MXPA98005825A - Methods and compositions against fine lines and / or arru - Google Patents

Abstract

The present invention relates to methods and compositions for improving and reducing the disorders comprising aging, particularly fine lines and / or wrinkles, including fine wrinkles, on human skin. The cosmetic compositions of the invention are formulated with less than the effective amounts of the active anti-wrinkle agents (eg, medicaments) or are devoid of such active agents, which include the alpha-hydroxyl acid and the derivatives and salts thereof, tretinoin and derivatives and salts thereof, or vitamin C, and which are typically used to treat and reduce skin lines and / or wrinkles. As tested in clinical trials, the compositions of the invention reduced and improved fine lines and / or wrinkles as well as, or were even better than, preparations containing alpha-hydroxyl acids, alpha-hydroxyl salts, tretinoin, or vitamin C, therefore, they achieve effective anti-wrinkle formulas that are safe, economical and stable, without the potential adverse effects for the user that may accompany the use of the aforementioned, typically used in antiarru preparations and products.

Description

METHODS AND COMPOSITIONS AGAINST FINE LINES AND / OR WRINKLES Field of Invention The present invention relates generally to the method for reducing fine lines and / or wrinkles on the skin and to topical compositions employed in such methods. The erasure of fine facial lines and / or wrinkles, as well as other beneficial effects, are achieved by the use of the present invention.

Background of the Invention A variety of topical treatments are known in the art to mitigate the dermatological conditions of the skin that are often related to the natural aging process. Other factors, such as exposure to the sun or the resulting ultraviolet radiation, care and / or inadequate diets, stresses, nutritional deficiencies, and genetic propensities also contribute to the development of adverse conditions to the skin, REF: 27740 such as fine lines, wrinkles, especially of the skin of the face, age spots, keratoses, dry skin, lack of flexibility and tightness of the skin, and depigmentation.

Many of the compositions described for topical skin treatment include components that have adverse side effects to the user, such as dryness, burning, stinging, scaling and itching, skin irritation, and induction of photosensitivity. Of course, the methods and compositions generally used to reduce fine lines and / or wrinkles contain acids, particularly, alpha (a) -hydroxyl acids, such as glycolic acid, lactic acid, tartaric acid, and citric acid, and salts of them, or they contain tretinoin, also known as trans-total retinoic acid or retinol (Vitamin A), or ascorbic acid (Vitamin C), all of which can induce the disadvantageous effects mentioned above, often due to a decrease in pH of the skin, among other factors. Particularly with respect to topical compositions containing tretinoin, medical reports have documented a number of other skin adverse reactions typically associated with its use, namely, burn, tightness, stinging, dryness, scaly, erythema, itching, dermatitis of the skin, localized swelling and sensitivity to the sun.

Particular examples of compositions and methods containing retinol or retinoic acid for treating skin conditions and / or reducing wrinkles are found in U.S. Patent Nos. 4,826,828 to J.M. Wilmont et al .; U.S. Patents Nos. 4,603,146, 4,877,805 and 4,888,342 to A.M. Kligman Particular examples of compositions and methods employed, among other ingredients, various percentages of one or more α-hydroxyl acids to treat skin conditions and / or reduce wrinkles are found in U.S. Patent No. 5,547,988 to R.J. Yu et al .; U.S. Patent No. 5,422,370 to R.J. Yu et al .; U.S. Patent No. 5,389,677 to R.J. Yu et al .; U.S. Patent No. 5,407,958 to J. Heath et al .; U.S. Patent Nos. 5,091,171, 5,093,360, 5,561,158, 5,561,157, 5,554,597 and 5,554,652 to E.J. Van Van Scott and col .; U.S. Patent No. 5,441,740 to S.N. Ozlen and U.S. Patent No. 5,407,958 to J.L. Heath et al.

Methods and compositions containing infiltration enhancers to improve and / or control the penetration of pharmacologically active agents applied topically are additionally known in the art. Specifically, U.S. Patent No. 5,326,566 to P.V. Parab describes the use of dibutyl adipate (DBA) and isopropyl myristate (IPM) to increase skin infiltration of an active substance or drug, for example, α-hydroxyl acid, or a cosmetically acceptable form of α-hydroxyl acid salt , and retinoids, after topical application. However, prior to the present invention, those skilled in the art have had no reason or incentive to employ an infiltration enhancer, much less DBA / IPM, in methods and formulas containing less than the effective amounts of the above-mentioned active agents. previously, or that are devoid of such agents, in the treatments of fine lines and / or wrinkles associated with intrinsic or extrinsic evej ecimiento.

U.S. Patent No. 5,326,566 also discloses vehicle compositions that are similar, but not identical, to the compositions of the present invention. Those skilled in the art will learn from this patent that the disclosed compositions are useful only to improve the penetration into the skin of a pharmacologically active agent contained therein. The teachings of this patent do not allow those skilled in the art to learn or appreciate that a vehicle composition that contains less than the effective amount of an active agent, or that does not contain the active agent, would have some important or beneficial effect for the user. , particularly, to reduce fine lines and / or wrinkles in the skin.

