The invention relates to novel compositions that protect humans and objects from damaging exposure to solar radiation. The invention also relates to active compounds which occur naturally in plants, algae and cyanobacteria as well as to the chemical derivatives of these compounds that protect against solar radiation.
The various layers of the earth""s atmosphere absorb most of the solar radiation reaching earth with the more energetic ultraviolet radiation (UV) filtered out by the ozone layer. Of the solar radiation reaching the earth""s surface that is of biological interest, only about 2% of the radiation is UV-B with its characteristic wavelength range of 280 to 315 nm. The remainder consists mainly of UV-A with the characteristic wavelength range of 315 to 400 nm, visible light of 400 to 700 nm and infrared radiation ( greater than 740 nm). Anthropogenic depletion of the stratospheric ozone layer (Madronich et al., 1995, Ambio 24: 143) has resulted in elevated levels of UV radiation reaching the earth and these levels are expected to increase In the future. The higher levels of radiation have been linked to a significant rise in the incidence of skin lesions and skin cancer in humans (Jagger, 1985, Solar-UV Actions on Living Cells, Praeger Pub., N.Y.). Skin cancer now occurs more frequently than all other cancers combined. In 1998, there will be approximately one million new cases of skin cancer in North America alone. According to the American Cancer Society, diagnosed cases of skin cancer have increased at a rate of about 4% per year in the U.S. since 1973 (Science News 1997, 151: 383). Thus, increased incidence of skin cancer has become a serious health concern.
Skin damage is caused by both UV-A and UV-B radiation. Although damage caused by UV-B radiation has been extensively studied (Motoyoshi et al., 1998, Cosmetics and Toiletries 113: 51), only a few published papers describe the effects of UV-radiation on human hair or quantify photodamage (Hoting et al., 1995, J. Soc. Cosm. Chem. 46: 85). Erythma is the most apparent result of the sunburn reaction but sunburn can also disturb DNA and RNA structure and metabolism. The most serious results of chronic sun exposure are photoaging and photocarcinogenesis.
The natural human skin pigment, melanin, has evolved to provide a certain level of protection against the damaging effects of solar radiation (Kollias et al., 1991, J. Photochem. Photobiol. B: Biol. 9:135). The epidermis has the ability to interfere with the transmission of UV-radiation. Only about 20% of the incident radiation between 300 and 350 nm reaches the dermis. This penetration rises gradually to about 80% at or near 550 nm. Evidently, the cells of the stratum comeum are a remarkably effective block against UV-B radiation. Keratinocytes are, however, exposed to UV-A radiation even though the more energetic UV-B wavelengths are excluded. Moreover, UV-A radiation has been shown to induce mutations and to be potentially lethal (Jagger, 1985, Solar-UV Actions on Living Cells, Praeger Pub., N.Y.).
Strategies to protect skin against solar radiation have most often involved the application of compositions that either block the radiation or absorb the harmful UV component (Gasparro et al., 1998, Photochem. Photobiol. 68:243). Although sunscreens on the market today protect people from sunburn to varying degrees, they do not prevent skin cancer. The use of sunscreens has increased significantly in the last five to ten years but cases of melanoma have also continued to rise (ASP News, 1998, 27:7). Typical sunscreen preparations block UV-B but UV-A passes through very easily. It has been reported that although UV-B causes sunburn, UV-A plays a major role in inducing skin cancer (ASP News, 1998, 27:7). We believe that there is a clear need to devise strategies to supplement the body""s natural protective mechanisms against both UV-A and UV-B radiation. A suitable composition must have high activity against UV-A as well as UV-B, be safe for application to human skin and provide good cosmetic application and appearance.
Cosmetic chemists have incorporated sunscreen activities into formulations in order to achieve the desired protection. Formulating products with an improved UV screening capacity is a challenge for cosmetic chemists due to concerns over the use of high levels of organic actives (Dromgoole et al., 1990, Sunscreens: development, evaluation and regulatory aspects. Marcel Dekker, N.Y., pp 313-317). Sunscreen compounds are most effective when they remain on the surface of the epidermis but unfortunately, they are often absorbed to deeper layers of the skin, thereby limiting their efficacy and causing irritation. Cosmetic chemists use organic compounds in their sunscreen formulations. For example, combinations of nylon, butyl methoxydibenzoylmetan and octylmethoxycinnamate have been used as UV-screens in many solar lotions. (Cosmetics and Toiletries, 1998, 113: 83; Gasparro et al., 1998, Photochem. Photobiol. 68:243) (see Table 1).
