MX2010010668A

MX2010010668A - Compositions comprising anrnox-inhibitors for the inhibition of reactive oxygen species.

Info

Publication number: MX2010010668A
Application number: MX2010010668A
Authority: MX
Inventors: Dale Kern; Christiaan Meadows
Original assignee: Nu Skin International Inc
Priority date: 2008-03-28
Filing date: 2008-03-28
Publication date: 2011-04-26
Also published as: AU2008353441A2; KR20110000745A; AU2008353441A1; JP2011515466A; EA201001558A1; CA2719833A1; WO2009120214A1; ZA201007247B; CN102014930A; IL208324A0; EP2280714A1

Abstract

The invention relates to agents for sequestering serum aging factors, and methods for using the same. More particularly, the invention relates to agents termed herein 'Naractin' to denote any one of several naturally-occurring arNOX inhibitors either present in N. tazetta powder or capable of augmenting N. tazetta powder to an inhibitory level comparable to that of the fresh N. tazetta extracts, and to methods for using 'Naractins' to prevent or treat disorders and complications of disorders resulting from cell damage caused by an aging-related isoform of NADH oxidase (arNOX). In one exemplary embodiment the agents of the invention comprise at least one naturally occurring Naractin. Such naturally occurring naratins are also capable of augmenting the anti-arNOX effect of other naturally occurring arNOX inhibitory agents.

Description

COMPOSITIONS COMPRISING INHIBITORS OF NADH OXIDASE ASSOCIATED WITH AGING FOR INHIBITION OF REACTIVE OXYGEN SPECIES FIELD OF THE INVENTION The invention relates to extracts of natural products useful in the sequestration of serum aging factors that can be administered internally or topically. More particularly, the invention relates to agents and compositions for cosmetic use, to inhibit or improve oxidation related to aging and to methods for their use as skin care products.

BACKGROUND OF THE INVENTION Plasma membrane NADH oxidase (NOX) is a unique cell surface protein with hydroquinone (NADH) oxidase and disulfide-thiol protein activities for exchange that normally responds to hormones and growth factors. NOX (or CLOX) are a family of growth related proteins that associate with aged cells. A form insensitive to the hormone and receptive to the NOX drug designated tNOX has been described as specific for cancer cells. For example, see U.S. Pat. No. 5,605,810, which is incorporated herein by reference in its entirety.

The isoform of NADH oxidase related to aging (arNOX) is a member of this family of proteins. The circulation form of arNOX is markedly increased in the sera of humans and in the lymphocytes of individuals, especially between the ages of 30 to 65. The arNOX protein has been uniquely characterized by a superoxide radical generating capacity, which can contribute significantly to changes related to aging including atherogenesis and other phenomena of aging with action at a distance. The activity of arNOX in aged cells and in serum has been described above. See, for example, PCT Publication Application No. WO 00/57871, which is incorporated by reference in its entirety in the present invention.

This model of the effects of arNOX is consistent with the Mitochondrial Theory of Aging, which holds that during aging, the increase of reactive oxygen species in mitochondria causes mutations in mitochondrial DNA and damage to mitochondrial components, resulting in senescence. The mitochondrial theory of aging proposes that the accumulation of spontaneous somatic mutations in mitochondrial DNA (mtDNA) leads to errors in the mitochondrial DNA that encodes the polypeptide chains. (Manczak et al, J Neurochem, 2005 Feb; 92 (3): 494-504). These errors, which occur in mitochondrial DNA that encodes polypeptide chains, are stochastic and transmit randomly during cell and mitochondrial division. The consequence of these alterations is defective oxidative phosphorylation. Defects in the respiratory chain may be associated with an increase in oxidative stress that amplifies the original damage (Ozawa, 1995, Biochim Biophys Acta 1271: 177-189, and Lenaz, 1998, Biochim, Biophys Acta 1366: 53-67). ). In this view, therefore, mutated mitochondrial DNA, despite being present only in very small amounts in the body, may be the main generator of oxidative stress.

Where the accumulation of somatic mtDNA mutations leads to defective oxidative phosphorylation of a plasma membrane oxidoreductase system (PMOR), it has been suggested to increase the survival of mitochondrially deficient cells by regenerating the pyridine nucleotides oxidized, (de Gray, 1997, BioEssays 19: 161-166, de Gray, 1998, Anti-Aging Med 1: 53-66; Yoneda et al, 1995, Biochem Biophys Res Comm, 209: 723-729; Schon et al, 1996, Cellular Aging and Cell Death, Wiley and Sons, New York, pp 19-34, Ozawa, 1997, Physiol, Rev. 77: 425-464, and Lenaz, 1998, Biofactors 8: 195-204). A model to link the accumulation of mitochondrial DNA lesions to extracellular responses, such as the oxidation of lipids in low density lipoproteins (LDLs) and concomitant arterial changes, was first proposed with rho ° cells ( Larm et al., 1994, Biol. Chem. 269: 30097-30100; Lawen et al, 1994, Mol. Aspects Med. 15: s13-s27, de Gray, 1997, BioEssays 19: 161-166, and de Gray, 1998, Anti-Aging Med 1: 53-66). Similar studies have been carried out with human cells transformed in culture. (Vaillant et al., 1996, Bioenerg, Biomemb. 28: 53 1-540).

Under conditions where plasma membrane oxidoreductase (PMOR) is overexpressed, electrons are transferred from NADH to external receptors by a defined chain of electron transport, resulting in the generation of reactive oxygen species (ROS ) on the cell surface. Said ROS generated on the cell surface can then propagate an aging cascade that originates in the mitochondria of both adjacent cells and circulating blood components, such as low density lipoproteins. See PCT Publication Application No. WO 00/57871 incorporated by reference in the present invention in its entirety.

Accordingly, there is a need to find agents that reduce the ability of arNOX to generate reactive oxygen species (ROS) for the purposes of reducing or treating the resulting physiological conditions, such as the oxidation of lipids in low density lipoproteins ( LDLs) and the consequent arterial changes. The ArNOX activity of aged cells has been shown to be inhibited by naturally occurring agents, such as co-enzyme Q (ubiquinone). See PCT Publication Application No. WO 00/57871, WO 01/72318, and WO 01/72319 and, the disclosure of which is incorporated by reference in its entirety. However, the use of co-enzyme Q is not completely satisfactory for several reasons: it is expensive, it oxidizes easily losing its effectiveness, and the preparations containing the coenzyme Q must be packaged in a special way to avoid loss of function. Therefore, although there are currently some agents and methods that can inhibit arNOX activity, there are still challenges. Consequently, it would be an improvement in technique to increase or even replace previously disclosed agents and techniques with agents and techniques that inhibit arNOX but that are also non-toxic and that occur naturally.

The skin, in particular, is vulnerable to damage caused by reactive oxygen species. The skin is composed of two main layers. The stratum corneum, or epidermis, is the top layer and forms a protective covering that covers the skin and controls the flow of water and substances in and out of the skin. The dermis is the lowest level of the skin and provides the strength, elasticity and thickness of the skin. The main cell types of the dermis are fibroblasts, which are responsible for the synthesis and secretion of all the components of the dermal matrix, such as collagen, elastin and glycosaminoglycans. Collagen provides strength, elastin provides elasticity and glycosaminoglycans moisture and skin volume.

In addition to being damaged by reactive oxygen species, the skin is subject to various detrimental stress factors. The skin can be damaged or mistreated by many factors in the environment. Some are of natural origin such as UV radiation from the sun, wind and even injuries mechanics such as cuts, scrapes, and the like. Other injuries, carried out by the human being, also occur daily. These include the use of soaps, cosmetics based on emulsifier, hot water, organic solvents, air conditioning and central heating. In addition, other insults to the skin can result from or are part of dermatological disorders or the normal aging process (chrono aging), which can be accelerated by the exposure of the skin to several external stressors (for example, photo-aging).

Everyone's skin ages with time. However, in modern society, people live longer and the normal effects of aging have an opportunity to accumulate. Such effects can be purely cosmetic, such as increased wrinkles or "age spots" or can have an impact on health such as the incidence of skin cancer due to exposure to UV light. As people age, the skin becomes thinner, the connective tissue of the skin, collagen and elastin change, causing the skin to lose firmness and dry out. Also, the sweat and sebaceous glands in the skin become less active, causing the skin to lose moisture and dry out. In addition, the blood vessels in the skin become more fragile, so that they rupture and leak into the skin.

Symptoms of skin aging include dryness, itching, thinning or thickening of the skin, wrinkles and fine lines, areas of hyperpigmentation commonly referred to as liver spots. and areas below the skin where the blood vessels have ruptured (telangietasia).

"Anti-aging" cosmetic and medical products are desirable, which treat or delay the visible signs of real aging and skin subjected to the environment such as wrinkles, lines, sagging, hyperpigmentation and age spots. However, most cosmetic or medicinal products do not address the basis of such symptoms, for example, the production and accumulation of arNOX-related radicals derived from ROS. Accordingly, there is a demand for effective natural treatments for the skin and preventive compositions and methods for the use thereof.

BRIEF DESCRIPTION OF THE INVENTION The invention relates to agents for sequestering serum aging factors, and methods for the use thereof. More particularly, the invention relates to the agents named in the present invention "Naractin" to refer to any of several arNOX inhibitors of natural origin or present in N. tazetta powder or capable of increasing N. tazetta powder to a inhibitory level comparable to that of extracts recently obtained from N. tazetta, and to methods for using "Naractins" to prevent or treat disorders and complications of disorders derived from cellular damage caused by an isotherm of NADH oxidase related to aging ( arNOX). In an exemplary embodiment, the agents of the invention comprise at least one naractin of natural origin. Said naractins of natural origin are also capable of increasing the anti-arNOX effect of other arNOX inhibitors of natural origin.

Therefore, in an exemplary embodiment, the invention includes a topical composition useful for improving the effects of aging comprising an effective amount of at least one arNOX inhibitor. In accordance with this exemplary embodiment, the arNOX inhibitor is a naractin, naractin is effective in decreasing the effects of aging. In some exemplary embodiments according to the invention, naractin is extracted and / or purified from N. tazetta, willow, corn, crepe, poplar, viburnum, mold - especially Aspergillus, alangium, birch, bupleurum, colchicum, tartago, filipendulum, gardenia, lithospermum, tobacco or mistletoe.

In many other exemplary embodiments, naractin is a salicylate, or a derivative thereof. In some exemplary embodiments, the salicylate is salicin, salicylic acid, salicylic hydroxamate, derivatives or combinations thereof. In several exemplary embodiments, naractin is derived from Alangium chínense, A. Platanifolium, A. Premnifolium, Aspergillus niger, Betula alba, Bupleurum falcatum, Catharanthus roseus, Chosenia bracteosa, Colchicum autumnale, Crepis foetida, C. rhoeadifolia, Datura inoxia, Duboisia myoporoides, Eleutherococcus setchuensis, Euphorbia salicifolia, Philippine ulmaria, Foeniculum vulgare, Gardenia jasminoides, Lithospermum erythrorhizon, Nicotiana tabacum, Populus alba, P. balsamifera, P. davidiana, P. deltoides, P. euphratica, P. grandidentata, P. heterophylla, P. lasiocarpa, P. maximowiczii, P. nigra, P. sieboldii, P. simonii, P. tacamahaca, P. tomentosa, P. tremula, P. tremuloides, P. trichocarpa, Salix acutifolia, S. alba, S. americana, S. arctica, S. aurita, S. babylonica, S. basfordiana, S. caesia, S. calodendron, S. capitata, S. caprea, S. chaenomeloides, S. cinerea, S. daphnoides, S. fragilis, S. geminata, S. gracilis, S. gracilistyla, S. gracilistyloides, S. gymnolepis, S. hastata, S. herbaceous, S. incana, S. koriyanagi, S. lapponum, S. lasiandra, S. lasiolepis, S. matsudana, S. myrsinifolia, S. nigricans, S. orestera, S. pentandra, S. pentandroides, S. petiolaris, S. phylicifolia, S. purpurea, S. repens, S. rubra, S. schwerinii, S. scouleriana, S. smithiana, S. songarica, S. species, S. stipularis, S. tetrasperma, S. tremuloides, S. triandra, S. viminalis, Toisusu urbaniana, Viburnum henryi, V. prunifolium, V. rhytidophyllum or Viscum album.

In several exemplary embodiments, naractin is a salicylate or a derivative thereof. In some exemplary embodiments, the salicylate is salicin, salicylic acid, salicylic hydroxamate, derivatives or combinations thereof.

In various exemplary embodiments, the composition further includes a cosmetically or pharmaceutically acceptable vehicle. In some exemplary embodiments, the naractin inhibitor is present together with other arNOX inhibitors derived from sources of natural origin, including but not limited to, broccoli, shitake, rosemary coleus, lotus, artichoke, sea rose tangerine, Oenothera biennis, astaxanthin, red orange, Shizandra chinensis, Lonicera, phagopyrum, carrot or olive. In several exemplary embodiments, naractin increases the effects of the additional arNOX inhibitory agents.

Those skilled in the art will recognize that the arNOX inhibitor compositions described in the present invention can be administered in any convenient manner. In some exemplary embodiments said administration forms include a cream, a milk, a lotion, a gel, a suspension of microspheres or nanospheres or lipid or polymer vesicles, a soap, a shampoo or a sunscreen. In various exemplary embodiments, the effects of aging enhanced by the present invention include, but are not limited to, lines, wrinkles, hyperpigmentation, dehydration, loss of elasticity, angioma, dryness, itching, telangietasias, actinic purpura, seborrheic keratosis, lack of hydration. , decrease in collagen or actinic keratosis. In these and other exemplary embodiments, the invention, the arNOX inhibitory agent is provided at a concentration of between about 5 g / ml to about 500 pg / ml.

In even other exemplary embodiments, the invention comprises a method for inhibiting the generation of reactive oxygen species by the isoform of NADH oxidase related to aging, to improve the effects of aging comprising: administering a therapeutically effective amount of a composition that comprises at least one of salicin, salicylic acid, salicylic hydroxamate to a patient in need thereof, such that the generation of reactive oxygen species by the isoform of NADH oxidase related to aging, is inhibited and where it is improved an effect of aging. In several exemplary embodiments the method further comprises an extract, or purified extract, of at least one of broccoli, shitake, rosemary coleus, lotus, artichoke, tangerine sea rose, Oenothera biennis, astaxanthin, red orange, Schizandra chinensis, Lonicera, Fagopyrum , carrots, Narcissus tazetta, olives, willows, oats or corn. In various exemplary embodiments according to the invention, the composition is applied in the form of a cream, a milk, a lotion, a gel, a suspension of microspheres or nanospheres or lipid or polymer vesicles, a soap, a shampoo or a blocker solar. In these exemplary embodiments, the effects of aging include, but are not limited to, lines, wrinkles, hyperpigmentation, dehydration, loss of elasticity, angioma, dryness, itching, telangietasias, actinic purpura, seborrheic keratosis, lack of hydration, decrease of collagen or actinic keratosis.