In contrast to the present invention, pharmacologically active agents that address the problem disclosed by the present invention frequently include the use of skin proteins such as collagen and / or elastin, either singly or in combination (see, for example, US patents). Nos. 3,991,184; 4,179,333; 5,941,722; and German Patent No. 2,804,024). The other compositions include steroids, such as pregnenolone, in combination with elastin (U.S. Patent No. 4,474,763).

The present invention was discovered to produce surprising benefits and results in the reduction of fine lines and / or wrinkles, including fine wrinkles, by providing methods and compositions in the absence of, or containing non effective amounts of such purposes, active components. of anti-wrinkle compositions and methods, such as a-hydroxyl acids, retinoic acid and / or the derivatives and salts thereof.

Brief Description of the Invention It is an object of the present invention to provide methods and compositions for effecting at least a temporary physiological improvement in the condition of the skin, with the desired goal of lasting and permanent improvement and improvement of the condition and quality of the skin. It is a related object of the invention to improve, diminish or alleviate fine lines and / or wrinkles, including fine wrinkles, on the face, especially around the eyes, around the upper and lower lips, and in the minor area of the cheeks , such fine lines and / or wrinkles being physical signals associated with intrinsic or extrinsic dermatological aging.

It is still another object of the invention to provide formulas, i.e., compositions, for improving, reducing or alleviating fine lines and / or wrinkles, including fine wrinkles, associated with intrinsic or extrinsic aging, wherein the formulas do not require active components, such as retinoids, for example, retinoic acid or Vitamin A, α-hydroxyl acids and / or Vitamin C, which can cause pernicious side effects after continued and prolonged use.

The formulas of the present invention comprise, among other components, one or more infiltration enhancers, particularly, the combination of DBA / IPM, and, if desired, ingredients that improve the moisturizing properties of the composition after application, so which improve the beneficial effects and the sensitive comfort of the composition.

It is another object of the present invention to provide improved, safe and economical therapeutic and / or cosmetic compositions for the treatment of various skin conditions, more particularly for the treatment of fine lines and / or wrinkles, including fine wrinkles, of the facial area, without the concomitant dryness of the skin, scaling, irritation, burning, itching and irritation and / or other disadvantages that are associated with other methods and compositions of skin condition treatment and anti-wrinkle and related to aging.

It is yet another object of the present invention to provide stable, safe, economical and effective anti-wrinkle compositions as a cosmetic to reduce facial lines, wrinkles, crow's feet and otherwise improve the quality of the skin, and methods employing such compositions.

The advantages and additional objects introduced by the present invention will be apparent upon reading the detailed description below.

Description of the Drawings The drawings of the appended figures are set forth to further describe the present invention and to aid its understanding by clarifying its various aspects.

Figure 1 shows the results of a 24-week clinical study (described in example 1) performed to evaluate the improvement in fine facial wrinkles after topical application of a cream composition prepared in accordance with the present invention (full circles ), as exemplified in Table 1, compared to cream compositions containing 30% ammonium lactate (filled squares), 21% ammonium lactate (triangles pointing up), or 12% ammonium lactate (the triangles upside down).

Figure 2 shows the results of a 25 week clinical study (described in example 2) carried out to evaluate the improvement in fine facial wrinkles after the topical application of a cream composition prepared according to the present invention (triangles upwards) ), as exemplified in Table 3, compared to cream compositions containing 30% ammonium lactate (full circles) or 12% ammonium lactate (filled squares).

The present invention provides methods and compositions for reducing and / or eliminating fine lines and / or wrinkles, including fine wrinkles, on the skin by means of topical application on the desired site. The invention further provides such methods and pharmaceutically acceptable compositions for topical application to human tissues for the purpose of improving the condition of the skin and reducing or alleviating fine lines and / or wrinkles that may be caused intrinsically or extrinsically.

As mentioned above, the technique has typically described the use of retinoic acid and the like, as well as α-hydroxyl acids, α-hydroxyl acid salts and Vitamin C in skin treatment compositions, fine line and / or wrinkle. In addition, the DBA and IPM permeation enhancers have been shown to increase skin infiltration of both α-hydroxyl acids and salts thereof in compositions containing these ingredients as components (U.S. Patent No. 5,326,566). However, the present inventor has surprisingly found that a formula containing DBA / IPM, in the absence of an α-hydroxyl acid, or a physiologically acceptable acid salt of α-hydroxyl, is useful for treating fine lines and / or wrinkles, including fine wrinkles, and crow's feet, when applied topically to areas of the body, such as the face, neck and hands.

