. As the condition progresses, there is some central involution, and the ring of papules slowly increases from 0.5 to 5.0 cm in diameter. The lesions may be isolated or coalesce into plaques. They are found on the lateral or dorsal surfaces of the hands and feet.
[0039] The Disseminated or generalized granuloma annulare is similar to the localized variant but is more widespread, having 10 or more lesions. The papules may fuse to form annular lesions on the extremities, trunk, and neck. In contrast to the localized form, these lesions may persist for three to four years or longer.
[0040] The Subcutaneous granuloma annulare is diagnosed primarily in children two to five years of age. The lesions are asymptomatic, rapidly growing subcutaneous nodules on the extremities, hands, scalp, buttocks, and pretibial and periorbital areas.
[0041 ] The Perforating granuloma annulare is rare and occurs most often in children and young adults. It is also more common in women. Perforating granuloma annulare can have localized and generalized forms.
[0042] The localized form is found on the upper limbs and pelvis, and the generalized form, which is more common, is present on the abdominal area, trunk, and upper and lower limbs.
LICHEN PLANUS
[0043] Lichen planus is a T cell-mediated autoimmune disorder, in which inflammatory cells attack an unknown protein within the skin and mucosal keratinocytes.
[0044] Lichen planus is a condition that can cause swelling and irritation in the skin, hair, nails and mucous membranes. On the skin, lichen planus usually appears as purplish, itchy, flat bumps that develop over several weeks. In the mouth, vagina and other areas covered by a mucous membrane, lichen planus forms lacy white patches, sometimes with painful sores.
URTICARIA
[0045] Urticaria, also known as hives, is an outbreak of swollen, pale red bumps or plaques (wheals) on the skin that appear suddenly either as a result of the body's reaction to certain allergens, or for unknown reasons.
[0046] Hives usually cause itching, but may also bum or sting. They can appear anywhere on the body, including the face, lips, tongue, throat, or ears. Hives vary in size, and may join together to form larger areas known as plaques. They can last for hours, or up to one day before fading.
HERPES
[0047] Herpes simplex is a viral infection caused by the herpes simplex vims. Infections are categorized based on the part of the body infected. Oral herpes involves the face or mouth. It may result in small blisters in groups often called cold sores or fever blisters or may just cause a sore throat.
[0048] Herpes Zooster is a viral infection caused by the varicella-zoster vims characterized by a painful skin rash with blisters in a localized area.
COMPOSITION OF THIS DISCLOSURE
[0049] This invention provides and makes use, in one aspect, of a topical composition comprising between about 0.5% w/w to about 10.0% w/w proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder. In another embodiment, the skin disorder is a skin inflammatory disorder. In another embodiment, the skin disorder is not induced by cancer therapy. In another embodiment, the skin disorder is not induced by for example radiation. In other embodiments, the skin disorder is selected from the group consisting of psoriasis (selected from plaque psoriasis, flexural/inverse psoriasis, scalp psoriasis, sebopsoriasis and genital psoriasis); dermatitis (also known as eczema) selected from atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis; acne selected from acne vulgaris, papulopustular acne and nodular acne; rosacea selected from erythematotelangiectatic rosacea, papulopustular rosacea, rhinophyma rosacea and ocular rosacea; prurigo nodularis; granuloma annulare; urticaria; hidradenitis suppurativa; lichen planus; dry skin; herpes simplex and herpes zoster. [0050] The PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 0.5 % to about 10.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 0.5 % to about 1.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 1.0 % to about 5.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 5.0 % to about 10 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 1.0 % to about 1.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 1.5 % to about 2.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 2.0 % to about 2.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 2.5 % to about 3.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 3.0 % to about 3.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 3.5 % to about 4.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 4.0 % to about 4.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 4.5 % to about 5.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 5.0 % to about 5.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 5.5 % to about 6.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 6.0 % to about 6.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 6.5 % to about 7.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 7.0 % to about 7.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 7.5 % to about 8.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 8.0 % to about 8.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 8.5 % to about 9.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 9.0 % to about 9.5 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 9.5 % to about 10.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 1.0 % to about 5.0 % w/w. In another embodiment, the PPI or a pharmaceutically acceptable salt thereof is in an amount of between about 5.0 % to about 10.0 % w/w. In another embodiment, the amount is 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 %, 5.0
%, 5.1 %, 5.2 % , 5.3 %, 5.4 %, 5.5 %, 5.6 %, 5.7 %, 5.8 %, 5.9 %, 6.0 %, 6.1 %, 6.2 %, 6.3 % , 6.4 %, 6.5 %, 6.6 %, 6.7 %, 6.8 %, 6.9 %, 7.0 %, 7.1 %, 7.2 %, 7.3 %, 7.4 %, 7.5 %, 7.6 %, 7.7 %,
7.8 %, 7.9 %, 8.0 %, 8.1 %, 8.2 %, 8.3 %, 8.4 %, 8.5 %, 8.6 %, 8.7 %, 8.8 %, 8.9 %, 9.0 %, 9.1 %,
9.2 %, 9.3 %, 9.4 %, 9.5 %, 9.6 %, 9.7 %, 9.8 %, 9.9 % or 10.0 % w/w. Each possibility represents a separate embodiment of this invention.
