EP3065750A1 - Système de distribution et d'administration topique pour agent de protection stabilisé, compositions et leurs procédés de fabrication - Google Patents

Système de distribution et d'administration topique pour agent de protection stabilisé, compositions et leurs procédés de fabrication

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Publication number
EP3065750A1
EP3065750A1 EP13897235.1A EP13897235A EP3065750A1 EP 3065750 A1 EP3065750 A1 EP 3065750A1 EP 13897235 A EP13897235 A EP 13897235A EP 3065750 A1 EP3065750 A1 EP 3065750A1
Authority
EP
European Patent Office
Prior art keywords
polypodium
extract
composition
composition according
skin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP13897235.1A
Other languages
German (de)
English (en)
Other versions
EP3065750A4 (fr
Inventor
Pankaj Modi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Transdermal Corp
Original Assignee
Transdermal Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Transdermal Corp filed Critical Transdermal Corp
Publication of EP3065750A1 publication Critical patent/EP3065750A1/fr
Publication of EP3065750A4 publication Critical patent/EP3065750A4/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/11—Pteridophyta or Filicophyta (ferns)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0291—Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/044—Suspensions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/55—Phosphorus compounds
    • A61K8/553—Phospholipids, e.g. lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9741—Pteridophyta [ferns]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52—Stabilizers
    • 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

Definitions

  • the present invention relates to the field of anti -photo-aging and formulations for use in conjunction with a method and product for topical delivery and administration of stabilized protection agents and compositions thereof and methods for making the composition and use thereof.
  • the method and system comprises pharmaceutical compositions for facilitating topical delivery of protection agents and skin anti -photo -aging agents for inhibiting cellular degradation in response to sun damage.
  • the compositions are topically applied on a patient in a cream, lotion or gel form and are in a dissolved and suspended micellar-like form for use as a component in a topical system for delivery of the inhibitor system.
  • the compositions are particularly effective in topical applications.
  • the present invention further relates to methods for preparing and using these compositions, as well as methods for enhancing the stability and the topical retention on the skin of the user of the cellular degradation inhibiting agent.
  • Stabilizers may also be effective in reducing adhesion of the active agent to surfaces, such as the surfaces of laboratory glassware, vessels, the vial in which the pharmaceutical composition is reconstituted or the inside surface of a syringe used to inject the pharmaceutical composition.
  • an ideal stabilizing agent should have negligible immunogenicity when administered to a human patient.
  • UV radiation is divided into three categories according to wavelength:
  • UVA rays range from .about.320-400 nm (nanometers), UVB rays from .about.290-320 nm, and UVC rays from .about.100-290 nm. Both UVA and UVB are found in sunlight, while UVC is completely filtered by the ozone layer. UVA is .about.100 times more prevalent than UVB; and because UVA has the longest wavelengths, it penetrates the skin more deeply than UVB. UVA is subdivided into two wavelength ranges which are known as UVA-I (.about.340-400 nm) and UVA-II (.about.320-340 nm). While all UV light directly interacts with the skin's DNA to induce mutations, the primary method of destruction is the formation of reactive oxygen species (ROS), destructive molecules known as a "free radicals", which cause cumulative damage to healthy cells, including cells of the immune system.
  • ROS reactive oxygen species
  • Non-melanoma skin cancer is by far the most common cancer seen in man. Melanoma, the most deadly form of skin cancer, has recently been identified as the cancer with the sharpest increase in prevalence among all cancers.
  • UV light is a primary carcinogen in non-melanoma skin cancers, and a co-carcinogen in melanomas.
  • Most of the more than 1 million eases of non-melanoma skin cancer diagnosed in the United States each year are sun-related. With ozone depletion progressing and recreational time in the sun increasing, the rates of skin cancer are expected to increase in the future, despite already being at epidemic levels in certain countries such as Australia. Accordingly, the development of improved sunscreens and sunblocks is critical to protect against the deleterious health effects of UV light.
  • Photo-aging is a term presently used to describe the changes in appearance and/or function of human skin as a result of repeated exposure to sunlight, and especially regarding wrinkles and other changes in the appearance of the skin.
