Skin treatment methods and compositions for transdermal delivery of active agents

Abstract

A stable, non-irritating skin treatment active agent containing formulation and delivery system for topical application to the skin is provided.SOLUTION: Topical formulations comprising a skin treatment active agent and an activating solvent system comprising isopentyl diol, dimethyl isosorbide, and a nonionic surfactant are provided.SELECTED DRAWING: None

Description

[Technical Field]

[0001] This application was filed on January 10, 2020, and is incorporated herein by reference in its entirety. This application claims priority to U.S. Provisional Patent Application No. 62 / 959,874.

[0002] The present invention provides a method for the transdermal delivery of at least one retinoid and / or other active agent. Dermatological compositions and methods for treating skin with delivery systems therefor - Patent application Certain disclosed embodiments relate to retinol and activating and skin Dermatological compositions and methods having delivery systems thereof for topical application to skin, and methods for their preparation, manufacture, and use. provides a catalyst system. [Background technology]

[0003] The active agent is a compound that is useful for treating various and diverse dermatological conditions, such as psoriasis, photoaging, and age spots. Spots, extrinsic and intrinsic aging appearance of the skin, skin wrinkles, acne, hyperpigmentation and Active agents are typically prescription and non-prescription active agents. The solvents used in dermatological formulations with skin treatment active agents are acetone, hydroxybenzoates ... The solvent may be a strong solvent such as toluene, or a mild, i.e., gentle solvent. The mediators can cause skin condition effects requiring further treatment, including disruption of the skin barrier. are known to interfere with patient compliance with skin treatment regimens. Solvents, on the other hand, are known to be ineffective in delivering active agents in transdermal and dermal applications. Furthermore, the current trend towards the expanded use of dermatological preparations in skin care Because of this trend, there continues to be a need for topical formulations of active agents for various skin treatments.

[0004] Retinoids are useful in treating inflammatory disorders, conditions characterized by increased cell turnover, e.g. , psoriasis, photoaging, age spots, skin wrinkles, enlarged pores, oily skin, prematurely aged skin Effective in treating a variety of dermatological conditions, including eczema, acne, and skin cancer It is useful.

[0005] However, retinoids, especially retinol, are unstable and may deteriorate in the presence of air. It is easily oxidized in the presence of ingredients commonly used in skin and cosmetic formulations. When applied as a thin layer to a relatively large surface area of ​​the skin, and when used in retinol-containing products There are also serious issues regarding validity period.

[0006] Retinol is also effectively released and driven into the skin from prior art delivery systems. Even at relatively high concentrations of retinol in the formulation, delivery efficiency is extremely difficult. Therefore, the first formulation may produce a higher concentration than the second formulation. Even if the formulation contains a high level of retinoid or retinol, the latter is more effective than the former. and providing enhanced release and transdermal penetration of the active agent, retinoid or retinol, when If so, it may be more effective at delivering retinoids or retinol.

[0007] Retinol is, moreover, irritating to the skin, and treatment with retinol-containing preparations to prevent continued application by those in need, thereby eliminating or limiting the effectiveness of the treatment. Retinoid and retinol preparations available are , including solvent-based systems, ointments, water-based formulations, emulsions, gels and lotions , all of which vary in their stability and their efficiency. Retinoid and retinol preparations are often used in skin care procedures due to their tendency to cause irritation. and is not being fully utilized.

[0008] Therefore, to the skin of those who need it, the illustrative conditions noted above or One or more other products of interest in the field of dermatological and cosmetic skin care procedures Providing retinoids and / or other active agents that can reduce and relieve the condition There is a need in the art for topical formulations and delivery systems that can.

[0009] The present disclosure provides methods and methods for retinol and other members of the retinoid family. and other skin care active agents known in the art of skin care formulations, such as Certain embodiments provide formulations and delivery systems for product safety. maintains its integrity, exhibits low irritation, and / or is free of retinol or retinoid and / or other active agents, such as another member of the family. Provides increased efficiency. Summary of the Invention

[0010] In certain embodiments, the present disclosure provides active agents and transdermal delivery and skin activation and Skin care treatment formulations, and more particularly retinol formulations, having a solvent system are provided. The skin care formulations have the advantages of product stability, low irritation, and delivery of formulated active agents. In particular, the present disclosure provides improved product stability, low irritation, and formulated A delivery system is provided that exhibits improved efficiency in the delivery of retinol.

[0011] Without wishing to be bound by theory, the inventors believe that the Certain skin care formulations containing hydroxybenzoates may be formulated with the solvent combination of certain embodiments of the present disclosure. Surprising and unexpected results as noted in clinical studies for skin treatment active agents The results of the clinical study were stronger than expected. low-dose, consumer, take-home, cosmetic retinol formulations, and new counterintuitive A novel solvent combination was used, including a new solvent. Retinol was not very sensitive to this new solvent. Since it is not soluble, the inventors have a special step-by-step preparation process to make it work. As a result, the inventors have discovered that certain retinol formulations are prescription drugs known as tretinoin. The clinical studies discussed in more detail below Using Ortho's brand of Retin-A, the inventors have demonstrated that the stinging sensation in the tested embodiment While scoring better than prescription active drugs in terms of sensitivity and consumer preference, had comparable or better efficacy.

[0012] The present disclosure provides, in certain embodiments, a composition comprising one or more skin treatment active agents, such as retinol and an activated solvent system, the solvent system comprising: isopentyldiol, dimethyl isosorbide, or one of the nonionic surfactants The formulation may contain one or more of an antioxidant, a xanthine, a moisturizer, and an emollient. Or, more than one. In one embodiment, the formulation further comprises an antioxidant.

[0013] Skin treatment active agents include retinoids, steroids, skin lightening agents, hydroquinones, Acne medications, salicylic acid, kojic acid, resorcinol, hexylresorcinol, Benzoyl peroxide, sulfur, anti-aging agents, peptides, growth factors, alpha hydroxy Acid, enzymes, DNA repair enzymes, vitamins, antipruritic agents, cooling agents, menthol, painkillers, essential oils , anti-inflammatory, antipruritic, hydrating agent, osmotic agent, natural moisturizing factor, urea, emollient, occlusive, Mino Acid, Exfoliant, Skin Conditioner, Cleanser, Sebum Reducer, Anti-infective, Hair Growth Agent, Acid Active agents prone to oxidation, polar and non-polar skin treatment agents, herbal active agents, bacteriostatic agents In one embodiment, the skin treatment active agent may be one or more of: a hydroxybenzoate, a natural therapeutic oil, or an essential oil. In one embodiment, the skin treatment active agent comprises retinol and / or its derivatives. Contains retinol.

[0014] Nonionic surfactants include ethoxylates, fatty ethoxylates, and propoxylates. , block copolymer, poloxamer, polyglyceryl ester, polyglyceryl emulsifier , sorbitol anhydride, bipolar agents, phenolic nonionic materials. That's fine.

[0015] The nonionic surfactant may be polysorbate 80 and the antioxidant may be green tea polysorbate 80. phenol, licorice extract, resveratrol, silymarin, curcuminoids, caffeine , astaxanthin, flavones, flavonoids, flavanols, tocopherols, asco Rubate, Coenzyme Q10, Ergothioneine, Glutathione, Ectoine, Bisabo It may be one or more of: roll, emblica.

[0016] In certain embodiments, the formulation further comprises polysorbate 20.

[0017] In certain embodiments, the present disclosure is directed to methods for the therapeutic treatment of dermatological conditions. and the method comprises administering to the subject a topical formulation having a skin treatment active agent as disclosed herein. In certain embodiments, the formulation comprises topically applying to the affected area a therapeutically effective amount of Activated containing isopentyldiol, dimethyl isosorbide and non-ionic surfactants Includes a solvent system.

[0018] The affected area may be one or more of human skin, scalp, hair, or nails. In one embodiment, the skin is human skin. In another embodiment of the present disclosure, the skin is a companion animal skin. The skins are those of animals, domestic animals, or commercially useful animals.