In even other exemplary embodiments, the invention includes a cosmetic method for improving the effects of aging comprising applying to the skin a cosmetic composition comprising: an effective amount of a naractin suitable for inhibiting arNOX, wherein at least one effect is inhibited of aging mediated by arNOX. In these embodiments, naractin is a salicylate, a salt or a derivative thereof. In several exemplary embodiments, the salicylate is salicin, salicylic hydroxamate or salicylic acid. In various other embodiments of the method according to the invention, the cosmetic composition further includes a vegetable extract comprising: carrot extract, olive extract, broccoli extract, shitake extract, coleus extract, rosemary extract, lotus extract, artichoke extract, sea rose extract extract of tangerine, extract of Oenothera biennis, red orange extract, extract of Schizandra chinensis, extract of Lonicera, extract of Fagopyrum, extract of willow, extract of corn, of oats or of Narcissus tazetta. In these exemplary embodiments, naractin is provided together with a cosmetically acceptable vehicle.

In several exemplary embodiments, the effects of aging improved by the method according to the invention include lines, wrinkles, hyperpigmentation, dehydration, loss of elasticity, angioma, dryness, itching, telangietasias, actinic purpura, seborrheic keratosis, lack of hydration, decrease of collagen or actinic keratosis.

In various embodiments of the method according to the invention, naractin is applied at least once a day. In some exemplary embodiments, naractin is provided in a cosmetic preparation at a concentration of between about 5 pg / ml to approximately 500 Mg / ml. In these exemplary embodiments, the cosmetic composition according to the invention is administered in the form of a cream, a milk, a lotion, a gel, a suspension of microspheres or nanospheres or lipid or polymer vesicles, a soap, a shampoo or a sunscreen.

In still other embodiments according to the invention, the invention comprises a kit for the application of a cosmetic useful in improving the effects of aging comprising: at least one naractin, and instructions for its use. In some exemplary embodiments the kit further comprises a cosmetic preparation suitable as a vehicle for the at least one plant extract inhibiting arNOX.

These and other features and advantages of the present invention will be established or made more apparent in the following description and the appended claims. The features and advantages can be observed and obtained by means of the instruments and combinations particularly pointed out in the appended claims. In addition, the features and advantages of the invention can be learned by practicing the invention or will be apparent from the description, as indicated below.

BRIEF DESCRIPTION OF THE FIGURES Various exemplary embodiments of the compositions and methods in accordance with the invention will be described in detail, with reference to the following figures wherein: Figure 1a shows the activity pattern of the arNOX isoforms from a saliva sample of a 72-year-old man (and / or) (BL = baseline) and partial inhibition after the addition of an extract of N. tazetta powder (central panel). The panel on the right shows almost complete inhibition of activity after addition to the N. tazetta powder of the salicylic hydroxamate ingredient (SIMULATED) (Naractin 1). Figure 1b is the same as 1a, except that instead of SIMULATION the inhibitory effect of N. tazetta powder was increased with salicin (Naractin 3). The naractins form reddish complexes with iron with spectral properties similar to the reddish colors that characterize portions of the bulbous parts of N. tazetta and extracts containing arNOX-inhibiting substances as shown in Figures 2a-2f.

Figures 2a-2f illustrate the regions of the N. tazetta bulb and extracts containing substances inhibiting the activity of arNOX. The inhibitory substances are absent from the parts of the bulbs and / or extracts that do not turn red or pink. Figure 2a is a figure of a bulb divided into the region composed of the leaves and the stem region. Figure 2b is a photograph showing the compounds of red color Associated with the inhibition of arNOX are located in the stem region. Figure 2c shows the different regions of the bulb from which the extracts are made and have different levels of development of the red color from different regions, as shown in figures 2d, 2e and 2f. The development of color is fast. The bulbs of the N. tazetta varieties where the extracts do not inhibit the activity of arNOX can not develop the red color either.

Figure 3 illustrates a similar reddish color of the vasculature in the macular vascular cylinder (the central conductive tissues of the root water), after the addition of iron chloride. The substance that results in the color red is a hydroxamate of natural origin.

Figure 4 shows the inhibition of the arNOX activity of the saliva (72-year-old male) in the baseline (BL) panel and the inhibition by the addition of a homogenate prepared from the mast vascular cylinder. The corn pods (the tissue surrounding the vascular cylinders) did not stain after the addition of iron, nor did they inhibit the activity of arNOX.

Figures 5a-5b show examples from thin layer chromatography analyzes of the methanol extracts of N. tazetta bulbs (Figure 5b) as compared to the commercial powder of N. tazetta (Figure 5a). The plates with blue background (UV) show ultraviolet fluorescence. The plates with light background (BB) were stained with Berlin blue. The TLC system was subjected to dichloromethane: methanol: NH 4 OH (10: 1: 0.2). In the sample extracted in the laboratory, a component of reddish color above, but clearly separated from the material at the source and suggestive of the presence of hydroxamates was much more evident in the sample extracted in the laboratory than in the commercial powder. This was evident for both extracts with methanol (Figure 5a) and water (Figure 5b). Putative hydroxamate was also observed in the commercial powder, but at much lower levels than in the sample extracted in the laboratory, once it has been correlated again with the levels of inhibitory activity of arNOX.

Figure 6 shows a spectral analysis of extracts of the bulb of N. tazetta and of vascular cylinders of corn and pod compared to a known hydroxamate (SIMULATED) after the addition of ferric chloride to form ferric hydroxamates of red color. The ArNOX inhibitor extracts from N. tazetta bulbs were red and exhibited a maximum absorption of around 550 nm. Extracts of N. pseudo narcissus bulbs that lacked inhibitory activity were colorless and showed no absorbance at 550 nm. The fractions of vascular cylinders of the maize root (active) and corn root husk (inactive) were not colored to a large extent in the absence of added ferric chloride (FeFe). However, in the presence of ferric chloride (+ FeCl2), the red color appeared in the extracts of the vascular cylinders of maize with a maximum absorbance at approximately 550 nm, while there was no maximum absorbance at 550 nm for the corn pods . Salicylic hydroxamate (SIMULATED), a commercially available stable hydroxamate also available produced a red color with a maximum at approximately 550 nm. The negative control was not colored and showed no absorbance at 550 nm.

Figure 7 is a graph of the arNOX activity of ferricytochrome c as a function of the SIMULATED dilution (log). The graph illustrates the dose-dependent inhibition of arNOX activity of saliva (72-year-old man) by a commercially available SIMULADA preparation (Aigma-Aldrich, St. Louis, MO). Inhibition is practically complete at 11 mg / ml.

Figure 8 is a graph of the arNOX activity of ferricytochrome c as a function of the dilution of salicylic acid (log). The graph illustrates the dose-dependent inhibition of the arNOX activity of saliva (72-year-old male) as a function of salicylic acid concentration. Salicylic acid at a concentration of 1 mg / ml inhibits approximately 50%.

Figure 9 is a graph of the arNOX activity of ferricytochrome c as a function of the salicin dilution (log). The graph illustrates the dose-dependent inhibition of the arNOX activity of saliva (72-year-old male) as a function of salicin concentration. The maximum inhibition of arNOX activity is achieved at a concentration of 1 mg / ml.

Figures 10a and 10b are graphs showing the inhibition of arNOX from various combinations of "naractin". Figure 10a illustrates the increase in salicin of the inhibition of arNOX from a mixture of 4 mg / ml of Schizandra powder plus extract of N. tazetta (20 μ?) in the presence of 1 mg / ml of salicin. Figure 10b illustrates the inhibition of arNOX by a mixture of 4 mg / ml Schizandra powder plus 1 mg / ml N. tazetta powder in the presence of 1 mg / ml salicin. Of the mixture, 60 μ? a total of three ml of test mixture containing saliva (72-year-old man) was added as the source of arNOX activity.

DETAILED DESCRIPTION OF THE EXEMPLARY MODALITIES The invention relates to agents for sequestering aging factors in serum, and methods for the use thereof. More particularly, the invention relates to the agents referred to in the present invention as "Naractin" to refer to any of several arNOX inhibitors of natural origin or present in N. tazetta powder or capable of increasing N. tazetta powder. an inhibitory level comparable to that of fresh extracts of N. tazetta, and methods to use "Naractins" to prevent or treat disorders and complications of disorders resulting from cellular damage caused by an isoform of NADH oxidase related to aging ( arNOX). In an exemplary embodiment, the agents of the invention comprise at least one Naractin of natural origin. Said Naractins of natural origin are also capable of increasing the anti-arNOX effect of other arNOX inhibitors of natural origin.

The term "Naractin" is used in the present invention to denote any of several arNOX inhibitors of natural origin or present in N. tazetta powder (commercially available from, for example, Xian Aojing Science and Technology Developing CO., LTD, Xi'an, Shaanxi, CN) or capable of increasing N. tazetta powder to an inhibitory level comparable to that of recently obtained N. tazetta extracts. Currently, the inventors have identified three known substances, chemically pure, with "Naractin" activity. In addition, it should be noted that, although the "Naractinas" have been identified here from N. tazetta extract these may be present from other natural sources such as, for example, willow, corn and oats and, of course , the invention encompasses Naractins regardless of their source of origin.

As used in the present invention, the term "cosmetic" refers to a substance intended to be applied to the body to cleanse, beautify, promote attractiveness, or alter appearance.

As used in the present invention, the term "extract" refers to a solution obtained by steeping or soaking a substance in a solvent and removing the active ingredient. The solvent can be any suitable solvent, including but not limited to alcohol, water or the like. In some cases, the extract is concentrated or the solvent can be evaporated and the active ingredient is resuspended or solubilized in a different solvent. As described in the present invention, the extract of N. tazetta is made by separating the stem region from the bulb and a stem region is homogenized in 3 ml of distilled water.

As used in the present invention, the term "disorder" refers to any condition of a living animal or body of a plant or of a part thereof that affects normal functioning comprising any ailment, disease, condition, clinical condition, pathological condition, weakened condition, poor condition, and any abnormal or undesirable physical condition.

As used in the present invention, the term "reactive oxygen species" refers to the oxygen derivatives of oxygen metabolism or the transfer of free electrons, resulting in the formation of free radicals (eg, superoxide radicals). or hydroxyl).

As used in the present invention, the term "antioxidant" refers to compounds that neutralize the activity of reactive oxygen species or inhibit cellular damage by said reactive species.

As used in the present invention, the term "pharmaceutically acceptable carrier" refers to a transport medium that does not interfere with the effectiveness of the biological activity of the active ingredient, is chemically inert, and is not toxic to the patient to whom it is intended. administers it As used in the present invention, the term "pharmaceutically acceptable derivative" refers to any homologue, analog, or fragment corresponding to the formulations described in the present application, which possess antioxidant activity, and is relatively non-toxic to the subject .

The term "therapeutic agent" refers to any molecule, compound, or treatment, preferably an antioxidant, that aids in the prevention or treatment of disorders or complications of disorders caused by reactive oxygen species.

The term "agent that sequesters arNOX" refers to any molecule, compound, or treatment that interacts with arNOX, thereby decreasing the reaction of arNOX with other substrates and inhibits the ability of arNOX to generate reactive oxygen species.

The term "salicylates" as used in the present invention, refers to salts, conjugates or derivatives of salicylates if they are derived from sources of natural origin or synthesized de novo. Said salicylates, include, for example, salicylic acid, hydroxamate salicin and salicin by itself, its derivatives, salts and conjugates.

During the course of their investigation, the inventors have found that certain commercial preparations of N. tazetta extract contain active agents having anti-arNOX activity. The present invention was motivated by the observation that some samples of IBR-Dormin® from the bulb extract of N. tazetta (Israeli Biotechnology Research Ltd., Israel) had virtually no inhibitory activity towards arNOX while other batches from the same manufacturer they were strongly inhibitory. The inventors hypothesized that neither the arNOX inhibitor was unstable in the absence of special preservatives nor the arNOX inhibitor had lost during the purification of N. tazetta extract. However, it should be noted that commercially available N. tazetta powder is available under the trade name IBR-Dormin® is specially processed with N. tazetta bulbs that are latent. The theory that in the growth stage the bulbs produce quantities of unidentified compounds is referred to as "dormins". It is further hypothesized that said "dormins" induce a state of dormancy in cells or tissues. Therefore, from the immediately disclosed data it is demonstrated that the "dormina" of N. tazetta is not the same agent as those identified in the present invention as "Naractinas".

To evaluate these possibilities, the inventors obtained a small number of white paper bulbs (N. tazetta). Extracts with water and ethanolic inhibited arNOX. Comparisons were made with N. pseudo-narcissus (narcissus) and N. jonquilla (jonquil), both of which were largely inactive. The activity was correlated with a red coloration enhanced by the addition of ferric iron, a characteristic of hydroxamates of natural origin as found in corn and oat seedlings, data not shown), which also inhibit arNOX. Hydroxamates have a chemistry that can be expected to be favorable to an inhibition of arNOX. The hydroxamate most readily available for evaluation was salicylic hydroxamate (Naractin 1), also known as SIMULATION, a known inhibitor of alternative plant oxidase. SIMULATION was evaluated and found to increase the arNOX inhibitory response of N. tazetta powder. A level of inhibition of more than 90% was obtained with N. tazetta powder increased with low levels of SIMULATION. While there were not enough bulbs of N. tazetta to complete the characterization of the active component, but work was continued with N. tazetta powder (extract) (Xi'an Aojing Science and Technology Developing CO., LTD, Xi'an, Shaanxi, China; 20: 1 available in both bulb extract and flower extract). N. tazetta powder does not appear to contain low levels of a hydroxamate of natural origin, but at much lower levels than extracts prepared from N. tazetta bulbs.

One question asked is whether the hydroxamate or the salicylic acid portion was more important for the inhibitory activity of arNOX. The results suggest that both are important. Salicylic acid (Naractin 2) itself is a very potent inhibitor of arNOX that also gives a red color when it reacts with ferric iron. Esters of salicylic acid or aspirin do not inhibit arNOX. A watery extract of willow bark, a natural source of salicylates, was evaluated and was also found to inhibit arNOX. The main salicylate of willow bark, salicin, a glycoside, was also effective as an inhibitor (Naractin 3).

Therefore, an exemplary embodiment of the invention includes a topical composition useful for improving the effects of aging comprising an effective amount of at least one arNOX inhibiting agent. In accordance with this exemplary embodiment, the arNOX inhibitor is a naractin, naractin is effective in decreasing the effects of aging. In some exemplary embodiments according to the invention, naractin is purified from N. tazetta, willow, corn, crepis, poplar, viburnum, mold especially Aspergillus, alangium, birch, bupleurum, colchicum, tartago, filipendulum, gardenia, lithospermum , tobacco or mistletoe.