[0051] The PPI within the compositions of this invention is at least one compound selected from the group consisting of: omeprazole, lansoprazole, esomeprazole, dexlansoprazole, pantoprazole, rabeprazole and ilaprazole. In one embodiment, the PPI consists essentially of one compound of the list described hereinabove. In one embodiment, the PPI consists essentially of two compounds of the list described hereinabove. In one embodiment, the PPI consists essentially of more than two compounds of the list described hereinabove. In one embodiment, the PPI is omeprazole. In one embodiment, the PPI is lansoprazole. In one embodiment, the PPI is esomeprazole.
[0052] Non-limiting examples of pharmaceutically acceptable salts of PPI within the compositions of this invention include: chloride, acetate, citrate, lactate, mesylate, nitrate, sulfate, phosphate, diphosphate, tartrate, carbonate and bicarbonate. Each possibility represents a separate embodiment of this invention. In one embodiment, the salt is phosphate.
[0053] The composition can be administered using a variety of routes such as topical application or transdermal application. The preferred route is the topical route and the preferred formulations are the cream, the gel and the lotion.
[0054] The composition can be formulated as a cream, a gel, an ointment, an emulsion, a solution, a suspension, an elixir, a lotion, a tincture, a paste, a foam, an aerosol, a spray, a patch, a stick, a transdermal patch, a sebum control product or an applicator syringe. Each possibility represents a separate embodiment of this invention. The composition provided herein is an ophthalmic composition, formulated as an ointment, a paste, drops, a solution or a suspension. [0055] Sebum control products may include ingredients selected from the group consisting of: azelaic acid, salicylic acid, sulfur, nicotinamide, L-carnitine and combinations thereof. Each possibility represents a separate embodiment of this invention.
[0056] Some pharmaceutical compositions have chemical stability problems, caused either by interaction of the active agent with the carrier and/or other excipient and/or by interaction of the active agent with, for example, the subject’s skin - in case of topical compositions.
[0057] One of the solutions for this chemical stability problem is the encapsulation of PPI or pharmaceutically acceptable salt thereof in the composition. The preferred encapsulation method of this invention is detailed in U.S. PatentNo. 9687465 and published U.S. Patent Application No. 2018147165 (to Sol-Gel Technologies), whose contents are enclosed herein in their entirety. Thus, for example, PPI or pharmaceutically acceptable salt thereof in the compositions of this invention may be encapsulated as disclosed above.
[0058] The PPI or pharmaceutically acceptable salt thereof is included in the carrier in an amount sufficient to exert a therapeutically useful effect i.e., treatment, prevention or alleviation of a non-cancer therapy induced skin disorder (or non-cancer therapy induced skin inflammatory disorder) with minimal or no toxicity or other side effects. Generally, emollient or lubricating vehicles that help hydrate the skin are more preferred than volatile vehicles, such as ethanol, that dry the skin. Examples of suitable bases or vehicles for preparing compositions for use with human skin are petrolatum, petrolatum plus volatile silicones, lanolin, cetostearyl alcohol, cold cream and hydrophilic ointment. Each possibility represents a separate embodiment of this invention. [0059] In some embodiment, the compositions of this invention comprise PPI or pharmaceutically acceptable salt thereof; and a carrier, a solvent, an emollient, a surfactant, an anti-oxidant, a chelating agent, a gelling agent, a wetting agent, a penetration enhancer, a moisturizing agent, a preservative (e.g. imidurea and methylparaben), an anti-oxidant, a buffer or any combination thereof. Each possibility represents a separate embodiment of this invention. [0060] In some embodiments, the compositions of this invention comprise a penetration enhancer. In another embodiment, the penetration enhancer is selected from the group consisting of dimethylsulfoxide (DMSO), diethylene glycol monoethyl ether (Transcutol), methyl sulfonylmethane (MSM), oleic acid, oleyl alcohol, propylene glycol, dimethyl isosorbide, isopropyl myristate, diethyl sebacate, ethanol, isopropyl alcohol, a polyethylene glycol, hexylene glycol, glycofurol and any combination thereof. Each possibility represents a separate embodiment of this invention.