[0019] The disclosed activated solvent system may contain one or more solubilizers, rheology modifiers, emulsifiers, In one aspect of this embodiment, the solubilizing agent / dispersing aid may also be included. The emulsifier is a non-ionic solubilizer / emulsifier.

[0020] The disclosed formulations may also include at least one retinoid source. In one aspect of the embodiment, the retinoid is retinol, retinaldehyde, e.g., retinoic acid. Esters of retinol, including palmitate and stearate esters of retinol, retinoids, tretinoin or synthetic retinoids, e.g., adapalene, bexarotene, tazapine In one aspect of this embodiment, the retinoic acid may be retinoic acid, retinoic acid, or a combination of two or more thereof. In another embodiment, the retinoid is all-trans-retinol. It is.

[0021] The disclosed formulations may also include one or more antioxidants. In one aspect, the antioxidant is a polyphenol. The antioxidants include polyphenol isolates from the tea plant (Camellia sinensis). In some embodiments, the antioxidant is 90% or 95% polysaccharide from tea plant (Camellia sinensis). Contains phenolic isolates.

[0022] The disclosed formulations contain xanthine-related compounds, polymeric derivatives thereof, or compounds with antioxidant activity. Contains a mixture of xanthine-related materials that can function as antioxidants or stimulants for In one particular embodiment, the xanthine-related compound is caffeine.

[0023] In certain embodiments, the disclosed formulations can also include bakuchiol.

[0024] The disclosed formulations may also include one or more emollients. In one aspect, the emollient is an ester or an oil. In various aspects of this embodiment, the emollient Medications include the following: shea butter, cocoa butter, mineral oil, lanolin, petrolatum, paraffin, Beeswax, squalene, cetyl alcohol, olive oil, triethylhexanoin, ya one or more of the following vegetable oils: oat oil, jojoba oil, sesame oil, almond oil or other vegetable oils; Combinations of two or more may be mentioned.

[0025] In certain embodiments, the present disclosure provides a method for preparing the topical formulations described herein. The method may be directed to a method for treating a bacterial infection comprising the use of an antioxidant system and isopentyldiol, dimethicone, or the like. forming a first mixture of an activated solvent system comprising leucosorbide and a non-ionic surfactant; active agents, e.g., retinol, and isopentyldiol and dimethylisothiazolinone; and separately combining the first mixture with rubido to form an active agent mixture; and In certain embodiments, the method may include combining the compound with the active agent mixture. The method is carried out under an inert atmosphere.

[0026] The drawings described below are for illustrative purposes only and are not necessarily drawn to scale. These drawings are not intended to limit the scope of the present disclosure in any way. Wherever possible, references throughout the drawings to the same or like parts will be used. The same or similar reference numbers will be used throughout. [Brief explanation of the drawings]

[0027] [Figure 1] 1 shows an investigator efficacy chart at week 4 for mean clinical scores for smoothness, softness, brightness, and radiance of skin treated with a formulation according to certain embodiments described herein compared to a comparative tretinoin formulation. [Figure 2] 1 shows an investigator efficacy chart at week 8 for mean clinical scores for dryness and visual smoothness of skin treated with a formulation according to certain embodiments described herein compared to a comparative tretinoin formulation. [Figure 3]1 shows an efficacy chart at week 8 by subject for mean clinical scores for dryness and visual smoothness of skin treated with a formulation according to certain embodiments described herein compared to a comparative tretinoin formulation. [Figure 4] 1 shows an efficacy chart at week 4 by subject with respect to mean clinical scores for overall appearance, dyschromia, crow's feet, softness, and visual smoothness of skin treated with a formulation according to certain embodiments described herein compared to a comparative tretinoin formulation. [Figure 5] 1 shows a chart of mean tolerability scores by subjects at weeks 4 and 12 for mean tolerability scores for swelling, redness, burning, stinging, and itching of skin treated with a formulation according to certain embodiments described herein compared to a comparative tretinoin formulation. [Figure 6] 6A and 6C show the histology of skin treated with formulations according to certain embodiments described herein at week 12 (FIGS. 6B and 6D) compared to baseline (FIGS. 6A and 6C). DETAILED DESCRIPTION OF THE INVENTION

[0028] The present disclosure provides methods for treating skin with retinoids, including retinol, and other skin treatment active agents. Skin care formulations and delivery for the treatment, relief or amelioration of acceptable dermatological conditions The present invention provides a system and method of use thereof. Acceptable conditions include, but are not limited to: Psoriasis, photoaging, sunburned appearance, yellowing, loss of elasticity, collagen-rich appearance and / or or loss of youthfulness, redness, dryness, age spots, skin wrinkles, acne, rosacea, ichthyosis, etc. and skin cancer, characterized by inflammatory disorders of the skin and increased cell turnover. The disclosed formulations include, but are not limited to, skin conditions that appear Skin age, skin tone, sunburned appearance, yellowing, loss of elasticity, redness, dryness, age pigmentation For dark spots, wrinkles, smooth skin, brightness, radiance, and less noticeable skin pores The present invention is also useful for improving one or more aesthetic criteria, including the perception of improvement in appearance.

[0029] As used herein, the terms "treatment" or "treating" in reference to a skin condition The term generally refers to administration with the intent to provide a pharmacodynamic effect regardless of outcome. In certain embodiments, "treatment" or "treating" refers to "having a positive effect on a skin condition." "having the effect of reducing, alleviating and / or treating at least one symptom of a skin condition" reduction, relief and / or reduction in the severity of the skin condition, progression of the skin condition delay, prevention, or inhibition of, or the perception of improvement or benefit as a result of treatment It is believed that non-prescription products can provide comparable or better treatment results than prescription drugs. Treatment, as used herein, can also mean achieving a desired effect. In certain embodiments, the formulation or delivery method of the present disclosure may be used to treat a condition without requiring a complete cure. The system reduces the severity of the skin condition, reduces the severity of symptoms associated therewith, and improves the patient's Providing an improvement in quality of life or delaying or preventing the onset of one or more symptoms of a skin condition As used herein, this can be used to inhibit, inhibit, or provide a perception of benefit. These terms also encompass aesthetic improvements to the skin upon application of the disclosed active agent-containing formulations.

[0030] As used herein, the disclosed topical formulations or The terms "apply," "apply," and "applying" in reference to the method used are used in medicine. topical formulations to the skin of a patient in a dermatological or cosmetology practice, refers to any method of administering a drug to a patient with or without the aid of a suitable device onto the patient's skin. without rubbing, rubbing, spreading, or spraying the disclosed topical formulations. All of these are included within the scope of the term "application" as used herein. The use of "topical" or "topically" in reference to the administration or application of the disclosed formulations The term refers to administration or application onto the skin or administration onto the skin.