In several exemplary embodiments, naractin is a salicylate, or a derivative thereof. In some exemplary embodiments, the salicylate is salicin, salicylic acid, salicylic hydroxamate, derivatives or combinations thereof. In several exemplary embodiments, naractin is derived from Alangium chínense, A. Platanifolium, A. Premnifolium, Aspergillus niger, Betula alba, Bupleurum falcatum, Catharanthus roseus, Chosenia bracteosa, Colchicum autumnale, Crepis foetida, C. rhoeadifolia, Datura inoxia, Duboisia myoporoides, Eleutherococcus setchuensis, Euphorbia salicifolia, Philippine ulmaria, Foeniculum vulgare, Gardenia jasminoides, Lithospermum erythrorhizon, Nicotiana tabacum, Populus alba, P. balsamifera, P. davidiana, P. deltoides, P. euphratica, P. grandidentata, P. heterophylla, P. lasiocarpa, P. maximowiczii, P. nigra, P. sieboldii, P. simonii, P. tacamahaca, P. tomentosa, P. tremula, P. tremuloides, P. trichocarpa, Salix acutifolia, S. alba, S. americana , S. arctica, S. aurita, S. babylonica, S. basfordiana, S. caesia, S. calodendron, S. capitata, S. caprea, S. chaenomeloides, S. cinerea, S. daphnoides, S. fragilis, S. geminata, S. gracilis, S. gracilistyla, S. gracilistyloides, S. gymnolepis, S. hastata, S. herbaceous, S. incana, S. koriyanagi, S. lapponum, S. lasiandra, S. lasiolepis, S. matsudana, S. myrsinifolia, S. nigricans, S. orestera, S. pentandra, S. pentandroides, S. petiolaris, S. phylicifolia, S. purpurea, S. repens, S. rubra, S. schwerinii, S. scouleriana, S. smithiana, S. songarica, S. species, S. stipularis, S. tetrasperma, S. tremuloides, S. triandra, S. viminalis, Toisusu urbaniana, Viburnum henryi, V. prunifolium, V. rhytidophyllum or Viscum album.

In various exemplary embodiments, the composition further includes a cosmetically or pharmaceutically acceptable vehicle. In some exemplary embodiments, the naractin inhibiting agent is present together with other arNOX inhibitors derived from sources of natural origin, including but not limited to, broccoli, shitake, rosemary coleus, lotus, artichoke, sea rose tangerine, Oenothera biennis, astaxanthin, red orange, Shizandra chinensis, Lonicera, phagopyrum, carrot or olive. In several exemplary embodiments, naractin increases the effects of the additional arNOX inhibitory agents.

Those skilled in the art will recognize that the arNOX inhibitor compositions described in the present invention can be administered in any convenient manner. In some exemplary embodiments said administration forms include a cream, a milk, a lotion, a gel, a suspension of microspheres or nanospheres or lipid or polymer vesicles, a soap, a shampoo or a sunscreen. In various exemplary embodiments, the effects of aging enhanced by the present invention include, but are not limited to, lines, wrinkles, hyperpigmentation, dehydration, loss of elasticity, angioma, dryness, itching, telangietasias, actinic purpura, seborrheic keratosis, lack of hydration. , decrease in collagen or actinic keratosis. In these and other exemplary embodiments, the invention, the arNOX inhibitory agent is provided at a concentration of between about 5 pg / ml to about 500 pg / ml.

In even other exemplary embodiments, the invention comprises a method for inhibiting the generation of reactive oxygen species by the isoform of NADH oxidase related to aging, to improve the effects of aging comprising: administering a therapeutically effective amount of a composition that comprises at least one of salicin, salicylic acid, salicylic hydroxamate to a patient in need thereof, such that the generation of reactive oxygen species by the isoform of NADH oxidase related to aging, is inhibited and where it is improved an effect of aging. In several exemplary embodiments the method further comprises an extract, or purified extract, of at least one of broccoli, shitake, rosemary coleus, lotus, artichoke, tangerine rose of the sea, Oenothera biennis, astaxanthin, red orange, Schizandra chinensis, Lonicera, Fagopyrum , carrots, Narcissus tazetta, olives, willows, oats, corn, crayfish, poplar, viburnum, mold especially Aspergillus, alangium, birch, bupleurum, colchicum, tartago, filipendulum, gardenia, lithospermum, tobacco or mistletoe.

In various exemplary embodiments according to the invention, the composition is applied in the form of a cream, a milk, a lotion, a gel, a suspension of microspheres or nanospheres or lipid or polymer vesicles, a soap, a shampoo, an elixir or a sunscreen.

In these exemplary embodiments, the effects of aging include, but are not limited to, lines, wrinkles, hyperpigmentation, dehydration, loss of elasticity, angioma, dryness, itching, telangietasias, actinic purpura, seborrheic keratosis, lack of hydration, decrease in collagen or actinic keratosis.

Even in other exemplary embodiments, the invention includes a cosmetic method for improving the effects of aging comprising applying to the skin a cosmetic composition comprising: an effective amount of a naractin suitable for inhibiting arNOX, wherein at least one aging effect mediated by arNOX. In these embodiments, naractin is a salicylate, a salt or a derivative thereof. In several exemplary embodiments, the salicylate is salicin, salicylic hydroxamate or salicylic acid. In various other embodiments of the method according to the invention, the cosmetic composition further includes a plant extract comprising: carrot extract, olive extract, broccoli extract, shitake extract, coleus, rosemary extract, lotus extract, extract artichoke, sea rose tangerine extract, Oenothera biennis extract, red orange extract, Schizandra chinensis extract, Lonicera extract, Fagopyrum extract, willow extract, corn, crepe, poplar, viburnum, mold especially Aspergillus, alangium , birch, bupleurum, colchicum, tartago, filipendulum, gardenia, lithospermum, tobacco, mistletoe, oats or extract of Narcissus tazetta. In these exemplary embodiments, naractin is provided together with a cosmetically acceptable vehicle.

In various exemplary embodiments, the effects of aging enhanced by the method according to the invention include lines, wrinkles, hyperpigmentation, dehydration, loss of elasticity, angioma, dryness, itching, telangietasias, actinic purpura, seborrheic keratosis, lack of hydration, decrease in collagen or actinic keratosis.

In various embodiments of the method according to the invention, naractin is applied at least once a day. In some exemplary embodiments, naractin is provided in a cosmetic preparation at a concentration of between about 5 pg / ml to about 500 g / ml. In these exemplary embodiments, the cosmetic composition according to the invention is administered in the form of a cream, a milk, a lotion, a gel, an elixir, a suspension of lipid or polymer microspheres or nanospheres or vesicles, a soap, a shampoo or a sunscreen.

In even other embodiments according to the invention, the invention comprises a kit for applying a cosmetic useful in improving the effects of aging comprising: at least one naractin, and the instructions for use. In some exemplary embodiments, the kit further comprises a cosmetic preparation suitable as a vehicle for the at least one plant extract inhibiting arNOX.

The antioxidants, cellular components and white proteins defined in the present invention are abbreviated as follows: Mitochondrial DNA DNA mt nicotinamide adenine dinucleotide NADH hydroquinone (NADH) cell surface oxidase with protein activity disulfide thiol isomerase NOX NOX specific to non-cancerous cells cNOX NOX specific to aged cells arNOX NOX specific to cancer cells tNOX LDL low density liporpheine Oxygen-red membrane chain uctase plasma PMOR ubiquinone or coenzyme Q CoQ coenzyme Q-io C0Q10 reactive oxygen species ROS The invention The present invention is directed to agents of natural origin and purified from the bulb of Narcissus tazetta and corn and can be administered either internally or topically. These agents specifically inhibit arNOX and improve some of its effects related to aging. These agents can take the form of isolated agents or plant extracts. Still further, while the arNOX inhibiting agents can be used alone, they can also be used as compositions comprising multiple arNOX inhibitory agents and / or formulations including compounds that have other beneficial effects on the body. In particular, the inventors have found that the addition of arNOX inhibitors to cosmetics, the inhibitors may have beneficial effects that increase the normal skin care regimen.

In yet another exemplary embodiment, the invention comprises a cosmetic composition for improving the effects of aging comprising a cosmetically effective amount of at least one arNOX inhibitor wherein the arNOX inhibitor is effective in decreasing the effects of aging on the skin. In a version of this exemplary embodiment, the invention includes a cosmetically acceptable vehicle. In this embodiment, the vehicle may include powders, emollients, lotions, creams, liquids, and the like. In some exemplary embodiments, the arNOX inhibitory agent is derived from a plant. In particular exemplary embodiments, the plant is selected from broccoli, shitake, coleus, rosemary, lotus, artichoke, sea rose, tangerine, Oenothera biennis, astaxanthin, red orange, Schizandra chinensis, Lonicera, Fagopyrum, carrot, Narcissus tazetta, willow, corn, corn, crepis, poplar viburnum, mold especially Aspergillus, alangium, birch, bupleurum, colchicum, tartago, filipendulum, gardenia, lithospermum, tobacco, mistletoe, oats or olive.

It should be appreciated that the cosmetic composition in accordance with this exemplary embodiment can be administered in any exemplary manner. For example, in some exemplary embodiments, the cosmetic composition according to the invention is applied topically, orally, parenterally, transdermally or rectally. In some exemplary embodiments, the composition is formulated as a cream, a milk, a lotion, a gel, a suspension of microspheres or nanospheres or lipid or polymer vesicles, a soap or a shampoo.

Even in other exemplary embodiments, the invention includes a cosmetic method for improving the effects of aging comprising applying to the skin a cosmetic composition comprising an effective amount of an arNOX inhibitor, wherein at least one effect of mediated aging is inhibited. by arNOX. In some exemplary embodiments according to the invention, the arNOX inhibitor is an extract of the plant. In other exemplary modalities, the arNOX inhibitor is purified from an extract of the plant. In various exemplary embodiments according to the invention, the arNOX inhibitory agent is present at a concentration of between about 5 pg / ml to about 500 g / ml. In several exemplary embodiments, the concentration of the active agent is present in a concentration of between about 15 to 100 pg / ml. In some exemplary embodiments, the cosmetic composition according to the invention is applied topically, orally, parenterally, transdermally, rectally or by any other effective method. In some exemplary embodiments, the composition is formulated as a cream, a milk, a lotion, a gel, a suspension of microspheres or nanospheres or lipid or polymer vesicles, a soap or a shampoo.

In even other exemplary embodiments, the invention comprises a kit. In this embodiment, the kit can include a volume of an arNOX inhibitory agent and instruction for its use. In several exemplary embodiments, the kit may further include a cosmetic preparation such that the arNOX inhibitory agent may be added to the cosmetic preparation before use.

It should be appreciated that, although in some exemplary embodiments of the invention, an arNOX inhibiting agent is used, in other exemplary embodiments more than one arNOX extract or inhibitor agent is used together. Furthermore, it should be appreciated that in several exemplary embodiments of the invention, the one or more arNOX inhibiting agents can be applied or administered in various ways. Such as, for example, topical administration, in the form of a cream, a milk, a lotion, a gel, a suspension of microspheres or nanospheres or lipid or polymer vesicles, soap, shampoo or a sunscreen and in the form of a tea or capsules or any other effective way.

Hydroquinone (NADH) oxidase of the plasma membrane (NOX): NADH oxidase of the plasma membrane (NOX) is a unique cell surface protein with hydroquinone (NADH) oxidase activities and the disulfide-thiol exchange protein that normally responds to hormones and growth factors. A hormone-insensitive and drug-receptive form of the designated tNOX activity has also been described, which is specific for cancer cells. There is evidence that NOX proteins, under certain conditions, are capable of producing ROS. For example, ultraviolet light as a source of oxidative stress in cells in culture is used to initiate the generation of superoxide (Morré et al., 1999, Biofactors 9: 179-187) (See U.S. Patent No. 5,605,810, which it is incorporated herein by reference in its entirety).

Isolation and characterization of arNOX inhibitors from N. tazetta The research series leading to the invention was motivated by samples of some observation of an extract from commercially available N. tazetta (commercially available as IBR-Dormin®, IBR, Inc., Israel) were often strongly inhibitors of arNOX while other samples and different batches, but the same type of preparation were not. The inventors hypothesized that any inhibition of arNOX was due to something unstable in the absence of special preservatives or that the arNOX inhibitor constituents of the active preparations had been lost from the inactive preparations during the purification of the extract. It should be noted that, recently, a product known as IBR-Dormin® has been described, which refers to anti-proliferative agents derived from plants. See, Patent Application of E.U.A. Publication No. 20060160702, the application Serial No. 1 1 / 289,156 (the application? 56) to Soudant et al. In accordance with the request? 56, anti-proliferative agents are found in plants that are capable of inducing a plant organ into a dormant state (Summary). Therefore, anti-proliferative agents called "dormins" are suggested to work by delaying aging through the brake of cell proliferation. The "dorminas" are harvested when elaborating extracts of the plants that have entered in their latent phase. Therefore, only the extract of dormant plants can be used as "dormins" for this property.

Because the inventors realized that different extracts of N. tazetta from N. tazetta powder commercially available from both the bulb and the flower (Xian Aojing Science and Technology Developing CO., LTD, Xi'an, Shaanxi, CN ) have different degrees of arNOX inhibition, the inventors carried out a series of experiments to identify the arNOX inhibitory substance. To test the above possibilities, white paper narcissus bulbs. { N. tazetta) were obtained from a commercial garden supplier (Brent and Becky's bulbs, Gloucester, VA). Comparisons were made with N. pseudo-narcissus (narcissus) and N. jonquilla (jonquil), both without great activity. The activity was correlated with a red coloration enhanced by the addition of ferric iron, a characteristic hydroxamate of natural origin. The hydroxamate most readily available for evaluation was salicylic hydroxamate (SIMULATED) (Naractin 1). The aqueous and ethanolic extracts were prepared, which inhibited arNOX and increased the inhibition when combined with N. tazetta powder of the low activity flower (eg, figure 1a). Figure 1b is similar to 1a showing the increase in N. tazetta powder derived from the bulb (Xian Aojing, LTD) was extracted with water and increased using salicin (Aigma-Aldrich, St. Louis, MO) (Naractin 3) . The comparisons were made with similar extracts of Narcissus pseudo-narcissus (narcissus) and extracts of Narcissus jonquilla (jonquil) that lack inhibitory activity to arNOX completely.