An important and unexpected finding related to the present invention is that when an α-hydroxyl acid or α-hydroxyl acid salt is incorporated in the compositions of the present invention, the resulting composition containing these components does not provide any additional statistically significant reduction or improvement in fine wrinkles over that which is produced by compositions of the present invention that do not contain the α-hydroxyl acid or the α-hydroxyl acid salt. Of course, the same composition without containing α-hydroxyl acid or α-hydroxyl acid salt demonstrates a marked improvement effect on clinically proven fine wrinkles, as further described herein. Accordingly, the present inventor unexpectedly discovered that a formula comprising a physiologically acceptable composition alone (ie, without an antiwrinkle active agent typically used) that acts to improve fine lines and / or wrinkles, including fine wrinkles, without the addition of a a-hydroxyl acid, or a-hydroxyl acid salts, or retinoic acid and related compounds, following topical application on the skin of living human.

The present invention thus provides compositions comprising a pharmaceutically acceptable cosmetic formula which is suitable for contact with living animal tissue., including human tissue, without adverse physiological effects to the user. Of course, the compositions of the present invention achieve a surprising improvement and decrease of fine lines and / or wrinkles of the skin in the absence of any pharmacologically active agent (eg, a medicament) that has been conventionally described and used in the treatment of fine lines and / or wrinkles, and the like, on the skin.

The formulas (also called cosmetic compositions) of the present invention include the following essential components: high water level, for example, at least 40%, preferably at least 60%, more preferably 70 to 80% in weight, based on the total weight of the composition; one or more infiltration enhancers or a combination or mixture thereof; one or more fatty alcohols or mixtures thereof, and an emollient and / or a humectant, preferably a moisturizing humectant, or combinations or mixtures thereof. The formulas may also contain an occlusive agent. A preferred but non-limiting example of an occlusion agent for use in the formulas of the present invention is mineral oil. As indicated above, the mineral oil may also serve as an emollient in the compositions of the present invention.

As used herein, an emollient refers to the material that deposits an oily film on the surface of the skin, thereby placing a showy physical barrier on the skin to protect the skin from moisture loss. Mineral oil is a non-limiting example of an emollient "suitable for use in the compositions of the present invention." A humectant, or moisturizing moisturizer, refers to the material that behaves hygroscopically and absorbs moisture from the atmosphere to attract moisture to the body. After application to the skin, the moisturizer is absorbed into the skin, leaving only a minimal oily film on the surface of the skin and provides a soft sensation Non-limiting examples of appropriate humectants are propylene glycol, glycerin and amino acids for use in the compositions of the present invention.

The compositions of the present invention can be formulated in oil, water, or combinations thereof. A dermatologically acceptable formula comprising an oil-in-water emulsion is preferable. Examples of other dermatologically acceptable vehicle formulas of the present invention include, but are not limited to, any appropriate nontoxic or pharmaceutically acceptable local vehicle, such as a solution, suspension, emulsion, lotion, ointment, cream, gel, plaster, patch, film, prescription preparation or tape, all of which is well known to the skilled artisan of local preparations and skin formulas. The lotion and cream formulas are preferred.

Examples of infiltration enhancers suitable for use in the compositions of the present invention include dibutyl adipate, isopropyl myristate and mixtures and / or combinations thereof.

Preferred examples of infiltration enhancers suitable for use in the compositions of the present invention are dibutyl adipate (DBA) and isopropyl myristate (IPM), or combinations thereof, designated as DBA / IPM. Infiltration enhancers may be present in the compositions of the invention in an amount of from about 0.05% to about 35% by weight preferably, from 0.2% to about 25% by weight, and more preferably from about 2% to about 6%. % in weigh. It should be understood that, unless otherwise specified, when "indicated by weight, it is based on the total weight of the composition.

Examples of suitable fatty alcohols for use in the compositions of the present invention include, but are not limited to, those possessing from about 4 to about 30 carbon atoms. More specifically, non-limiting examples of fatty alcohols include stearyl alcohol, cetyl alcohol, acetostearyl alcohol, myristyl alcohol and mixtures or combinations thereof. Fatty alcohols such as stearyl alcohol and cetyl alcohol are preferred. Fatty alcohols can be used in the compositions of the present invention in amounts of from about 0.5% to about 15%, preferably from 1% to about 10%, and more preferably from 2% to about 5% by weight.

Examples of suitable emollients for use in the compositions of the present invention include, but are not limited to, dibutyl adipate, diisobutyl adipate, diisopropyl adipate, dimethicone, triglyceride esters of fatty acids such as caprylic / capric triglycerides, hydroxylated lanolin, isopropyl myristate, mineral oil, soy sterol, acetyl stearate and petrolatum and mixtures or combinations thereof The emollients in the compositions of the present invention are present in the range from about 1% to about 50%, preferably from 2% to about 30%, and more preferably from 3% to about 20% by weight The preferred emollients are mineral oil, dimethicone, stearyl alcohol, cetyl alcohol, dibutyl adipate, isopropyl myristate and petrolatum.