[0031] As used herein, the phrase "effective amount" refers to an amount that is detectable in the area of ​​topical application. Possible localized improvement to substantial relief of symptoms, including but not limited to sun exposure (UVB, Damage from free radicals from UVA (visible light), HEV (blue) light, and infrared (IR) light , pollution, irritants, allergens, or various environmental toxins, apparent skin age, radiation damage, Sun or UV damage, skin tone, tanned appearance, yellowing, fine line appearance, rough skin, peeling Sagging skin, skin firmness, dryness, age spots, wrinkles, smoothness, brightness, radiance , as well as less noticeable skin pores, hyperpigmentation, scars, skin surface irregularities, and rosacea acne, psoriasis, skin repair and regeneration process, redness, ichthyosis, severity of photodamage, sensitivity to touch Lack of visual smoothness, lack of visual smoothness, lack of softness, lack of brightness, lack of brilliance , skin texture, fine facial wrinkles, crow's feet, pigmentation disorders, fine skin texture, skin elasticity and one or more aesthetic criteria, including a reduction in sebum production and a perceived improvement in other damaging skin conditions. Alleviate or reduce skin conditions as noted above, including effects ranging from improvement in An effective amount refers to an amount of a formulation or component thereof that is effective to alleviate a particular condition or treatment. the condition being treated, the severity of the condition, the duration of treatment, the particular components of the composition being used, and other factors. In certain embodiments, the disclosed compositions and The formulations deliver active agents (e.g., retinoic acid, including retinol) to the skin in an effective manner. Certain disclosed methods for stabilizing and delivering retinoids are provided. The compositions, formulations, delivery systems and methods of use thereof are useful for treating, among other things, pruritus, severe skin irritation, and Common side effects include peeling, breakdown of the skin barrier, discomfort, extreme dryness, cracking of the skin, and sensitization. Commonly observed retinoid-induced skin conditions can be reduced, minimized, or eliminated. In certain embodiments, the disclosed compositions, formulations, delivery systems and methods of use thereof , including but not limited to, younger looking skin, skin with a more even tone, pores Skin with less visible wrinkles and that is perceived as smoother by the user to / on its sun-damaged or aged appearance, yellowing, loss of elasticity, redness, dryness This includes skin that has been judged to have improved in terms of dryness, age spots, and / or skin wrinkles. It also provides cosmetic improvements in the skin.

[0032] In certain embodiments, the activation and solvent systems disclosed herein are formulated Product stability, including stability of added active agents (e.g., retinoids) as well as antioxidants Not only does it maintain the efficacy of the active agent, but it also provides greater efficacy of the active agent. In certain embodiments, the inventors have surprisingly found that typical home skin care products Certain disclosed products are comparable to prescription active agents in comparison with pharmaceutical preparations. Thus, the effectiveness of certain disclosed retinoid formulations and their The method of use of the active ingredient may be compared to the prescribed dose of the active ingredient, as discussed in more detail below. In some cases, non-prescription doses work well in skin care treatments by themselves. In embodiments, the formulations are particularly suitable for daily, long-term use, as typically associated with such formulations. This causes skin irritation and other possible side effects to be reduced, minimized or eliminated altogether.

[0033] Antioxidants may be chemically synthesized polyphenols isolated from plants; Antioxidants are prepared by modification of natural polyphenols or mixtures of polyphenols. In certain embodiments of the present disclosure, antioxidants include: "Green tea polyphenols" isolated and purified from the leaves of the tea plant (Camellia sinensis) These antioxidants, when formulated and delivered herein, , can provide antioxidant or anti-inflammatory activity, and furthermore, can provide skin soothing, protective, anti-irritant or may provide repair activity. The inventors have unexpectedly found that certain embodiments In the retinoid formulations of the present disclosure, antioxidants, e.g. For example, the presence of polyphenols provides better tolerance for retinoid formulations, i.e. to reduce irritation or redness resulting from the use of the formulation, for example as a non-prescription product for daily use and / or eliminate.

[0034] In certain embodiments, the present disclosure is useful in the disclosed delivery systems. In certain embodiments, formulations containing one or more retinoids, including retinol, are provided. The formulation shown is a retinoic acid formulation of the active agent retinoid / retinol when applied to the skin. The present disclosure provides a method for the preparation of a pharmaceutical composition that can provide stable, low irritation, or effective release. In another aspect of the present disclosure, the skin is a companion animal skin. , domestic animals, or commercially useful animals.

[0035] Without wishing to be bound by theory, the inventors believe that retinoids / retinols Unexpected results associated with certain embodiments of the agent are described herein in connection with activation and solvent The synergistic effect of the system, i.e., activation and release of the retinoid active agent(s), resulting in controlled release It is further believed that this is achieved by function of the solvent system. The disclosed formulations have minimal or no skin irritation and are optimal for release. The active agent is released with optimal intensity and speed.

[0036] The disclosed formulations may also include at least one retinoid source. In one aspect of the embodiment, the retinoid is retinol, retinoic acid, tretinoin, retinoic acid, or the like. aldehydes, such as palmitate or acetate of retinol or retinoic acid; Propionate, butyrate, hexanoate, heptanoate, caprylate and sulfonate Esters of retinol or retinoic acid, including tearates, or synthetic Retinoids, including but not limited to, adapalene, bexarotene, tazarotene, or a combination of two or more thereof. Retinoids or retinol are defined herein as In one aspect of this embodiment, the oily substance is solubilized by the formulation disclosed in In another embodiment, the retinoid is retinol. In another embodiment, the retinoid is all trans- Retinol (i.e., tretinoin). In one embodiment, retinol and / or The derivative is the only active agent in the formulation. In another embodiment, another active agent Retinol and / or its derivatives in combination with (e.g., bakuchiol) Although it is the only active agent in the formulations described herein, the present invention provides There is no limit to the number.

[0037] In certain embodiments, the formulations and delivery systems of the present disclosure comprise, based on the total weight of the formulation: about 0.01 wt% to about 1.0 wt% retinol and / or one or more thereof In various aspects of these embodiments, the formulations and delivery systems of the present disclosure include derivatives of is about 0.02 wt% to about 1.0 wt%, about 0.03 wt%, based on the total weight of the formulation to about 1.0 wt%, about 0.04 wt% to about 1.0 wt%, about 0.05 wt% to about 1 0.0wt%, about 0.06wt% to about 1.0wt%, about 0.07wt% to about 1.0wt %, about 0.08wt% to about 1.0wt%, about 0.09wt% to about 1.0wt%, about 0 0.1wt% to about 1.0wt%, about 0.2wt% to about 1.0wt%, about 0.3wt% to about 1.0 wt%, about 0.4 wt% to about 1.0 wt%, or about 0.5 wt% to about Contains 1.0 wt% retinol and / or one or more of its derivatives. The formulations and delivery systems may be, for example, those used in consumer products. .

[0038] In certain aspects of these embodiments, the formulations and delivery systems of the present disclosure comprise a total weight of the formulation. Based on the amount, about 0.1wt%, about 0.2wt%, 0.3wt%, 0.5wt%, 0.7 5 wt%, or 1.0 wt% retinol and / or one or more of its derivatives Includes conductors.

[0039] In certain embodiments, the formulations and delivery systems of the present disclosure comprise from about 1.0 wt% to 50 wt% % of retinol and / or one or more of its derivatives. The device and delivery system are intended for use by physicians in in-office procedures, for example. That's fine.

[0040] Retinoids are the most effective anti-inflammatory agents used in over-the-counter (OTC) cosmetic moisturizers. These OTC retinoids include retinyl esters, These include retinol and retinaldehyde, which are interconvertible. The ester can be hydrolyzed to retinol, which is then converted to retinol within the keratinocyte. It is oxidized to aldehyde and then re-oxidized to retinoic acid, also known as tretinoin. The anti-aging activity of retinoids can be summarized as follows: You can: Retinoic acid > Retinaldehyde > Retinol > Retinyl ester Unfortunately, the tolerability ranking is exactly the opposite: Retinyl esters>Retinol~Retinaldehyde>>Retinoic acid The associated irritation, particularly noted with retinoic acid and retinaldehyde, occurs in the skin. Excessive amounts of exogenous retinoic acid exceed the normal physiological level, resulting in overload of the retinoic acid-dependent pathway. Therefore, the poor tolerability of retinoids has limited their use. .

[0041] In certain embodiments, the derivative of retinol is retinaldehyde, retinyl ester, or the like. It may contain one or more of: benzoyl peroxide or tretinoin (retinoic acid). In embodiments, the formulations and delivery systems described herein are Based on the total weight of retinol and its derivatives in the formulation and delivery system used less than about 50 wt%, less than about 40 wt%, less than about 30 wt%, less than about 20 wt%, Less than 15wt%, less than about 10wt%, less than about 8wt%, less than about 5wt%, less than about 3wt% , or may contain less than about 1 wt% tretinoin (retinoic acid) It may not be contained at all (for example, 0 wt%).

