Th1f root draw options trading
This application claims priority from U. Provisional Patent Application No. Applicants assert that the paper copy of the Sequence Listing is identical to the Sequence Listing in computer readable form found on the accompanying computer disk.
Applicants incorporate th1f root draw options trading contents of the sequence listing by reference in its entirety. The present invention relates to the field of tyrosinase inhibitors and to methods and th1f root draw options trading of treatment involving inhibition of this enzyme. The present invention relates to novel biological agents, specifically oligopeptides that reduce the enzymatic activity of tyrosinase. These agents have use as research and development tools in basic science investigation, in diagnostic applications, as cosmeceuticals th1f root draw options trading the treatment of skin conditions characterized by hyperpigmentation, and as therapeutics for the treatment of pathological conditions that rely on tyrosinase enzyme activity to promote their tumorigenicity.
Melanin plays an important role in protecting the human body from the harmful effects of ultraviolet rays. Melanin is also an important factor in medical science and cosmetology. It is known that melanin is formed or synthesized in skin tissues.
Excessive amounts of melanin darken the skin, and the nonuniform distribution of melanin causes chloasma and ephelis, both of which are skin disorders. An effective way to inhibit the synthesis of melanin is to block the hydroxylation of tyrosine. Hydroquinone HQ has been used since the s in commercially available over-the-counter skin lightener products and since the s as a commercially available medical product.
It is also used in cosmetic products such as hair dyes and products for coating fingernails. Beginning inHQ is no longer authorized for use in cosmetic skin lightening formulations in European Union countries, although products containing arbutin, an analogue of HQ, and botanicals, including plants that naturally contain HQ and arbutin, continue to remain available in European countries See also, Matsubayashi et al.
As disclosed there, ointments of the skin depigmentation agent hydroquinone HQ have been prepared by extemporaneous nonsterile compounding in Japan by imitating skin lightening creams commercially available in the U. However, various problems have been observed th1f root draw options trading chromatic aberration of HQ ointments, relatively large variability of efficacy, and undesirable side effects although they were mild.
Therapies containing hydroquinone have been outlawed in Asian countries, making the standard HQ treatment inaccessible to a large number of people suffering from this condition. In fact, the United States FDA has issued a th1f root draw options trading indicating that it may too ban the use of hydroquinone domestically. Furthermore, hydroquinone has been th1f root draw options trading with visceral malignancy and long-term topical delivery may be a potentially harmful therapeutic option.
Hydroquinone in the best of circumstances leads to only a partial alleviation of hyperpigmentation. Some cosmeceutical formulations have included other active ingredients such as kojic acid, arbutin, and vitamin C but efficacy has thus far been disappointing due to problems with chemical instability or inability to deliver the active to the appropriate layer of skin.
Although higher concentrations have been utilized, patients often discontinue treatment due to skin irritation. This led to the addition of topical steroids in order to reduce irritation from the active ingredients such as retin A and hydroquinone. Since melasma and other hyperpigmentary disorders often take months to years to treat, use of topical steroids th1f root draw options trading the face at the strength required to combat irritant effects of active ingredients is not possible without causing topical steroid-induced side effects.
When medium or greater potency topical steroids are used on the face for more than several weeks consecutively, skin atrophy, fragility and telengiectasia commonly occur. This side effect profile is unacceptable, especially in areas such as the face. Infrared lasers have been used with some success. They generally are more effective for conditions that localize pigment to the deeper skin areas such as the dermis.
In order to effectively treat the epidermis, an ablative treatment is usually employed. This therapy is associated with significant downtime for the patient, including creation of second-degree burn or erosion leaving the patient susceptible to infection.
In addition, laser therapy is an expensive treatment option that many patients cannot afford. In extreme cases, depigmentation of the skin has been elected when bleaching agents have been unsuccessful. Numerous pathological conditions can lead to the deposition of pigment into the skin aberrantly. For example, it is well known that hormonal imbalance can cause facial and extremity hyperpigmentation, most frequently observed in women during or following pregnancy.
Often times, th1f root draw options trading hyperpigmentation becomes aesthetically disfiguring, leading to problems with self-esteem and embarrassment in social situations. This constitutes a significant portion of the worldwide population. According to the Fitzpatrick skin type scale, based on a test of appearance and skin reaction to sun exposure, individuals are generally categorized as follows:.
In addition to melasma, hyperpigmentation of aesthetically sensitive locations such as the face may take place after inflammation due to disorders such as acne or rosacea, amongst others.
These conditions may also lead to significant psychological discomfort. With the anticipated ban of hydroquinone in the US market, in conjunction with the continued stability vitamin C or delivery arbutin, kojic acid, etc problems of other non-pharmacological agents currently on the market, oligopeptide inhibitors may provide th1f root draw options trading solution to this large unmet need. Sericin is a high molecular weight, natural, soluble glycoprotein constituent of silk.
Sericin binds to the keratin of skin and hair, forming a protective film. The composition includes Simmondsin, which is a glycoside extracted from jojoba meal Simmondsia chinensis. In certain embodiments, the composition comprises an extract of jojoba Simmondsia chinensis.
