WO2002003942A2 - B complex vitamin compositions that protect against cellular damage caused by ultraviolet light - Google Patents
B complex vitamin compositions that protect against cellular damage caused by ultraviolet light Download PDFInfo
- Publication number
- WO2002003942A2 WO2002003942A2 PCT/CA2001/001006 CA0101006W WO0203942A2 WO 2002003942 A2 WO2002003942 A2 WO 2002003942A2 CA 0101006 W CA0101006 W CA 0101006W WO 0203942 A2 WO0203942 A2 WO 0203942A2
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- Prior art keywords
- vitamin
- acid
- composition
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- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 238000003466 welding Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
- A61Q1/02—Preparations containing skin colorants, e.g. pigments
-
- 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
- A61K8/0216—Solid or semisolid forms
-
- 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
- A61K8/67—Vitamins
-
- 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
- A61K8/67—Vitamins
- A61K8/673—Vitamin B group
-
- 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
- A61K8/67—Vitamins
- A61K8/673—Vitamin B group
- A61K8/675—Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde
-
- 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
- A61Q5/00—Preparations for care of the hair
- A61Q5/02—Preparations for cleaning the hair
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/06—Preparations for styling the hair, e.g. by temporary shaping or colouring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/10—Preparations for permanently dyeing the hair
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/12—Preparations containing hair conditioners
Definitions
- the invention relates generally to sunscreens and sunfilters, and to methods and compositions for protecting cells against the damaging effects of sunlight and artificial sources of UV light such as lamps and arc welding equipment.
- the invention is directed to the use of vitamin B12, alone or in combination with folate (used here to refer to all of the folic acid derivatives found commonly in nature), and niacin (specifically niacinamide) in methods and compositions for protecting cells and organisms including humans against the burning, genotoxic, immunosuppressive and photoaging effects of exposure to UV light.
- UVB but not UVA sunscreens that protect against some but not all of the sun's harmful UV radiation
- NCI National Cancer Institute
- the skin cancers induced by sunlight can be broadly categorized into two types: melanomas and non-melanomas (basal cell and squamous). It was generally accepted for some time that exposure to UVB (the burning rays of the sun with the wavelengths ranging from 280 to 315 nm) was responsible for the induction of melanomas, the most serious form of skin cancer and the tumor type responsible for most deaths. This was held to be especially true in those individuals who had at least one episode of severe sunburn early in childhood. It seems likely from more recent studies, (especially an elegant series of experiments by Dr Richard Setlow reported recently to the annual meeting of the American Academy of Dermatology) that this is simply not the case.
- UVB the burning rays of the sun with the wavelengths ranging from 280 to 315 nm
- UVA spectral and mutational fingerprint analysis
- UVA ultraviolet A light passes easily through the atmosphere and is not absorbed by the ozone layer. It is the main type of solar UV irradiation (about 95%) that reaches the surface of the earth. In the past, it was generally believed that UVA had only beneficial effects to humans such as stimulation of vitamin D formation and tanning. However, this is clearly not the case. Wavelengths in the UVA range are damaging to the skin, cause photoaging and are causally related to the induction of melanomas. Second, depletion of the ozone layer and the concomitant increase in the amount of UVB light reaching the surface of the earth cannot be the explanation for the dramatic increase in melanomas seen worldwide in recent years.
- UVA and UVB filters The mechanism of UV damage to skin is only partly understood.
- the harmful effects of UVA and UVB light on human skin are due primarily to direct cellular damage (see Principles and Practice of Dermatology, 2nd Edition, Williams and Wilkins, Churchill/Livingston, N.Y.). Suppression of the immune system also occurs but by an indirect mechanism.
- the genotoxic potential of solar light resides mainly in the ability of UV to damage DNA (DNA absorbs maximally at 254nm). UV light causes the formation of various photoproducts in the strands of the DNA molecule.
- UV light The major photoproducts caused by UV light are dimers (fusions) of adjacent pyrimidines (thymine or cytosine residues) in one of the two strands of the DNA molecule. Other minor products like 6,4 photoproducts also occur.
- DNA is not the only target of UV light. UV also damages other cellular components such as collagen and causes photoaging of the skin. But the main genotoxic (mutagenic and carcinogenic) effects of UV light seem to reside in the ability of UV wavelengths to damage DNA. The cancer causing effects of UV light are can also reside in the ability of these wavelengths to impair the body's immunosurveillance system whose job it is to detect and destroy potentially malignant cells.
