WO2023021533A1 - Combinaison d'astaxanthine et de céramide destinée à être utilisée dans le traitement de la kératose pilaire - Google Patents

Combinaison d'astaxanthine et de céramide destinée à être utilisée dans le traitement de la kératose pilaire Download PDF

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Publication number
WO2023021533A1
WO2023021533A1 PCT/IS2022/050005 IS2022050005W WO2023021533A1 WO 2023021533 A1 WO2023021533 A1 WO 2023021533A1 IS 2022050005 W IS2022050005 W IS 2022050005W WO 2023021533 A1 WO2023021533 A1 WO 2023021533A1
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WIPO (PCT)
Prior art keywords
composition
ceramide
astaxanthin
vitamin
use according
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PCT/IS2022/050005
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English (en)
Inventor
Lilja KJALARSDOTTIR
Snaefridur ARNARDOTTIR
Steinthor SIGURDSSON
Pall Arnar HAUKSSON
Original Assignee
Saganatura Ehf.
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Application filed by Saganatura Ehf. filed Critical Saganatura Ehf.
Publication of WO2023021533A1 publication Critical patent/WO2023021533A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • 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
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
    • 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

Definitions

  • the present invention relates to compositions for the treatment of keratosis pilaris.
  • the invention also relates to methods of treatment of keratosis pilaris.
  • Keratosis pilaris is a common genetic condition of the skin's hair follicles characterized by the appearance of possibly itchy, small, gooseflesh-like bumps, with varying degrees of reddening or inflammation. It most often appears on the outer sides of the upper arms, thighs, face, back, and buttock.
  • KP occurs when the human body produces excess amounts of the skin protein keratin, resulting in the formation of small, raised bumps in the skin, often with surrounding redness. The excess keratin surrounds and entraps the hair follicles in the pore. This causes the formation of hard plugs.
  • KP alba characterized by rough, bumpy skin with no irritation
  • KP rubra characterized by red, inflamed bumps, which can be on arms, head, legs.
  • KP (ICD L11.0, Q82.8) is medically relatively harmless, but many individuals may seek treatment, as the condition can cause emotional distress.
  • Topical creams and lotions are currently the most commonly used treatment for KP, specifically those consisting of moisturizing or keratolytic treatments. Improvement of the skin often takes months, and the bumps are likely to return.
  • the present invention seeks to overcome some of the above mentioned deficiencies of the prior art.
  • the invention provides a composition comprising astaxanthin and ceramide for use in the treatment of keratosis pilaris.
  • Keratosis pilaris can preferably be keratosis pilaris alba.
  • composition can be for use in topical or oral administration, preferably in oral administration.
  • composition can be provided in tablet or capsule form for such oral administration.
  • the composition can generally contain in the range of about 1 to 15 mg astaxanthin and in the range of about 0.2 to 20 mg ceramide.
  • the composition can contain in the range of about 2 to 15 mg astaxanthin, in the range of 2 to 10 mg astaxanthin, in the range of about 3 to 10 mg astaxanthin or in the range of about 3 to 8 mg astaxanthin.
  • the lower limit of the range can be about 1 , 2, 3, 4, or about 5 mg astaxanthin.
  • the upper limit of the range can be about 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, or about 20 mg astaxanthin.
  • the composition can further contain in the range of about 0.2 to 20 mg ceramide, in the range of about 0.2 to 10 mg ceramide, in the range of about 0.2 to 5 mg ceramide, in the range of about 0.3 to 5 mg ceramide, in the range of about 0.4 to 4 mg ceramide, or in the range of about 0.4 to 2 mg ceramide.
  • the lower limit of the range can be about 0.1 , 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5 or 4.0 mg ceramide.
  • the upper limit of the range can be about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, or about 20 mg ceramide.
  • Ceramides are fatty acid amide derivatives of long-chain bases (LCB).
  • Long-chain bases can be aliphatic amino alcohol moieties, varying in length, unsaturation and number of hydroxygroups.
  • Examples of LCBs are sphingosine (2-amino-4-octadecene-1 ,3-diol), phytosphingosine (2-aminooctadecane-1 ,3,4-triol) and 2-aminooctadeca-4,8-diene-1 ,3-diol.
  • the fatty acids can be of varying chain length and unsaturation. Additionally, they may have a hydroxyl functional group attached to the principal chain.
  • a ceramide can have additional substituent attached to the 1 -hydroxy group of the LCB, such as carbohydrates.
  • additional substituent attached to the 1 -hydroxy group of the LCB such as carbohydrates.
  • a glucose moiety is attached to the LCB at the 1 -hydroxy position.
  • Ceramide is the main component of the stratum corneum of the epidermis layer of human skin.
  • Ceramide can have the general formula where R is a fatty acid moiety, and wherein the 1 -hydroxy group can be substituted with a carbohydrate group, such as glucose.
  • R can be any suitable fatty acid, and the 1- hydroxy group can be modified with any suitable carbohydrate group.
  • the ceramide can contain the LCB 2-aminooctadeca-4,8-diene-1 ,3- diol, the fatty acid 2-hydroxy-icosanoic acid, containing a glucose group in the 1 -position, i.e. the 1 -hydroxy group on the ceramide is modified by a glucose group.
  • Astaxanthin is a keto-carotenoid having the general IIIPAC name (3S,3'S)-3,3'-Dihydroxy- P,P-carotene-4,4'-dione. Astaxanthin can be all-trans, but can also have the cis-configuration at position 9, either partially or completely.