This formulation provides some protection against UV-B but provides minimal protection against UV-A.
Based on recent reports showing the harmful effect of UV-A exposure on skin tissue, it is imperative that the cosmetic industry develops as soon as possible protective lotions by broadening the light absorption range of skin lotions (Gasparro et al., 1998, Photochem. Photobiol. 68:243).
Photoautotrophic plants and microorganisms such as green algae and cyanobacteria have evolved to protect the sensitive photosynthetic process against the damaging effects of UV-radiation. Photosynthetic organisms as well as heterotrophic organisms such as fungi and bacteria produce naturally occurring compounds that protect them from the damaging effects of solar radiation. To date, these organisms have not been exploited as sources for sunscreen compounds that can be applied to human skin. This is probably due in part, to the scientific background of the industrial scientists involved in the cosmetic industry. These scientists are typically synthetic organic chemists with limited knowledge and expertise in photosynthesis research and the biology and biochemistry of terrestrial plants, green algae and cyanobacteria. It would be helpful if the naturally occurring sunscreens from these organisms could be adapted to protect humans from solar radiation.
We identified several naturally occurring compounds which: (1) act as natural sunscreening agents; (2) protect not only against visible light and UV-B radiation but also protect against UV-A radiation; (3) can be produced in large quantities; (4) are easily isolated; (5) are easily incorporated in sunscreen lotions which will offer protection to humans against both harmful forms of ultraviolet radiation (UV-A and UV-B); (6) and as a consequence, should reduce the development of skin cancers, sunburn, photoaging and photodamage to hair and eyes upon exposure to sunlight.
The invention includes several main components: First, we showed that cyanobacteria principally use a combination of three different types of compounds to protect themselves from the harmful affects of solar radiation: (i) carotenoids (ii) scytonemin and (iii) mycosporine amino acids. These compounds may be used to formulate sunscreen compositions that provide significant protection from solar radiation. The compositions are non-toxic, resistant to absorption by the skin, non-irritating to the skin and capable of application to the skin in compositions that create a uniform, continuous film. In addition, the compounds are chemically stable and resistant to chemical and photodegradation when on the skin. The formulations will not only protect human skin from photoaging and photodamage but also will provide protection to human hair and other surfaces. In addition, these compounds can be integrated into or coated on objects such as windows, contact lenses, sunglasses, paints and films for protection against the damaging effects of prolonged exposure to solar radiation. The invention also relates to a method of protecting human skin and other surfaces against the deleterious effects of solar radiation by topically applying thereto an effective amount of a composition of the invention.
Second, we have shown a novel method to induce overproduction of these natural screening compounds. For example, these compounds are very easy to produce in cyanobacteria. Cyanobacteria are amenable to manipulation by controlling culturing conditions. Since these compounds are produced naturally by photosynthetic organisms, the formulations are xe2x80x9ceco-friendlyxe2x80x9d and can be extracted from organisms easily and efficiently. The compounds may also be chemically synthesized.
Next, based on the results of research described above, we developed a sensitive, relevant biological assay to test the potential of various screening compounds to protect against UV-radiation. This is accomplished by exploiting the sensitivity of cyanobacterial photosystems to UV-radiation.
Finally, we identify useful naturally occurring sunscreen compounds from other organisms and methods for their isolation and use.
The sunscreen agents, in particular those from cyanobacteria, provide a synergistic effect. Compositions containing the three compounds isolated from cyanobacteria with a carrier are superior to those which may be obtained, with an equal amount of sunscreen compound and a carrier identical in nature, employing either of the compounds alone. The three compounds are preferably present in the final composition in relative proportions chosen so that the synergistic effect, at the level of the sun protection factor conferred by the resulting composition, is optimal.