- Para-aminobenzoic acid was one of the first sunfiltering agents to be identified in the art. It is now seldom used because of problems with contact dermatitis. Due to widespread use of pABA over many years about 10% of all users of sunscreen products have some degree of contact sensitivity to the compound. However, esters of pABA, particularly octyl, dimethyl, para-aminobenzoic acid, do not elicit these same skin reactions.
- Other commonly used sunfilters are compounds from the salicyclate, cinnamate, benzophenone, anthranilate, and dibenzoylmethane families of molecules. It is well known in the art to combine sunfiltering agents that absorb UV light in different portions of the spectrum.
- sunscreen compositions exert their effects through filtering or absorbing UV light so that the damaging wavelengths do not penetrate the various layers of the skin.
- sunscreens must be present on the skin as a continuous film, and must remain on the surface of the skin throughout the period of UV exposure.
- topical compositions that act as sunscreen carriers and remain on the surface of the skin (see U.S. Patent No. 5,087,445), sunscreens tend to rub off on towels and clothing, and wash off in perspiration, or during swimming, showering and bathing.
- Figure 1 is the chemical structure of vitamin B12 wherein R is defined as OH, CN, NO 2 , CH 3 , or 5'-deoxy-adenosyl.
- FIG. 1 is the chemical structure of folate (vitamin B9)
- Figure 3 is the chemical structure of niacinamide (vitamin B3)
- the object of the invention is to provide a means of reducing the burning, genotoxic, immunosuppressive and photoaging effects of UV light by application of three common B vitamins to the skin.
- vitamin B12 derivative includes the parent compounds, precursors (pro-vitamins), metabolites, derivatives, and their conjugates, all of which may be either naturally occurring or synthetic, as well as the salts of the compounds.
- Folate derivatives include polyglutamated derivatives. Results of experiments with human volunteers described below have shown that the combination folic acid, vitamin B12 and niacinamide when taken in pill form prevented sunburning for many hours. Topical application would be effective in a similar fashion.
- the invention provides a method for reducing or inhibiting a disease or disorder in a mammal caused by ultraviolet radiation comprising exposing the cells to an amount of at least one of vitamin B12 or B9 but preferably the two vitamins in combination with niacinamide, in appropriate concentration, which is sufficient to reduce UV damage to cells, specifically skin cells.
- the invention is a method for reducing or inhibiting a disease or disorder in a mammal caused by UV radiation comprising administering to the subject a formulation of vitamin B12, vitamin B9 and vitamin B3, in a suitable carrier, the amounts of each individual component sufficient to reduce UV damage to cells.
- the carriers are compatible (cosmetically or otherwise) with the route of administration.
- the carriers for oral, parenteral, enteral, entranasal, rectal or ocular administration are preferably at least one of water, gas, a water-based liquid, an oil, a gel, an emulsion, a dispersion or a mixture thereof.
- the carriers for topical administration are preferably at least one of a lipid, water, gas, a water-based liquid, oil, a gel, an emulsion, dispersion or a mixture thereof.
- the carrier is an ester, preferably an ester of para-aminobenzate, such as, ocytl- and dimethyl-para- aminobenzoic acid.
- the vitamin B9 is preferably at least one of either folic acid, dihydrofolic acid, tetrahydrofolic acid, 5-formyltetrahydrofolic acid, 10- formyltetrahydrofolic acid, 5-10 methylenetetrahydrofolic acid, 5-10 methenyltetrahydrofolic acid and 5-methyltetrahydrofolic acid or derivatives thereof.
- the folate is leucovorin, folic acid, or a combination of these two folates.
- folate is present in the composition at a concentration in the range of approximately 0.2mg/ml to 10mg/ml and, the carrier is suitable for topical application.
- Niacinamide is present at 2.0mg/ml to 100mg/ml.
- Vitamin B12 is present in the range 0.1 mg/ml to 1 mg/ml.
- a folate is present in the composition in an amount of about 200ug to about 10mg by dry weight, niacinamide in an amount of about 20mg to about 1g by dry weight, vitamin B12 is present in an amount of about 20ug to about 1.5mg by dry weight and the carrier is suitable for oral administration to children.