  • the astaxanthin can contain up to a total of 25% of cis-9 astaxanthin ((3S,3'S, 9-cis)-3,3'-Dihydroxy-p,p-carotene-4,4'-dione) and cis-13 astaxanthin ((3S,3'S, 13-cis)-3,3'-Dihydroxy-p,p-carotene-4,4'-dione)
  • the composition can be for administration once daily in one or multiple tablets or capsules that in total contain the above stated quantities of astaxanthin and ceramide.
  • the composition can be in the form of tablets or capsules that each contain 3 mg astaxanthin and 0.9 mg ceramide, where in the range of 1 to 4 capsules are administered daily.
  • composition can additionally contain at least one vitamin, mineral or skin-enhancing agent.
  • the composition can be in the form of capsules or tablets, wherein each capsule or tablet comprises 3 mg astaxanthin, 0.9 mg ceramide, 400 pg Vitamin A, 0.7 mg Vitamin B2, 8 mg Vitamin B3, 1.25 pg Vitamin B12, 125 mg collagen, 25 pg Vitamin B7, 40 mg Vitamin C, and 2.5 pg Vitamin D3.
  • the composition can also be in liquid form.
  • Liquid compositions can contain additional liquid health-promoting agents, such as fatty acids.
  • fatty acids include eicosapentaenoic acid (EPA) in the range of 20 mg to 250 mg and docosahexaenoic acid (DHA) in the range of 20 mg to 250 mg per administered daily dose.
  • EPA eicosapentaenoic acid
  • DHA docosahexaenoic acid
  • Other edible oils such as sunflower oil, coconut oil, olive oil may also be present in the composition.
  • the composition can generally be provided as a pharmaceutical composition, a nutraceutical or as a food supplement.
  • Symptoms of keratosis pilaris alba include bumps, itch and dry skin.
  • the bumps can be gooseflesh like, and can be absent of irritation (e.g., itching or inflammation).
  • the compositions are therefore suitable for relieving or ameliorating symptoms associated with keratosis pilaris alba, such as bumps, itch and/or dry skin.
  • compositions comprising astaxanthin and ceramide.
  • Such compositions can be administered in oral or topical form.
  • the compositions can comprise a dose as described in the foregoing, for example a dose that each comprises in the range of about 1-15 mg astaxanthin and in the range of about 0.2-20 mg ceramide.
  • compositions can be administered once daily or two or more times daily.
  • Oral compositions can be in the form of tablets, capsules, softgels, liquid or suspension.
  • the compositions can contain one or more further agent such as at least one vitamin, mineral or skin-enhancing agent, as described further herein.
  • FIG. 1 shows the proportions of participants finding improvement of keratosis pilaris (KP) symptoms after taking two capsules daily as described in Example 1.
  • KP keratosis pilaris
  • the participants are divided in two groups based on whether their condition is KP alba or KP rubra.
  • A shows the proportions after 30 days of treatment and
  • B shows the proportions after 60 days of treatment.
  • FIG. 2 shows the proportions of participants finding no improvement, slight improvement and much improvement of keratosis pilaris alba symptoms after taking two capsules daily as described in Example 2.
  • compositions according to the invention provide a significant improvement of the symptoms of keratosis pilaris (KP), in particular keratosis pilaris alba.
  • KP keratosis pilaris
  • the invention is based on the observation that oral administration of ceramides and astaxanthin improves the symptoms of KP alba (see examples 1 and 2), in particular alleviation of symptoms including dry skin and the appearance of raised bumps on the affected skin area.
  • Astaxanthin is a red carotenoid compound, responsible for the red color of various organisms such as trout or shrimps. Astaxanthin is produced naturally in monocellular algae, most notably Haematococcis pluvialis, and thus found in animals feeding on it. Astaxanthin is considered one of the most potent naturally occurring antioxidants.
  • Ceramides are a class of lipid molecules mainly occurring in cell membranes. Ceramides are composed of sphingosine and fatty acid and possibly other substituents, such as carbohydrates. Ceramide is the main component of the stratum corneum of the epidermis layer of human skin.
  • an effective combination of astaxanthin and ceramide generally comprises a daily dose of from about 1 mg to 15 mg of astaxanthin and from about 0.2 mg to 20 mg of ceramide.
  • the daily (24 hour) dose can be administered by single dosing or through administration of two or more doses in a 24 hour period.
  • compositions described herein can be formulated for use in nutraceuticals (e.g., food supplements), or they can be formulated for pharmaceutical use.
  • the compositions can be formulated for non-invasive or invasive administration.
  • the compositions can generally be formulated for oral, topical, transmucosal, vaginal, ocular, rectal or inhalation administration, or they can be formulated for injection.
  • the compositions can be formulated for oral or topical administration. It can be especially preferable to formulate the compositions for oral administration.
  • Formulations can generally be pharmaceutical or nutraceutical.
  • compositions can in general be in the form of tablets, capsules or liquid formulations.
  • the formulations can be in the form of tablets or capsules.
  • the compositions can include one or more additional nutritional and/or pharmaceutical agent, such as vitamins, minerals or skin enhancing agents.
  • additional health-promoting agents such as Vitamins A, B2, B3, B7, B12, C and D3 and collagen.
  • Vitamin A and more specifically, retinoic acid, appears to maintain normal skin health by switching on genes and differentiating keratinocytes (immature skin cells) into mature epidermal cells.
  • Vitamin B2 or riboflavin is necessary for cellular respiration.
  • Vitamin B3 or nicotinamide is essential for cellular metabolism. Furthermore, it increases the biosynthesis of ceramides in human keratinocytes.