  • UV radiation reaching the earth's surface that effects and enables various animals, including humans comprises ultraviolet (UV) (.lambda. ⁇ 400 nm), visible (400 nm ⁇ .lambda. ⁇ 700 nm ), and infrared (IR) (.lambda.>700 nm).
  • UV radiation is generally divided into UVA (320-400 nm), UVB (290-320 nm), and UVC ( ⁇ 290 nm); UVC radiation is blocked from reaching the earth's surface by stratospheric ozone.
  • the ultraviolet (UV) component of sunlight, particularly UVB is generally believed to be the principal causative agent in photo-aging.
  • UVB wavelengths of 290-300 nm are the most erythmogenic.
  • the effectiveness of UV radiation in causing erythema decreases rapidly as the UV wavelength is increased beyond about 300 nm; wavelengths of 320 nm and 340 nm are, respectively, one hundred and one thousand times less potent at causing skin reddening than wavelengths of about 298 nm.
  • UVA is considered both melanogenic and erythemogenic and UVA exposure induces synthesis of a 32 kDa stress protein in human skin, as well as immediate erythema not apparent after UVB exposure.
  • Photo-aging in human skin is characterized clinically by coarseness, wrinkles, mottled pigmentation, sallowness, laxity, eventually premalignant, and ultimately malignant neoplasms.
  • Photo-aging commonly occurs in skin that is habitually exposed to sunlight, such as the face, ears, bald areas of the scalp, neck, forearms, and hands.
  • Sunscreens are commonly used to prevent photo-aging of skin areas that are exposed to sunlight. Sunscreens are topical preparations that contain ingredients that absorb, reflect, and/or scatter UV light. Some sunscreens are based on opaque particulate materials, among them zinc oxide, titanium oxide, clays, and ferric chloride. Because such preparations are visible and occlusive, many people consider these opaque formulations cosmetically unacceptable.
  • sunscreens contain chemicals such a p- aminobenzoic acid (PABA), oxybenzone, dioxybenzone, ethylhexyl-methoxy cinnamate, octocrylene, octyl methoxycinnamate, and butylmethoxydibenzoylmethane that are transparent or translucent on the skin. While these sunscreens may be more acceptable cosmetically, they are still relatively short-lived and susceptible to being removed by washing or perspiration. Sunscreen formulations for use on human skin are well-known and many different types are commercially available to satisfy diverse consumer needs.
  • PABA p- aminobenzoic acid
  • sunscreen formulations having different sun protection factor (SPF) values are available, thus allowing consumers to choose the amount of protection desired.
  • SPF values range from zero upward with higher values indicating greater amounts of sun protection.
  • SPF values of 2-4 indicate minimal sun protection, 4-6 indicate moderate sun protection, 8-15 indicate maximal sun protection and above 15 indicate ultrasun protection.
  • compositions and methods for inhibiting photo-aging include the use compounds that block or absorb UVB, and that such compositions need be used only when there is sufficient likelihood that exposure to sunlight will result in erythema. More recent sunscreen compositions include combinations of compounds that block both UVA and UVB radiation.
  • ROS reactive oxygen species
  • MMPs Matrix metalloproteinases
  • Inhibitors of MMPs i.e., direct inhibitors of the proteinase
  • molecular pathways i.e., inhibitors of AP-1
  • UV exposure insufficient to cause erythema there may still be connective tissue damage at the dermal level via MMP induction.
  • suberythemal doses of UV radiation induce MMPs that degrade skin connective tissue and thus are likely responsible for photo- aging.
  • a UV exposure (with UVA and/or UVB) insufficient to cause erythema nevertheless is sufficient to cause photo-damage via MMP induction.
  • photo-damage should be redefined in the art so as not to require erythema.
  • a combination of UVA and/or UVB radiation can significantly damage the skin.
  • the present invention addresses those needs and provides a delivery system to permit the application and retention of anti -photo -aging compositions to reduce damage and cellular degradation from exposure to both UVA and UVB radiation, retard photo-aging, provide an immunomodulatory effect and otherwise assist in MMP (matrix metalloproteinase) inhibition.