[0042] Without wishing to be bound by theory, the inventors believe that in certain embodiments: Combined with the significant reduction in irritation observed with administration of the retinoid formulations disclosed herein, The efficiency of delivery of the active agent retinoid (e.g., retinol and / or its derivatives) The increase in retinoid activity was observed at significantly higher concentrations than previously used (e.g., It is believed that the present invention enables the formulation and use of retinoid systems using Thus, certain disclosed retinoid formulations and delivery systems provides effective skin care treatment at non-prescription doses while still providing gentle consumer It is well tolerated and has been shown to be effective against rheumatoid arthritis.

[0043] Without wishing to be bound by theory, the inventors believe that in certain embodiments: Retinoids, retinol and / or All-trans-retinol increases skin cell turnover, collagen production in the skin, Supporting pigment production and / or brightening hyperpigmented areas of the skin Thus, without being bound by theory, the inventors believe that These beneficial skin activities in certain embodiments include the retinoids disclosed herein. It is further thought that this may be the result of different genes being switched on by retinol preparations. It is available.

[0044] The inventors have demonstrated that in certain embodiments, as formulated and delivered herein, The pure and active form of vitamin A, i.e., all-trans-retinol, is an effective Treatment, low incidence of irritation, support of the skin barrier, or increased cell turnover in the skin It is believed to provide one or more of the following: Reduction in age spots and improvement of skin texture or tone, or As used herein, the term "promoting a nutritious and healthy appearance" may result in one or more of the following: When used in a pharmaceutical composition, "pure" refers to efficacy measured as the percentage content of a reference ingredient or drug. In certain embodiments, the retinoids / anti-inflammatory agents described herein are The retinol contained in the retinol formulation or delivery system may be any of the retinols described herein. Based on the total weight of retinol and its derivatives in the formulation and delivery system, at least about 80 wt%, at least about 85 wt%, at least about 90 wt%, at least about 95wt%, at least about 96wt%, at least about 97wt%, at least about 98wt %, at least about 99 wt%, or at least about 99.5 wt% retinol.

[0045] In certain embodiments, retinol is protected from exposure to light and air, which can reduce its effectiveness. May decompose into biologically inactive forms when exposed to sunlight. Without further ado, the effectiveness of retinol in treating the skin conditions described herein is This may depend on the oxidative stability of the compound and / or the delivery system in which it is formulated. can be obtained.

[0046] In certain embodiments, the formulations and / or delivery systems disclosed herein The retinol and / or its derivatives are partitioned into a dispersed phase and the solvent system is continuous. In certain embodiments, the formulation The micro-emulsion properties are believed to contribute to the stability of retinol. The term "micro-emulsion" as used herein refers to a formulation based on the total weight of the formulation. less than about 5 wt% water, less than about 4 wt% water, less than about 3 wt% water, less than about 2 wt% water water, less than about 1 wt% water, less than about 0.5 wt% water, or no water at all (e.g. For example, 0 wt % refers to a micro-emulsion.

[0047] In certain embodiments, the solvent system may be part of the continuous phase of the micro-emulsion. In certain embodiments, the solvent system comprises a polyol that is capable of dissolving the micro-emulsion. Illustrative diols include, but are not limited to, propyl diols. Ethylene glycol, butanediol, butenediol, butynediol, pentanediol , hexanediol, octanediol, neopentyl glycol, 2-methyl-1,3 -Propanediol, diethylene glycol, triethylene glycol, tetraethylene Glycol, dipropylene glycol, dibutylene glycol, isopentyl diol, ethoxydiglycol, or a combination thereof. In embodiments, the solvent system is an isoprene solvent that may be part of the continuous phase of the micro-emulsion. In one embodiment, the solvent system described herein comprises ethoxydiglycol. In one embodiment, the solvent system disclosed herein comprises isopentyl diisopropyl ether. In certain embodiments, polyols (e.g., ethoxydiglycol) are used. Diols such as isopentyldiol also help retain water in the skin. and acts as a moisturizing agent by creating a smooth film on the skin surface.

[0048] In certain embodiments, the diol is present in an amount of about 10 wt%, about 1 wt%, based on the total weight of the formulation. 5wt%, about 20wt%, about 25wt%, about 30wt%, about 35wt%, about 40wt%, From about 45wt% or about 50wt%, to about 55wt%, about 60wt%, about 6 5wt%, approximately 70wt%, approximately 75wt%, approximately 80wt%, approximately 85wt% or approximately 90w t%, or any subrange or single value therein. , may be included in the formulations or delivery systems described herein. In some embodiments, the diol is present in an amount of about 10 wt % to about 90 wt %, about 25 wt %, based on the total weight of the formulation. wt% to about 75wt%, about 45wt% to about 65wt%, or about 50wt% to about 60 wt%, or any subrange or single value therein, The compositions may be contained in formulations or delivery systems described in the literature.

[0049] In certain embodiments, the formulations or delivery systems described herein are Based on the total weight of the 0wt%, approximately 35wt%, approximately 40wt%, approximately 45wt%, or approximately 50wt% From about 55wt%, about 60wt%, about 65wt%, about 70wt%, about 75wt%, about 8 0 wt%, about 85 wt%, or about 90 wt%, or any subrange. or isopentyl diol in an amount ranging from any single value therein. In certain embodiments, the formulations or delivery systems described herein comprise Based on the total weight, about 10 wt% to about 90 wt%, about 25 wt% to about 75 wt%, about 45wt% to about 65wt%, or about 50wt% to about 60wt%, or any lower It may contain isopentyldiol in an amount ranging from 100 to 1500 ppm or a single value therein. can.

[0050] In certain embodiments, the formulations or delivery systems described herein are Based on the total weight of the t%, about 25wt%, about 30wt%, about 35wt%, about 40wt%, about 45wt% or From about 50wt%, about 55wt%, about 60wt%, about 65wt%, about 70wt % by weight, up to about 75 wt. % or about 80 wt. % or any subrange or can contain ethoxydiglycol in an amount ranging from any single value therein. In certain embodiments, the formulations or delivery systems described herein comprise a total weight of the formulation. Based on the amount, about 1 wt% to about 80 wt%, about 1 wt% to about 10 wt%, about 1 wt% to about 5 wt%, or about 2 wt% to about 3 wt%, or any subrange or range therebetween. Ethoxydiglycol may be included in an amount ranging from a single value within the range of

[0051] In certain embodiments, the formulations or delivery systems described herein are isoforms. Pentyldiol and ethoxydiglycol were mixed in a ratio of about 100:1, about 90:1, about 80: 1, approx. 70:1, approx. 60:1, approx. 50:1, approx. 40:1, approx. 30:1, approx. 20:1, approx. 1 From either 0:1 or about 5:1 to about 1:5, about 1:10, about 1:20, about 1: 30, approx. 1:40, approx. 1:50, approx. 1:60, approx. 1:70, approx. 1:80, approx. 1:90, or to about 1:100, or any subrange or single ratio value therein In certain embodiments, the formulations or delivery methods described herein comprise The resulting system is a mixture of isopentyldiol and ethoxydiglycol in a ratio of about 50:1 to about 1:1, about 40:1 to about 10:1, or about 30:1 to about 20:1, or any Including weight-to-weight ratios of any subrange or single ratio value therein.

[0052] In certain embodiments, in the formulations or delivery systems described herein The solvent system further comprises dimethyl isosorbide. The formulation or delivery system described contains about 5 wt%, about 10 wt%, based on the total weight of the formulation. wt%, approx. 15wt%, approx. 20wt%, approx. 25wt%, approx. 30wt%, approx. 35wt%, approx. From about 40wt%, about 45wt%, or about 50wt%, to about 55wt%, about 60 wt%, about 65wt%, about 70wt%, about 75wt%, about 80wt%, about 85wt% or up to about 90 wt%, or any subrange or single value therein. Dimethyl isosorbide (DMI) may be included in the amount of In some embodiments, the formulations or delivery systems described herein may contain 100 mg of 10 ... , about 5wt% to about 90wt%, about 15wt% to about 60wt%, about 20wt% to about 4 0 wt%, or about 25 wt% to about 35 wt%, or any subrange or therebetween A quantity ranging from a single value in the range, including DMI.