[0061] In some embodiments, the compositions of this invention comprise an emollient. In another embodiment, the emollient is selected from the group consisting of castor oil, mineral oil, vegetable oil, soybean oil, shea butter, cocoa butter, paraffin, beeswax, oleic acid, squalene, cetyl alcohol, isopropyl myristate, urea, glycerol, propylene glycol, lactic acid, cetostearyl alcohol, lanoin and any combination thereof. Each possibility represents a separate embodiment of this invention. In another embodiment, the emollient is cetostearyl alcohol. In another embodiment, the emollient is lanoin.
[0062] In some embodiments, the compositions of this invention comprise a chelating agent. In another embodiment, the chelating agent is selected from the group consisting of EDTA deferoxamine, deferiprone, deferasirox, dimercaptosuccinic acid (succimer) triethylenetetramine (trientine) and any combination thereof. Each possibility represents a separate embodiment of this invention.
[0063] In some embodiments, the compositions of this invention comprise an anti-oxidant. In another embodiment, the anti-oxidant is selected from the group consisting of butylated hydroxytoluene (BHT), parabens, propyl gallate, ascorbic acid, flavones, flavanones, flavonols, stilbenoids, gallic acid, cinnamic acid, ellagic acid, salicylic acid, curcumin, eugenol, citric acid, tocopherols and any combination thereof. Each possibility represents a separate embodiment of this invention.
[0064] In some embodiments, the compositions of this invention comprise a solvent. In another embodiment the solvent is selected from the group consisting of propylene glycol, diethylene glycol monoethyl ether (Transcutol), dimethylsulfoxide (DMSO), diethyl sebacate, polyethylene glycol, oleyl alcohol, isosorbide dimethyl ether, ethanol, isopropyl alcohol, isopropyl myristate, oleic acid, hexylene glycol, glycerin, glycofurol and any combination thereof. Each possibility represents a separate embodiment of this invention.
[0065] In some embodiments, the compositions of this invention comprise a preservative. In another embodiment the preservative is selected from the group consisting of benzoic acid, methylparaben, , imidurea, chlorocresol, Phenoxyethanol, propyl paraben, benzalkonium chloride, benzyl alcohol, imidazolidinyl urea, sodium benzoate, sorbic acid, thimerosal sorbic acid, sodium sorbate, sodium sulfite, ethanol, and any combination thereof. In another embodiment, the preservative is imidurea and methylparaben. Each possibility represents a separate embodiment of this invention.
[0066] In some embodiments, the compositions of this invention comprise a buffer. In another embodiment, the buffer is selected from the group consisting of citric acid, phosphoric acid, acetic acid, tartaric acid, glutamic acid, aspartic acid, malic acid, succinic acid, fumaric acid, salt thereof, and any combination thereof. Each possibility represents a separate embodiment of this invention. [0067] In some embodiments, the compositions of this invention comprise a gelling agent. In another embodiment, the gelling agent is selected from the group consisting of carbomer homopolymer type A (Carbopol®981, Carbopol®980), Sepineo P600, Natrosol hydroxy ethylcellulose, starch, pectin, gelatin, agar, alginic acid and salts thereof, Carbomer® 934, carboxymethylcellulose, hydroxypropylmethylcellulose and any combination thereof. Each possibility represents a separate embodiment of this invention.
[0068] In some embodiments, the compositions of this invention comprise a surfactant. In another embodiment, the surfactant is selected from the group consisting of carbomer copolymer type B (Pemulen®TR-l), sorbitan monooleate (Span80), polysorbate 80 (Tween 80), polysorbate 20, polysorbate 60 (Tween 60), sodium dodecyl sulfate, cetearyl alcohol, dioctyl sodium sulfosuccinate, glyceryl oleate, glyceryl stearate, poloxamers and any combination thereof. Each possibility represents a separate embodiment of this invention.
[0069] In some embodiments, the compositions of this invention comprise a wetting agent. In another embodiment, the wetting agent is selected from the group consisting of PEG 400, glycerin, poloxamers, sorbitan monooleate (Span80), polysorbate 80 (Tween 80), polysorbate 20, polysorbate 60 (Tween 60), benzalkonium chloride, sodium dodecyl sulfate and any combination thereof. Each possibility represents a separate embodiment of this invention.
[0070] In some embodiments, the compositions of this invention comprise a moisturizing agent. In another embodiment, the moisturizing agent is selected from the group consisting of lanolin, cetostearyl alcohol, hyaluronic acid or its salt, pyrrolidone, glycerin, diglycerin, polyglycerin, a polyol such as propylene glycol, hexylene glycol, dipropylene glycol and 1,3-butylene glycol, shea butter, hyaluronic acid, dimethicone, petrolatum, stearic acid, proteins, urea, mineral oil and any combination thereof . Each possibility represents a separate embodiment of this invention. In another embodiments, the moisturizing agent is lanolin. In another embodiment, the moisturizing agent is cetostearyl alcohol.