- a folate is present in the composition in an amount of about 1 mg to 10mg by dry weight, nicacinamide in an amount of about 100mg to about 1g by dry weight, vitamin B12 is present in an amount of about 0.1 mg to about 1.5mg by dry weight and the carrier is suitable for administration to adults.
- the folate is leucovorin, folic acid, or a combination of these two folates or their pharmaceutically acceptable salts.
- the invention is a method for reducing or inhibiting a disease or disorder in a mammal caused by UV wherein the pharmaceutical composition for use as a sunscreen further includes at least one cosmetically acceptable adjuvant or additive, such as preservative, organic solvent, browning agent, antioxidant, stabilizer, emollient, silicone, alpha-hydroxy acid, demulcent, anti-foaming agent, moisturizing agent, vitamin, fragrance, ionic or nonionic thickener, surfactant, filler, thickener, sequestrant, polymer, propellant, alkalinizing or acidifying agent, opacifier, fatty compound or colorant.
- at least one cosmetically acceptable adjuvant or additive such as preservative, organic solvent, browning agent, antioxidant, stabilizer, emollient, silicone, alpha-hydroxy acid, demulcent, anti-foaming agent, moisturizing agent,
- the invention is a method for reducing or inhibiting a disease or disorder in a mammal caused by UV wherein the pharmaceutical composition for use as a sunscreen further includes at least one sunfiltering or sunscreening compound such as para-aminobenzoic acid, salicyclate, cinnamate, benzophenone, anthranilate, dibenzoylmethane, beta- carotene and alpha-hydroxy acids.
- sunscreening compound such as para-aminobenzoic acid, salicyclate, cinnamate, benzophenone, anthranilate, dibenzoylmethane, beta- carotene and alpha-hydroxy acids.
- compositions for use as a sunscreen for protecting the human skin, human hair or another surface from ultraviolet radiation include vitamin B12, niacinamide, at least one folate, and a suitable carrier.
- the carriers are compatible (cosmetically or otherwise) with the route of administration.
- the carriers for oral, parenteral, enteral, entranasal, rectal or ocular administration are preferably at least one of water, gas, a water-based liquid, an oil, a gel, an emulsion, a dispersion or a mixture thereof.
- the carriers for topical administration are preferably at least one of a lipid, water, gas, a water-based liquid, oil, a gel, an emulsion, dispersion or a mixture thereof.
- the carrier is an ester, preferably an ester of para-aminobenzate, such as, ocytl- and dimethyl-para- aminobenzoic acid.
- compositions protect skin, hair and eyes from solar radiation.
- Suitable compositions include an oil-in-water emulsion or a water-in-oil emulsion.
- the pharmaceutical composition for use as a sunscreen further includes at least one cosmetically acceptable adjuvant or additive, such as preservative, organic solvent, browning agent, antioxidant, stabilizer, emollient, silicone, alpha-hydroxy acid, demulcent, anti- foaming agent, moisturizing agent, vitamin, fragrance, ionic or nonionic thickener, surfactant, filler, thickener, sequestrant, polymer, propellant, alkalinizing or acidifying agent, opacifier, fatty compound or colorant.
- at least one cosmetically acceptable adjuvant or additive such as preservative, organic solvent, browning agent, antioxidant, stabilizer, emollient, silicone, alpha-hydroxy acid, demulcent, anti- foaming agent, moisturizing agent, vitamin, fragrance, ionic or nonionic thickener, surfactant, filler,
- the pharmaceutical composition further includes at least one sunfiltering or sunscreening compound such as para- aminobenzoic acid, salicyclate, cinnamate, benzophenone, anthranilate, dibenzoylmethane, beta-carotene and alpha-hydroxy acids.
- sunfiltering or sunscreening compound such as para- aminobenzoic acid, salicyclate, cinnamate, benzophenone, anthranilate, dibenzoylmethane, beta-carotene and alpha-hydroxy acids.
- Other useful compositions are a nonionic vesicle dispersion, emulsion, cream, milk, gel, ointment, suspension, dispersion, powder, solid stick, foam or spray.
- the composition may also include a hair rinse, spray, mist, gel, mousse, shampoo, conditioner, lotion, emulsion and coloring product.
- the claimed invention has the advantage that administration of the vitamin mixture containing vitamin B12, such as, cobalamin, cyanocobalamin, methylcobalamin and adenosylcobalamin., a folate, and niacinamide, for the purposes of reducing UV damage to the cells of a subject can be done either topically, systemically (orally or by injection), or via a combination of routes.