  • MMP matrix metalloproteinase
  • Extracts of Polypodium leucotomos have been found effective in the treatment of psoriasis, atopic dermatitis and other skin disorders (see, e.g., H. Corrales Padilla, et al, Int. J. Dermatol. 13(5):276-282 (1974); D. Jimenez, et al, Allergol. et Immunopathol. 15(4): 185-189 (1987)).
  • the extract was found to cause decreases in hyperkeratosis, parakeratosis, epidermal mitosis, epidermal thickening, epidermal prolongations, and the severity and extent of epidermal lesions.
  • the present invention concerns the subject of the claims incorporated herein by reference and addresses the need for improved dermatological delivery of active protective agents by stabilizing those active agents and allowing them to be dissolved and suspended in a maclle-like formation and for enhancing the retention of the active ingredients on the skin.
  • the invention also provides compositions prepared using the method for the topical delivery of at least one active protective agent.
  • the method comprises suspending an active protective agent in a phospholipid micelle-like coating.
  • the active agent is then admixed with a solution containing collagen and/or elastin.
  • compositions for topical delivery of at least one active protective agent comprises the active protective agent in a micelle-like suspension and an acceptable carrier.
  • the composition also optionally includes elastin, preferably low molecular weight cross-linked elastin.
  • Polypodium extract comprises an extract of a plant selected from the group consisting of Polypodium aureum, Polypodium crassifolium, Polypodium decumanum, Polypodium lanceolatum, Polypodium leucotomos, Polypodium percussum, Polypodium triseriale and Polypodium vulgare.
  • the extract is more preferably Polypodium leucotomos extract.
  • the active protective agent is selected from the group consisting of Polypodium leucotomos, Vitamin A, Vitamin C, Vitamin E, Zinc, Selenium, lycopene, N-Acetyl-Cysteine, natural plant extracts of Grape Skin, Bilberry and Green Tea and combinations thereof.
  • Another mode of the invention provides a composition prepared by combining at least one carotenoid with a Polypodium extract in connection with the micelle-like suspension delivery system where the preferred mode employs an extract of Polypodium leucotomos as the Polypodium extract.
  • the invention provides a pharmaceutical or cosmetic composition including an effective photo-protectant amount of at least one carotenoid and a Polypodium extract, together with a pharmaceutically-acceptable carrier.
  • the at least one carotenoid is a carotenoid selected from the group consisting of astaxanthin, lycopene, canthaxanthin, .beta.-carotene, lutein, and zeaxanthin, more preferably astaxanthin and/or lycopene.
  • the carotenoid is selected from the group consisting of astaxanthin, lycopene, canthaxanthin, .beta.-carotene, lutein, and zeaxanthin, more preferably astaxanthin and/or lycopene.
  • retinoids are used to assist in the prevention of photo-damage in conjunction with one or more of the active protective agents.
  • Compounds which may also be useful in preventing photo-damage by inhibiting the production and/or activity of MMPs are termed "antioxidants" and may prevent erythema and are also employed in the embodiment to reduce the concentration of MMPs in UV-exposed human skin and where the use does not correlate with inhibiting UV- mediated increases in MMPs.
  • Preferred phospholipids include sphingosine and cerebroside.
  • the micelle comprises both sphingosine and cerebroside.
  • the sphingosine and cerebroside are combined in equal amounts.
  • the composition is formulated in a format selected from the group consisting of a cream, a lotion, a spray, an ointment, a gel, a powdered mask, a paste, a cleanser, and a foundation.
  • composition of the invention may optionally include an additive selected from the group consisting of a perfume, colorant, thickening agent, vegetable oil, emulsifier, solvent, pH adjusting agent, antiseptic agent, preservative, vitamin, sun-block, surfactants and combinations thereof.
  • a perfume colorant, thickening agent, vegetable oil, emulsifier, solvent, pH adjusting agent, antiseptic agent, preservative, vitamin, sun-block, surfactants and combinations thereof.