[0071 ] Pharmaceutical carriers or vehicles suitable for preparation of the compositions provided herein include any such carriers known to those skilled in the art to be suitable for the particular mode of administration.
[0072] Suitable pharmaceutically and dermatologically acceptable carriers or vehicles for topical application include lotions, creams, foams, solutions, gels, patches, a stick and the like. Generally, the carrier or vehicle is either organic in nature or an aqueous emulsion and capable of accommodating the selected active agent(s), which may be micronized, dispersed, suspended or dissolved therein. Each possibility represents a separate embodiment of this invention. The vehicle or carrier may include pharmaceutically-acceptable emollients, moisturizers, including lactic acid, ammonium lactate and urea, skin penetration enhancers, coloring agents, fragrances, emulsifiers, thickening agents, vegetable oils, essential oils, zinc oxide and solvents. Each possibility represents a separate embodiment of this invention.
[0073] In some embodiments, this invention provides a dosage form comprising a composition as described hereinabove. In one embodiment, the dosage form is used in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder (or non-cancer therapy induced skin inflammatory) disorder. In other embodiments, the skin disorder is selected from the group consisting of psoriasis (selected from plaque psoriasis, flexural/inverse psoriasis, scalp psoriasis, sebopsoriasis and genital psoriasis); dermatitis (also known as eczema) selected from atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis; acne selected from acne vulgaris, papulopustular acne and nodular acne; rosacea selected from erythematotelangiectatic rosacea, papulopustular rosacea, rhinophyma rosacea and ocular rosacea; prurigo nodularis; granuloma annulare; urticaria; hidradenitis suppurativa; lichen planus; dry skin; herpes simplex and herpes zoster.
[0074] In some embodiments, the compositions or dosage forms of this invention are used in the methods as described hereinbelow and/or are used in the preparation of medicaments that are used in said methods.
REGIMEN OF TREATMENT
[0075] In some embodiments, this invention provides a regimen for the treatment, prevention or alleviation of non-cancer therapy induced skin disorder (or non-cancer therapy induced skin inflammatory disorder), comprising topically applying onto an affected skin area of a subject in need thereof, once a day, twice a day, more than twice a day, weekly, bi-weekly a topical composition which comprises between about 0.5% w/w to about 10.0% w/w proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. In another embodiment, the skin disorder is a skin inflammatory disorder. In another embodiment, the skin disorder is not induced by cancer therapy. In another embodiment, the skin disorder is not induced by for example radiation.
[0076] In some embodiments, the skin disorder (or the skin inflammatory disorder) is selected from the group consisting of: dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster. Each possibility represents a separate embodiment of this invention. In one embodiment, the dermatitis is selected from the group consisting of: atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis. Each possibility represents a separate embodiment of this invention. In one embodiment, the psoriasis is selected from the group consisting of: plaque (vulgaris), guttate, flexural/inverse, pustular, and erythrodermic. Each possibility represents a separate embodiment of this invention. In one embodiment, the rosacea is selected from the group consisting of: erythematotelangiectatic rosacea (ETR), papulopustular (or acne) rosacea, rhinophyma and ocular rosacea. Each possibility represents a separate embodiment of this invention.
[0077] In some embodiments, the effective amount is a therapeutically effective amount of the PPI or pharmaceutically acceptable salt thereof, namely an amount which will treat, prevent or alleviate a non-cancer therapy induced skin disorder (or non-cancer therapy induced skin inflammatory disorder).
[0078] The frequency of administration (of compositions or dosage forms) can be determined empirically.
[0079] Exemplary frequencies of the administration are once daily, twice daily, weekly, bi weekly or monthly. Typical administration frequencies of the compositions of this invention are once daily and twice daily. Each possibility represents a separate embodiment of this invention. [0080] Dosage frequencies can be gradually decreased over time and maintained at a steady dose suitable for long-term - six months, 1 year, 5 years, 10 years or more, up to lifelong administration to control the symptoms of non-cancer therapy induced topical skin disease, disorder or condition. For example, dosage administration can begin at from once a day, to two times a week, to once a week, to once every two weeks or less frequent than once every two weeks. Each possibility represents a separate embodiment of this invention.
METHODS OF TREATMENT
[0081] In one additional aspect, this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced skin disorder, wherein the method comprises administering to a subject in need thereof, a topical composition or the dosage form as described herein.