- Systemic delivery of the vitamin mixture might afford protection to the eye, something that cannot readily be accomplished by commercially available topical sunscreens. Such a treatment might be expected to lessen the risk of cataracts induced by UV light.
- the invention provides a method to filter or absorb harmful UV rays through the use of bioavailable compounds.
- Bioavailable compounds are chemicals, usually from natural sources, that are readily taken up and metabolized by cells. Because these compounds are simple B complex vitamins with other known effects their ingestion or topical application may have other health benefits than those described herein.
- subjects who have taken the three vitamin formulation described herein have reported an amelioration of symptoms of a variety of dermatological conditions including acne vulgaris, actinic keratoses, photodermatitis and certain types of psoriasis "sun allergy" including discoid lupus erythematosus.
- the claimed invention may be used for the prevention and treatment of disorders of the skin, the immune system, disorders of the hematopoietic system and cancer.
- the invention may also be used for protecting plant cells from solar UV.
- the invention may be sprayed onto plants.
- the invention relates to a method for reducing the damaging effects of ultraviolet radiation to cells of a subject comprising exposing the cells to an effective amount of a composition containing vitamin B12 wherein the composition is taken orally, applied to the skin or the composition is taken by injection.
- the invention contains vitamin B12 and at least one anti-photo aging compound.
- the invention comprises vitamin B12, at least one sun filtering or sun screening compound including other vitamins.
- the invention can be administered to animals. In an alternate embodiment the animal is a human.
- the invention is a method for reducing or inhibiting a disease or disorder in a animal or human caused by UV radiation comprising administering to the subject a composition containing vitamin B12 wherein the composition is incorporated into a liposome.
- the composition also comprises at least one DNA repair enzyme.
- the amount of vitamin B12 present in a composition to be ingested is between 0.1 mg and 1.5mg. In another preferred embodiment the amount of vitamin B12 to be ingested is between 0.1g and 1.5mg and the composition also contains any folate in the range of 1 mg to 10mg. In yet another preferred embodiment, vitamin B12 is present at between 0.1 mg and 1.5mg, any folate is present at 1 mg to 10mg and niacinamide or any derivative of niacin is present in the range of 100mg to 1g.
- the invention can also be applied to the skin of a subject in a continuous film.
- the subject of the invention is an animal. In a variation, the animal is a human.
- the composition to be applied to the skin of the subject comprises vitamin B12 at a concentration of between 0.1 mg/ml and 10mg/ml in a pharmaceutically acceptable carrier.
- the composition comprises in addition to vitamin B12 any folate at a concentration of between 0.2mg/ml and the upper limit of solubility of the compound in a pharmaceutically acceptable carrier.
- the composition comprises in addition to vitamin B12, niacinamide or any derivative of niacin in the concentration range 2mg/ml and the upper limit of solubility of the compound, in a pharmaceutically acceptable carrier.
- the invention is a method for reducing the damaging effects of ultraviolet radiation to cells of the subject comprising exposing the cells to an effective amount of a composition containing vitamin B12 wherein the composition is administered by injection.
- vitamin B12 is present in an amount between 0.1 mg and 1.5mg in a composition to be taken by injection.
- the composition to be taken by injection contains, in addition to vitamin B12, niaicinamide or any derivative of niacin, in the range of 100mg to 1g.
- the composition to be taken by injection contains, in addition to vitamin B12, any folate in the range 1mg to 10mg.
- a number of folates are applicable to the invention.
- “Reduced folates” means folates at the dihydro and tetrahydro level of oxidation, for example folinic acid or folinate.
- the folates referred to above include, but are not limited to, the following: folic acid, dihydrofolic acid, tetrahydrofolic acid, 5-formyltetrahydrofolic acid (folinic acid, leucovorin), 10- formyltetrahydrofolic acid, 5-10 methylenetetrahydrofolic acid, 5-10 methenyltetrahydrofolic acid and 5-methyltetrahydrofolic acid. Of these, folic acid and folinic acid and their salts are preferred.
- Folic acid is formed from three separate chemical building blocks:
- pABA p-aminobenzoic acid
- glutamic acid • p-aminobenzoic acid (pABA), and • glutamic acid.
- the 6-methylpterin moiety is linked through the amino group on pABA to form pteric acid, which is in turn linked through an amide to glutamate.
- Pteric acid that is linked to a single glutamate is known as pteroylmonoglutamate.