[0053] In certain embodiments, the formulations or delivery systems described herein are The ratios of ethanol and DMI were approximately 20:1, approximately 15:1, approximately 10:1, approximately 8:1, approximately 5:1, and approximately 3:1. :1, or about 2:1, to about 1:2, about 1:3, about 1:5, about 1:8, about up to about 1:10, about 1:15, or about 1:20, or any subrange or In certain embodiments, the weight to weight ratios of the compounds described herein are included in a single ratio value therein. The formulation or delivery system may be a mixture of diol and DMI in a ratio of about 20:1 to about 1:1. , about 10:1 to about 1:1, or about 3:1 to about 1:1, or any subrange or a single ratio value weight to weight therein.

[0054] In certain embodiments, the solvent system of the formulation or delivery system described herein The surfactants further include surfactants such as non-ionic surfactants. Surfactants include, but are not limited to, ethoxylates, fatty ethoxylates, propoxylates, esters, block copolymers, poloxamers, polyglyceryl esters, polyglyceryl lactate ionic surfactants, sorbitol anhydride, bipolar agents, phenolic nonionics, or combinations thereof In certain embodiments, the present invention may include one or more of the following: Non-ionic surfactants in the formulation include polysorbate 80.

[0055] In certain embodiments, the formulations or delivery systems described herein are Based on the total weight of the , from about 15 wt% or about 20 wt%, to about 25 wt%, about 30 wt%, about Up to either 35 wt% or about 40 wt%, or any subrange or range therebetween The surfactant (e.g., nonionic surfactant) is contained in an amount ranging from a single value of In certain embodiments, the formulations or delivery systems described herein can is from about 1 wt% to about 40 wt%, from about 3 wt% to about 15 wt%, based on the total weight of the formulation. %, about 6 wt% to about 10 wt%, or about 7 wt% to about 9 wt%, or any lower A surfactant (e.g., a nonionic surfactant) is added in an amount ranging from 0.1 to 1.0 ... Contains surfactants.

[0056] In certain embodiments, the formulations or delivery systems described herein are Based on the total weight of the , from about 15 wt% or about 20 wt%, to about 25 wt%, about 30 wt%, about Up to either 35 wt% or about 40 wt%, or any subrange or range therebetween In certain embodiments, the polysorbate 80 may be present in an amount ranging from a single value of In some embodiments, the formulations or delivery systems described herein may be administered in a dosage form based on the total weight of the formulation. , about 1 wt% to about 40 wt%, about 3 wt% to about 15 wt%, about 6 wt% to about 10 wt%, or about 7 wt% to about 9 wt%, or any subrange or unit therein It contains polysorbate 80 in an amount ranging from one value.

[0057] In certain embodiments, the formulations or delivery systems described herein are alcohols (e.g., isopentyldiol and / or ethoxydiglycol) and surfactants The active agent (e.g., polysorbate 80) is added in a ratio of about 20:1, about 15:1, or about 10: 1 to about 8:1, about 5:1, about 3:1, or about 1:1, or any subrange or single ratio value weight to weight therein. In some embodiments, the formulations or delivery systems described herein may comprise a diol and a surfactant. The ratio of the active ingredient to the active ingredient is about 20:1 to about 1:1, about 10:1 to about 1:1, or about 5:1 to about 1 :1, or any subrange or single ratio value therein.

[0058] The disclosed formulations may contain one or more solubilizing agents and / or emulsifying agents and / or In one aspect of this embodiment, the solubilizer / emulsifier / dispersant is a non-ionic It is a solubilizer / emulsifier / dispersant.

[0059] In certain embodiments, the formulations described herein further comprise bakuchiol. Without being construed as limiting, bakuchiol may be used in certain embodiments. It is believed to enhance retinol. Derived from the seeds of the Dutch ibis (Psoralea corylifolia) Bakuchiol, a relatively new development in dermatology, has antioxidant, anti-inflammatory and antibacterial properties. It is not a retinoid and, in certain embodiments, remains photostable. It involves upregulation of collagen types I, III, and IV and extracellular matrix synthesis enzymes. It appears to have retinol-like functionality through retinol-like regulation of gene expression that induces vasodilatory responses. can be.

[0060] One of the challenges associated with retinol formulations is how to apply retinol to the skin without causing irritation. In certain embodiments, the compositions described herein are preformed and penetrated through the skin. The solvent system described contributes to enhancing the penetration of retinol into the skin, which is This is further enhanced by bakuchiol, thereby enhancing the effectiveness of tretinoin without the associated irritation. In certain embodiments, bakuchiol is a compound similar in chemical structure to It is believed that this may act as a co-solvent for retinol.

[0061] In certain embodiments, the formulations described herein are, for example, with any of the delivery systems listed and / or with any of the excipients listed It may also contain retinoids (e.g., retinol) and bakuchiol. do.

[0062] In certain embodiments, the formulations described herein comprise, based on the total weight of the formulation, , over 0 wt%, about 0.1 wt%, about 0.3 wt%, about 0.5 wt%, about 0.7 wt% or From about 1 wt%, to about 3 wt%, about 5 wt%, about 7 wt%, about 10 wt%, Up to either about 15 wt% or about 20 wt%, or any subrange or therebetween Bakuchiol can be included in an amount ranging from a single value in a particular embodiment. In the formulations described herein, the amount of hydroxybenzoates ranges from greater than 0 wt% to about 2 wt%, based on the total weight of the formulation. 0 wt%, about 0.1 wt% to about 3 wt%, about 0.5 wt% to about 2 wt%, or any bakuchiol in an amount ranging from any subrange of or any single value therein. do.

[0063] In certain embodiments, the weight to weight ratio of retinol to bakuchiol is about 10:1 or to about 1:10, about 8:1 to about 1:8, about 5:1 to about 1:5, about 3:1 to about 1:3, or from about 2:1 to about 1:2, or any subrange or single ratio value therein. Let's say.

[0064] In certain embodiments, the formulations described herein are complexed with retinol. and / or polysorbate 20, which can solubilize it. In certain embodiments, the formulations described herein contain 0 wt % PEG-10 ... %, about 0.01wt%, about 0.1wt%, about 0.3wt%, about 0.5wt%, about 0.7 From either about 1 wt% or about 3 wt%, about 5 wt%, about 7 wt%, about 1 0 wt%, about 15 wt%, about 20 wt%, or about 30 wt%, or The present invention may contain polysorbate 20 in an amount ranging from any subrange or single value therein. In certain embodiments, the formulations described herein can be prepared in a manner that provides a total weight of the formulation. Based on the above, from greater than 0.01 wt% to about 30 wt%, from about 0.1 wt% to about 3 wt%, and from about 0 Range: 0.2wt% to about 0.5wt%, or any subrange or single value therein The composition may contain bakuchiol in an amount such that:

[0065] In certain embodiments, the weight to weight ratio of retinol to polysorbate 20 is about 10 :1 to about 1:10, about 8:1 to about 1:8, about 5:1 to about 1:5, about 3:1 to about 1 :3, about 2:1 to about 1:2, or about 1:1, or any subrange or range therebetween. The range is a single ratio value of .

[0066] In certain embodiments, the formulations described herein may contain a polyol (e.g., a diol). diols, e.g., isopentyldiol and / or ethoxydiglycol), DMI , surfactants (such as polysorbate 80), bakuchiol, or a combination thereof. One or more of the components of the solvent system provide effective delivery of retinol. In embodiments, the effectiveness of the solvent system is determined by the presence of isopentyldiol, DMI, polysorbate 80 , bakuchiol, or a combination thereof.