The emulsifiers can be formulated in the compositions of the present invention. Examples of suitable emulsifiers include, but are not limited to, "streareth-2", "streareth-21", "Tweens" "," Spans "", glyceryl monostearate SE (a mixture of glyceryl stearate and PEG-100 stearate) and "laureth-4", and mixtures or combinations thereof. Emulsifiers may be present in the compositions in amounts from about 1% to about 12%, preferably from about 2% to about 10%, and more preferably, from about 3% to about 8% by weight. Preferred emulsifiers for use in the present compositions include "streareth-2", "streareth-21", "glyceryl monostearate SE" and "laureth-4". It is also appreciated that the addition of ingredients such as "laureth-4" and the like may have some improvement in the infiltration effect when the composition is applied to the skin.

Moisturizing moisturizers can also be formulated in the compositions of the present invention. Non-limiting examples of such humectant moisturizers include glycerin, propylene glycol, sorbitol, lactose, mannitol, pyrrolidone sodium carboxylic acid (sodium PCA) and combinations or mixtures thereof.

Moisturizing moisturizers are present in the compositions of the present invention in amounts of from about 0.5% to about 15%, preferably from about 2% to about 12% and more preferably, from about 3% to about 5% by weight. Glycerin and propylene glycol are preferred as humectant moisturizers in the compositions of the present invention.

The other additives as components can be formulated in the compositions of the present invention, such as ultraviolet or sunscreen buffers, antioxidants, preservatives and the like, for improved stability during use and storage. Non-limiting examples of ultraviolet buffers can be employed in the formulas of the present invention include paraminobenzoic acid octyl dimethyl (ie, PABA) and benzophenone-3. Non-limiting examples of suitable antioxidants and preservatives include, but are not limited to, butylated hydroxytoluene, butylated hydroxyanisole (BHA), sorbic acid, benzoic acid, benzyl alcohol, imidazolidinyl urea, diazolidinyl urea, methylparaben, propylparaben, "Kathon CG ®" , potassium sorbate and mixtures or combinations thereof. The preservatives are present in the compositions of the invention in amounts from about 0.005% to about 2%, preferably from about 0.05% to about 1%, and more preferably from about 0.1% to about 0.3% by weight . A preferred preservative in the present compositions is sorbic acid. It should be understood that the compositions of the present invention may include another conventional formula of local cosmetic components such as suspending agents, thickeners, film formers, preservatives and flavor oils. The thickeners are those that are compatible with the total composition, such as bentones, xanthan gum, fumed silica and ethyl cellulose. Dyes, fragrances and other cosmetic additives may also be present, if desired. In view of the foregoing, the cosmetic components specifically enumerated and exemplified can be freely substituted with other conventional and well-known components to achieve a desired lubricity and texture for the compositions, as long as the substitutes do not react adversely with any component of the composition and do not interfere with the homogeneity of the composition.

The composition of the present invention is generally acidic, having a pH in the range from about 2.0 to about 6.8, preferably from about 2.5 to about 6, more preferably from about 2.8 to about 5.0. The pH is preferably adjusted with sorbic acid. The compositions of the invention can also be formulated in concentrated form and then diluted to produce desired levels of components therein.

The present invention also provides important advantages in the art; specifically, the use of the methods and compositions described herein avoids the need to use retinoic acid and the side effects that are known and that accompany its use. In addition, the invention avoids the use of α-hydroxyl acids and a-hydroxyl acid salts, which have associated adverse effects, such as possible skin irritation (e.g., dryness, scaling, itching, burning / stinging, erythema and peeling). ) and possible sensitization to sun exposure.

As will be appreciated by experts, in the art, dibutyl adipate (DBA) and isopropyl myristate (IPM), in combination, has been taught by the present inventor as an infiltration enhancer (U.S. Patent No. 5,326,566). While not wishing to be limited by any particular theory, a possible mechanism for the action of DBA / IPM in the compositions and methods of the present invention is the combination that causes the infiltration of the fatty alcohols, for example, stearyl alcohol and / or cetil alcohol, in the skin, aided by it to retain moisture inside it. Without wishing to be limited by a particular theory, the beneficial effect can be increased by the high level of water contained in the formula and the occlusive effect of its emollient / occlusive agent component, for example, mineral oil, etc. This can cause hydration of the skin that serves to mask fine lines and / or wrinkles, to improve the tone of the skin and to help in the incorporation of lipid component in the skin after topical application.

The compositions formulated as described herein are topically applied to the skin, generally to the face, to result in an application of from about 1 to 4 mg / cm, preferably from about 2 mg / cm2, of skin area, depending on the viscosity of the products. The compositions are generally applied in areas of the body where fine lines and / or wrinkles are evident or can be observed. A moisturizer may be applied concomitantly at the time or after the application of the compositions of the present invention to improve the tactile comfort associated with the application of the composition and to improve the fine line and / or wrinkle erasure and other benefits achieved by the compositions of the present invention. However, as described, the compositions of the invention can be formulated to contain the component ingredients that provide the moisturizing properties to the composition as a whole by application to the skin. In this way, the need for added or separate moisturizer is avoided.