[0082] In one additional aspect, this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof, a topical composition or the dosage form as described herein.
[0083] In some aspects this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced skin disorder (or non-cancer therapy induced skin inflammatory disorder), wherein the method comprises administering to a subject in need thereof, a topical composition comprising between 0.5% w/w to about 10.0% w/w PPI or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
[0084] In one additional aspect, this invention provides a method of treatment, prevention or alleviation of a skin disorder, wherein the method comprises administering to a subject in need thereof, a topical composition comprising between 0.5% w/w to about 10.0% w/w PPI or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein the skin disorder is not induced by cancer therapy, or was not induced by radiation.
[0085] In one additional aspect, this invention provides a method of treatment, prevention or alleviation of a skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof, a topical composition comprising between 0.5% w/w to about 10.0% w/w PPI or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein the skin disorder is not induced by cancer therapy, or was not induced by radiation. [0086] In one additional aspect, this invention provides a method of treatment, prevention or alleviation of a skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof, a topical composition comprising between 0.5% w/w to about 10.0% w/w PPI or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein the skin disorder is selected from the group consisting of psoriasis (selected from plaque psoriasis, flexural/inverse psoriasis, scalp psoriasis, sebopsoriasis and genital psoriasis); dermatitis (also known as eczema) selected from atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis; acne selected from acne vulgaris, papulopustular acne and nodular acne; rosacea selected from erythematotelangiectatic rosacea, papulopustular rosacea, rhinophyma rosacea and ocular rosacea; prurigo nodularis; granuloma annulare; urticaria; hidradenitis suppurativa; lichen planus; dry skin; herpes simplex and herpes zoster.
[0087] In some embodiments, the skin disorders being treated by the composition of this invention is selected from the group consisting of: dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster. Each possibility represents a separate embodiment of this invention. In one embodiment, the dermatitis is selected from the group consisting of: atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis. Each possibility represents a separate embodiment of this invention. In one embodiment, the In one embodiment, the psoriasis is selected from the group consisting of: plaque (vulgaris), guttate, flexural/inverse, pustular, and erythrodermic. Each possibility represents a separate embodiment of this invention. In one embodiment, the In one embodiment, the rosacea is selected from the group consisting of: erythematotelangiectatic rosacea (ETR), papulopustular (or acne) rosacea, rhinophyma and ocular rosacea. Each possibility represents a separate embodiment of this invention.
[0088] In some embodiments, the effective amount is a therapeutically effective amount of the PPI or pharmaceutically acceptable salt thereof, namely an amount which will treat, prevent or alleviate a skin disorder, or skin inflammatory disorder.
[0089] Dosage frequencies can be gradually decreased over time and maintained at a steady dose suitable for long-term - six months, 1 year, 5 years, 10 years or more, up to lifelong administration to control the symptoms of the non-cancer therapy induced topical skin disease, disorder or condition. For example, dosage administration can begin at from once a day, to two times a week, to once a week, to once every two weeks or less frequent than once every two weeks. Each possibility represents a separate embodiment of this invention.
KITS
[0090] In one further aspect, this invention provides a kit comprising the compositions or dosage forms as described hereinabove. In one embodiment, the kit further comprises instructions for administration.
[0091] The compositions provided herein can be packaged as articles of manufacture containing packaging material, a composition provided herein, and a label that indicates that the composition is for treating a non-cancer therapy induced topical skin disease, disorder or condition, and is formulated for e.g. topical delivery.
[0092] The articles of manufacture provided herein contain packaging materials. Packaging materials for use in packaging pharmaceutical products are well known to those of skill in the art. Examples of pharmaceutical packaging materials include, but are not limited to bottles, tubes, containers, application syringes or dual chamber application syringes and any packaging material suitable for the selected formulation and intended mode of administration and treatment. Each possibility represents a separate embodiment of this invention.