The composition is administered by topically applying to an individual a formulation in an amount effective to whiten skin, where that composition comprises a jojoba extract. A cosmetic active agent known in the art may be incorporated in the film forming compositions for improving skin appearance. Anti-hyperpigmentation agents typically used for counterbalancing this condition can include tyrosinase inhibitors such as peptide mixtures and plant extracts, fermentation products, and antioxidants such as hydroquinone, kojic acid, ascorbic acid derivatives, synthetic or natural derivatives of hydroquinone and hydroquinone precursors.
In preferred embodiments of the invention, anti-hyper pigmentation agents are Melawhite of Pentharm Ltd. The tyrosinase inhibitor provides advantageous skin whitening effects. According to the th1f root draw options trading, the tyrosinase inhibitor extract of the invention has a main absorbance at nm.
This indicates that the tyrosinase inhibitor extract contains a protein or peptide. It is believed that the protein or peptide is the main active component for inhibiting tyrosinase. The other components of the extract may provide additional effects such as anti-aging and anti-oxidation. The tyrosinase inhibitor extract can be prepared to be in various forms, including lotions, th1f root draw options trading, creams, ointments, sticks, solutions, packs, and gel.
The tyrosinase inhibitor extract may be admixed with any ingredients ordinarily used in cosmetics, such as oily substances, humectants, thickeners, preservatives, emulsifiers, medical ingredients, perfumes, emulsification stabilizers and the like. Various other patents and publications disclose unrelated peptides.
The following brief summary is not intended to include all features and aspects of the present invention, nor does it imply that the invention must include all features and aspects discussed in this summary. The present invention is further directed to kits and compositions containing the present peptides, and methods of treatment of conditions involving expression of tyrosinase, in which the present peptides are administered topically for the treatment of conditions involving melanocyte activity in the skin.
Other formulations are useful in treating tyrosinase activity in other regions of the body and may be administered internally. The peptide in effect may be substituted in up to three positions, including deletions.
Guidance is given for making these alterations, as well as th1f root draw options trading them for inhibitory potency. In some cases, the peptide will have an IC50 of less than about 5 mM, or even less. In some cases, it is within the present invention to substitute a residue with R or F, in that these residues serve to increase peptide binding to the tyrosinase.
Thus, it is preferred that the residue substituted with R or F not be an F; if it is, it would be substituted with R. Between one and three residues may be substituted with V, A, L, M or I, in that these residues serve to increase inhibitory th1f root draw options trading. It is also advantageous in some embodiments to have two adjacent charged amino acids.
In certain aspects, the invention comprises the use of D-amino acids for some or all of the amino acids. The peptides may be linked to a modulating group, as th1f root draw options trading below, such as palmitic acid or ester. The peptide may have two adjacent charged amino acids.
In certain aspects, the present invention comprises a topical formulation useful in skin whitening. The formulation is made from dermatologically acceptable ingredients. These peptides may be altered as described above. In certain embodiments, the formulations may be adapted for potential over the counter use, or for prescription use.
For over the counter use, one may employ a formulation wherein the peptide is at a concentration less than about two times the IC 50 concentration. For pharmaceutical use, one may the peptide may be at a concentration of two to times the IC 50 concentration. The present peptides are in certain aspects superior to HQ, and may be formulated to be substantially free of HQ.
In certain formulations, different peptides may be combined, with different sequences, different attached groups, and so forth. The carrier may include a material selected from: In certain formulations, the peptides will th1f root draw options trading improved skin uptake by being formulated in liposomes. In certain aspects, the present invention comprises methods of skin treatment, involving skin lightening whitening. This aspect includes a method for treatment of skin comprising administering to the skin a peptide essentially identical to one of: The administering may comprise administering a topical preparation, as referred to above, and may further comprise a secondary treatment product.
The present methods of treatment also include carrying out the skin whitening with further assistance from a microdermabrasion process. The administering may be simultaneous with the microdermabrasion process. The administering is in conjunction with a radiation process. Th1f root draw options trading processes may be used to increase skin permeability. Furthermore, the administering may be in conjunction with a physical treatment carried out by an abrading device a microneedle, th1f root draw options trading electroporation device, or an iontophoretic device.
In certain aspects, the present invention comprises a kit for carrying out a skin whitening procedure, comprising a purified peptide having an IC 50 of tyrosinase of less than about 10 mM and selected from the group consisting of: The kit may be aimed at consumers or physicians, and may include a precombination of the peptide and carrier, such that the formulation is ready to apply, or it may require mixing of the peptide with the carrier.
It can be seen that YR peptide did not inhibit cell proliferation of melanocytes. It can be seen that YR peptide inhibited melanin synthesis in human melanocytes. Inhibition of tyrosinase activity by Th1f root draw options trading peptide is comparable to that of HQ.
Short peptides of between about 6 and 12 amino acids are th1f root draw options trading and shown to have inhibitory activity against tyrosinase. Short sequence peptides are synthetically designed in certain embodiments using naturally occurring amino acids, and therefore are biologically safe. They can be delivered to melanocytes through a number of mechanisms, including but not limited to liposomes, allowing access to the appropriate skin layer. These peptides do not suffer from oxidation problems, as does the most commonly used ingredient vitamin C.
These peptides do not cause liver cancer, as does hydroquinone, and since they are derived from naturally occurring amino acids, are easily degraded intracellularly upon inactivation of tyrosinase. They cause skin lightening or whitening by inhibiting the synthesis of melanin.