  • Vitamin B7 or biotin is essential for normal cellular metabolism. Deficiency in vitamin B7 can cause skin rash.
  • Vitamin B12 or cobalamin is involved in the metabolism of every cell of the human body and is particularly important in the normal functioning of the nervous system and in the maturation of developing red blood cells in the bone marrow.
  • Vitamin C or ascorbic acid is an essential nutrient involved in the repair of tissue and the enzymatic production of certain neurotransmitters besides being an antioxidant.
  • Vitamin D3 or colecalciferol is important for maintaining calcium levels and promoting bone health and development.
  • Collagen is the main structural protein in the extracellular matrix found in the body's various connective tissues. It is mostly found in connective tissue such as cartilage, bones, tendons, ligaments, and skin. Accordingly, the compositions described can contain any one or any combination of these additional bioactive agents, in addition to astaxanthin and ceramide.
  • compositions can further comprise any suitable pharmaceutically acceptable excipient.
  • suitable pharmaceutically acceptable excipients are known in the art, and generally serve the role of providing the resulting composition with increased longterm stability, facilitate adsorption, enhance solubility, providing flowability or non-stick properties and also prevent degradation or aggregation over time.
  • Exemplary pharmaceutical excipients include fillers, binders, disintegrants, coatings, sorbents, antiadherents, lubricants, glidants, preservatives, antioxidants, flavouring agents, sweeteners, colouring agents, solvents, buffering agents, chelating agents, viscosity imparting agents, surface active agents and humectants.
  • diluents, excipients or carriers that may be used are well known in the formulation art and the form chosen for any particular regimen will depend on the given context and the formulator's choice.
  • Topical formulations can include one or more skin enhancing agents, such as moisturizing agents. Topical formulations can be designed to be moisturizing or to maximise the penetration of an active ingredient, often a medicine, into or through the skin.
  • topical formulations can comprise collagen, a known skin-enhancing agent, urea, lactic acid, glycolic acid, salicylic acid, fish oil (e.g., fatty acids such as ERA and/or DHA), and/or topical retinoids.
  • composition comprising astaxanthin and ceramide for use in the treatment of keratosis pilaris.
  • composition for use according to embodiment 1 wherein the keratosis pilaris is keratosis pilaris alba.
  • composition for use according to any one of the previous embodiments comprising in the range of about 1-15 mg astaxanthin and in the range of about 0.2-20 mg ceramide.
  • composition for use according to any one of the previous embodiments, wherein the composition is to be administered once daily.
  • composition for use according to any one of the previous embodiments wherein the composition is formulated as a tablet or capsule.
  • composition for use according to the previous embodiment, wherein the composition is to be administered orally at least once daily.
  • composition for use according to any one of the previous embodiments wherein the composition is in the form of tablets or capsules that each contain about 3 mg astaxanthin and about 0.9 mg ceramide.
  • composition for use according to any one of the previous embodiments wherein the composition further comprises at least one vitamin, mineral or skin-enhancing agent.
  • the skinenhancing agent is collagen.
  • composition for use according to any one of the previous embodiments, wherein the composition further comprises at least one vitamin selected from Vitamin A, Vitamin B2, Vitamin B3, Vitamin B7, Vitamin B12, Vitamin C, Vitamin D3.
  • compositions for use according to any one of the previous embodiments wherein the composition is formulated as capsules or tablets, wherein each capsule or tablet comprises 3 mg astaxanthin, 0.9 mg ceramide, 400 pg Vitamin A, 0.7 mg Vitamin B2, 8 mg Vitamin B3, 1.25 pg Vitamin B12, 125 mg collagen, 25 pg Vitamin B7, 40 mg Vitamin C, and 2.5 pg Vitamin D3.
  • composition for use according to the previous embodiment wherein the composition further comprises at least one fatty acid.
  • composition for use according to the previous embodiment, wherein the at least one fatty acid comprises EPA and/or DHA.
  • compositions for use according to any one of the previous embodiments wherein the composition is a pharmaceutical composition, wherein the composition optionally contains one or more pharmaceutically acceptable excipient.
  • a method of treatment of keratosis pilaris alba comprising administering to an individual in need thereof a composition comprising astaxanthin and ceramide.
  • composition is administered orally.
  • composition comprises is in dose format wherein each dose comprises in the range of about 1-15 mg astaxanthin and in the range of about 0.2-20 mg ceramide.
  • composition is administered once daily.
  • composition is formulated as a tablet or capsule.
  • composition further comprises at least one vitamin, mineral or skin-enhancing agent.
  • the present invention also covers the exact terms, features, values and ranges etc. in case these terms, features, values and ranges etc. are used in conjunction with terms such as about, around, generally, substantially, essentially, at least etc. (i.e. , "about 3" shall also cover exactly 3 or “substantially constant” shall also cover exactly constant).
  • KP Keratosis pilaris
  • Vitamin D3 5 pg Two capsules daily were given to a6 group of 9 participants suffering from Keratosis pilaris alba, determined by self-assessment at the start of the experiment. In 30, 60 and 120 days they assessed if their condition was much worse, slightly worse, unchanged, slightly better or much better. The example is summarized in the table below.