As illustrated in Figures 2a-2f, the activity of the extracts of N. tazetta was correlated with an enhanced red coloration by the addition of ferric iron, a characteristic of hydroxamates of natural origin, such as those found in seedlings. of corn (corn) (figure 3) and oats (not shown) that also inhibit arNOX (figure 4). Further evidence of the potential ability of the active components of the extracts of N. tazetta to comprise hydroxamates of natural origin was provided by the thin-layer chromatography analyzes (Figures 5a-5b), from the spectral studies of their iron adducts. , of the vascular cylinders (the central vasculature of the corn root, where the hydroxamates correspond to the vasculature of the stem potentially rich in hydroxamate of the bulb of N. tazetta Illustrated in figures 2a-2f) of the roots of corn (figure 6) and by comparison with a commercially available hydroxamate (salicylic hydroxamate (SIMULATED) commercially available from, for example, Sigma-Aldrich, St Louis, MO.) SIMULATION was evaluated for the inhibition of arNOX activity and more than 90% inhibition of arNOX activity was obtained from the saliva of a 72-year-old man at a concentration of 1 mg / ml (Figure 7). It was also found that SIMULATION increases the inhibition of arNOX activity of partially active N. tazetta powders (Figures 1a-1b). The powder of N. commercially available N-tazetta powder appears to contain low levels of a hydroxamate of natural origin possibly similar to SIMULATION, but at much lower levels than those found in extracts prepared from fresh N. tazetta bulbs ( Figures 5a and 5b).

To answer the question of whether or not the salicylic portion of stabilized salicylic hydroxamate was important for the inhibition of arNOX activity, salicylic acid (Naractin 2, commercially available from, for example, Sigma-Aldrich, St Louis, MO It was evaluated as an inhibitor of saline arNOX activity (72-year-old man) and was found to inhibit arNOX (Figure 8) .Salicylic acid also gave it a red color when reacted with ferric iron similar to that provided by the hydroxamates Salicylic acid esters and / or aspirin do not inhibit arNOX An aqueous extract of willow bark, a natural source of salicylates, was tested and found to also inhibit arNOX. Aldrich, St Louis, MO) (designated in the present invention as Naractin 3), the main salicylate of the willow bark, was subsequently tested and found to be activated at a concentration ten times as much. nor that its process of SIMULATION (Naractina 1) or salicylic acid (Naractina 2) (figure 9).

Not only salicin was active as a single agent (figure 9), but it has also actively participated in the increase the inhibition of arNOX from mixtures of other arNOX inhibitory agents that come from natural sources such as Schizandra chinensis powder and that comes from N. tazetta powder (figures 10a and 10b). Of the three chemically pure Naractins (a term used to refer to any of several naturally occurring arNOX inhibitors that are either present in N. tazetta powder or that are capable of increasing N. tazetta powder at an inhibitory level comparable to that of the most active extracts of fresh N. tazetta) identified and tested, salicin seemed to be the most promising. In addition, salicin is stable, soluble in water, non-irritating and relatively inexpensive.

In general, the characteristics of aged cells include those that express and / or emit arNOX, and include, but are not limited to, those that exhibit one or more of the following characteristics: PMOR system related to age, the ability to generate reactive oxygen species, and have functionally defective mitochondria. One embodiment of the invention is the use of agents to reduce the negative effects of aged cells.

Symptoms of skin aging include dryness, itching, thinning or thickening of the skin, wrinkles and fine lines, areas of hyperpigmentation (called age spots or liver spots), and a mottled appearance. The aged skin has been shown to have a decrease in collagen and the consequent decrease in elasticity. In addition, aged skin has increased amounts of cleaved collagen and cross-linked proteins. Superoxide radicals have been indicated in these processes. The skin may take longer to heal when it is injured. The blood vessels are easier to see through the thinning of the skin, also because they dilate with age. These blood vessels may be visible as red dome-shaped formations on the skin (cherry-colored angiomas), or as broken capillaries on the face (telangietasias). Many people develop senile or actinic purple, which are purple spots or spots on the skin created by small hemorrhages on the skin. The skin of an older person has less protection against sun damage, because the protective cells called melanocytes decrease with age. It is also more likely that aged skin develops a variety of benign and precancerous tumors, such as seborrheic and actinic keratoses. Seborrheic keratoses usually look rough, brown, and look like a wart. These are benign. Actinic keratosis are small growths, with scales in areas of the skin that have received sun exposure. They are an early sign of skin cancer.

The invention encompasses the use of topical administration of natural plant extracts, alone or in the form of an emollient cream, lotion, gel, emollient or the like, to maintain the vitality of the skin. A preferred embodiment of the invention comprises the topical administration of a cream, comprising an extract of the inhibition of arNOX, to the skin of patients to maintain and improve the vitality of the skin.

Cosmetic treatment of the skin The present invention provides compositions comprising active agent (s), which prevent and / or improve damage to the skin and associated conditions, in particular those arising from aging and associated with arNOX. In addition, the invention encompasses methods for the use of said compositions. The stratum corneum is the layer of skin that forms the top surface layer and serves to protect the skin while controlling moisture and the flow of substances in and out of the skin. As this barrier function is lost, the skin suffers the detrimental effects, which is why it contributes to premature aging. These damaging effects of premature aging of the skin are a concern for many people who want to maintain healthy skin. youthful appearance and with a good feeling. Reactive oxygen species participate in a series of potentially destructive reactions lethal to cells. Reactive oxygen species are partly responsible for harmful cellular interactions including fibroblasts that alter the cells' ability to produce healthy collagen and elastin. In addition, the skin is subject to deterioration through dermatological disorders, environmental abuse (wind, air conditioning, central heating) or through the normal aging process (chrono aging), which can be accelerated by exposing the skin to the sun ( photo-aging).

A preferred embodiment of the invention provides active agents of natural origin from plants for the treatment of arNOX-related damage to tissues, especially the skin. The active agents prevent and / or improve the skin damage and the corresponding conditions. In one embodiment of the invention, the processed plant products sequester the activity of arNOX. In another embodiment of the invention, the processed plant products inhibit the reactive oxygen species. In other embodiments, the agents and methods of the invention prevent and / or improve the health of the skin. For example, agents can improve skin tightness, color and appearance of pores, elasticity, hydration and / or help diminish the appearance of fine lines and visible signs of aging. In another exemplary embodiment of the invention, the agents positively affect the natural production of the collagen and elastin body. In another embodiment, the agents of the invention minimize the effects of environmental agitators such as pollution, sun, free radicals and stress.

One embodiment of the invention provides compositions and methods for use thereof, for preventing and / or improving dermatological disorders and the effects thereof.

One embodiment of the invention provides a composition for the prevention and reduction of the effects of the production of reactive oxygen species and methods for the use thereof. For example, the invention encompasses the use of active agents derived from plants, to sequester or at least partially inhibit the activity of arNOX. In addition, the invention contemplates the use of other synthetic and natural compounds to sequester the activity of arNOX.

The present invention describes compositions, which treat the skin and delay the visible signs of real aging and environmental damage to the skin such as wrinkles, lines, sagging, hyperpigmentation and age spots. The present invention also decreases the appearance and condition of sensitive, dry or scaly skin, serves to soothe redness, and / or irritated skin, and treats the spots, pimples, spots and irregularities of the skin.

The invention provides pharmaceutical or cosmetic compositions, methods of use, and kits of pharmaceutical or cosmetic products for the treatment of disorders resulting from changes oxidants in the cells that produce aging by directing an isoform of the NADH oxidase related to aging (arNOX), emitted towards the serum by the aged cells. The compositions may contain agents extracted from the plants. For example, the compositions of the invention may comprise at least one extract that is shown to inhibit the activity of arNOX, either alone or with other inhibiting agents and, at least partially inhibit or block the activity of an isoform of NADH oxidase. related to the aging emitted to the serum by the aged cells. The composition may comprise ubiquinones, natural extracts or agents derived therefrom which are known to comprise active agents useful in the inhibition of arNOX, together with other compounds known in the art to make creams, lotions, emollients, gels, and the like. These other compounds may comprise gums, fillers, preservatives, and the like.

In one embodiment, a portion of, or all of these ingredients can be combined with other ingredients commonly found in anti-aging and serum repair formulations. Vehicles, other than, or in addition to water may include liquid or solid emollients, solvents, humectants, thickeners and powders. The vehicle can be from 0.1% to 99.9%, preferably from 25% to 80% by weight of the composition, and can, in the absence of other cosmetic adjuncts, form the remainder of the composition. In one embodiment, the vehicle is at least 80% water, by weight of the vehicle. In another embodiment, water comprises between 50% to 85% of the composition by weight. In yet another embodiment, water is present between about 0.1% to 55%, by weight of the composition. In other embodiments, other vehicles are used in the aforementioned concentrations.

An oil or oily material may be present, together with an emulsifier to provide either a water-in-oil emulsion or an oil-in-water emulsion, depending to a large extent on the average hydrophilic-lipophilic balance (HLB) of the emulsifier employed.

The compositions of the invention may also include sunscreens. Sunscreens include those materials commonly used to block ultraviolet light. Illustrative compounds are the derivatives of PABA, cinnamate and salicylate. For example, octyl methoxycinnamate and 2-hydroxy-4-methoxy benzophenone (also known as oxybenzone) can be used. Octyl methoxycinnamate and 2-hydroxy-4-methoxy benzophenone are commercially available under the trademarks, Parsol MCX and Benzophenone- 3, respectively. The exact amount of sunscreen used in the emulsions can vary depending on the degree of protection desired from the sun's ultraviolet radiation.

The emollients can be further incorporated into cosmetic compositions of the present invention. The levels of said emollients can range between 0.5% to 50%, preferably between 5% and 30% by weight of the total composition. The emollients can be classified under said general chemical categories such as esters, fatty acids and alcohols, polyols and hydrocarbons.

The esters can be mono- or di-esters. Acceptable examples of fatty di-esters include dibutyl adipate, diethyl sebacate, diisopropyl dimerate, and dioctyl succinate. Acceptable branched fatty acid esters include 2-ethylhexyl myristate, isopropyl stearate and isostearyl palmitate. Acceptable tribasic acid esters include triisopropyl trilinoleate and trilauryl citrate. Acceptable straight chain fatty esters include lauryl palmitate, myristyl lactate, and stearyl oleate. Preferred esters include coco-caprylate / caprate (a mixture of coco-caprylate and coco-caprate), propylene glycol myristyl ether acetate, diisopropyl adipate and cetyl octanoate.

Suitable fatty alcohols and acids include those compounds having from 10 to 20 carbon atoms. Especially preferred are compounds such as cetyl, myristic, palmitic and stearic alcohols and acids.

Among the polyols, which can serve as emollients are the polyhydroxyl alkyl compounds of straight and branched chain. For example, propylene glycol, sorbitol and glycerin are preferred. Polymeric polyols such as polypropylene glycol and polyethylene glycol may also be useful. Butylene and propylene glycol are also especially preferred as penetration enhancers.

The exemplary hydrocarbons that can serve as emollients are those hydrocarbon chains that have between 12 to 30 cardboard atoms. Specific examples include mineral oil, petrolatum, squalene and isoparaffins.

Other embodiments of the compositions of the present invention comprise thickeners. A thickener is usually present in amounts between 0.1 to 20% by weight, preferably from about 0.5% to 10% by weight of the composition. Exemplary thickeners are crosslinked polyacrylate materials available under the trademark CARBOPOL® from B.F. Goodrich Co. The gums can be used such as xanthan, carrageenan, gelatin, karaya, pectin and locust bean gum. Under certain circumstances, the thickener function can be achieved by a material that also serves as a silicone or emollient. For example, silicone gums of more than 10 centistokes and esters such as glycerol stearate have a dual functionality.

The powders can be incorporated into the cosmetic composition of the invention.

These powders include gypsum, kaolin, talc, starch, smectite clays, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, octenil starch aluminum succinate and mixtures thereof.

Other minor components attached may also be incorporated into the cosmetic compositions. These ingredients may include colorants, opacifiers and perfumes. The quantities of these others minor components attached may vary from 0.001% to 20% by weight of the composition.

The composition of the invention can be used for topical application to human skin, as an agent for the conditioning, hydration and softg of the skin, increasing flexibility and elasticity and preventing or reducing the appearance of wrinkles, lines or aged skin. . The formulations of the present invention offer a response to the loss of skin tone and promote benefits to effectively promote hydration and firmness of the surface layer of the skin, all while working to repair the underlying layers of the skin with antioxidants. and other beneficial ingredients to help diminish the appearance of fine lines and wrinkles and restore visible tone and elasticity. In some exemplary embodiments said anti-oxidants are specifically directed to inhibit arNOX.

In one embodiment, a small amount of the composition comprising about 1 to 1000 ml of the active agent is applied to the skin. In an exemplary embodiment, an amount of the composition comprising 1 to 100 ml of the active agent is applied to the skin. This process can be repeated several times a day for a period of time. Preferably, the composition is applied to the skin once in the morning and once at night.

The topical skin care composition of the invention can be formulated in the form of a lotion, a cream, a gel or the like. The The composition can be packaged in a suitable container to adapt to its viscosity and to the intended use by the consumer. For example, a lotion or cream can be packaged in a bottle or a ball applicator or a propellant-driven aerosol or a container fitted with a pump suitable for the operation of the fingers. When the composition is a cream, it can simply be stored in a non-deformable bottle or compression container, such as a tube or a bottle with a lid. Accordingly the invention also provides a closed container containing a cosmetically acceptable composition as defined in the present invention.

The following examples are offered by way of illustration and not as a limitation.

EXAMPLES EXAMPLE 1 Characterization of extracts of Narcissus tazetta To test the hypothesis that N. tazetta may have arNOX inhibitory agents, the white paper narcissus bulbs (Narcissus tazetta) were obtained from a commercial supplier (Brent and Becky's Bulbs, Gloucester, VA). The aqueous and ethanolic extracts were prepared which inhibited the activity of arNOX and increased the inhibition when combined with Narcissus tazetta powder (Xian Aojing Science and Technology Developing Co., LTD, Xi'an, Shaanxi, CN) of low activity. The increase in powder derived from N. tazetta bulbs with SIMULATED (Sigma Aldrich, St. Louis, MO) is shown in figure la. The confirmation of the ability of naractins to increase the inhibition of arNOX was made following the same protocol, but using salicin (Sigma-Aldrich) and N. tazetta powder derived from the flower (Xian Aojing Science and Technology Developing CO., LTD , Xian, CN) to increase the inhibition of arNOX, figure 1 b. Comparisons were made with similar extracts of extracts of Narcissus pseudo-narcissus (narcissus) and Narcissus jonquilla (jonquil) that lack arNOX inhibitory activity. As illustrated in Figures 2a-2f, the activity of the extracts of N. tazetta was correlated with an enhanced red coloration by the addition of ferric iron, a characteristic of hydroxamates of natural origin, as found in corn seedlings (corn ) (figure 3) and oats (not shown) that also inhibit arNOX (figure 4). Further evidence of the potential ability of the active components of the extracts of N. tazetta to represent hydroxamates of natural origin was provided by the thin-layer chromatography analyzes (Figures 5a-5b) and the spectral studies of their iron adducts. and also of vascular cylinders of (the central vasculature of the root of the corn, where the hydroxamates are concentrated and correspond to the vascularity of the stem potentially rich in hydroxamate of the bulb of N. tazetta (illustrated in Figures 2a-2f) and of the roots of corn (Figure 6) by comparison with a hydroxamate commercially available (salicylic hydroxamate (SIMULATED), Sigma-Aldrich) SIMULATED, a known inhibitor of the alternative oxidase activity of plants, has been tested for the inhibition of arNOX activity and more than 90% inhibition of arNOX activity from the saliva of a 72-year-old man was obtained at a concentration of 1 mg / ml (figure 7). It was also found that SIMULATE increases the inhibition of arNOX activity of partially active powdery Narcissus tazetta (Figures 1a-1b). The commercially available Narcissus tazetta powder (IBR-DORMIN®, Israel) appears to contain low levels of a hydroxamate of natural origin possibly similar to SIMULATED, but at much lower levels than those found in extracts prepared from fresh bulbs of Narcissus tazetta (Figures 5a and 5b).