- many naturally occurring folates have additional glutamate residues attached to pteric acid (pterylpolyglutamates).
- the additional glutamate residues linked by means of a modified peptide bond involving the alpha-amino group of one glutamate and the gamma- carboxyl group of another, allow for compartmentalization of different reduced folates in cells and provide an additional level of regulation for folate interconversion enzymes.
- folate as used herein includes such polyglutamated derivatives.
- folic acid is metabolized to dihydrofolate and then to tetrahydrofolate by means of an enzyme known as dihydrofolate reductase (DHFR).
- DHFR dihydrofolate reductase
- Tetrahydrofolate is converted to a variety of reduced intermediates involved in the mobilization and utilization of single-carbon functional groups (i.e. methyl, methenyl, methylene and formyl).
- single-carbon functional groups i.e. methyl, methenyl, methylene and formyl.
- These one-carbon donors function in the metabolism of certain amino acids such as serine, glycine, methionine, and histidine, and in the biosynthesis of purine and pyrimidine nucleotides.
- folates exist in nature, but they can also be manufactured by chemical synthesis.
- the term folate encompasses both naturally occurring and synthetic forms.
- Folates can be used as a single chemical species or a mixture of two or more species. It is anticipated that a mixture of folates may be more effective than a single species.
- the UV absorption spectra of folic acid and folinic acid cover a broader spectrum of absorption than either compound alone.
- folates of the invention can be obtained commercially from a number of sources. Folic acid, folinic acid and 5- methyltetrahydrofolate acids are available from Sigma Chemical Co., St Louis
- Conjugates of the folates such as those with amino acid side chains can be prepared by published methods (see Ayling, J. and Baugh, N.,
- the folates of the invention need not be highly purified. Mixtures of partially purified folates can be used. Folates or combinations of folates can be tested for their ability to protect cells from UV light, by using the a screen such as the human fibroblast cell culture system described herein. The folates to be tested would be added to cultures of mammalian cells before, during or after exposure to UV light. Folates that are effective blocks to UV light would increase cell survival.
- the methods of the invention are applicable to cells of any organism that can potentially be damaged by UV light.
- the term "subject” means a whole multi-cellular organism, which includes humans, lower animals and plants.
- the methods and compositions are applied to human cells, particularly human cells which are subject to sun exposure, such as melanocytes, and the squamous and basal cells of the dermis and epidermis.
- the vitamins are administered by adding them to the growth medium in which the cells are maintained.
- the compounds may be administered topically, by applying them to the outside skin or surface of the organism.
- the B complex vitamins used in the invention act both inside and outside the treated cells.
- Many types of cells are permeable to at least some of the vitamins that are used to carry out the invention.
- mouse L1210 cells can take up folates such as 5-methyltetrahydrofolate, by at least two mechanisms; a specific transporter in the cell membrane that operates in the micromolar range and a second transport system that takes up folates in the nanomolar range.
- a lack of permeability to a particular vitamin does not necessarily exclude the compound from intracellular use.
- Various methods can be used to facilitate the entry of the folates into cells.
- the liposome- mediated methods which have been developed for the delivery of DNA repair enzymes (i.e. T4 endonuclease or photolyase), as mentioned above, can be adapted to deliver the three B complex vitamins into cells.
- DNA repair enzymes i.e. T4 endonuclease or photolyase
- T4 endonuclease or photolyase can be adapted to deliver the three B complex vitamins into cells.
- Such methods are disclosed in US Patent Numbers 5,077,211 and 5,352,458, which are hereby incorporated by reference in their entirety.
- a pharmaceutically acceptable carrier which can take many different forms.
- pharmaceutically-acceptable is meant that the carrier comprises common pharmaceutical and cosmetic ingredients that are generally recognized as safe for human use.
- Useful pharmaceutical carriers for the preparation of the pharmaceutical compositions hereof can be solids, liquids or gases.
- Water, saline, aqueous dextrose and glycols are preferred liquid carriers, particularly for injectable solutions.
- the carrier can be selected from various oils including those of petroleum, animal, vegetable or synthetic origin, for example, peanut oil, soybean oil, mineral oil, sesame oil, and the like.
- Suitable pharmaceutical excipients include starch, cellulose, talc, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, magnesium stearate, sodium stearate, glyerol, monosterate, sodium chloride, dried skim milk, glycerol, propylene glycol, water, ethanol, and the like.