  • Various physical sunscreen agents such as titanium dioxide, silicone-treated titanium dioxide, zinc oxide, ferrous oxide, ferric chloride, talc, chromium oxide, or cobalt oxides may be included.
  • a chemical sunscreen agent such as para-amino benzoic acid, esters of para-amino benzoic acid, salicylates, cinnamates, benzophenones, dihydroxyacetone, parsol 1789, or melanin may be included.
  • compositions of the invention may contain at least 1%, 10%, 25%, or 50% Polypodium extract by weight.
  • preparations may provide a sun protection factor (SPF) for the minimal erythematic dose (MED) evaluated at 24 hours of at least 2, 5, 10 or 15 when applied at 2 ⁇ 1 ⁇ ; ⁇ 2 to normal skin of Types I to Type IV.
  • SPDF sun protection factor
  • MED minimal erythematic dose
  • the present invention provides a composition comprising:
  • the present invention provides a method for making a stabilized active protective agent composition.
  • the method comprises the steps of: i. preparing a phospholipid solution comprising a phospholipid in a solvent; ii. admixing the phospholipid solution with an active protective agent so as provide a phospholipid micelle-like dissolved and suspended active protective agent solution; iii. combining the carotenoid and maintaining the activee protective agent in a dissolved, micella-like suspension; and, iv. combining the suspension with a solution of solubilized collagen and elastin.
  • the phospholipid is selected from the group consisting of sphingosine, cerebroside and combinations thereof. More preferably, sphingosine and cerebroside are used in equal amounts.
  • the solvent used is an alcohol.
  • Preferred alcohols include isopropanol, ethanol and mixtures thereof.
  • the solution of solubilized collagen and elastin comprises equal amounts of collagen and elastin.
  • Active agents that can be used in the method of the invention include botulinum toxin, hyaluronic acid, Vitamin A, Vitamin C, Vitamin E, Zinc, Selenium, lycopene, N-Acetyl-Cysteine, natural plant extracts of Grape Skin, Bilberry and Green Tea, vasodilators, hormones, growth factors, vaccine agents, drugs, therapeutic proteins, small molecules, antiperspirant agents, analgesics and combinations thereof.
  • Preferred active agents for use in the method are hyaluronic acid and/or botulinum toxin.
  • the method of the present invention may include the further step of adding a permeation enhancing compound.
  • the enhancing compound is preferably selected from the group consisting of d-limonene, allantoin, fulvic acid, myrrh, hydroquinone glyquin, quillaja saponaria, and acanthophyllum squarrusom.
  • micellar coating from (about) 0.1 % to (about) 15 wt/wt % of sphingosine and from (about) 0.1% to (about) 15 wt/wt % of cerebroside are used to form the micellar coating.
  • additional ingredients are added to form a cream, lotion, gel, ointment, or spray.
  • a method of treating skin is provided.
  • the method comprises applying the composition described above daily to areas of the skin which are wrinkled or damaged and preferably prior to exposure to sunlight.
  • compositions can be formulated as a cream or lotion and can be stored at room temperature for extended periods of time without any loss of activity of the active ingredient. It can also be applied without having a whitening appearance and may provide extended retention on the skin's surface to provide extended protection.
  • compositions of the invention are useful to reduce fine lines and wrinkles, increase the moisture level of the skin, increase skin elasticity and resilience, increase the firmness of the skin, improve skin tone, texture and overall radiance, diminish bags under the eyes, rejuvenate the skin, prevent damage from chemical stress, protect the skin from UV rays and free- radical damage, promote wound healing and remove irregular pigmentation.