[0067] In certain embodiments, the formulations described herein may be used to reduce irritation. In certain embodiments, the compositions described herein further comprise an antioxidant system, such as a botanical anti-inflammatory agent. The formulations described include, but are not limited to, tea plant (Camellia Sinensis) polyphenols ( Green Tea), Black Tea Extract, Glycyrrhiza Glabra (Licorice) Root Extract, includes one or more of the combinations thereof.

[0068] Antioxidants, especially green tea polyphenols, as well as retinol, are generally stabilized It is recognized that they are notoriously difficult to grow. This is because they are both subject to oxygen, moisture, light, and trace elements. susceptible to oxidation and / or degradation by the genus and other ingredients frequently included in formulations This is especially true because the spread of the applied formulation on the skin can lead to the development of sensitive components. If the formulation is to be easily air-oxidized within 2 minutes, and / or if the formulation is to have a stable long-term shelf life, e.g., 2 Surprisingly, this is evident for topical formulations that exhibit large surface areas. And unexpectedly, certain disclosed formulations overcome these challenges and provide effective topical application to the skin. Stable, non-irritating or minimally irritating or effective systems for topical application to provide.

[0069] The antioxidants contained in the disclosed retinoid formulations include tea plant (Camellia sinensis) ensis (green tea) polyphenols. A purified isolate of Camellia sinensis (green tea) polyphenols is included in the formulation. The purity of polyphenols can be increased from extremely small amounts obtained, for example, to 100% pure polyphenols from green tea extracts. It is contemplated that the range of polyphenols may be as high as or lower than 100%. Any Camellia sinensis (green tea) preparation of polyphenols can be formulated. However, in certain aspects of this embodiment, Camellia sinensis (green tea) polyphenols are used. 90% or 95% purified preparations of phenol are formulated. The amount of polyphenol antioxidant added is inversely proportional to its purity.

[0070] The antioxidants contained in the disclosed retinoid formulations include a mixture of polyphenol species. Examples of suitable substances include Camellia sinensis (green tea) polyphenols. Suitable green tea polyphenols include, but are not limited to, catechins, e.g., garlic Epigallocatechin (EGCG), epigallocatechin (EGC), epigallocatechin catechin (ECG) and epicatechin (EC), their cis and trans isomers, and salts thereof , their equivalent derivatives, and combinations thereof. The main component of the phenolic antioxidant is epigallocatechin gallate (EGCG).

[0071] In certain embodiments, the formulations described herein include, but are not limited to, black tea extract. and / or licorice root extract, in combination with at least one additional antioxidant. The present invention further includes an antioxidant system comprising any of the green tea polyphenols described herein.

[0072] In one embodiment, the additional antioxidants in the antioxidant system are cinnamic acid, ferulic acid, cocoa, coumaric acid, p-coumaric acid, sinapic acid, their cis and trans isomers, their salts, and their equivalents In another embodiment, the antioxidant may be selected from the group consisting of: Additional antioxidants in antioxidant systems (and in topical compositions in general) include cinnamic acid, phenylalanine ... luric acid, caffeic acid, p-coumaric acid, sinapic acid, their cis and trans isomers, It may be free or substantially free of salts, equivalent derivatives thereof, and combinations thereof.

[0073] In certain embodiments, the additional antioxidant in the antioxidant system is gallic acid, delphinium. Nidin, Luteolin, Quercetin, Cyanidin, Taxifolin, Kaempferol, Mal Visin, hesperidin, pelargonidin, apigenin, naringenin, chrysin, ergo Thionein, glutathione, emblica, its cis and trans isomers, its salts, its The compound may be selected from the group of equivalent derivatives, as well as combinations thereof.

[0074] In certain embodiments, the additional antioxidant in the antioxidant system is apigenin, ergo Thionein, glutathione, emblica, its cis and trans isomers, its salts, its The compound may be selected from the group of equivalent derivatives, as well as combinations thereof.

[0075] The disclosed formulations contain xanthine-related compounds, polymeric derivatives thereof, or compounds with antioxidant activity. It may also contain a mixture of xanthine-related materials that may function as antioxidants or stimulants. In one particular embodiment, the xanthine-related compound is caffeine. In embodiments, the caffeine in the disclosed formulations and delivery systems is pure, highly pure, or It is pure or USP grade caffeine.

[0076] The disclosed formulations may also include one or more moisturizing and / or humectant agents. The disclosed formulations may also include one or more emollients. In one aspect, the emollient may be an ester, oil, or silicone. In various embodiments, the emollient may be any of the following: shea butter, cocoa butter, mineral oil, lanolin, petrolatum. Paraffin, beeswax, squalene, cetyl alcohol, olive oil, triethyl Hexanoin, coconut oil, jojoba oil, sesame oil, almond oil, or other vegetable oil, omega- 6 fatty acids, ceramides, primrose oil, grape seed oil, ceramides, and combinations of two or more thereof The combination may include one or more of the following:

[0077] Each of the antioxidants in the antioxidant system may be present in an amount greater than about 0 wt.%, based on the total weight of the formulation. .001wt%, approximately 0.01wt.%, approximately 0.05wt.%, approximately 0.1wt.%, approximately 0. 15wt.%, approx. 0.2wt.%, approx. 0.25wt.%, approx. 0.3wt.%, approx. 0.35 wt.%, or about 0.4wt.%, to about 0.45wt.%, about 0.5w t.%, approx. 0.55wt.%, approx. 0.6wt.%, approx. 0.65wt.%, approx. 0.7wt. %, approx. 0.75wt.%, approx. 0.8wt.%, approx. 0.85wt.%, approx. 0.9wt.%, Approx. 0.95wt.%, Approx. 1wt.%, Approx. 1.5wt.%, Approx. 2wt.%, Approx. 3wt.%, Approx. 4wt.%, approx. 5wt.%, approx. 6wt.%, approx. 7wt.%, approx. 8wt.%, approx. 9wt. %, about 10 wt.%, about 15 wt.% or about 20 wt.%, or any Can occur individually or cumulatively at concentrations of subranges or single values ​​therein do.

[0078] In certain embodiments, the antioxidant system comprises from greater than 0 wt.% to Approximately 20 wt.%, approximately 0.001 wt.% to approximately 5 wt.%, or approximately 0.001 wt. % to about 0.5 wt.%, or any subrange or single value therein The formulation contains black tea extract present in an amount of

[0079] In certain embodiments, the antioxidant system comprises from greater than 0 wt.% to Approximately 20 wt.%, approximately 0.001 wt.% to approximately 5 wt.%, or approximately 0.001 wt. % to about 0.5 wt.%, or any subrange or single value therein The topical composition may comprise licorice root extract present in an amount of

[0080] In certain embodiments, the antioxidant system comprises about 0.1 wt.% based on the total weight of the formulation. to about 15 wt.%, about 0.1 wt.% to about 5 wt.%, or about 0.5 wt.% to about 2 wt.%, or any subrange or single value therein, Contains tea polyphenols.

[0081] In certain embodiments, the antioxidant system comprises about 0.01 wt., based on the total weight of the formulation. % to about 10 wt.%, about 0.1 wt.% to about 5 wt.%, or about 0.5 wt.% to about 2.5 wt.%, or any subrange or single value therein and contains xanthines (e.g., caffeine).