EMBODIMENTS
[0093] In one embodiment, this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
[0094] In one embodiment, this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin inflammatory disorder. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
[0095] In one embodiment, this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder, wherein the PPI is selected from the group consisting of: omeprazole, lansoprazole, esomeprazole, dexlansoprazole, pantoprazole, rabeprazole and ilaprazole. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
[0096] In one embodiment, this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin inflammatory disorder, wherein the PPI is selected from the group consisting of: omeprazole, lansoprazole, esomeprazole, dexlansoprazole, pantoprazole, rabeprazole and ilaprazole. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
[0097] In one embodiment, this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder, wherein the skin disorder is selected form the group consisting of: dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the dermatitis is selected from the group consisting of: atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis. In another embodiment, the psoriasis is selected from the group consisting of: plaque (vulgaris), guttate, flexural/inverse, pustular, and erythrodermic. In another embodiment, the rosacea is selected from the group consisting of: erythematotelangiectatic rosacea (ETR), papulopustular (or acne) rosacea, rhinophyma and ocular rosacea. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
[0098] In one embodiment, this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin inflammatory disorder, wherein the skin inflammatory disorder is selected form the group consisting of: dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the dermatitis is selected from the group consisting of atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis. In another embodiment, the psoriasis is selected from the group consisting of: plaque (vulgaris), guttate, flexural/inverse, pustular, and erythrodermic. In another embodiment, the rosacea is selected from the group consisting of: erythematotelangiectatic rosacea (ETR), papulopustular (or acne) rosacea, rhinophyma and ocular rosacea. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
[0099] In one embodiment, this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder, wherein the composition is formulated as a cream, a gel, an ointment, an emulsion, a solution, a suspension, an elixir, a lotion, a tincture, a paste, a foam, an aerosol, a spray, a patch, a stick, a transdermal patch or an applicator syringe. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
[00100] In one embodiment, this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin inflammatory disorder, wherein the composition is formulated as a cream, a gel, an ointment, an emulsion, a solution, a suspension, an elixir, a lotion, a tincture, a paste, a foam, an aerosol, a spray, a patch, a stick, a transdermal patch or an applicator syringe. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
[00101] In one embodiment, this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder, wherein the topical composition is an ophthalmic composition. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the ophthalmic composition is formulated as an ointment, a paste, a gel, a cream, drops, a solution or a suspension. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
[00102] In one embodiment, this invention provides a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin inflammatory disorder, wherein the topical composition is an ophthalmic composition. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the ophthalmic composition is formulated as an ointment, a paste, a gel, a cream, drops, a solution or a suspension. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated.
[00103] In one embodiment, this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
[00104] In one embodiment, this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
[00105] In one embodiment, this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the PPI is selected from the group consisting of: omeprazole, lansoprazole, esomeprazole, dexlansoprazole, pantoprazole, rabeprazole and ilaprazole. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
[00106] In one embodiment, this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the PPI is selected from the group consisting of: omeprazole, lansoprazole, esomeprazole, dexlansoprazole, pantoprazole, rabeprazole and ilaprazole. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
[00107] In one embodiment, this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the skin disorder is selected form the group consisting of: dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the dermatitis is selected from the group consisting of: atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis. In another embodiment, the psoriasis is selected from the group consisting of: plaque (vulgaris), guttate, flexural/inverse, pustular, and erythrodermic. In another embodiment, the rosacea is selected from the group consisting of: erythematotelangiectatic rosacea (ETR), papulopustular (or acne) rosacea, rhinophyma and ocular rosacea. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
[00108] In one embodiment, this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the skin inflammatory disorder is selected form the group consisting of: dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the dermatitis is selected from the group consisting of: atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis. In another embodiment, the psoriasis is selected from the group consisting of: plaque (vulgaris), guttate, flexural/inverse, pustular, and erythrodermic. In another embodiment, the rosacea is selected from the group consisting of: erythematotelangiectatic rosacea (ETR), papulopustular (or acne) rosacea, rhinophyma and ocular rosacea. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
[00109] In one embodiment, this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the composition is formulated as a cream, a gel, an ointment, an emulsion, a solution, a suspension, an elixir, a lotion, a tincture, a paste, a foam, an aerosol, a spray, a patch, a stick, a transdermal patch or an applicator syringe. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPL In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPL In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly. [00110] In one embodiment, this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the composition is formulated as a cream, a gel, an ointment, an emulsion, a solution, a suspension, an elixir, a lotion, a tincture, a paste, a foam, an aerosol, a spray, a patch, a stick, a transdermal patch or an applicator syringe. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPL In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPL In another embodiments, the topical composition comprises 1 % w/w PPL In another embodiments, the topical composition comprises 5 % w/w PPL In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPL In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi weekly or monthly.
[00111] In one embodiment, this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the topical composition is an ophthalmic composition. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPL In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPL In another embodiments, the topical composition comprises 1 % w/w PPL In another embodiments, the topical composition comprises 5 % w/w PPL In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPL In another embodiment, the ophthalmic composition is formulated as an ointment, a paste, a gel, a cream, drops, a solution or a suspension. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
[00112] In one embodiment, this invention provides a method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin inflammatory disorder, wherein the method comprises administering to a subject in need thereof a topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the topical composition is an ophthalmic composition. In another embodiment, the topical composition comprises between about 0.5 % w/w to about 1% w/w PPI. In another embodiment, the topical composition comprises between about 1 % w/w to about 5% w/w PPI. In another embodiments, the topical composition comprises 1 % w/w PPI. In another embodiments, the topical composition comprises 5 % w/w PPI. In another embodiment, the topical composition comprises between about 5 % w/w to about 10 % w/w PPI. In another embodiment, the ophthalmic composition is formulated as an ointment, a paste, a gel, a cream, drops, a solution or a suspension. In another embodiment, the PPI is encapsulated. In another embodiment, the PPI is not encapsulated. In another embodiment, the administration is once daily, twice daily, weekly, bi-weekly or monthly.