  • Figure 1 illustrates a chart detailing a testing protocol for the MED testing for NB-UVB light
  • Figure 2 is a photograph of the test area of Test Subject No. 1 with demarcations for test window identified thereon in relationship to a 10% Polypodium MED test employing the composition of the present invention
  • Figure 3 is a series of photographs of Test Subject No. 1 with various levels of Polypodium and test protocol employing the composition of the present invention
  • Figure 4 is a photograph of the test area of Test Subject No. 2 with demarcations for test window identified thereon in relationship to a 10% Polypodium MED test employing the composition of the present invention
  • Figure 5 is a series of photographs of Test Subject No. 2 with various levels of Polypodium and test protocol employing the composition of the present invention
  • Figure 6 is a photograph of the test area of Test Subject No. 3 with demarcations for test window identified thereon in relationship to a 10% Polypodium MED test employing the composition of the present invention
  • Figure 7 is a series of photographs of Test Subject No. 3 with various levels of Polypodium and test protocol employing the composition of the present invention. DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT OF THE INVENTION
  • the present invention provides methods of preparing a stabilized composition for enhanced topical delivery of at least one active protective agent and compositions prepared by the methods.
  • the method of the invention comprises dissolving an active protective agent in a phospholipid micelle-like suspension.
  • the micelle-like suspension is then preferably combined with a base composition that includes collagen.
  • the phospholipid is dissolved in a suitable solvent, such as an alcohol.
  • a suitable solvent such as an alcohol.
  • the phospholipid may be dissolved in ethanol or a mixture of ethanol and isopropanol.
  • the alcohol is removed by, for example, rotary vacuum evaporation.
  • the active protective agent is then dissolved and added to permit it to form a micelle-like suspension.
  • the active protective agent thus becomes encapsulated by a phospholipid micelle-like suspension structure.
  • This suspension can then be combined with a base solution comprising collagen. It has also been found to be advantageous to include elastin, especially cross-linked low molecular weight elastin, in the base composition.
  • Collagen can act as a stabilizer.
  • collagen helps improve the tissue's underlying foundation and contributes to hydration.
  • Collagen is able to penetrate the skin without the aid of any penetration enhancers to assist in the regenerative process.
  • a sphingoside is one preferred phospholipid.
  • Sphingolipid or sphingosine- 1- phosphate has been recognized as a bioactive molecule involved in the regulation of cell growth, differentiation, survival, and chemotaxis as well as angiogenesis and embryogenesis.
  • Other species of ceramides or sphingolipids such as ( -acyl-sphingosine) and dihydroceramide ( -acyl sphinganine) are also useful in the present invention.
  • Galactosylceramide (cerebroside) a metabolite of sphingolipids is also a preferred phospholipid.
  • Cerebroside is a myelin related protein that plays an important role in the regulation of cell growth, differentiation, survival, and chemotaxis. Cerebroside sulfates are important membrane constituents.
  • Both sphingosine and cerebroside have been found to be excellent phospholipids for use in the method of the present invention. While either of these phospholipids can be used alone, combinations of sphingosine and cerebroside are particularly effective. When used in equal amounts, sphingosine and cerebroside form a micelle structure that provides a very effective vehicle for delivery of active protective agents and for surface retention on the skin of the individual of the protective agent.
  • Other phospholipids, such as phosphatidyl choline or phosphatidyl serine are also highly effective, either alone or in combination.
  • Other phospholipids that can form a micellar- like structure and suspension are also useful in the invention.
  • Example 1 A preferred method for preparing a stabilized composition for topical application is described in Example 1 below.
  • the method of the present invention was used to stabilize in a cream/lotion format suitable for application to the skin. Briefly, equal amounts of collagen and elastin are solubilized in saline. In a separate flask, equal amounts of sphingosine and cerebroside are dissolved in alcohol. The alcohol is then removed. The Polypodium is dissolved and is then added to the flask and the flask is swirled to coat the Polypodium with a phospholipid micelle-like coating resulting in a suspension. This suspension is then added to the solution of collagen and elastin.
  • compositions of the present invention comprise a therapeutically effective amount of (i) at least one carotenoid and (ii) a Polypodium extract, formulated together with one or more pharmaceutically acceptable carriers.
  • pharmaceutically acceptable carrier means a non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type.
  • Some examples of materials which can serve as pharmaceutically acceptable carriers are sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil; safflower oil; sesame oil; olive oil; corn oil and soybean oil; glycols; such a propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as sodium lau
  • a topical preparation may include physical sunscreen agents, chemical sunscreen agents and/or cosmetic agents.