In one embodiment, the invention is a sunscreen composition including a carotenoid or a carotenoid derivative and a carrier. In an alternate embodiment, the invention is a sunscreen composition including a polyphenolic compound or a polyphenolic compound derivative and a carrier. In another embodiment, the invention is a sunscreen composition comprising a mycosporine amino acid or a mycosporine amino acid derivative and a carrier. In yet another embodiment, the invention is a sunscreen composition comprising a carotenoid or a carotenoid derivative, a polyphenolic compound or a polyphenolic compound derivative, a mycosporine amino acid or a mycosporine amino acid derivative and a carrier. The compositions protect skin, hair and other surfaces from solar radiation. The carriers are compatible (cosmetically and otherwise) with the surface to which the compositions to which they will be applied, for example, human skin or hair. The carriers are preferably at least one of either water, a gas, a water-based liquid, an oil, a gel, an emulsion, a dispersion or a mixture thereof.
The carotenoid preferably comprises a cyanobacterial carotenoid, such as a compound selected from the group consisting of xcex2-carotene, lutein, neoxanthin, zeaxanthin, violaxanthin, caloxanthin, nostoxanthin, echinenone, canthexanthin, oscillaxanthin and myxoxanthophyll. The polyphenolic compound is preferably a cyanobacterial polyphenolic compound such as scytonemin. The mycosporine amino acid is preferably a compound selected from the group consisting of mycosporinelycine, palythine, asterina-330, palythinol, palythene, porphyra-334, mycosporine-glycine:valine and shinorine. The carotenoid is preferably present in an amount of about 2 mg by weight. The polyphenolic compound is preferably present in an amount of about 1 mg by weight. The mycosporine amino acid is preferably present in an amount of about 1 mg by weight.
Suitable compositions include an oil-in-water emulsion or a water-in-oil emulsion. In a variation, the sunscreen composition further includes at least one cosmetically acceptable adjuvant or additive, such as a 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.
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 makeup or an anhydrous or aqueous solid or paste. The composition may also include a hair rinse, spray, mist, gel, mousse, shampoo, conditioner, lotion, emulsion and colouring product.
In another embodiment, the invention relates to a method of protecting human skin human hair or another surface from solar radiation, by topically applying thereto an effective amount of the compositions of the invention.
An alternate embodiment of the invention is a sunscreen composition including a photoautotrophic cell extract and a carrier. Carriers are compatible (cosmetically and otherwise) with the surface to which the compositions to which they will be applied, for example, human skin or hair. The carriers are preferably at least one of either water, a gas, a water-based liquid, an oil, a gel, an emulsion, a dispersion or a mixture thereof. The extract is preferably present in an amount of about 0.1 to 25% by weight or about 0.1 to 10% by weight. The sunscreen composition including a photoautotrophic cell extract and a carrier, wherein the photoautotrophic cell extract is preferably obtained by extraction of photoautotrophic cells with methanol and acetone.
In another embodiment, the invention is a kit for assaying a test compound to determine its sunscreen efficacy, comprising: a photoautotrophic cell culture, a chlorophyll fluorometer and an artificial filter for containing the test compound. The invention also includes a method for protecting the human skin, human hair or another surface from solar radiation, comprising topically applying thereto an effective amount of the sunscreen composition of the invention. The invention also includes a method of inducing cyanobacteria to produce myxoxanthophyll, scytonemin and/or mycosporine amino acid, the method comprising culturing the cyanobacteria under conditions of high excitation pressure. The invention also includes a method of producing an extract having an increased concentration of at least one of myxoxanthophyll, scytonemin and/or mycosporine amino acid, the method preferably including: culturing cyanobacteria under conditions of high excitation pressure and isolating an extract including at least one of myxoxanthophyll, scytonemin and mycosporine amino acid. In the methods the conditions of high excitation pressure are preferably about 5xc2x0 C. and a light intensity of about 150 xcexcmol mxe2x88x922 sxe2x88x921 or about 29xc2x0 C. and a light intensity of about 750 xcexcmol mxe2x88x922 sxe2x88x921. The methods preferably further comprising isolating at least one of myxoxanthophyll, scytonemin and/or mycosporine amino acid. The invention also includes a method of assaying a compound to determine its sunscreen efficacy, including extracting photoautotrophic cells to produce a solution; producing an artificial filter; determining whether the artificial filter protects photosystem II photochemical efficiency from UV radiation. The protection of photosystem II photochemical efficiency from UV radiation is determined by measuring chlorophyll a fluorescence.