[0082] In certain embodiments, the antioxidant system comprises greater than 0 wt.%, about 0.001wt%, approx. 0.01wt.%, approx. 0.05wt.%, approx. 0.1wt.%, approx. 0 .15wt.%, approx. 0.2wt.%, approx. 0.25wt.%, approx. 0.3wt.%, approx. 0.3 From either 5 wt.% or about 0.4 wt.%, to about 0.45 wt.%, about 0.5 wt. t.%, approx. 0.55wt.%, approx. 0.6wt.%, approx. 0.65wt.%, approx. 0.7wt. %, approx. 0.75wt.%, approx. 0.8wt.%, approx. 0.85wt.%, approx. 0.9wt.%, Approx. 0.95wt.%, Approx. 1wt.%, Approx. 1.5wt.%, Approx. 2wt.%, Approx. 3wt.%, Approx. 4wt.%, approx. 5wt.%, approx. 6wt.%, approx. 7wt.%, approx. 8wt.%, approx. 9wt. %, about 10 wt.%, about 15 wt.% or about 20 wt.%, or any The concentrations (individual or cumulative) of the subranges or single values ​​therein are as described herein. Any of the green tea polyphenols known to be effective in reducing blood cholesterol, as well as xanthines (e.g., caffeine), Includes at least one combination of tea extract and licorice root extract. rises), consisting of or essentially consisting of.

[0083] In certain embodiments, green tea polyphenols may be combined with one or more additional antioxidants (e.g., For example, weight-for-weight ratios of xanthines (e.g., caffeine), black tea extract, and licorice root extract The cumulative ratio is about 10:1 to about 1:10, about 8:1 to about 1:8, about 5:1 to about 1 :5, about 3:1 to about 1:3, about 2:1 to about 1:2, or about 1:1.

[0084] The inventors have discovered that certain embodiments provide potent antioxidant reduction of reactive oxygen species (ROS). Not only do they provide the benefits typically associated with retinol use, but they also, quite surprisingly, It has been noted that the present invention also provides a reduction in irritation. This observed reduction was dramatically better than other formulations. Inclusion of these materials in the formulation can boost patient compliance. Patients continued their treatment regimen as documented in the trial shown below. This is because they are not stimulated or only slightly stimulated. Therefore, irritation is a major problem with topical retinol applications, but it can be caused by certain No or very little side effects were observed in studies using the retinoid systems disclosed herein. was observed.

[0085] In a further embodiment, the all-trans-retinol in the formulations described above is One or more of the following retinoids at the percentages indicated by weight (% w / w) levels: Can be replaced or supplemented with: retinaldehyde (0.01% to 1%), retinoic acid Esters of retinoic acid (0.01-5%), retinoic acid (0.01%-0.2%), synthetic retinoic acid steroids, such as adapalene (0.02% to 0.5%), tazarotene (0.01% to 0.2%) %).

[0086] In yet a further embodiment, all trans-retinol in the formulations described above may be replaced or supplemented with one or more of the following retinoids at the levels indicated (% w / w): Retinaldehyde (0.05-0.10%), esters of retinol ( 0.1-2%), retinoic acid (0.02%-0.15%), synthetic retinoids, e.g. Adapalene (0.1% to 0.3%), tazarotene (0.05% to 0.1%).

[0087] In certain embodiments, the dosage of the formulation of the present disclosure to be applied to the skin is 0.01 g from 5g, 0.02g to 4g, 0.05g to 3g, 0.1g to 2g, 0.2g to In one aspect of these embodiments, the composition of the present disclosure to be applied to the skin is in the range of 1 g. The dosage of the agent may be 0.4 g. The actual dosage to be applied depends, inter alia, on the patient being treated. It depends on the condition to be treated, the particular regimen to be followed, and the personal preferences of the user. For example, different dosages may be used for spot treatment, multi-spot treatment, full or partial facial coverage, etc. It can be used for treatment, especially of body parts such as the neck, hands, etc.

[0088] In certain embodiments, the formulation comprises at least one additional cosmetically acceptable excipient. Illustrative cosmetically acceptable excipients include, but are not limited to, epidermal penetration enhancers, solvents, Mild surfactants, oil bodies, emulsifiers, pearlescent waxes, consistency regulators, thickeners, rheology Modifiers, suspending agents, chelating agents, preservatives, superfatting agents, stabilizers, polymers, silicones or siloxane compounds (e.g., caprylyl methicone, PEG / PPG-18 / 18 Dimethicone), fats, waxes, lecithin, phospholipids, UV photoprotective factors, bioactive ingredients, Additional antioxidant, deodorant, antiperspirant, anti-dandruff, film-forming agent, swelling agent, insect repellent, self Tanning agents, tyrosinase inhibitors, hydrotropes, solubilizers, perfume oils, pigments, zinc oxide , fatty alcohols, esters of fatty acids, adjuvants, glyceryl esters and derivatives Natural or synthetic triglycerides, hydrocarbon oils, superfatting agents, polymers, bioactives, including Ingredients, hydrotropic agents, bacterial inhibitors, colorants, UV screening agents, absorb UV light and and agents, or combinations thereof, that provide photoprotection to the skin.

[0089] Additional cosmetically acceptable excipients In certain embodiments, the cosmetically acceptable excipients include natural gums (e.g., natural gums). Suitable natural gums include, but are not limited to, guar gum, carob gum, and the like. Gum, konjac gum, xanthan gum, sclerotium gum, acacia gum, cellulose Sugars (modified or not), or combinations thereof.

[0090] In certain embodiments, the cosmetically acceptable excipients include emulsifiers. Suitable emulsifiers include, but are not limited to, PEG-30 dipolyhydroxystearate, dilauroyl hydroxystearate, PEG-30 ... PEG-4 Phosphate, PEG-8 Dioleate, PEG-40 Sorbitan Peroleate, PEG-7 Glyceryl Cocoate, PEG-20 Almond Glycerides, PEG-25 Hydrogenated Castor Oil, Glyceryl Stearate (and) PEG-100 Stearate, Olive PEG-7 fatty acid, PEG-8 oleate, PEG-8 laurate, PEG-60 arsenate Mondoglyceride, PEG-20 methyl glucose sesquistearate, P stearate EG-40, PEG-100 Stearate, PEG-80 Sorbitan Laurate, Stearic Acid Laureth-2, Steareth-12, Oleth-2, Ceteth-2, Laureth-4, Oleth-10, Oleth-10 / Polyoxyl 10 Oleyl Ether, Ceteth-10, Isosteareth-2 0, Ceteareth-20, Oleth-20, Steareth-20, Steareth-21, Ceteth- 20, Isoceteth-20, Laureth-23, Steareth-100, Glyceryl Steareth Tocitrate, Glyceryl Stearate SE (Self-Emulsifying), Stearic Acid, Stearyl salts of carboxylic acids, polyglyceryl-3-methylglucose distearate, or combinations thereof Examples include:

[0091] Further suitable emulsifiers are phosphate esters and salts thereof, such as cetyl phosphate (Amp hisol® A), cetyl phosphate diethanolamine (Amphisol® DEA), potassium cetyl phosphate (Amphisol® K), cetea Sodium glyceryl sulfate, sodium glyceryl oleate phosphate, hydrogenated vegetable glyceryl phosphate Further suitable emulsifiers are sorbitan oleate, sesquioleate, and mixtures thereof. Sorbitan oleate, sorbitan isostearate, sorbitan trioleate, cetyl Allyl glucoside, lauryl glucoside, decyl glucoside, stearoyl glutamic acid sodium, sucrose polystearate and hydrated polyisobutene. One or more synthetic polymers can be used as emulsifiers. For example, PVP elastomers. Icosene Copolymer, Acrylate / C 10 ~ 30 alkyl acrylate crosspolymer, Acrylates / Steareth-20 Methacrylate Copolymer, PEG-22 / Dodecyl glycol copolymer, PEG-45 / dodecyl glycol copolymer, and mixtures thereof .

[0092] In certain embodiments, cosmetically acceptable excipients include chelating agents. Suitable chelating agents include, but are not limited to, disodium ethylenediaminetetraacetic acid ( EDTA), diethylenetriaminepentaacetic acid (DTPA), N-(hydroxyethyl) -ethylenediaminetriacetic acid (HEDTA), and nitrilotriacetic acid (NTA). do.