  • a physical sunscreen agent such as titanium dioxide, silicone -treated titanium dioxide, zinc oxide, ferrous oxide, ferric chloride, talc, chromium oxide, or cobalt oxides may be included.
  • a chemical sunscreen agent such as para-amino benzoic acid, esters of para-amino benzoic acid, salicylates, cinnamates, benzophenones, dihydroxyacetone, parsol 1789, or melanin may be included.
  • carotenoid is art-recognized and refers to a member of a family of organic pigments characterized by a polyene chain.
  • carotenoids include carotenes, such as lycopene, .alpha.-carotene and .beta.-carotene, and xanthophylls, such as canthaxanthin, astaxanthin, lutein and zeaxanthin.
  • Polypodium extract refers to an extract of a plant of the genus Polypodium.
  • Polypodium species include Polypodium aureum, Polypodium crassifolium, Polypodium decumanum, Polypodium lanceolatum, Polypodium leucotomos, Polypodium percussum, Polypodium triseriale and Polypodium vulgare.
  • An extract of Polypodium for use in the compositions and methods of the present invention should have photo-protectant activity.
  • Plant extracts can be described based on a reference compound found in the plant, or can refer to a concentration (e.g., weight/weight) of the total extract compared to the whole or dried plant material.
  • An extract can be, e.g., a 30: 1 or 50: 1 extract.
  • photo -protective and “photo-pro tectant”, as used herein, refer to the property of protecting skin from damage due to exposure of the skin to ultraviolet (UV) radiation (e.g., sunlight), including UVA (long-wave UV), UVB (shorter-wave UV), or both UVA and UVB, or to a composition having such a property.
  • UV radiation e.g., sunlight
  • UVA long-wave UV
  • UVB shorter-wave UV
  • Compounds and compositions of the invention are generally capable of achieving one or more of the following effects: the inhibition or retardation of skin inflammation, erythema or sunburn reaction and tissue damage to skin and/or the inhibition or retardation of the immediate pigment darkening reaction and/or the inhibition or retardation of the delayed tanning reaction and/or the inhibition or retardation of phototoxic reaction produced by psoralens.
  • a compound or composition providing such photo -protection is said to be “photo- protective” and may be referred to as a "photo-protectant.”
  • compositions, kits and methods for preventing, treating, or ameliorating damage to skin caused by exposure to ultraviolet radiation from sources other than the sun e.g., from tanning beds and the like.
  • suitable topical vitamins include, but are not limited to: vitamin A as esters (such as retinyl palmitate, retinyl acetate), as alcohol (such as retinol), as acid (such as retinoic acid), as its natural plant form beta-carotene (retinaldehyde dimer); vitamin C as acid (ascorbic acid), as a salt (such as sodium or magnesium ascorbyl phosphate), as a fat (such as ascorbyl tetraisopalmitate), or as an ester-C; vitamin E as a fat (such as alpha tocopherol), or other; and the like.
  • vitamin A as esters (such as retinyl palmitate, retinyl acetate), as alcohol (such as retinol), as acid (such as retinoic acid), as its natural plant form beta-carotene (retinaldehyde dimer); vitamin C as acid (ascorbic acid), as a salt (such as sodium or magnesium
  • topical cofactors includes, but is not limited to: coenzyme Q10 (CoQIO), and the like.
  • suitable topical minerals include, but are not limited to: zinc, magnesium, silicone and the like.
  • topical antioxidants and/or quenchers include, but are not limited to, alpha-lipoic acid, lipochromalin-6, idebenone, coffee berry, green tea polyphenols, Polypodium leucotomos (a fern plant extract), Tinogard TS.TM. (octadecyl di-t-butyl-4-hydroxyhydrocinnamate), Tinogard NOA.TM. (tetrabutyl ethylidinebisphenol), Tinogard Q.TM.