- compositions may be subjected to conventional pharmaceutical expedients such as sterilization and may contain conventional pharmaceutical additives such as preservatives, stabilizing agents, wetting or emulsifying agents, salts for adjusting osmotic pressure, buffers, and the like.
- conventional pharmaceutical additives such as preservatives, stabilizing agents, wetting or emulsifying agents, salts for adjusting osmotic pressure, buffers, and the like.
- Suitable pharmaceutical carriers and their formulations are described in Martin, Remington's Pharmaceutical Sciences, 15 th Ed. (Mack Publishing Co., Easton 1975) (see, e.g., pp. 1405-1412, 1461-1487).
- Such compositions will, in general, contain an effective amount of the active compound together with a suitable amount of carrier so as to prepare the proper dosage form for proper administration in the host.
- the therapeutic methods of the present invention are practiced when the relief of symptoms is specifically required or perhaps imminent; in another preferred embodiment, the method hereof is effectively practiced as continuous or prophylactic treatment.
- a suitable topical carrier can be in the form of a water-in-oil emulsion; these emulsions can be thin or thick in consistency, so as to be adaptable to spray or aerosol delivery, lotions, creams, etc.
- Other useful carriers for topical administration include any of gases, water, water-based liquids, lotions, dispersions, oils, oil-based solutions, powder, gels, emulsions, dispersions or mixtures thereof.
- Some folates are water-soluble, and can be used without an oil component in the carrier.
- the appropriate amount of carrier can readily be determine by those skilled in the art according to the SPF desired. Hydrophobic carriers as well as hydrophilic carriers may be employed with the sunscreen compositions.
- Carriers to be applied to the skin or hair are compatible with human skin or hair, respectively.
- Ansel et al. describe many appropriate carriers for topical administration in the above-noted reference.
- Other appropriate carriers are disclosed in the following patents, hereby incorporated by reference: US 4,401 ,664, US 4,938,969, US 5,607,622, and US 5,153,230.
- Additional sunscreen agents known in the art may also be added to the compositions, for example, at least one additional hydrophilic or lipophilic organic UV-A and/or UV-B sunscreen agent such as cinnamate, benzophenone, beta-carotene, and alpha-hydroxy acids.
- additional hydrophilic or lipophilic organic UV-A and/or UV-B sunscreen agent such as cinnamate, benzophenone, beta-carotene, and alpha-hydroxy acids.
- Vitamin E alpha-tocopherol
- compositions of the invention may also include, in addition, conventional cosmetic adjuvants and additives such as preservatives, organic solvents, browning agents, antioxidants, stabilizers, emollients, silicones, alpha-hydroxy acids, demulcents, anti-foaming agents, moisturizing agents, vitamins, fragrances, ionic or nonionic thickeners, surfactants, fillers, thickeners, sequestrants, polymers, propellants, alkalinizing or acidifying agents, opacifiers, fatty compounds (e.g. oil, wax, alcohols, esters, fatty acids), colorants, or mixtures thereof or any other ingredient that may be used in cosmetics and in particular for the production of sunscreen compositions.
- conventional cosmetic adjuvants and additives such as preservatives, organic solvents, browning agents, antioxidants, stabilizers, emollients, silicones, alpha-hydroxy acids, demulcents, anti-foaming agents, moisturizing agents, vitamins, fragrances,
- the invention also relates to a method of protecting human skin or hair against the deleterious effects of solar radiation by topically applying thereto an effective amount of a composition of the invention.
- compositions for hair or other personal care may be prepared by adding UV screening compounds in hair rinses, aerosol sprays, mists, gels, mousses, shampoos, conditioners, lotions, films, emulsions and coloring products to reduce photodamage to hair and photobleaching of hair and hair dyes.
- the invention also relates to a method of protecting human hair against the deleterious effects of solar radiation by topically applying thereto an effective amount of a composition of the invention.
- Makeup products such as foundation, lipstick, eyeshadow, blush, nail polish, mascara, moisturizing creams and lotions or eyeliner may also contain the compounds of the invention. These are formulated according to known methods for makeup products such as those for preparation of an anhydrous or aqueous solid or paste, emulsion, suspension or dispersion.
- composition may also contain agents that promote absorption into the skin, for example, propylene glycol, which was used in Example 1 and 2.
- agents that promote absorption into the skin for example, propylene glycol, which was used in Example 1 and 2.