The present invention further comprises pharmaceutical compositions for topical administration, wherein the compositions are as described heretofore and include a pharmaceutically acceptable carrier, buffer, diluent or excipient as known to those skilled in the art. The acceptable vehicle and the like are those that are compatible with other ingredients in the formula and that are not harmful to the user.

In general, it is intended that the compositions of the present invention be applied in an amount and for a sufficient time to effect a reduction of the appearance of a skin with fine lines and / or wrinkles, including fine wrinkles. It is also intended that the compositions of the present invention be applied to the skin daily. In addition, the application of the compositions to the skin may occur one or more times per day, preferably twice per day, for example, once in the morning and once at night. Preferably, the user will not clean the application site for six hours after the application of the composition on the skin.

An application plan of the compositions of the present invention is for a period of at least four weeks, preferably, of at least four weeks to about twelve weeks, more preferably, of at least twelve weeks. After an application plan (for example, at least four to about twelve weeks), fine lines and / or wrinkles, including fine wrinkles, will be reduced and an improvement in fine lines and / or wrinkles will be evidenced by a minimum to no irritating effect. In addition, the application of the product of the present invention causes neither discomfort nor collateral effects and the tone of the skin and texture will improve.

Examples Examples as described herein are indicated to exemplify the various aspects of the embodiment of the present invention and are not intended to limit the invention in any way. Unless otherwise specified, it is understood that the concentrations of the component ingredients in the compositions of the present invention are in% by weight (w / w), based on the total weight of the composition.

A number of clinical studies were conducted to evaluate changes in human skin condition as a result of topical application of the compositions of the present invention according to the examples herein.

Clinical Studies I and II as illustrated in Examples 1 and 2, respectively, involve at least eighty subjects exhibiting facial photoenvection and fine wrinkles. Each treatment group had a parallel group design. The men and women chosen were asked to be in an age group of 35 years or more (the average age 59 years) with the total severity of signs associated with 1) photo-veining of the face greater than or equal to Grade 5 on a graduated scale from 0 to 8; and 2) fine wrinkles of the face greater than or equal to Grade 5 on a graduated scale from 0 to 8. Subjects applied the product to the face twice a day for 24 weeks. Each subject was evaluated by a certified dermatologist with diploma at weeks 0, 1, 4, 8, 12, 16, 20 and 24 or 25 to observe the fine wrinkle improvement on a graduated scale from 0 to 8 as follows: Grade d_ = scale ß-a-r-a &? improvement of fine grits Grade Description of grade 0 None (No evidence of fine wrinkles) 1 * 2 Mild (slight evidence of fine wrinkles) 3 * 4 Moderate (moderate evidence of fine wrinkles) 5 * 6 Severe (severe evidence of fine wrinkles) 7 * 8 Very severe (very severe evidence of fine wrinkles) *: The intermediate intervals (ie, 1, 3, 5 and 7) are midpoints between the defined degrees.

Example 1.

Clinical Study I described in this example was designed to test the ability of the compositions of the present invention to reduce and improve the condition of fine wrinkles on facial areas of human test subjects and to compare the effectiveness of various different cream compositions. The first composition of the present invention, formulated as a cream according to the invention, comprises the ingredients presented in Table 1. Three other test compositions comprise the ingredients presented in Table 1, and also included the ammonium lactate salt of the acid alpha-hydroxyl, lactic acid, in amounts of 30%, 21% and 12% respectively. In essence, the composition of the present invention constitutes a physiologically acceptable cosmetic formula in which the active agent is added, for example, the α-hydroxyl acid salt.

TABLE 1 Ingredient% w / w Propylene Glycol 5.0 Stearyl Alcohol 4.0 Dibutyl Adipate 3.0 Isopropyl Myristrate 3.0 Stearteh-2 2.5 Steareth-21 2.5 Aluminum Magnesium Silicate 2.0 Dimethicone 1.0 Laureth-4 1.0 Cetyl alcohol 0.5 Glyceryl monostearate SE 0.5 Sorbic acid 0.2 Water 74, 8 The results of these comparative studies are illustrated in Figure 1. As can be seen from the results illustrated in Figure 1, during the course of 24 weeks, the cosmetic composition of the present invention, ie, a composition in the absence of lactate of ammonium as active component (full circles), surprisingly it worked also improving and / or reducing fine facial wrinkles as the composition that has 21% of active ammonium lactate contained within it.

The change in the degree of fine wrinkles was determined during the course of the 24-week trial period. It is represented numerically as a delta (?) Value (see Table 2). The delta value represents the initial value determined at time 0 minus the value determined at the time point of the final measurement, such as at week 24. As the present inventor unexpectedly discovered, the composition of the present invention, containing the components presented in Table 1, it produces a delta value (0.56) that was almost identical to that of a composition comprising the active ammonium lactate at a concentration of 21% in the composition (delta value of 0.54).