  • UV blockers e.g. avobenzone or the like
  • manuka oil from Leptospermum scoparium (manuka) honey
  • enzogenol from Pinus radiata pine bark
  • Both of the latter 2 originate in New Zealand and have potent antioxidant and wound healing capabilities.
  • ingredients in this class compliment all the requirements of, and other ingredients in, the formulation; and also remain optimally active on the cutaneous/adherent aspect of the user's skin.
  • an embodiment may contain vitamins, cofactors, minerals, or antioxidants and/or quenchers in concentrations—either solely, or in combination with each other—of about 0.1% to about 10% by weight (including about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, and about 9%, also including percentages between these recited percentages, as well as ranges of percentages bordered on each end by the recited percentages).
  • the topical composition of the present invention further comprises a natural extract component.
  • the natural extract component may comprise an extract derived from a plant, fruit, fungus, or a mixture thereof.
  • the amount of a natural extract component may be adjusted such that a final cosmetic product comprises from about 1.0% to about 25% by weight of natural extract component.
  • the natural extract component preferably has high anti-oxidative capacity, MMP inhibitory activity, and SOD inducing ability, thereby providing both short-term and long-term anti-aging benefits to the skin.
  • the short-term anti-aging effects are caused by agents that are antioxidants and/or MMP inhibitors.
  • Anti-oxidative agents often contain effective reducing agents such as polyphenols, glutathione, vitamin C, and vitamin E.
  • the long-term anti-oxidative benefits are provided by certain agents that are capable of either stimulating the production of body's endogenous antioxidants (e.g. superoxide dismutase) or enhancing the activity of such endogenous antioxidants.
  • the natural extract(s) used in the present invention may be obtained through conventional methods known in the art, such as solvent extraction, distillation, enfleurage, and ram press method.
  • Polypodium leucotomos a fern plant extract from central America
  • an embodiment may contain this plant extract in a concentration of about 0.1% to about 10% by weight (including about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, and about 9%, also including percentages between these recited percentages, as well as ranges of percentages bordered on each end by the recited percentages).
  • compositions and formulations of the invention are useful to reduce the signs of aging by minimizing the photo-aging process and assisting in the regenerative process by reducing the free radicals and acting as radical scavengers.
  • a pharmaceutical or cosmetic formulation containing an effective amount of an active protective agent and an effective amount of the stabilizing enhancing composition, and a pharmaceutically acceptable carrier suitable for topical administration.
  • the formulation may be in any form suitable for application to the skin. For example, it may take the form of a cream, a lotion, a gel, an ointment, a paste, or a solution.
  • the formulation may include liposomes, micelles, or microspheres.
  • the formulation may be a cosmetic composition that includes in addition to the stabilizers and the active ingredients water and other additives that are normally used in cosmetics.
  • the cosmetic composition may include thickening agents, preservatives, emulsifiers, perfumes, dyes or coloring, vegetable or mineral oil, antiseptic agents, acidifying or alkalizing agents, vitamins, anti-UV agents, surfactant, solvents, pH stabilizing agents, and other active ingredients known to be effective on the skin.
  • the cosmetic composition may also be provided as skin foundation, lip balm, etc.
  • Liquid dosage forms for topical administration include pharmaceutically acceptable emulsions, micro-emulsions, solutions, suspensions, syrups and elixirs.
  • the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof.
  • inert diluents commonly used in the art such as, for example, water or other solvents, solubil
  • compositions of the invention include various types of anti-oxidants.
  • free radical scavengers that maybe included in compositions of the invention include, but are not limited to, Vitamins A, C and E, the minerals Zinc and Selenium, lycopene, the amino acid N-Acetyl- Cysteine and natural plant extracts of Grape Skin and Bilberry.
  • the delivery system of the present invention can be used to deliver agents that promote healing.
  • Polypodium and other protective agents can be suspended in a phospholipid micelle-like and then combined with collagen and/or elastin in a lotion or cream formulation and applied to the skin.
  • the formulation of the protection agents in a topical composition according to the invention enhances the protection and the rate of scavenging for free radicals and otherwise damaged skin.