EXAMPLE 2 Identification of arNOX inhibitors To answer the question of whether or not the salicylic portion of stabilized salicylic hydroxamate was important for the inhibition of arNOX activity, salicylic acid (Naractin 2) was tested as an inhibitor of the arNOX activity of a man's saliva of 72 years of age and was found to inhibit the activity of arNOX (figure 8). Salicylic acid also gave a red color when reacted with ferric iron similar to that provided by hydroxamates. The esters of salicylic acid and / or aspirin do not inhibit the activity of arNOX. An aqueous extract of willow bark, a natural source of salicylates, was tested and found to also inhibit arNOX. The glycoside salicin (Naractin 3), the main salicylate of willow bark, was subsequently tested and found to be active at a concentration ten times lower compared to SIMULATED (Naractin 1) or salicylic acid (Naractin 2) (Figure 2). 9).

EXAMPLE 3 Identification of plants that produce salicylate A search was made to identify the plants that were natural producers of salicylates. The search was conducted using the Natural Products database created at the University of Illinois at Chicago by Professor Norman Farnsworth (available at napralert.org). The search identified the following plants that produce salicylates in the various identified tissues: A. chínense (alangiaceae) dry leaf of China, A. chínense (alangiaceae) dry leaf of Japan (cultivated), A. platanifolium (alangiaceae) dry leaf of France , A. platanifolium var. platanifolium (alangiaceae) dry leaf of Japan, A. platanifolium var. trilobum (alangiaceae) dry leaf of Japan, A. platanifolium var. trilobum (alangiaceae) dry leaf of Japan, A. premnifolium (alangiaceae) dry leaf of Japan, A. premnifolium (alangiaceae) dry stem of Japan, filtrate of culture of Aspergillus niger (hiphomicetos) South Korea, Betula alba (betulaceae) bark dried from Germany, suspension culture of Bupleurum falcatum. { apiaceae) from Japan leaf, suspension culture of Catharanthus roseus. { apocinaceae) of Japanese leaf, Chosenia bracteosa (salicaceae) dried bark of Japan, Colchicum autumnale. { liliaceaé) fresh bulb from Japan, Crepis foetida (asteraceae) dry root of Poland, Crepis rhoeadifolia (asteraceae) dried root of Poland (cultivation), Datura inoxia (solanaceae) suspension culture of anthers of Japan, D. inoxia (solanaceae) cultivation in suspension of root of Japan, Duboisia myoporoides (solanaceae) suspension culture of Japan leaf, Eleutherococcus setchuensis (araliaceae) dry stem of China, Euphorbia salicifolia (euphorbiaceae) whole fresh plant of Hungary, Filéndula ulmaría (rosaceae) dry aerial parts of Europe, F. ulmaría (rosaceae) all the dry plant, F. ulmaría (rosaceae) dry entire plant of Switzerland, F. ulmaría (rosaceae) dried flowers of the USSR, Foeniculum vulgare (apiaceae) commercial fruit sample of China, Gardenia jasminoides (rubiaceae) suspension culture of Japan leaf, Lithospermum erythrorhizon (boraginaceae) suspension culture of seedlings of Japan, Nicotiana tabacum (solanaceae) suspension culture of the root of Japan, P. alba (salicaceae) dry bark of the USA, P. balsamifera (salicaceae) dry bark of USA-WI, P. balsamifera (salicaceae) fresh bark of USA-WI, P. balsamifera (salicaceae) bark of dry twigs of the USA -WI, P. balsamifera (salicaceae), dry buds from France, P. balsamifera (salicaceae), freeze-dried leaves from USA-AK, P. balsamifera (salicaceae), fresh USA Leaf-wi, P. balsamifera (salicaceae) leaf dried in oven from Finland (cultivation), P. balsamifera (salicaceae) dry trunk bark from USA-WI, P. davidiana (salicaceae) dry bark from China, P. davidiana ( salicaceae) dry bark of South Korea, P. deltoides (salicaceae) dry bark of USA-WI, P. deltoides (salicaceae) fresh bark of USA-WI, P. deltoides (salicaceae) fresh leaf of USA-WI, P. deltoides var. deltoides (salicaceae) dry bark of Canada (culture), P. deltoides var. occidentalis (salicaceae) dry bark of Canada (cultivation), P. euphratica, (salicaceae) dry bark of China, P. euphratica, (salicaceae) dry buds of Turkey, P. grandidentata (salicaceae) dry bark of USA-WI, P grandidentata (salicaceae) dry leaf of USA-WI, P. heterophylla (salicaceae) dry bark of USA-WI, P. lasiocarpa (salicaceae) dry buds of England, P. maximowiczii (salicaceae) dry bark of Japan, P. nigra (salicaceae) fresh bark from Germany, P. nigra (salicaceae) dry leaf from England (cultivation), P. nigra (salicaceae) dry leaf from Germany, P. sieboldii (salicaceae) dry cocoons from Japan, P. simonii (salicaceae) dry bark of China, P. tacamahaca (salicaceae) dry bark of USA-WI, P. tomentosa (salicaceae) dry bark of China, P. tomentosa (salicaceae) whole plant of China, P. tomentosa (salicaceae) dry leaf of China , P. tremula (salicaceae) dry bark of Germany, P tremula (salicaceae) dry leaf of Switzerland, P. tremula (s) alicaceae) oven dried leaf from Finland, P. tremula (salicaceae) stem bark infected with fungus from France, P. tremula (salicaceae) dry twig from Finland, P. tremuloides (salicaceae) Dry bark from E.U.A., P. tremuloides (salicaceae) dry bark of E.U.A.-WI, P. tremuloides (salicaceae) total young plant, P. tremuloides. { salicaceae) internodes dried by freezing E.U.A.-AK, P. tremuloides. { salicaceae) dry leaf of E.U.A.-WI, P. tremuloides triploides. { salicaceae) fresh leaves of E.U.A.-Wl, P. tremuloides triploides. { salicaceae) dry bark of E.U.A.-WI, P. tríchocarpa. { salicaceae) dry bark of E.U.A.-WA, P. tríchocarpa. { salicaceae) dry bark of E.U.A.-WI, P. tríchocarpa. { salicaceae) fresh leaves from E.U.A.-WI, P. tríchocarpa x P. deltoides. { salicaceae) fresh leaf of Belgium (cultivation), S. acutifolia. { salicaceae) dry bark of Russia, S. alba. { salicaceae) dry bark, S. alba. { salicaceae) dry bark of France, S. alba. { salicaceae) dry bark from Germany, S. alba. { salicaceae) dry bark of E.U.A., S. alba. { salicaceae) dry bark of E.U.A.-AR, S. alba. { salicaceae) dry bark of E.U.A.-UT, S. alba. { salicaceae) leaf dried in oven from England, S. alba. { salicaceae) leaf dried in oven from Finland (cultivation), S. alba cv. cardinalis. { salicaceae) dry leaf of England, S. alba female sex. { salicaceae) dry bark of Germany, S. alba male sex. { salicaceae) dried bark of Germany, S. alba x S. babylonica (S. sepula { salicaceae) dried leaf oven in England, S. alba x S. fragilis. { S. russellia. { salicaceae) leaf dried in oven from England, S. alba x S. pentadra. { S.ehrhardt. { salicaceae) leaf dried in oven from England, S. alba x S. babylonica. { salicaceae) whole plant of USSR, S. americana. { salicaceae) dry leaf of England, S. arctica. { salicaceae) dry leaf of Iceland, S. aurita. { salicaceae) dry bark from Germany, S. aurita (salicaceae) oven-dried leaf from Finland, S. aurita female sex (salicaceae) dried bark from Germany, S. babylonica (salicaceae) dried leaf from India, S. babylonica (salicaceae) oven-dried leaf from England, S. babylonica cv. fardon (salicaceae) dry leaf from England, S. babylonica x S. fragills (S. soft) (salicaceae) dried leaf from the oven of England, S. basfordiana (salicaceae) fresh leaf from England, S. basfordiana (salicaceae) frozen leaf , S. caesia (salicaceae) fresh branches from France, S. caesia (salicaceae) fresh leaf from France, S. caesia (salicaceae) fresh stem from France, S. calodendron (salicaceae) fresh leaf from England, S. calodendron (salicaceae) ) frozen leaf, S. capitata (salicaceae) dry leaf of China, S. caprea (salicaceae) dry bark of Finland, S. caprea (salicaceae) dry bark of Germany, S. caprea (salicaceae) dry bark of Mexico, S. caprea (salicaceae) dry leaf of Mexico, S. caprea (salicaceae) dry leaf of the USSR, S. caprea female sex (salicaceae) leaf dried in furnace of England, S. caprea (salicaceae) leaf dried in furnace of Finland, S caprea female sex (salicaceae) dry bark from Germany, S. caprea male sex (salicaceae) bark ca from Germany, S. caprea var. lanata (salicaceae) dried leaf of England, S. caprea x S. lanata (S. balfourii) (salicaceae) oven-dried leaf of England, S. caprea x S. viminalis (S. serican (salicaceae) leaf dried in oven England, S. chaenomeloides (salicaceae) dry leaf from Japan, S. cinérea (salicaceae) dry bark from Germany, S. cinérea (salicaceae) dry bark from Switzerland, S. cinérea (salicaceae) oven-dried flowers from Finland, S. cinérea (salicaceae) dry leaf of England, S. cinérea (salicaceae) oven-dried leaf of England, S. cinérea female sex (salicaceae) dry bark of Germany, S. cinérea male sex (salicaceae) dry bark of Germany, S. daphnoides (salicaceae) dry bark, S. daphnoides (salicaceae) dry bark from Switzerland, S. daphnoides (salicaceae) fresh leaf from England, S. daphnoides (salicaceae) frozen leaf, S. daphnoides clone 1 (salicaceae) dry twig from Finland , S. daphnoides clone 2 (salicaceae) dry twig from Finland, S. daphnoides spp. cordaph (salicaceae) dry bark of Madeira, S. daphnoides var. acutifolia (salicaceae) dry leaf of England, S. fragilis (salicaceae) dry bark of Germany, S. fragilis (salicaceae) dry leaf of England, S. fragilis (salicaceae) dry leaf of Germany, S. fragilis (salicaceae) fresh leaf from England, S. fragilis (salicaceae) frozen leaf, S. fragilis (salicaceae) oven-dried leaf from England, S. fragilis (salicaceae) oven-dried leaf from Finland (cultivation), S. fragilis (salicaceae) dry twig from Finland, S. fragilis male sex (salicaceae) dry bark from Germany, S. fragilis male sex (salicaceae) dry leaf from Germany, S. fragilis var. latifolia (salicaceae) fresh leaf from England, S. fragilis var. latifolia (salicaceae) frozen leaf, S. fragilis x S. pentandra (S. meyeran (salicaceae) oven-dried leaf from England, S. fragilis x S. triandra (S. decipien (salicaceae) oven-dried leaf from England, S hybrid geminata (salicaceae) dry leaf of England, S. geminata hybrid (S. cinérea x S. vi (salicaceae) oven-dried leaf of England, S. gracilis var. textoris (salicaceae) oven-dried bark of Canada, S gracilistyla (salicaceae) dry bark from Japan, S. gracilistyla (salicaceae) dry leaf from Japan, S. gracilistyloides (salicaceae) dry bark from Japan, S. gymnolepis (salicaceae) dry bark from Japan, S. hastata (salicaceae) dry bark from Switzerland, S. herbacea x S. phylicifolla (S. moore (salicaceae) oven-dried leaf from England, S. incana (salicaceae) dry leaf from England, S. koriyanagi (salicaceae) dry bark from Japan, S. lapponum (salicaceae) ) oven dried leaf from England, S. lapponum (salicaceae) oven dried leaf from Finland, S. lapponum (salicaceae) dry twig from Finland, S. lasiandra (salicaceae) lyophilized from leaves + stem from EUA-AK, S. lasiolepis (salicaceae) dry leaf of USA-CA, S. matsudana (salicaceae) dry leaf of China, S. myrsinifolia (salicaceae) dry bark of Germany, S. myrsinifolia (salicaceae) dry leaf of Finland (cultivation), S. myrsinifolia (salicaceae) dry leaf of Germany, S. myrsinifolia (salicaceae) fresh leaf of Finland, S. myr sinifolia (salicaceae) oven-dried leaf from Finland, S. myrsinifolia (salicaceae) dry stem (cultivation) from Finland, S. myrsinifolia (salicaceae) fresh stem from Finland, S. myrsinifolia (salicaceae) dry twig from Finland, S. myrsinifolia male sex (salicaceae) dried bark of Germany, S. nigrícans (salicaceae) dried leaf of England, S. nigrícans (salicaceae) dry leaf of Switzerland, S. nigrícans (salicaceae) fresh leaf of England, S. nigrícans (salicaceae) leaf frozen, S. orestera (salicaceae) dry leaf of USA-CA, S. pentandra (salicaceae) dry bark of Germany, S. pentandra (salicaceae) USA leaf, S. pentandra (salicaceae) dry leaf of Germany, S. pentandra (salicaceae) fresh leaf from England, S. pentandra (salicaceae) frozen leaf, S. pentandra (salicaceae) leaf dried in oven from England, S. pentandra (salicaceae) leaf dried in oven from Finland, S. pentandra (salicaceae) twig dry of Finland, S. pentandra cv. lumley (salicaceae) dry leaf of England, S. pentandra female sex (salicaceae) dry bark of Germany, S. pentandra x S. fragilis (salicaceae) fresh leaf of England, S. pentandra x S. fragilis (salicaceae) frozen leaf, S. pentandroides (salicaceae) dry leaf of USSR, S. pentandroides (salicaceae) fresh root bark, S. petiolaris (salicaceae) dry bark of Canada, S. phylicifolia (salicaceae) dry leaf of England, S. phylicifolia (salicaceae) oven-dried leaf from England, S. phylicifolia (salicaceae) oven-dried leaf from Finland, S. phylicifolia (salicaceae) dry twig from Finland, S. phylicifolia x S. myrsinifolia (salicaceae) oven-dried leaf from Finland, S. purpurea (salicaceae) dry bark, S. purpurea (salicaceae) dry bark from Germany, S. purpurea (salicaceae) dry bark from Switzerland, S. purpurea (salicaceae) dry leaf from Germany, S. purpurea (salicaceae) dry leaf from Germany (cultivation), S. purpurea (salicaceae) dry leaf of Switzerland, S purpurea (salicaceae) fresh leaf, S. purpurea (salicaceae) fresh leaf from England, S. purpurea (salicaceae) frozen leaf, S. purpurea (salicaceae) oven-dried leaf from England, S. purpurea female sex (salicaceae) bark dried from Germany, S. purpurea female sex (salicaceae) dried leaf from Germany, S. purpurea male sex (salicaceae) dried bark from Germany, S. icurea var. goldstones (salicaceae) dry leaf of England, S. purpurea x S. triandra (S. leiophyl (salicaceae) dry leaf of England, S. repens (salicaceae) dry bark of France, S. repens (salicaceae) dry bark of Germany, S. repens (salicaceae) dry leaf of Germany, S. repens (salicaceae) dry leaf of England, S. repens (salicaceae) dry bark of France, S. repens (salicaceae) dry bark from Germany, S. repens male sex (salicaceae) dry bark from Germany, S. rubra hybrid (salicaceae) dry leaf from England, S. rubra hybrid (S. purpurea x vimi (salicaceae ) oven dried leaf of England, S. schwerinii (salicaceae) dried bark of USSR, S. scouleriana (salicaceae) dry bark of USA-UT, S. smithiana (salicaceae) dry leaf of England, S. songarica (salicaceae) leaf of USSR, S. songarica (salicaceae) dry leaf of USSR, S. species (S. salicaceae) dry entire plant of Switzerland, S. species (salicaceae) bark of the dry stem of France, S. stipularis hybrid (S. viminalis x a (salicaceae) leaf dried in furnace of England, S. tetrasperma (salicaceae) dry root of Thailand, S. tetrasperma (salicaceae) dry stem bark from Thailand, S. tremuloides (salicaceae) dry bark from the USA, S. triad (salicaceae) dry bark from Germany, S. triandra (salicaceae) kiln dried from England, S. triandra cv. Maul black (salicaceae) dry leaf of England, S. triandra female sex (salicaceae) dry bark of Germany, S. triandra male sex (salicaceae) dry bark of Germany, S. triandra x S. viminalis x S hippopha (salicaceae) leaf dried in oven from England, S. viminalis (salicaceae) dried leaf in Finland oven (culture), S. viminalis (salicaceae) dry twig from Finland (cultivation), S. viminalis cv. aquatic (salicaceae) branch dried in oven from Finland (cultivation), S. viminalis female sex (salicaceae) dried bark from Germany, Toisusu urbaniana (salicaceaé) dried bark from Japan, Viburnum henryi (caprífoliaceae) leaf, Viburnum prunifolium (caprífoliaceae) bark of the root of the USA, Viburnum rhytidophyllum. { caprífoliaceae) dried flowers of Egypt, Viscum album e / S. alba (loranthaceae) of the leaf stem, France.