DEFINITIONS
[001] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the invention pertains. In case of conflict, the specification, including definitions, takes precedence. All patents, patent applications, published applications, articles, publications and other published materials referred to throughout the entire disclosure herein, unless noted otherwise, are incorporated by reference in their entirety.
[002] As used herein, the indefinite articles "a" and "an" mean "at least one" or "one or more" unless the context clearly dictates otherwise.
[003] As used herein, the term "treating" or” treatment" includes curing a condition, treating a condition, preventing a condition, treating symptoms of a condition, curing symptoms of a condition, ameliorating symptoms of a condition, treating effects of a condition, ameliorating effects of a condition, and preventing results of a condition.
[004] As used herein, the terms “inflammatory skin conditions”, “inflammatory skin disorders”, “inflammatory skin diseases” and “inflammatory cutaneous conditions” are any medical conditions affecting the integumentary system and are used interchangeably.
[005] As used herein, a "pharmaceutical composition" refers to a composition comprising one or more active ingredients with other components such as pharmaceutically acceptable ingredients or excipients. The purpose of a pharmaceutical composition is to facilitate administration of an active ingredient to a subject.
[006] Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases “ranging/ranges between” a first indicate number and a second indicate number and “ranging/ranges from” a first indicate number “to” a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween.
[007] As used herein, numerical ranges preceded by the term “about” should not be considered to be limited to the recited range. Rather, numerical ranges preceded by the term “about” should be understood to include a range accepted by those skilled in the art for any given element in formulations according to the present invention.
[008] As used herein, when a numerical value is preceded by the term "about", the term "about" is intended to indicate +/ - 10% . [009] The terms "comprise", "comprising", "includes", "including", “having” and their conjugates mean "including but not limited to".
[0010] The term “consisting of’ means “including and limited to”.
[0011] The term "consisting essentially of means that the composition, method formulation may include additional ingredients, steps and/or parts, but only if the additional ingredients, steps and/or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure.
[0012] As used herein the term "method" refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.
[0013] It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub combination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements. [0014] While it is preferred that the protecting group be removed by a pharmaceutical salt creating compound, the present invention is not limited to such embodiments. It is apparent to a person of skill in the art that the protecting group can be removed by other deprotecting agents, and the salt form of the drug may be generated in a separate, subsequent step.
EXAMPLES
Example 1
Pantoprazole Topical Compositions Preparation of 4 developed formulations of Pantoprazole (PPZ) ointment 1% and 5% for preliminary short term stability study were prepared.
Formulation 1:
Table 1: 1% PPZ in Lanolin matrix
Figure imgf000028_0001
* PPZ 17% suspension is in mineral oil/cyclometicone 5 (in a ratio of 17:43:40) was prepared using Dyno mill.
Formulation 2:
Table 2: 5% PPZ in Lanolin matrix
Figure imgf000028_0002
Figure imgf000029_0001
* PPZ 17% suspension is in mineral oil/cyclometicone 5 (in a ratio of 17:43:40) was prepared using Dyno mill.
Formulation 3: Table 3: 1% PPZ in Cetostearyl alcohol matrix
Figure imgf000029_0002
3PZ 17% suspension is in mineral oil/cyclometicone 5 (in a ratio of 17:43:40) was prepared using Dyno mill.
Formulation 4: 5% PPZ in Cetostearyl alcohol matrix
Figure imgf000029_0003
Figure imgf000030_0001
PPZ 17% suspension is in mineral oil/cyclometicone 5 (in a ratio of 17:43:40) was prepared using Dyno mill.
Preparation procedure (for all Formulations 1-4) 1. Weigh excipients 1, 2, 3, 4 and 5 to a glass beaker. Place the beaker on a hot plate with a water bath and heat at 65°C - 70°C to melt all excipients.
2. When all excipients are melted, add PPZ 17% suspension to the beaker.
3. Homogenize the mixture at 7000rpm for few minutes (2-5 min).
4. Place the beaker to the upper mixer platform and start moderate mixing. 5. Keep moderate mixing for cooling down.
Example 2 Stability Results
Figure imgf000030_0002
Figure imgf000031_0001
Figure imgf000031_0002
Figure imgf000032_0001
[0015] As can be seen in the stability results, the Pantoprazole (PPZ) ointments at 1% w/w or 5% w/w is stable for at least 2 months at 25 °C, as no phase separation was observed and no degradation.