  • Liquid dosage forms for topical administration include pharmaceutically acceptable emulsions, micro-emulsions, solutions, suspensions, syrups and elixirs.
  • the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof.
  • inert diluents commonly used in the art such as, for example, water or other solvents, solubil
  • a topical preparation may include physical sunscreen agents, chemical sunscreen agents and/or cosmetic agents.
  • a physical sunscreen agent such as titanium dioxide, silicone-treated titanium dioxide, zinc oxide, ferrous oxide, ferric chloride, talc, chromium oxide, or cobalt oxides may be included.
  • compositions of the present invention may contain a single active agent or multiple active agents in the same composition.
  • a composition for topical delivery may comprise micelle encapsulated or suspended protective agents of retenoid and/or carotenoids or both.
  • Various combinations of active agents are contemplated for inclusion in the compositions of the invention.
  • the stabilized Polypodium and carotenoid composition was formulated into a cream/lotion for topical administration as outlined below.
  • Phase A De-ionized Water 74.7% Tetra Sodium EDTA 0.5-0.7% Methyl Paraben 0.2% Propylene Glycol 3.0%-4.0% Glycerin 3.0%-4.0%
  • Hyaluronic Acid pure
  • Talcum Powder Talcum Powder
  • Phase A Add Phase A to Phase B and mix 30 minutes at 75C. Cool down to 20-22 C and then add Phase C, D and E and continue to agitate until homogenous and one phase.
  • Figure 2 is a photograph of the test area of Test Subject No. 1 with demarcations for test window identified thereon in relationship to a 10% Polypodium MED test employing the composition of the present invention.
  • Figure 3 is a series of photographs of Test Subject No. 1 with various levels of Polypodium and test protocol employing the composition of the present invention.
  • Figure 4 is a photograph of the test area of Test Subject No. 2 with demarcations for test window identified thereon in relationship to a 10% Polypodium MED test employing the composition of the present invention.
  • Figure 5 is a series of photographs of Test Subject No. 2 with various levels of Polypodium and test protocol employing the composition of the present invention.
  • Figure 6 is a photograph of the test area of Test Subject No. 3 with demarcations for test window identified thereon in relationship to a 10% Polypodium MED test employing the composition of the present invention.
  • Figure 7 is a series of photographs of Test Subject No. 3 with various levels of Polypodium and test protocol employing the composition of the present invention.
  • the foregoing description is meant to be illustrative and not limiting. Various changes, modifications, and additions may become apparent to the skilled artisan upon a perusal of this specification, and such are meant to be within the scope and spirit of the invention as defined by the claims.

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Abstract

La présente invention concerne un procédé et un produit pour la distribution et l'administration topique d'agents de protection stabilisés, leurs compositions, et des procédés pour fabriquer la composition et l'utilisation de cette dernière. Le procédé et le système comprennent des compositions pharmaceutiques pour faciliter la distribution topique d'agents de protection et d'agents anti-photo-vieillissement cutané pour inhiber une dégradation cellulaire en réponse à une lésion due au soleil. Les compositions pharmaceutiques sont appliquées topiquement sur un patient et se trouvent généralement sous la forme d'une crème, d'une lotion ou d'un gel.
EP13897235.1A 2013-11-06 2013-11-06 Système de distribution et d'administration topique pour agent de protection stabilisé, compositions et leurs procédés de fabrication Withdrawn EP3065750A4 (fr)

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US5306486A (en) * 1993-03-01 1994-04-26 Elizabeth Arden Co., Division Of Conopco, Inc. Cosmetic sunscreen composition containing green tea and a sunscreen
US5614197A (en) * 1995-02-13 1997-03-25 Industrial Farmaceutica Cantabria, S.A. Polypodium extract as photoprotectant
EP1853303B1 (fr) * 2005-02-14 2015-12-02 DPM Therapeutics Corporation Préparations stabilisées pour administration locale et méthodes d'elaboration desdites préparations
US20120201857A1 (en) * 2010-03-17 2012-08-09 Pankaj Modi Transdermal delivery system for therapeutics

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