- the folate compounds of the invention could also be administered in liposomes, or liposomes that also contain DNA repair enzymes such as AP endonuclease
- oral, enteral, entranasal, rectal, ocular or parenteral routes can be used.
- Methods and compositions for administration via oral enteral, entranasal, rectal, ocular and parenteral routes are well known in the art. (For example, see Ansel, A. C, Popovich, N.G., and Allen Jr., L.V. Pharmaceutical Dosage Forms and Drug Delivery Systems. 6th Edition. 1995. Williams & Wilkings, Baltimore, which is hereby incorporated by reference in its entirety.)
- Topical application to the epidermis of a subject can also be an effective route to deliver bioavailable folates, niacinamide and vitamin B12, including cobalamin, cyanocobalamin, methylcobalamin and adenosylcobalamin.
- the B complex vitamin formulation could also be administered via micro sponge delivery system, as described in K. Embil and S. demo, 1996, "The micro sponge Delivery System (MDS): a topical delivery system with reduced irritancy incorporating multiple triggering mechanisms for the release of actives" J Microencapsul 13: 575-588.
- MDS micro sponge Delivery System
- compositions systemically by means of intravenous, subcutaneous or intramuscular routes.
- concentration of folates in the composition to be administered to a subject varies depending on the particular folate, the route of administration, and the cells to which it is targeted.
- concentration of folates should be tailored to result in the accumulation in the cells of sufficient concentrations of the three B complex vitamins to reduce UVR damage to the cells.
- concentration of vitamins should be adjusted to result in the desired degree of absorption or blocking.
- the concentration of folates in the composition is between (0.002 and 10 mg/ml), and more preferably between (0.002 mg/ml and the limits of solubility of the folate compound in any particular carrier).
- concentration of niacinamide will be 100 times this amount.
- the vitamin B12 concentration will be in the range 0.1 mg/ml to the limits of solubility of the vitamin.
- the composition in a suitable carrier can be administered in single unit dosage form with continuous therapy or in single dose therapy ad libitum.
- the composition could be administered in the form of tablets, pills, capsules, powders, enterically coated or other protected formulations (such as binding on ion exchange resins or other carriers, or packaging in lipid protein vesicles or adding additional terminal amino acids), sustained release formulations, solutions (e.g., ophthalmic drops), suspensions, elixirs, aerosols, and the like.
- the compositions could also be administered orally or sublingually or in the form of a juice or other suitable drink or other suitable dietetic composition.
- the particular dosage of pharmaceutical composition to be administered to the subject orally, parenterally, enterally, entranasally, rectally or ocularly will depend on a variety of considerations including the schedule of administration, the age and physical characteristics of the subject, and so forth.
- the pharmaceutical compositions to be administered orally, parenterally, enterally, entranasally, rectally or ocularly to an adult should be in the range of about 0.1 mg to about 1.5mg of vitamin B12, about 100mg to about 1g of vitamin B3 and about 1 mg to about 10mg of vitamin B9.
- compositions to be administered orally, parenterally, enterally, entranasally, rectally or ocularly to a child should be in the range of about 20ug to about 1.5mg of vitamin B12, about 20mg to about 1g of vitamin B3 and about 200ug to about 10mg of vitamin B9.
- Proper dosages may be established using clinical approaches familiar to the medicinal arts.
- a daily dosage of folates in the range of 0.02 mg/kg to 0.05mg/kg, and preferably between 0.02 mg/kg and 0.2 mg/kg, and more preferably between 0.02mg/kg and 1 mg/kg can be ingested orally.
- the amount of niacinamide will be 100 times this amount.
- Vitamin B12 can be ingested in the range 0.001 mg/kg to 1 mg/kg.
- the pharmaceutical compositions are used to treat diseases caused by ultraviolet radiation, such as diseases or conditions of the skin and immune system.
- the pharmaceutical compositions are used to treat actinic keratoses, photodermatitis, photo-induced (discoid) lupus erthermatosus.
- the most effective formulation was the combination 500 mg vitamin B12, 5mg folic acid and 500mg niacinamide which prevented sunburning over a period of 5 hours.
- the published UVB index gave an expected time of continuous exposure to sunlight in the Edmonton AB area of 45 minutes.