TABLE 2 In general, the delta value for an active composition should be at least 1.0. From the data presented in Table 2, it can be seen that the composition of the present invention gave a delta value of 0.56 against a delta value of 0.54 for the preparation with 21% ammonium lactate. Thus, there was statistically no significant difference in the delta value between the composition of the present invention and that of the preparation containing the acid salt of α-hydroxyl, ammonium lactate, at week 24. In addition, a preparation containing % of ammonium lactate merely increased the effect demonstrated by the composition of the present invention by a delta value of 0.2, as determined by a comparison of delta values (ie, 0.76 vs. 0.56 in the Table). 2) . In view of the potential adverse effects of α-hydroxyl acids, and salts thereof, for the user, the results of these clinical studies raises the question of why an individual would use a preparation containing α-hydroxyl acids or acid salts -hydroxyl if he or she could obtain virtually the same clinical effects with a composition that does not contain a component such as a-hydroxyl acids or a-hydroxyl acid salts. In sum, it can be determined from the present studies in this description that the presence of adverse active agents in anti-wrinkle compositions does not guarantee their use for the treatment of fine lines and / or wrinkles, including fine wrinkles and the like. The compositions provided by the present invention alleviate the pernicious effects to the user due to the mild nature of the product components formulated in the absence of irritants such as hydroxyl acids and salts thereof.

Example 2 This example describes a second clinical study II conducted on members of the human test group to determine the effect of the compositions of the present invention on the reduction of fine wrinkles of the face, using a cream of modified formula of the present invention comprising components aggregates to increase the hydrating capacity of the composition after application on the skin.

Accordingly, the modified composition of the present invention was formulated as a cream and comprised mineral oil and glycerin to improve hydration. An illustrative composition containing such moisturizing components is present in Table 3. The differences between the composition illustrated in Table 3 and that illustrated in Table 1 and used in the studies described in Example 1 are that the silicate Aluminum magnesium (2%) was extracted from the previous composition and glycerin (3%) and mineral oil (7%) were added. Additionally, dibutyl adipate and isopropyl myristate were reduced from 3% to 1%, and propylene glycol was reduced from 5% to 1%, in the composition present in Table 3. The other two cream compositions were formulated to include the component active ammonium lactate at 30% and 12%, respectively, in a base composition as presented in Table 3. These compositions containing ammonium lactate were employed in the comparative studies, such as those described in Example 1 , to determine the effect of the compositions of the present invention with respect to the effects of the test compositions containing active components for the improvement and / or reduction in fine facial wrinkles.

TABLE 3 The results of the studies described in Example 2 are shown in Figure 2 and the delta value is shown in Table 4. As graphically illustrated in Figure 2, over the 25-week time course of the study, the The composition of the present invention containing the mineral oil and glycerin (triangles) were as effective in improving / reducing fine wrinkles as were the compositions containing 30% ammonium lactate (full circles) and 12% ammonium lactate (filled squares) , respectively. The present composition, without containing the active component of the α-hydroxyl acid salt, improves / reduces fine facial wrinkles to a level that was not virtually different from the compositions containing the active agent, ammonium lactate, representing a novel and unexpected finding found by the present inventor. Thus, the present invention provides a safe, economical and effective medium and composition for treating wrinkles and finally for reducing fine lines and / or wrinkles, including fine wrinkles, without requiring the use of an active ingredient that is known to have associated deleterious effects to the user.

TABLE 4 As can be seen from the delta values presented in Table 4, there is little difference in these values between the composition of the present invention and the compositions comprising 30% and 12% active components (ammonium lactate) as determined by the fine wrinkle improvement / reduction after topical application over the course of 25 weeks of the clinical study. In addition, there was no significant difference between the treatment groups at the end of 25 weeks.

Example 3 Table 5 presents a compilation of the results of studies evaluating the efficacy on improving fine wrinkles of formulas comprising 30% and 12% of the active agent, ammonium lactate, compared to the composition of the present invention that does not comprise lactate. of active ammonium or the acid salt component of α-hydroxyl. Table 5 also presents the results of a Study III describing the efficacy of a cream containing 0.05% tretinoin (Renova cream) on the improvement of fine wrinkles compared to the vehicle Renova that does not contain tretinoma as an active component. Renova ® cream is a commercially available prescription product sold by Ortho Corporation Pharmaceutical (United States).

The Study III data are reported and described in "Physician's Desk Reference" (PDR), 51 ° Editing, medical consultant: R. Arky, doctor of medicine, Medical Economics Company, SA., Montvale, New Jersey, p. 1945-1946, 1997).