EXAMPLE 4 Increase in arNOX inhibitors Not only was salicin active as a single agent (figure 9), it was also actively involved in increasing the inhibition of arNOX from mixtures of other arNOX inhibitors that come from natural sources such as Schizandra chinensis powder and dust from N. tazetta (figure 10a and 10b). As shown in Figure 10a, an arNOX inhibition of a mixture of 4 mg / ml Schizandra powder plus N. tazetta extract (20 μ) with an added 1 mg / ml salicin is shown. Figure 1b illustrates the inhibition of arNOX by a mixture of 4 mg / ml Schizandra powder plus 1 mg / ml N. tazetta powder in the presence of 1 mg / ml salicin. Of the three chemically pure "naractins" (a term used to refer to any of several arNOX inhibitors of natural origin or present in N. tazetta powder or capable of increasing the powder of Narcissus tazetta to an inhibitory level comparable to that of the extracts of N. tazatta more active fresh) identified and tested, salicin that seemed to be the most promising. Salicin is stable, water soluble, non-irritating, relatively inexpensive and available from several commercial suppliers, such as, for example, Sigma-Aldrich, St. Louis, Mo. In addition, the increased low activity of N. tazetta in powder, is clearly shown in Figures 1a and 1b, where both SIMULATED and salicin especially decreased in the activity of arNOX.

EXAMPLE 5 Characterization of arNOX The production of superoxide by buffy coat layers: buffy coat, a mixture of lymphocytes and platelets. Said buffy coats are commercially available, for example, Rockland ImmunoChemicals (Gilbertsvi PA). Blood samples were kept at 4 ° C before cotion and analysis. Nearly 107 cells were added to each assay. The number of cells was determined using a hemocytometer.

The reduction of ferric cytochrome by superoxide was employed as a standard measure of superoxide formation (Mayo, LA and Cumutte, J. (1990) Meth. Enzyma, 186, 567-575, 7.Butler, J., koppenol and J, Koppenol, WH and Margollash, E. (1982) J. Biol. Chem. 257, 10747). This is a widely accepted method when combined with the inhibition of superoxide dismutase for the measurement of superoxide generation. The test is composed of 150 μ? of serum or 40 μ? of leukocytes in PBSG regulator (8.06 g NaCl, 0.2 g KCI, 0.18 g Na2HP04, KH2P04 0.26 g, 0.13 g of CaCl2, 0.1 MhCl2 1.35 g of glucose dissolved in 1000 ml of deionized water, adjusted to pH 7.4, filtered and stored at 4 ° C). The rates were determined by an SLM Aminco DW-2000 spectrophotometer (Milton Roy, Rochester, NY, E.U.A.) in the dual wavelength mode of the operation with continuous measurements of more than 1 min every 1.5 minutes. After 45 minutes, the test compounds were added and the reaction was followed for 45 min. After 45 min. a millimolar extinction with a coefficient of 19.1 was used to reduce ferricytochrome c. The results of the compounds of the test are given in Table 1. The extracts were made from the compounds in the water unless otherwise indicated.

Table 1 provides the results of some arNOX inhibition experiments.

TABLE 1 INHIBITION% (-) or SOLVENT SPECIMEN CONCENTRATION ACTIVITY ArNOX WITHOUT STIMULATION ADDITION (+) Extract from Water 25 μg / ml 85 -15 Broccoli (1.5%) Shütake Water 25 g / ml 82 -18 (10%) Coleus Water 25 g / ml 106 +6 Spark Water 25 Mg / ml +3 +3 Asian Extract from Water 25 g / ml 98 -2 Lotus leaf artichoke Water 25 Mg / ml 98 -2 (fifteen%) Sea rose Water 25 g / ml 96 -4 Tangerine Water 25 g / ml 94 -6 Seed of Oenothera Water 25 g / ml 94 -6 biennis Astaxanthin Ethanol 25 Mg / ml 62 -38 Natural Orange red ethanol 25 Mg / ml 98 -2 Water 0/84 -100/16 Schisandra 30% ethanol 20/2 Mg / ml 20/94 80/6 chinensis 70% ethanol 77/97 23/3 Lonicera Water 25 Mg / ml 20 -81 japonica Rhizoma Water 70% 25 Mg / ml 0 -100 Fagopyrum EtOH cymosum Rhizoma 25 Mg / ml - 50% ~ -50% Fagopyrum dibotrys Water 25 Mg / ml 28 -72 ethanol 25 Mg / ml 68 -32 ß- Carotene ethanol 2.5 Mg / ml 50 -50 ethanol 0.25 Mg / ml 73 -42 EXAMPLE 6 Topical cosmetic preparations An eight-week, split-face, controlled clinical use study was conducted to select four (4) prototype anti-aging formulations containing plant extracts with arNOX inhibitory properties for their efficacy and tolerability compared to two (2) control vehicles. Efficacy was evaluated by clinical classification, bio-instrumentation measures (chroma meter, corneometer, cutometer), and self-assessment questionnaires. Tolerability was assessed by classification irritation and follow-up of adverse events.

A total of 23 subjects completed participation in the study. Subjects qualified to participate in the study for having mild to moderate fine lines and thick wrinkles in the periocular areas and hyperpigmentation on the right and left sides of the face. Subjects were assigned to two of the following test materials (a control and a test material) in accordance with a random design: Controls A. A control gel of arNOX (without label) AB-87-04A transparent gel, transparent gel (12 subjects) B. The arNOX gel B control (red label) JZ-91-40 colorless, clear gel (contains glycerin) (1 1 subjects) Test materials: 1. An arNOX control gel of arNOX c / s Squizandra (non-encapsulated), extract of N. tazetta and Salicin (green label) JZ 91-39, peach, transparent gel (6 subjects) 2. Control gel of arNOX control with / Schizandra (blue label) TL-90-58 (containing glycerin) of peach, transparent gel (6 subjects) 3. Gel B control of arNOX with / Schizandra (not encapsulated), N. tazetta extracted and salicin (yellow label) TL-90-58 (contains glycerin) peach, transparent gel (6 subjects) 4. Control gel B with arNOX with / Salicin (half yellow, half black mark) Body weight control arNOX gel / salicin (medium yellow, half black label) KK-89-49, clear, clear gel (containing glycerin) ( 5 subjects) Subjects were instructed to apply the assigned test material to the right or left side of the face and to apply the control assigned to the opposite side of the face twice a day (morning and evening) after cleaning their faces.

The clinical evaluations were carried out in the baseline (Visit 1), week 4 (Visit 2), and week 8 (Visit 3). Subjects who participated in the following clinical ratings and instrumental procedures at each visit (unless otherwise indicated).

Efficiency and performance parameters The subjects were classified clinically on the right and left sides of the face for the following parameters: fine wrinkles (periocular), thick wrinkles (periocular), skin texture (cheeks), general discoloration, brightness (cheeks), clarity of the skin, pore size (front and nose area), distribution / pore structure, and especially the general skin luminosity.

Classification of Irritation / safety parameters The subjects were classified clinically on the right and left sides of the face of the parameters of the irritation objectives (erythema, edema, desquamation) and the subjective parameters irritation (burning, stinging, itching, tightness, Tingling sensation).

Skin Surface Moisture Measurements Skin surface hydration measurements were taken with the Corneometer® CM 825 hydration analyzer (Courage + Khazaka, Germany). The measurements were taken (in triplicate) in the lower center of the left and right cheek in order to quantify the moisture content of the stratum of the cornea.

Measurements of luminosity of the skin Skin luminosity measurements were made in triplicate with a Chroma Meter CR400 skin luminosity analyzer (Konica-Minolta, Japan) and were taken on pigmented lesions (selected by the researcher) on the right and left sides of the skin. face to instrumentally evaluate changes in skin color / tone. An additional measurement of the skin's brightness was taken in a non-pigmented (normal) area on one side of the face.

Measurements of viscoelasticity of the skin A single visco-elasticity measurement was taken using Cutometer® SEM 575 viscoeiastometer (Courage + Khazaka, Germany). The measurements were taken in the center of each right and left cheek in order to evaluate the viscoelastic properties of the skin.

Questionnaires The subjects completed the following questionnaires in Week 4 and Week 8.

Questionnaire on the evaluation of the changes in the skin of the subject with respect to the parameters of the skin condition from the beginning of the study Subject evaluation questionnaire regarding the current condition of the skin condition parameters and the materials and tolerance test attributes In general, the results of this study show that all the test materials and controls produced significant improvements in the appearance of fine lines, roughness to the touch, skin tone, and general discoloration / hyperpigmentation, compared to the reference scores , test material 1, arNOX control gel with / 'Schizandra (not encapsulated), extract of N. tazetta and Salicin (green label) JZ-91-39 and test material 3. Control gel of arNOX with / Schizandra (not encapsulated), extract of N. tazetta and Salicina (yellow label) TL-90-58 (contains glycerin) improving the appearance of coarse wrinkles. There were no significant increases in objective or subjective irritation with any of the test materials or controls.

Measurements of skin luminosity show that the only test material 1, the arNOX control gel with / Schizandra (non-encapsulated), N. tazetta extract and Salicin (green) JZ-91-39 produced a significant reduction in the values of b * in the non-pigmented site in week 8. The luminosity of the b * skin values taken in the pigmented lesion sites show that test material 1. The A control gel of arNOX with / Schizandra ( not encapsulated), extract of N. tazetta and Salicina (green) JZ-91-39 was superior to that of the test of materials 2. The gel A control of arNOX with / 'Schizandra (blue) TL-90-59 and the material test 3. The control gel of arNOX with / 'Schizandra (not encapsulated), the extract of N. tazetta and Salicin (yellow) TL90-58 (contains glycerin) in the reduction of dark lesions. Measurements of surface skin hydration show that all test materials and controls significantly improved hydration in week 4. The visco-elasticity measurement showed no significant differences between test materials and controls.

Informed consent Written informed consent under 21 CFR 50.25 (Code of Federal Regulations) was obtained from each subject prior to enrollment in the study. The signed, signed original consent agreement for each subject participating in the study will be retained in the study file. Each subject received a signed copy of the agreement. (Please see Appendix IV for a sample formulation.) Wear Twenty-three (23) subjects completed the study. Twenty-six (26) subjects signed up to participate in the study, and three (3) subjects discontinued participation in the study due to the following reasons: • Voluntary interruption / adverse event: Subject 021 • Failure to attend the scheduled visit (s): Subjects 004 and 026 • Voluntary interruption / scheduling conflict: 020, 022, 029 • Failure to attend the scheduled visit: 009, 034 • Investigator discretion: 010 Demographics of the subject Twenty-three (23) female subjects completed the study. Table 2 presents a summary of demographic information (age, ethnicity, and skin classification by Fitzpatrick) for all subjects. For ethnicity and skin type by Fitzpatrick, the number of subjects in each category is on the list with the percentage of the population studied in parentheses. The ethnicity information was obtained from the eligibility of each subject and the health questionnaire.

TABLE 2 Summary of demographic information Fitzpatrick skin classification is based on the unprotected response of the skin for the first 30-45 minutes of sun exposure after a winter season, without sun exposure. The categories of skin types are the following: Type I. It always burns easily, never tans; Type II. Always burns easily, tans minimally; Type III It burns moderately, tans gradually; Type IV. It burns minimally, always tans well; Type V. Rarely burns, tans profusely; Type VI. It never burns, deeply pigmented; Fitzpatrick reported an alternative classification system that is useful for assessing the degree of perioral and periorbital (periocular) wrinkle formation (rhytidosis): Class I - fine wrinkles; Class II - fine to moderately deep wrinkles and moderate number of wrinkles; Class III - fine (deep) wrinkles at depth, numerous lines of wrinkles and redundant folds that may be present.