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2001272274A AU2001272274B2 (en) | 2000-07-06 | 2001-07-06 | B complex vitamin compositions that protect against cellular damage caused by ultraviolet light |
EP01951290A EP1299078A2 (en) | 2000-07-06 | 2001-07-06 | B complex vitamin compositions that protect against cellular damage caused by ultraviolet light |
AU7227401A AU7227401A (en) | 2000-07-06 | 2001-07-06 | B complex vitamin compositions that protect against cellular damage caused by ultraviolet light |
US09/900,064 US7018623B2 (en) | 2000-07-06 | 2001-07-06 | B complex vitamin compositions that protect against cellular damage caused by ultraviolet light |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA2,313,659 | 2000-07-06 | ||
CA002313659A CA2313659A1 (en) | 2000-07-06 | 2000-07-06 | B complex vitamin compositions that protect against cellular damage caused by ultraviolet light |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2002003942A2 true WO2002003942A2 (en) | 2002-01-17 |
WO2002003942A3 WO2002003942A3 (en) | 2002-05-02 |
Family
ID=4166676
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CA2001/001006 WO2002003942A2 (en) | 2000-07-06 | 2001-07-06 | B complex vitamin compositions that protect against cellular damage caused by ultraviolet light |
Country Status (5)
Country | Link |
---|---|
US (1) | US7018623B2 (en) |
EP (1) | EP1299078A2 (en) |
AU (2) | AU7227401A (en) |
CA (1) | CA2313659A1 (en) |
WO (1) | WO2002003942A2 (en) |
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EP1912641A2 (en) * | 2005-06-21 | 2008-04-23 | South Alabama Medical Science Foundation | Methods and compositions containing natural folates for protecting against radiation damage |
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- 2001-07-06 AU AU7227401A patent/AU7227401A/en active Pending
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Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1214927A1 (en) * | 2000-12-14 | 2002-06-19 | Beiersdorf AG | Use of folic acid and/or its derivatives for the manufacture of topical compositions |
EP2193796A1 (en) * | 2001-06-28 | 2010-06-09 | Regeneratio Pharma GmbH | Use of corrinoids for the treatment of skin diseases |
WO2003002104A2 (en) * | 2001-06-28 | 2003-01-09 | Regeneratio Pharma Ag | Use of corrinoids in the treatment of skin diseases |
WO2003002104A3 (en) * | 2001-06-28 | 2003-03-20 | Regeneratio Pharma Ag | Use of corrinoids in the treatment of skin diseases |
EA007592B1 (en) * | 2001-06-28 | 2006-12-29 | Регенерацио Фарма Аг | Use of corrinoids in the treatment of skin diseases |
AU2002352566B2 (en) * | 2001-06-28 | 2007-06-14 | Regeneratio Pharma Gmbh | Use of corrinoids in the treatment of skin diseases |
EP2198872A1 (en) * | 2001-06-28 | 2010-06-23 | Regeneratio Pharma GmbH | Use of corrinoids for the treatment of skin diseases. |
EP2198871A1 (en) * | 2001-06-28 | 2010-06-23 | Regeneratio Pharma GmbH | Use of corrinoids for the treatment of skin diseases. |
WO2004043422A1 (en) * | 2002-11-13 | 2004-05-27 | Unilever Plc | Improved cosmetic composition |
EP1912641A4 (en) * | 2005-06-21 | 2008-12-31 | Univ South Alabama | Methods and compositions containing natural folates for protecting against radiation damage |
JP2008546799A (en) * | 2005-06-21 | 2008-12-25 | サウス、アラバマ、メディカル、サイエンス、ファウンデーション | Methods and compositions comprising natural folic acid for protection from radiation damage |
EP1912641A2 (en) * | 2005-06-21 | 2008-04-23 | South Alabama Medical Science Foundation | Methods and compositions containing natural folates for protecting against radiation damage |
AU2006262096B2 (en) * | 2005-06-21 | 2012-11-01 | Children's Hospital & Research Center At Oakland | Methods and compositions containing natural folates for protecting against radiation damage |
Also Published As
Publication number | Publication date |
---|---|
CA2313659A1 (en) | 2002-01-06 |
AU2001272274B2 (en) | 2007-01-18 |
AU7227401A (en) | 2002-01-21 |
WO2002003942A3 (en) | 2002-05-02 |
US20020035087A1 (en) | 2002-03-21 |
EP1299078A2 (en) | 2003-04-09 |
US7018623B2 (en) | 2006-03-28 |
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