The emollient Renova cream contains 0.05% tretinoin in a water-in-oil emulsion formula consisting of light mineral oil, sorbitol solution, hydroxystearate, methoxy PEG-22 / dodecyl glycol copolymer, PEG-45 / dodecyl glycol copolymer , stearoxytrimethylsilane and stearyl alcohol, dimethicone, fragrance, methylparaben, sodium edetate, "quatemium 15", butylated hydroxytoluene, water and citric acid.

According to the PDR publication, the design of the Renova study II consists of two well-controlled and appropriate trials involving 161 evaluable patients treated with the vehicle emollient cream on the face for 24 weeks as an adjunct to a comprehensive program for the prevention of sun and skin care to evaluate the effectiveness of fine wrinkles and other signs of photo-aging. Patients were evaluated on a 10-point scale basis and changes from the basic classification were categorized as follows: minimal improvement: 1 unit reduction; moderate improvement: reduction of 2 units or more. The results of Study III of Renova®, and its comparison with Studies I and II of the present invention, are set forth in Table 5.

TABLE 5 Evaluation of improvements on fine wrinkles As indicated by the results presented ® in Table 5, the Renova vehicle, formulated in the absence of active tretinoin, produces approximately 38% improvement over fine wrinkles, ® while the Renova product containing active tretinoin improves fine wrinkles approximately 64% .

In Studies I and II, which include compositions comprising the active component of lactic acid ammonium or lactic acid salt as compared to the compositions of the present invention without containing acid-hydroxyl salt, the effectiveness of the compositions of the present invention.

Study I represents a composition that does not contain ammonium lactic acid or lactic acid salt, no mineral oil and no glycerin, but contains dibutyl adipate and isopropyl myristate, compared to the compositions described containing ammonium lactate as an active component. Study II represents a composition of the present invention that does not contain any ammonium lactate, but contains mineral oil and glycerin to add the moisturizing properties and dibutyl adipate and isopropyl myristate, compared to the described compositions containing ammonium lactate.

In Study II, the composition of the present invention, which does not contain ammonium lactate, exceeds the compositions containing either 30% or 12% (w / w) of ammonium lactate in improving fine wrinkles, ie 61% against 52 % and 58%, respectively. In Study I, the composition of the present invention demonstrated 48% improvement in fine wrinkles, while compositions containing ammonium lactate in 30% and 12%, respectively, demonstrate 62% and 58% improvement in fine wrinkles According to the present invention, these results demonstrate an important effect on the improvement in fine wrinkles by the compositions of the present invention which do not possess formally known active anti-wrinkle compound or medicament, such as α-hydroxyl acids, α-hydroxyl acid salts, retinoic acids or vitamin C. In the particular case of the composition of the present invention containing mineral oil and glycerin, in addition to dibutyl adipate and isopropyl myristate, the performance of the composition of the present invention, without active compounds, was so good for improving fine wrinkles as the "conventional" compositions containing ammonium lactate in amounts of 30% and 10%. The composition of the present invention was also as good for improving fine wrinkles as the Renova product containing the active compound tretinoin. These findings demonstrate the surprising and unexpected clinically proven effects produced by the compositions of the present invention. The effects were the reduction / improvement in fine wrinkles at an equal level and still surpassing conventional anti-wrinkle formula levels containing known active compounds. In addition, the compositions of the present invention are benign to the health of the user and are free of adverse side effects, such as erythema, pruritus, burning, itching and scaling, which are frequently caused by products containing tretinoin (and containing acid). a-hydroxyl) after topical application. Additionally, the compositions of the present invention do not cause photosensitivity to the sun or ultraviolet radiation. The compositions of the present invention "are also safe and effective for administration to pregnant women and nursing mothers because there is no knowledge of teratogenic effects associated with their use.

The contents of all patents, patent applications, published articles, books, abstracts and reference manuals cited herein are incorporated herein by reference in their entirety to more fully describe the state of the art to which the invention belongs.

As various changes can be made to the object described above without departing from the scope and spirit of the invention, it is intended that all matter contained in the description above, illustrated with the accompanying drawings, or defined in the appended claims, be interpreted as descriptive and illustrative, and not in a limiting sense. Many modifications and variations of the present invention are possible in view of the foregoing teachings. It is therefore understood that within the scope of the appended claims, the invention may be practiced in a manner other than that specifically described.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Having described the invention as above, the content of the following is claimed as property.

Claims (28)

Claims

1. A topical composition for skin to reduce the visual appearance of a fine line and / or wrinkle, characterized in that the composition contains less than an effective amount of an active agent, or does not contain active agent; and the composition consists essentially of at least about 40% by weight, based on the total weight of the composition, of water; about 0.05% to about 35% by weight, based on total weight of the composition, of one or more infiltration enhancing compounds selected from the group consisting of dibutyl adipate, isopropyl myristate, and combinations thereof: from about 0 , 5% to about 15%, by weight, based on the total weight of the composition, of one or more fatty alcohols; and one or more emollients and / or moisturizing moisturizers; the emollient being in an amount of from about 1 to about 50% by weight, based on the total weight of the composition; the humectant being in an amount of from about 0.5% to about 15% by weight, based on the total weight of the composition; the composition acting to reduce the visual appearance of fine lines and / or wrinkles.