The invention also includes method for protecting human eyes from solar radiation, comprising applying at least one of a carotenoid, a polyphenolic compound and/or a mycosporine amino acid or a derivative of a carotenoid, a polyphenolic compound or a mycosporine amino acid to an eye wear lens or a window.
In another embodiment, the sunscreen composition includes a light absorbing amino acid or a light absorbing amino acid derivative and a carrier.
The invention also includes a sunscreen composition comprising: a carotenoid or a carotenoid derivative, a polyphenolic compound or a polyphenolic compound derivative, a light absorbing amino acid or a light absorbing amino acid derivative and a carrier. The amino acid or amino acid derivative is preferably selected from the group consisting of tyrosine, tryptophan, a tyrosine derivative and a tryptophan derivative. The derivatives have sunscreen activity which means that they are capable of absorbing light (preferably ultraviolet radiation) and are useful in the sunscreen compositions of the invention to reduce damage caused by light.
The invention relates to a sunscreen composition comprising a carrier and at least one compound selected from the group consisting of: a carotenoid, a carotenoid derivative having sunscreen activity, a polyphenolic compound, a polyphenolic compound derivative having sunscreen activity, sunscreen amino acid and a sunscreen amino acid derivative. Another aspect of the invention relates to a sunscreen composition including: a) a carotenoid or a carotenoid derivative having sunscreen activity; b) a polyphenolic compound or a polyphenolic compound derivative having sunscreen activity; and c) a light absorbing amino acid having sunscreen activity and a light absorbing amino acid derivative having sunscreen activity. The amino acid or amino acid derivative may be one of tyrosine, tryptophan, a tyrosine derivative having sunscreen activity and a tryptophan derivative having sunscreen activity.
The invention also includes a method of reducing degradation of a chemical that is sensitive to ultraviolet light comprising applying a composition of the invention to the chemical. The chemical is a herbicide, a pesticide, an auxin, a gibberellin, abscisic acid, a cytokinin, derivative of a carotenoid, a polyphenolic compound, a mycosporine amino acid and or a derivative of any of the foregoing (mixtures or pure preparations).
The invention also includes a method of determining the sunscreen activity of an extract, including: extracting photoautotrophic cells to produce a solution; producing an aqueous filter, determining whether the aqueous filter protects photosystem I or II from UV radiation wherein improved protection from UV radiation indicates that the compound has sunscreen activity. Compounds may also be purified from the extracts for use in the method.
The invention includes a system for determining the sunscreen activity of a test compound including:
a) light means or light member for generating ultraviolet radiation;
b) container means or container member, coupled to the light means, for containing a photoautotrophic bacterial culture, homogenate or extract thereof having PSI or PSII activity;
c) sample means or sample member for holding a test compound, interposed between the light means and the container means.
The system may further include a scoring means or a scoring member for assaying the culture, homogenate or extract to determine PSI or PSII activity, wherein the amount of decrease in PSI or PSII activity caused by ultraviolet radiation indicates the sunscreen activity of the test compound.
The invention also includes a method for determining the sunscreen activity of a test compound comprising the steps of:
(a) generating ultraviolet radiation for passing through the test compound;
(b) exposing a photoautotrophic bacterial culture, homogenate or extract thereof having PSII activity to the ultraviolet radiation being passed through the test compound, the test compound being spaced from the culture, homogenate or extract;
(d) assaying the culture, homogenate or extract for PSI or PSII activity; and
(e) correlating the PSI or PSII activity to the sunscreen activity of the test compound. Purified compounds (synthetic or isolated from culture, homogenate or extract), photoautotrophic bacterial culture, homogenate or extract may be tested in the systems or methods of the invention.
The method may further include determining the sun protection factor of the test compound.
The invention also includes a method for reducing ultraviolet light damage to a surface, including applying to the surface an effective amount of an extract from a photoautotroph, wherein the extract has sunscreen activity. The photoautotroph may be selected from the group consisting of photoautrotrophic bacteria, photoautrotrophic plants, photoautrotrophic fungi or heteroautotrophic bacteria. The surface may be skin (eg human skin). In the method, the extract includes at least one compound from the group consisting of: a carotenoid, a carotenoid derivative having light absorption activity, a polyphenolic compound, a polyphenolic compound derivative having light absorption activity, a light absorbing amino acid and a light absorbing amino acid derivative.
USPTO Backgrounds
USPTO Backgrounds