[0016] While certain features disclosed have been illustrated and described herein, many modifications, substitutions, changes, and equivalents will now occur to those of ordinary skill in the art. It is, therefore, to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the compounds and methods of use disclosed herein.

Claims

CLAIMS What is claimed is:
1. A topical composition comprising between about 0.5% w/w to about 10.0% w/w a proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier for use in the treatment, prevention or alleviation of a non-cancer therapy induced skin disorder.
2. The topical composition of claim 1, wherein the skin disorder is a skin inflammatory disorder.
3. The topical composition of claim 1 or claim 2, comprising between about 0.5 % w/w to about 1% w/w PPI.
4. The topical composition of claim 1 or claim 2, comprising between about 1 % w/w to about 5% w/w PPI.
5. The topical composition of claim 1 or claim 2, comprising between about 5 % w/w to about 10% w/w PPI.
6. The topical composition of any one of claims 1-5, wherein the PPI is selected from the group consisting of: omeprazole, lansoprazole, esomeprazole, dexlansoprazole, pantoprazole, rabeprazole and ilaprazole.
7. The topical composition of any one of claims 1-6, wherein the skin disorder is selected form the group consisting of: dermatitis, psoriasis, prurigo nodularis, granuloma annulare, acne, rosacea, urticaria, eczema, hidradenitis suppurativa, lichen planus, dry skin, herpes simplex and herpes zoster.
8. The topical composition of claim 7, wherein the dermatitis is selected from the group consisting of: atopic dermatitis, contact dermatitis, dyshidrotic dermatitis, dermatitis herpetiformis, nummular dermatitis and seborrheic dermatitis.
9. The topical composition of claim 7, wherein the psoriasis is selected from the group consisting of: plaque (vulgaris), guttate, flexural/inverse, pustular, and erythrodermic.
10. The topical composition of claim 7, wherein the rosacea is selected from the group consisting of: erythematotelangiectatic rosacea (ETR), papulopustular (or acne) rosacea, rhinophyma and ocular rosacea.
11. The topical composition of any one of claims 1-10, wherein the composition is formulated as a cream, a gel, an ointment, an emulsion, a solution, a suspension, an elixir, a lotion, a tincture, a paste, a foam, an aerosol, a spray, a patch, a stick, a transdermal patch or an applicator syringe.
12. The topical composition of any one of claims 1-10, wherein the topical composition is an ophthalmic composition.
13. The topical composition of claim 12, wherein the ophthalmic composition is formulated as an ointment, a gel, a cream, drops, a paste, a solution or a suspension.
14. The topical composition of any one of claims 1-13, wherein the PPI is encapsulated.
15. A method of treatment, prevention or alleviation of a non-cancer therapy induced topical skin disorder, wherein the method comprises administering to a subject in need thereof, a topical composition according to any one of claims 1-14.
16. The method of claim 15, wherein the administration is once daily, twice daily, weekly, bi weekly or monthly.
PCT/IL2021/051399 2020-11-24 2021-11-24 Topical compositions comprising proton pump inhibitors (ppis) for the treatment of skin disorders WO2022113072A1 (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010119102A2 (en) * 2009-04-15 2010-10-21 Agon Pharma Gmbh Pharmaceutical composition for treating dermatological autoimmune diseases
US20140135363A1 (en) * 2012-11-14 2014-05-15 Boehringer Ingelheim Vetmedica Gmbh Proton pump inhibitor for use in a method of treating dermatological diseases in canine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010119102A2 (en) * 2009-04-15 2010-10-21 Agon Pharma Gmbh Pharmaceutical composition for treating dermatological autoimmune diseases
US20140135363A1 (en) * 2012-11-14 2014-05-15 Boehringer Ingelheim Vetmedica Gmbh Proton pump inhibitor for use in a method of treating dermatological diseases in canine

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE clinicaltrials.gov ANONYMOUS : "Proton Pump Inhibitors Use in Patients With Psoriasis ", XP055934740 *
FARIBA JAFFARY, MOHAMMAD ALI NILFOROUSHZADEH, HANIEH SHARIFIAN KOUPAIEE, GITA FAGHIHI, SEYED MOHSEN HOSSEINI, FATEME SOKHANVARI, N: "Omeprazole versus doxycycline combination therapy with topical erythromycin the treatment of acne vulgaris: a randomized clinical trial", TEHRAN UNIV. MED. J., vol. 75, no. 1, 30 April 2017 (2017-04-30), pages 24 - 30, XP009537014 *

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