EXAMPLE 7 Procedures and methods Before the start of the study, prospective subjects participated in a three-day washout period, during which facial moisturizers were not applied to the face.

At the beginning of the study (Visit 1), prospective subjects washed their faces and removed all makeup at least 30 minutes before arriving at the clinic. Prospective subjects brought their regular skin care regimen products for eligibility consideration. Subjects completed an Eligibility and Health questionnaire and signed an Informed Consent Agreement, a Confidentiality Agreement, and a Release of Photograph Form.

Subjects participated in the following clinical classification procedures: Efficiency / performance parameters The subjects were classified clinically on the right and left sides of the face of the following parameters: Fine wrinkles - periocular area Thick wrinkles - periocular area Skin texture (visual appearance) - cheeks Touch roughness - cheeks General discoloration General luminosity of the skin The results of the efficiency / classification of the performance parameters were recorded using the following scale of 1 to 10 points: 1 = Positive (1 to 3 = Good / Desirable) 10 = Negative (8-10 = Undesirable) Half-point scores are used when necessary Subjects qualified to participate in the study continued to have a mild to moderate score of 3 to 7 for fine periocular lines and 2 to 5 for secondary periocular wrinkles, and 2-7 for hyperpigmentation on the right and left sides of the face. .

Irritation / classification of safety parameters The subjects were classified clinically on the right and left sides of the face for the objective parameters of irritation (erythema, edema, desquamation) and the subjective parameters of irritation (burning, stinging, itching, tightness, tingling sensation). The results of the classification of the irritation were recorded with the following scale: 0 = None 1 = Light 2 = Moderate 3 = Severe The half-points were used as necessary The qualified subjects participated in the following instrumentation measures: EXAMPLE 8 Hydration measurements on the surface of the skin Hydration measurements of the skin surface were taken using the CM 825 Corneometer® hydration analyzer (Courage + Khazaka, Germany). The measurements were made in triplicate and were taken in the lower center of the left and right cheek in order to quantify the moisture content of the stratum corneum. The measuring principle of the corneometer® is based on the measurement of the capacitance of a dielectric medium. Any change in the dielectric constant, due to the variation of hydration of the skin alters the surface of the capacitance of a precision measuring capacitor. These measurements can detect a very small change in the level of skin hydration with very high reproducibility. The readings are directly proportional to the electrical capacity of the skin and the measurements increase as the skin becomes more hydrated.

EXAMPLE 9 Measurements of luminosity of the skin Skin luminosity measurements were made in triplicate with a Chroma Meter CR400 skin luminosity analyzer (Konica-Minolta, Japan) and were taken on pigmented lesions (selected by the researcher) on the right and left sides of the skin. expensive. The corneometer instrumentally (and objectively) evaluates changes in skin color / tone. An additional measure of the corneometer was taken in a non-pigmented (normal) area on one side of the face. The corneometer is a sensitive colorimeter that allows adjustment and calibration of white colors with difference in color. The corneometer has a detachable head for easy and independent analysis of the selected areas. The following values were recorded: L *: Describes the relative brightness in a grayscale from black to white, the values increase as the skin becomes brighter and clearer a *: Describes the color tone that goes from red to green, the values increase with the improvements in the vascularization of the skin, increased blood flow and improved skin tone b *: Describes the color tone that goes from blue to yellow, the values usually decrease with the luminosity of the skin An additional measurement of the skin's luminosity was taken in a non-pigmented (normal) area on one side of each subject's face.

EXAMPLE 10 Measurements of viscoelasticity of the skin A single visco-elasticity measurement was taken using the cutometer® SEM 575 viscometer (Courage + Khazaka, Germany). The measurements were taken in the center of the right and left cheeks of each subject in order to evaluate the viscoelastic properties of the skin. The principle of measurement is based on aspiration. Negative pressure is created in the device and the skin is introduced into the opening of the probe. Inside the probe, the penetration depth is determined by a non-contact optical measurement system. The intensity of the light varies due to the penetration depth of the skin. The resistance of the skin to be aspirated by the negative pressure (firmness and its ability to return to its original position (elasticity) are visualized in the instrument in the form of curves at the end of each measurement, three hundred (300) mbar negative pressure applied and released through an 8 millimeter (mm) probe.The movement of the skin in and out of the probe was recorded during the application and release of the suction, and the elasticity and extensibility were calculated.

The subjects were assigned to one of the following groups of test material, in accordance with a randomized design: Controls A. Control gel of arNOX (without label) AB-87-04a B. Control gel of arNOX (red label) JZ-91-40 (contains Test materials 1. Control gel of arNOX with / Schizandra (not encapsulated), extract of N. tazetta and Salicin (green label) JZ91-39 2. Control gel of arNOX with / Schizandra (blue label) TL- 3. Control gel of arNOX conlSchizandra (not encapsulated), extract of N. tazetta and Saliclna (yellow label) TL-90-58 (contains glycerin) 4. Control gel of arNOX with / Salicin (yellow label, half black) KK-89-49 (contains glycerin) The subjects were instructed to apply the assigned test material to the right or left side of the face and to apply the control assigned to the opposite side of the face in accordance with the following instructions for use: Apply a thin layer twice a day in the morning and at night after cleaning your face. Moisturizers and makeup products can be applied after applications of the test material.

Subjects were provided with written instructions for use, a calendar of future visits, and a diary to record the application times for the test material and comments.

Subjects returned to the clinic in Week 4 (visit 2) and Week 8 (visit 3), after having washed their face and removed all makeup at least 30 minutes before each visit. The diaries and the test materials were returned to the clinic and the compliance of use was verified; new diaries (and test materials, if necessary) were distributed in Week 4. Subjects received a clinical classification and bio-instrumentation measurements (chroma meter, corneometer and cutometer), in accordance with the reference procedures. Each subject also completed a questionnaire evaluating the change of the subject's skin and an evaluation questionnaire to the subject regarding the test material, tolerance, and improvements in the condition of the skin on the right and left sides of the face.

The formulations for each of the compositions are shown in Table 3, below.

TABLE 3 Control Gel by arNOX Without Label Quantitative Product Formulation Number of the Lab Formula: AB-87-04A INCI P / P% Supplier Water (Aqua) 98.980000 House Cross polymer of Acrylates / C10-31 Alkyl Acrylate 0.300000 Noveon Metilparaben 0.150000 Clariant Chlorphenesin 0.300000 House Aminomethyl Propanol 0.150000 Angus Polisorbate 20 0.100000 Symrise Fragrance (Perfume) 0.020000 Ungerer Total: 100.000000 TABLE 3 (Contd) TABLE 3 (Cont.) A control gel of arNOX with Schizandra (not encapsulated), extract of N. tazetta Salicina Quantitative Product Formulation Green Label Number of Lab Formula: JZ-91-39 INCI P / P% Supplier Water (Aqua) 98.735000 House Cross polymer of Acrylates / C10-31 Alkyl Acrylate 0.300000 Noveon Metilparaben 0.150000 Clariant Chlorphenesin 0.300000 House Aminomethyl Propanol 0.150000 Angus Fruit extract from Shizandra you crack 0.040000 Draco Water (Aqua) 0.140000 House Bulb extract Narcissus Tazetta 0.060000 Symrise Salicin 0.005000 Kaden Bio.

Polysorbate 20 0.100000 Unigema Fragrance (Perfume) 0.020000 Ungerer Total: 100.000000 TABLE 3 (Cont.) TABLE 3 (Cont.) Control gel of arNOX with Schizandra (not encapsulated), N. tazetta and Salicina Quantitative Product Formulation Yellow Label Number of the Lab Formula: TL-90-58 INCI P / P% Supplier Water (Aqua) 84.805000 House Cross polymer of Acrylate / Alkyl C10-31 Acrylate 0.300000 Noveon Metilparaben 0.150000 Clariant Chlorphenesin 0.300000 House Aminomethyl Propanol 0.150000 Angus Water (Aqua) 0.140000 House Bulb Extract Narcissus Tazetta 0.060000 Symrise Salicina 0.005000 Kaden Bio Glycerin 13.930000 House Fruit extract from Schizandra chinensis 0.040000 Draco Polysorbate 20 0.100000 Unigema Fragrance (Perfume) 0.020000 Ungerer Total: 100.000000 TABLE 3 (Cont.) ** Noveon IP Holding Corp. Cleveland, Ohio, E.U.A.

Clariant, Corp. Charlotte, N.C., E.U.A.

Angus Chemical Co., Buffalo Grove, E.U.A.

Unigema, New Castle, DE, E.U.A.

Symrise Inc., Teterboro, NJ Draco Natural Products, Inc., San Jose, CA, E.U.A.

Xuancheng Baicao Plants Industry and Trade CO., LTD, Anhui, China The subjects were given written instructions for use, a calendar of future visits, and a diary to record the times of application of the material test and comments.

The subjects returned to the clinic in Week 4 (visit 2) and Week 8 (visit 3). The subjects washed their faces and removed the make-up at least 30 minutes before arriving at the test area for each visit. Subjects were also brought their test materials for each visit to monitor compliance with the use. Subjects participated in the following procedures at each visit: Efficiency / performance of classification parameters irritation / classification of safety parameters Hydration measurements of the skin surface (Corneometer®) Measurements of luminosity of the skin (Chroma Metro) measurements Measurements of visco-elasticity of the skin (cutometer®) The subjects also completed a subject skin change evaluation questionnaire and an evaluation questionnaire on the subject attributes of the test material, tolerance, and improvements in skin condition parameters on the right and left sides of the face .

Daily records were returned to the clinic at each visit, and new journals were distributed at Visit 2. Subjects returned the materials testing units to the clinic at the end of the study. Daily records were reviewed by clinic staff and material testing units were weighed at each visit to ensure compliance.

EXAMPLE 11 Biostatistics and data management The mean values for classification of clinical measurements and instrumentation in Week 4 (Visit 2) and Week 8 (Visit 3) were statistically compared to baseline (Visit 1) values. using a level of significance p < 0.05. The average percentage change from the baseline and the incidence of the improvement were calculated for all attributes. Comparisons were made between test materials and controls by analysis of variance (ANOVA) with paired comparisons (Fisher's LSD).

Self-assessment questionnaires completed by subjects in Week 4 and Week 8 were tabulated and a superior box analysis was performed.

EXAMPLE 12 Topical application data At the beginning of the study (visit 1), Week 4 (Visit 2), and Week 8 (Visit 3), the subjects had a clinical classification and measures of bio-instrumentation (chroma meter, corneometer and cutometer) performed in the expensive. Table 4 presents the results for each test and control material. The mean values in Week 4 and Week 8 are statistically compared with the mean reference values of the significant differences. The average percentage change from the baseline is shown in parentheses.

TABLE 4 Line Week 4 Week 8 base Fine lines 4. 33 3.58 (-17.3%) 3.50 (-19.2%) (periocular) thick wrinkle 'skin folds 3.63 3.25 (-10.3%) 3.38 (-6.8%) (periocular) Touch hardness Classification of 3.46 2.33 (-32.5%) 1.63 (-53.0%) Effective Performance (cheeks) Skin tone 5.54 5.08 (-8.2%) 4.88 (-12.0%) Discoloration general / 5.17 4.63 (-10.4%) 4.50 (-12.9%) hyperpigmentation Brightness 5. 63 4.71 (-16.2%) 4.50 (-20.0%) general of the skin Erythema 0.54 0.42 (-23.0%) 0.25 (-53.8%) Edema 0.00 0.00 0.00 Formation of 0. 00 0.00 0.04 scales Clasification of Burns Irritation / Safety 0.08 0.08 (0.0%) 0.00 (-100.0%) Itching 0.00 0.33 0.00 Itching 0.08 0.08 (0.0%) 0.00 (-100.0%) Asperity 0.92 0.54 (-40.9%) 0.00 |0 (-100.0%) Hormigueo 0.00 0.00 0.00 Injury L * 63.28 62.60 (-1.0%) 63.38 (0.1%) Medlclone Plgmentad to * 11.84 12.88 (8.7%) 1 1.52 (-2.6%) s from a b * 15.33 14.16 (-7.6%) 14.72 (-4.0%) Cromómet Injury No L * 61.28 62.29 (.6%) 62.73 (2.3%) ro Plgmentad a * 10.62 1 1.73 (10.4%) 11.89 a (11.9%) a b * 14.92 14.28 (-4.3%) 14.16 (-5.1%) Measurements of Comeometer 39.31 62.69 a (59.5%) 45.72 (16.3%) Elasticity 0. 29 0.29 (1.2%) 0.32 (8.3%) Biological Measurements with Extensibility 1.52 1.39 (-8.1%) 1.01 a- (-32.3%) Pure elasticity 0.40 0.43 (5.2%) 0.50? (2. 3%) Elasticity 0.68 0.66 (-3.3%) 0.64 (-6.2%) |0 · Indicates a statistically significant decrease (p <0.05) compared to the baseline Indicates a statistically significant increase (p> 0.05) compared to the baseline * Subject 010 was removed in week 8 of the cutometer analysis due to an error in the calibration of the instrument in the rescheduled visit; n-values equal to 1 1 for the measurements with the cutometer in week 8.

TABLE 4 (ConU |0- Indicates a statistically significant decrease (p <0.05) in comparison with the baseline · Indicates a statistically significant increase (p> 0.05) compared to the baseline TABLE 4 fCont.) |0 · Indicates a statistically significant decrease (p <0.05) compared to the baseline ü Indicates a statistically significant increase (p> 0.05) compared to the baseline TABLE 4 ÍCont.) ? - Indicates a statistically significant decrease (p <0.05) compared to the baseline 1 Indicates a statistically significant increase (p> 0.05) compared to the baseline TABLE 4 (Cont.) • 0 Indicates a statistically significant decrease (p <0.05) compared to the baseline ü Indicates a statistically significant increase (p> 0.05) compared to the baseline TABLE 4 fConU Indicates a statistically significant decrease (p <0.05) compared to the baseline Indicates a statistically significant increase (p> 0.05) compared to the baseline EXAMPLE 13 Average change from the baseline Table 5 provides comparisons of the mean variation of the baseline for clinical classification and instrumentation studies.