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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract

L'invention concerne une composition comprenant de l'astaxanthine et un céramide pour une utilisation dans le traitement de la kératose pilaire, de préférence la kératose pilaire alba.
PCT/IS2022/050005 2021-08-20 2022-08-19 Combinaison d'astaxanthine et de céramide destinée à être utilisée dans le traitement de la kératose pilaire WO2023021533A1 (fr)

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IS9153 2021-08-20
IS9153 2021-08-20

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WO2023021533A1 true WO2023021533A1 (fr) 2023-02-23

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220142897A1 (en) * 2020-11-11 2022-05-12 Devin Beaubien Formulation and Use Thereof in the Treatment of Keratosis Pilaris

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220142897A1 (en) * 2020-11-11 2022-05-12 Devin Beaubien Formulation and Use Thereof in the Treatment of Keratosis Pilaris

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
ANONYMOUS: "Amazon Customer reviews AstaSkin US", 18 January 2021 (2021-01-18), pages 1 - 3, XP055979468, Retrieved from the Internet <URL:https://www.amazon.com/Icelandic-Astaxanthin-Ceramides-Elasticity-Supplement/product-reviews/B085HDZVBM?pageNumber=2&reviewerType=all_reviews> [retrieved on 20221109] *
ANONYMOUS: "AstaSkin lausn á algengu hú vandamáli", ALLT KYNNIGARBLA, 28 August 2021 (2021-08-28), pages 1 - 8, XP055979488, Retrieved from the Internet <URL:https://frettabladid.overcastcdn.com/documents/SC210828.pdf> [retrieved on 20221109] *
ANONYMOUS: "What inspiration can the 2021 high-potential ingredient list for beauty products bring to oral beauty foods?", ECHEMI.COM, 27 April 2021 (2021-04-27), pages 1 - 2, XP055979599, Retrieved from the Internet <URL:https://www.echemi.com/cms/207537.html> [retrieved on 20221109] *
DAVINELLI SERGIO ET AL: "Astaxanthin in Skin Health, Repair, and Disease: A Comprehensive Review", NUTRIENTS, vol. 10, no. 4, 22 April 2018 (2018-04-22), pages 1 - 12, XP055979591, Retrieved from the Internet <URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946307/pdf/nutrients-10-00522.pdf> DOI: 10.3390/nu10040522 *
HEIMISDÓTTIR THELMA: "AstaSkin", 7 October 2018 (2018-10-07), pages 1 - 8, XP055979541, Retrieved from the Internet <URL:https://www.linkedin.com/pulse/astaskin-hafsteinn-eyland/> [retrieved on 20221109] *
ORTIZ JILLIAN: "Dealing with rough, bumpy skin? Dermatologists say this popular lotion can help", TODAY, 28 July 2020 (2020-07-28), pages 1 - 4, XP055979567, Retrieved from the Internet <URL:https://www.today.com/shop/cerave-sa-lotion-t187939> [retrieved on 20221109] *

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