2. The composition according to claim 1, characterized in that the composition is devoid of the active agent.

3. The composition according to claim 1, characterized in that at least about 60% water is present in the composition.

4. The composition according to claim 1, characterized in that the fatty alcohol contains from four to thirty carbon atoms, and mixtures or combinations thereof.

5. The composition according to claim 4, characterized in that the fatty alcohol is "selected from the group consisting of stearyl alcohol, acetyl alcohol, myristyl alcohol and mixtures or combinations thereof.

6. The composition according to claim 1, characterized in that the emollient is selected from the group consisting of dibutyl adipate, diisobutyl adipate, diisopropyl adipate, dimethicone, caprylic triglyceride, capric triglyceride, hydroxylated lanolin, isopropyl myristate, mineral oil, sterol, glyceryl stearate, acetyl stearate and petrolatum, and mixtures thereof.

7. The composition according to claim 6, characterized in that the emollient is selected from the group consisting of mineral oil, dimethicone, stearyl alcohol, cetyl alcohol, dibutyl adipate, isopropyl myristate, glyceryl monostearate, petrolatum and mixtures thereof.

8. The composition according to claim 1, characterized in that the fatty alcohol is present in the composition in an amount from about 1% to 10% by weight, based on the weight of the composition.

9. The composition according to claim 1, characterized in that the emollient is present in the composition in an amount from about 2% to about 30% by weight, based on the weight of the composition.

10. The composition according to claim 1, characterized in that the humectant is present in the composition in an amount from about 2% to about 12% by weight, based on the weight of the composition.

11. The composition according to claim 1, characterized in that the humectant moisturizer is selected from the group consisting of glycerin, propylene glycol, sorbitol, lactose, mannitol, sodium pyrrolidone carboxylic acid, and mixtures thereof.

12. The composition according to claim 11, characterized in that the humectant moisturizer is glycerin or propylene glycol.

13. The composition according to claim 1, characterized in that the infiltration improving compound is present in said composition in an amount from about 0.2% to about 25% by weight, based on the total weight of the composition.

14. The composition according to claim 1, characterized in that the composition is formulated as an oil-in-water emulsion.

15. The composition according to claim 1, characterized in that the composition has a pH from about 2.0 to about 6.8.

16. A method for reducing the visible appearance of a line on the skin and / or wrinkle, characterized in that it comprises: applying topically to an area of the skin containing the line or wrinkle a topical composition for skin that does not contain an effective amount of a known drug that has anti-wrinkle effect when applied topically on the fine line or wrinkle, being the medically selected from the group consisting of ammonium lactate and tretinoin; the composition comprises at least about 40% by weight, based on the weight of the composition, of water; about 0.05% to about 35% by weight, based on the weight of the composition, from one or more infiltration enhancing compounds selected from the group consisting of dibutyl adipate, isopropyl myristate, and combinations thereof; from 0.5% to about 15% by weight, based on the weight of the composition, from one or more fatty alcohols; and one or more emollients and / or moisturizing moisturizers; the emollient being in an amount of from about 1 to about 50% by weight, based on the weight of the composition; the humectant being in an amount from about 0.5% to about 15% by weight, based on the weight of the composition; said composition being applied in an amount and for a time sufficient to effect a reduction of the appearance of said skin or wrinkle line.

17. The method according to the claim 16, characterized in that the composition is applied to the skin for a period of at least four weeks.

18. The method according to claim 16, characterized in that the composition is applied to the skin for a period of at least four weeks to approximately twelve weeks.

19. The method according to claim 16, characterized in that the composition is applied to the skin for a period of at least twelve weeks.

20. The method according to claim 16, characterized in that the composition is applied to the skin twice a day.

21. The method according to claim 16, characterized in that the composition is applied to the skin in an amount from about 1 mg / cm to 4 mg / cm.

22. The method according to claim 16, characterized in that the topical composition for skin does not contain ammonium lactate or tretinoin.

23. The composition according to claim 1, characterized in that the compound that improves the permeation is a mixture of dibutyl adipate and isopropyl myristate.

24. The composition according to claim 23, characterized in that the dibutyl adipate and isopropyl myristate are present in said mixture in a 1: 1 ratio.

25. The composition according to claim 23, characterized in that the composition contains from 1 to 3% of dibutyl adipate and from 1 to 3% of isopropyl myristate.

26. The method according to claim 16, characterized in that the compounds that improve the permeation are a mixture of dibutyl adipate and isopropyl myristate.

27. The method according to claim 16, characterized in that the dibutyl adipate and isopropyl myristate are present in the mixture in a 1: 1 ratio.

28. The method according to claim 16, characterized in that the composition contains from 1 to 3% of dibutyl adipate and from 1 to 3 of isopropyl myristate.