PICTURE tingle Measurements with Chromometer s L * (-1.0%) (-0.1%) (-1.3%) (0.2%) (-0.4%) (2.8%) Pigmented lesions a * (8.7%) (6.8%) (9.7%) (2.8%) (0.3%) (-13.8%) b * (-7.6%) (-5.2%) (-6.9%) (1.2%) (4.1%) (0.3%) L * (1.6%) (1.0%) (2.1%) (2.6%) (1.0%) (2.4%) Injuries not a »(10.4%)) (-2.1%) (1.8%) (-8.6%) pigmented (3.5%) (5.5%) b * (-4.3%) (-4.9%) (-4.2%) (-5.4%) (-2.7%) (-6.0%) Measurements with the Corneometer (59.5%) (75.4%) (60.0%) (40.1 %) (78.6%) (78.7%) Measurements with the Cutometer Biological Elasticity (1.2%) (16.2%) (9.8%) (5.3%) (5.1%) (19.1%) Extensibility (-8.1%) (-12.0%) (-17.4%) (-10.4%) (-3.8%) (-23.3%) Pure elasticity (5.2%) (23.5%) (13.7%) (15.9%) (9.6%) (31.7%) Elasticity (-3.3%) (9.9%) (5.2%) (-0.5%) (-7.5%) (4.2%) TABLE 5 ÍCont.) Tingle Measurements with Cremometer; r ' L * (0.1%) (0.0%) (2.0%) (1.5%) (1.7%) (2.8%) Pigmented lesions a * (-2.6%) (9.6%) (3.8%) (-4.4%) (-6.2%) (-0.3%) b * (-4.0%) (-3.9%) (-5.8%) ( 6.0%) (3.5%) (-1.3%) L * (2.3%) (1.9%) (2.9%) (3.2%) (2.4%) (3.4%) Non-pigmented lesions a * (1 1.9%) (8.9%) (8.4%) (-1.9%) (-0.4%) (1.5%) b * (-5.1%) (-6.6%) (-3.6%) ( -3.6%) (-4.6%) (-6.3%) Measurements with Corneometer (16.3%) (1 1.0%) (4.5%) (5.9%) (1 1.1%) (38.8%) Measurements with the Cutometerjf Biological Elasticity ¾.3%) (24.4%) (8.8%) (5.2%) (-9.0%) (3.0%) Extensibility (-32.3%) (-29.9%) (-37.0%) (-9.8%) (-1 1.1%) (-26.4%) Pure elasticity (21.3%) (37.0%) (25.7%) (27.3%) (6.0%) (15.2%) Elasticity (-6.2%) (-2.0%) (-17.6%) (-10.0%) (-28.1%) (-12.8%) * Subject 010 was eliminated from the cutometer analysis at 8 weeks due to an error in the calibration of the instrument in the rescheduled visit, n-11 for equal values measured with the cutometer in week 8.

EXAMPLE 14 Comparison between groups The comparisons, based on the average change of the baseline, were made between the treatments (test materials and controls) by analysis of variance (ANOVA) with paired comparisons (Fisher's LSD). The following classifications, provided in table 6, illustrate the statistical significance (p = 0.05) between the experimental groups. The classifications are presented in order from highest to lowest level of improvement, and the parameters, without significant differences are not included. The average change from the beginning appears below each treatment.

TABLE 6 Discoloration General Material Material Material of - test test test test Control Control Week 4 2 4 1 3 A B (p = 0.0074) (-1.17) (-1.10) (-0.75) (-0.67) (-0.54) (-0.32) Discoloration General Material Material Material of - test test test test Control Control Week 8 2 1 4 3 A B (p = 0.0000) (-1.67) (-1.33) (-1.20) (-1.08) (-0.67) (-0.18) Material Material Material of Skin Tino- test test test test Control Control Week 8 2 3 4 1 B A (p = 0.0020) (-1 -58) (-1.25) (-1.20) (-1.17) (-0.68) (-0.67) Cremometer b * Material Injury Material Material of pigmented material- test Control Control test test Week 8 1 B A 4 3 2 (p = 0.0388) (-0.94) (-0.65) (-0.62) (-0.23) (0.53) (0.94) EXAMPLE 15 Results of the statistical comparison for the measurements of the instruments The subjects were classified according to the fine lines (periocular), thick wrinkles / folds of the skin (periocular), roughness to the touch (cheeks), the tone of the skin, general discoloration / hyperpigmentation, and the luminosity of the skin in general on the right and left side of the face . The results of the clinical classification revealed the following significant improvements, in comparison with the initial value shown in Table 7.

TABLE 7 | 0 Indicates a statistically significant decrease (p <0.05), improvement, compared to the baseline S4 = Week 4 S8 = Week 8 EXAMPLE 16 Irritation / safety The subjects were classified according to erythema, edema, scaling, burning, stinging, pruritus, roughness, and tingling on the right and left side of the face.

The results of the clinical classification revealed improvements significant, as compared to the baseline value as shown in the Table 8, for example: TABLE 8 | O- Indicates a statistically significant decrease (p < 0. 05), improvement, compared to the baseline S4 = Week 4 S8 = Week 8 EXAMPLE 17 Measurements of the luminosity of the skin The luminosity of the skin was measured in triplicate, with a skin luminosity analyzer (Chroma Meter CR400, Konica Minolta, Japan). The measurements were taken on pigmented lesions (selected by the researcher) on the right and left sides of the face in order to instrumentally evaluate changes in color / tone in the skin. A measurement Additional skin luminosity was taken in a non-pigmented area (normal) on one side of the face.

The results of skin luminosity measurements are shown in Table 9 and reveal significant differences, compared to the initial value, for example: TABLE 9 | O Indicates a statistically significant decrease (p <0.05) compared to the baseline | 0 Indicates a statistically significant increase (p <0.05) compared to the baseline S4 = Week 4 S8 = Week 8 EXAMPLE 18 Hydration measurements on the skin surface Measurements of hydration of the surface of the skin They took in a (Corneometer CM 825, Coutage + Khazaka, Germany) in triplicate. The measurements were taken in the lower center of the right and left cheeks in order to quantify the moisture content of the stratum corneum.

The results of measurements of hydration of the skin surface revealed a significant increase (improvements) in hydration for each treatment in Week 4, when compared with the baseline value. No significant differences were found in Week 8.

EXAMPLE 19 Measurements of viscoelasticity in the skin Only one single visco-elasticity measurement was taken using a MPA 580 cutter (Courage + Khazaka, Germany). The measure was taken in the center of the right and left cheeks of each subject in order to evaluate the viscoelastic properties of the skin.

The results of the visco-elasticity measurement, which is shown in Table 10, revealed the following significant differences, when compared with the baseline, for example: TABLE 10 0- Indicates a statistically significant decrease (p <0.05) compared to the baseline | 0 Indicates a statistically significant increase (p <0.05) compared to the baseline S4 = Week 4 S8 = Week 8 EXAMPLE 20 General conclusions The results of this pilot study demonstrate that all test materials and controls produced significant improvements in the appearance of fine lines, roughness to the touch, skin tone, and general discoloration / hyperpigmentation, compared to the reference ratings. Specifically, test material 1, arNOX control gel with / Schizandra (non-encapsulated), N. tazetta extract and Salicin (green label) JZ-91-39 and test material 3, Control Gel B, is designated of arNOX with / Schizandra (non-encapsulated), extract of Narcissus tazetta and Aalicin (yellow label) TL-90-58 (contains glycerin), even had a positive effect on the appearance of coarse wrinkles show significant improvements in week 4 (material from test 3, yellow label) and week 8 (test materials 1, green label, and 3, yellow label). There were no significant increases in objective or subjective irritation with any of the test materials or controls.

Measurements of skin luminosity show that only test material 1, arNOX control gel with Schizandra (non-encapsulated), N. tazetta extract and Salicin (green label) JZ-91-39 produced a reduction significant in the b * values in the non-pigmented site at week 8. The b * skin luminosity values taken at the sites of pigmented lesion show that the test material 1. arNOX control gel with / schizandra ( not encapsulated), extract of N. tazetta and salicin (green label) JZ-91-39 was superior in comparison with the materiale of test 2. The control gel of arNOX with / Schizandra (blue label) TL-90-59 and the test material 3. The control gel of arNOX with / Schizandra (non-encapsulated), extract of N. tazetta and Salicin (yellow label) TL 90-58 (contains glycerin) in the reduction of dark lesion.

Measurements of skin surface hydration show that all the test materials and skin hydration controls improved significantly at week 4.

Skin viscoelasticity measurements showed no significant differences between test materials and controls.

ANOVA comparisons between test materials and controls indicate that the test material 1, (control gel of arNOX with / Schizandra (non-encapsulated), extract of Narcissus tazetta and salicin (green label) JZ-91-39) and two test materials, (control gel of arNOX with / Schizandra (blue label) TL-90-59) were superior to a control, (a control gel of arNOX (without label) AB-87-04A) and control B, (control gel of arNOX (red label) JZ- 91 to 40 (contains glycerin)) improves total discoloration at week 4. In addition, test materials 1 and 2 were superior to control B, (control gel arNOX (red label) JZ-91-40 (contains glycerin)) in week 8. Test material 2, (control gel arNOX with / Schizandra (blue label) TL-90-59), test material 3 (control gel arNOX with / Schizandra (no encapsulated), extract of Narcissus tazetta and Salicin (yellow label) TL-90-58 (contains glycerin)), and the test material 4 (control gel of arNOX with / Salicin (label half of yellow medium, half of black) KK-89-49 (contains glycerin)) were superior to a control A, (control gel arNOX (unlabeled) AB-87-04A) and control B (control gel arNOX (red label) JZ -91-40 (contains glycerin)) to improve appearance at week 8.

Claims

NOVELTY OF THE INVENTION CLAIMS 1. A topical composition useful for improving the effects of aging comprising: an effective amount of an extract of Narcissus tazetta and at least one salicylate, in addition to salicylates of the Narcissus tazetta extract, wherein the composition is effective in reducing the effects of aging. 2. - The composition according to claim 1, further characterized in that the salicylate is derived from a plant extract. 3. - The composition according to claim 2, further characterized in that the salicylate is purified from Narcissus tazetta, willow, corn, crepis, poplar, viburnum, Aspergillus, alangium, birch, bupleurum, colchicum, tartago, filipendulum, gardenia, lithospermum, tobacco or mistletoe 4. - The composition according to claim 1, further characterized in that the salicylate is salicin, salicylic acid, salicylic hydroxamate or combinations thereof. 5. The topical composition according to claim 1, further characterized in that the composition further includes a cosmetically or pharmaceutically acceptable vehicle. 6. - The topical composition according to claim 1, further characterized in that it additionally comprises an extract selected from at least one of broccoli, shitake, rosemary coleus, lotus, artichoke, pink sea tangerine, Oenothera biennis, astaxanthin, red orange, Schisandra chinensis , Lonicera, Phagopyrum, carrot, olive, willow, oats or corn. 7. The topical composition according to claim 6, further characterized in that the Lonicera is Lonicera japonica or Lonicera caprifolium. 8 -. 8 - The topical composition according to claim 1, further characterized in that it additionally comprises β-carotene and astaxanthin. 9. The topical composition according to claim 6, further characterized in that the salicylate increases the effects of the extracts. 10. - The topical composition in accordance with the claim 1, further characterized in that the composition is administered in the form of a cream, a milk, a lotion, a gel, a suspension of microspheres or nanospheres or lipid vesicles or polymers, a soap, a shampoo or a sunscreen. 1 1.- The topical composition in accordance with the claim 1, characterized also because the effects of aging include: lines, wrinkles, hyperpigmentation, dehydration, loss of elasticity, angioma, dryness, itching, telangietasias, actinic purpura, seborrheic keratosis, lack of hydration, decrease in collagen or actinic keratosis. 12. The topical composition according to claim 1, further characterized in that the arNOX inhibiting agent is provided at a concentration of between about 5 pg / ml to about 500 g / ml. 13. - A method to inhibit the generation of reactive oxygen species by the isoform of NADH oxidase related to aging, to alleviate the effects of aging comprising: administering a therapeutically effective amount of a composition comprising an extract of Narcissus tazetta, at less one of salicin, salicylic acid or salicylic hydroxamate to a patient who needs it, in such a way that the generation of reactive oxygen species by the isoform of NADH oxidase related to aging is inhibited and where an effect of the aging. 14. - The method according to claim 13, further characterized in that the composition further comprises an extract of at least one of broccoli, shitake, rosemary coleus, lotus, artichoke, tangerine sea rose, Oenothera biennis, astaxanthin, red orange, schisandra chinensis , Lonicera, Fagopyrum, carrot, olive, willows, oats or corn. 15. - The method according to claim 13, further characterized in that the composition is applied as a cream, a milk, a lotion, a gel, a suspension of microspheres or nanospheres or lipid vesicles or polymers, a soap, a shampoo or a sunscreen. 16. - The method according to claim 13, further characterized because the effects of aging include: lines, wrinkles, hyperpigmentation, dehydration, loss of elasticity, angioma, dryness, itching, telangietasias, actinic purpura, seborrheic keratosis, lack of hydration, decrease of collagen or actinic keratosis. 17. - A cosmetic method for improving the effects of aging consisting in applying to the skin a cosmetic composition comprising: an effective amount of an extract of Narcissus tazetta and at least one salicylate, in addition to the salicylates of the extract of Narcissus tazetta sufficient to inhibit to arNOX, where at least one aging effect mediated by arNOX is inhibited. 18. - The method according to claim 17, further characterized in that the salicylate is salicin, salicylic hydroxamate or salicylic acid. 19. - The method according to claim 17, further characterized in that the cosmetic composition additionally comprises a plant extract selected from at least one of carrot extract, olive extract, broccoli extract, shitake extract, coleus, rosemary extract, extract lotus, artichoke extract, sea rose tangerine extract, Oenothera biennis extract, red orange extract, Schisandra chinensis extract, Lonicera extract, Fagopyrum extract, willow extract, corn vascular cylinder extract, or extract of oat vascular cylinders. 20. - The cosmetic method according to claim 17, further characterized in that the salicylate is provided together with a cosmetically acceptable vehicle. 21. - The cosmetic method according to claim 17, further characterized by the effects of aging include: lines, wrinkles, hyperpigmentation, dehydration, loss of elasticity, angioma, dryness, itching, telangietasias, actinic purpura, seborrheic keratosis, lack of hydration, decrease in collagen or actinic keratosis. 22. - The cosmetic method according to claim 17, further characterized in that the salicylate is applied at least once a day. 23. - The cosmetic method according to claim 17, further characterized in that the salicylate is provided in a cosmetic preparation at a concentration of between about 5 pg / ml to about 500 g / ml. 24. - The cosmetic process according to the invention 17, further characterized in that the composition is administered in the form of a cream, a milk, a lotion, a gel, a suspension of microspheres or nanospheres or lipid vesicles or polymers, a soap, a shampoo or a sunscreen. 25. - A kit for applying a cosmetic useful in improving the effects of aging comprising: an extract of Narcissus tazetta and at least one salicylate, in addition to the salicylates of the extract of Narcissus tazetta; and instructions for use. 26. - The kit according to claim 25, further characterized in that it additionally comprises a cosmetically acceptable vehicle.