[0093] In certain embodiments, cosmetically acceptable excipients include, but are not limited to, forms of vitamin E. Additional antioxidants include: Suitable forms of vitamin E that can be included in the topical composition include: , alpha, beta, delta and gamma tocopherols, and alpha, beta, It may be selected from delta and gamma tocotrienols, and combinations thereof.

[0094] In certain embodiments, cosmetically acceptable excipients in topical compositions include preservatives. Suitable preservatives include, for example, phenoxyethanol, parabens, A solution of benzophenonediol and sorbic acid, and the commercial reference Surfacine (R silver complexes known under the trade mark (SCR) and those set out in Appendix 6, Parts A and B of the Cosmetics Regulations Another class of substances that is considered suitable is preservatives.

[0095] In certain embodiments, cosmetically acceptable excipients include perfume oils. Suitable perfume oils include mixtures of natural and synthetic fragrances. Natural fragrances are derived from flowers ( lavender, rose, jasmine, neroli, ylang-ylang), stems and leaves (geranium , patchouli, petitgrain), fruits (aniseed, coriander, cumin, juniper), Fruit peels (bergamot, lemon, orange), roots (mace, angelica, celery, cardamom) Mon, Costus, Iris, Calmus), wood (pine, sandalwood, guaiac wood, cedar, rosewood), herbs and grasses (tarragon, lemongrass, sage, thyme), needles and Branches (spruce, fir, pine, low pine), resins and balsams (galbanum, elemi, benzyl alcohol) It is an extract from zoin, myrrh, olibanum, and opoponax. The compounds include esters, ethers, aldehydes, ketones, alcohols and hydrocarbons. Ester-type aroma compounds are, for example, benzyl acetate, phenyl isobutyrate, hydroxyethyl, p-tert-butylcyclohexyl acetate, linalyl acetate, diacetate Methylbenzylcarbinyl, phenylethyl acetate, linalyl benzoate, benzyl formate, ethoxylated ethyl-methylphenylglycinate, allyl cyclohexylpropionate, propionic acid styrallyl and benzyl salicylate. Ethers include, for example, benzyl ethyl Examples of the aldehyde include aldehydes having 8 to 18 carbon atoms. Straight-chain alkanals, citral, citronellal, citronellyloxyacetaldehyde , cyclamen aldehyde, hydroxycitronellal, lilial and bourgeonal Examples of ketones include ionone, α-isomethylionone, and methyl Examples of alcohols include anethole, citronellol, and eucalyptus. ethanol, isoeugenol, geraniol, linalool, phenylethyl alcohol and and terpineol, and hydrocarbons include mainly terpenes and balsams. can be done.

[0096] Essential oils of relatively low volatility are primarily used as fragrance ingredients, as well as perfume oils, e.g. Sage oil, chamomile oil, clove oil, melissa oil, mint oil, cinnamon leaf oil , Linden flower oil, Juniper berry oil, Vetiver oil, Olibanum oil, Galbanum oil, Rub Suitable oils include danum oil and lavandin oil. Other suitable oils include benzoyl perilla oil, ... Bergamot oil, dihydromyrcenol, lilial, lyral, citronellol in the mixture phenylethyl alcohol, α-hexylcinnamaldehyde, geraniol, benzoyl Diacetone, Cyclamen Aldehyde, Linalool, Boisambren Forte, Amb Loxane, indole, hedione, sandelice, lemon oil, mandarin oil, orange oil, Allyl amyl glycolate, cyclovertal, lavandin oil, clary sage oil, beta-dama Scon, Geranium Oil Bourbon, Cyclohexyl Salicylate, Vertofix Sew Lu, Iso-E-Super, Fixolide NP, Evernil, Iraldein Gamma, Pheny Acetic acid, geranyl acetate, benzyl acetate, rose oxide, romilate, irrityl and fluorine Loramate is one example.

[0097] In certain embodiments, cosmetically acceptable excipients include lavender oil, bergamot oil, oil, eucalyptus oil, chamomile oil, melaleuca oil, or a combination thereof. In one embodiment, the cosmetically acceptable excipients include perfume oils, which are essential oils. Benson oil, chamomile oil, or a combination thereof.

[0098] In certain embodiments, the perfume oils (individually each perfume oil or cumulatively all perfume oils in the topical composition) Perfume oil) is from greater than 0 wt.% to about 5 wt.%, 0 wt.% based on the total weight of the topical composition in an amount of greater than to about 1 wt.%, or from about 0.01 wt.% to about 0.3 wt.%, of the local composition It exists in things.

[0099] In certain embodiments, the pH of the topical composition is about 2.0, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, about 2.10, about 2.11, about 2.12, about 2.13, about 2.14, about 2.15, about 2.16, about 2.17 0.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.8 or about 2.9 From either, approximately 3.0, approximately 3.1, approximately 3.2, approximately 3.3, approximately 3.4, approximately 3.5, approximately 3. 6, about 3.7, about 3.8, about 3.8, about 3.9 or about 4.0. In certain embodiments, the pH of the topical composition is from about 2.0 to about 4.0, from about 2.5 to about 4.0. to about 3.5, or from about 2.7 to about 3.3.

[0100] The formulations described herein may be used in the form of serums, emulsions, creams, foams, sprays, softeners, or other cosmetic products. in any dermatologically acceptable form such as a plaster, gel, lotion, or any other suitable form, or if physically or may contain ingredients to cosmetically improve, modify or stabilize the composition. It can be formulated as a pad or roll-on application.

[0101] Formulations according to the present disclosure may also contain one or more additional cosmetically acceptable The composition may also contain excipients that are useful in the preparation of pharmaceutical compositions.

[0102] fatty alcohols Cetyl alcohol, stearyl alcohol, cetearyl alcohol, oleyl alcohol benzoates of C12-C15 alcohols, acetylated lanthanides Alcohols containing 6 to 18, preferably 8 to 10 carbon atoms, including phosphorus alcohols. Guerbet alcohols are based on fatty alcohols having:

[0103] Esters of fatty acids Straight chain C3~C 24 Straight chain C6-C with alcohol 24 Esters of fatty acids, straight chain C6-C2 4. Branched C6-C with fatty alcohols 13 Esters of carboxylic acids with branched alcohols Straight chain C6~C 24 Esters of fatty acids, especially 2-ethylhexanol, linear or branched C6 ~C 22 Esters of hydroxycarboxylic acids with fatty alcohols, especially dioctyl malate , polyhydric alcohols (e.g., propylene glycol, dimer diols or trimer triols) alcohols) and / or Guerbet alcohols, e.g. caproic acid, caprylic acid, 2-ethylhexyl alcohols Xanthic acid, capric acid, lauric acid, isotridecanoic acid, myristic acid, palmitic acid, Palmitoleic acid, stearic acid, isostearic acid, oleic acid, elaidic acid, Trocerinic acid, linoleic acid, linolenic acid, elaeostearic acid, arachidic acid, gadole acetic acid, behenic acid and erucic acid and technical grade mixtures thereof (e.g., natural fats and and oil pressure removal, reduction of aldehydes from the Roelen oxo synthesis, or unsaturated fats with alcohols such as isopropyl alcohol, caprylic / capric triglycerides (obtained by dimerization of fatty acids) Sodium benzoate, caprylic alcohol, 2-ethylhexyl alcohol, capric alcohol Cole, lauryl alcohol, isotridecyl alcohol, myristyl alcohol, cetyl Alcohol, Palmoleyl Alcohol, Stearyl Alcohol, Isostearyl Alcohol alcohol, oleyl alcohol, elaidyl alcohol, petroselinyl alcohol, linoleyl Alcohol, Linolenyl Alcohol, Ethylstearyl Alcohol, Arachidyl Alcohol Kohl, Gadoleyl Alcohol, Behenyl Alcohol, Erucyl Alcohol and Brush Dimethyl alcohol and technical grade mixtures thereof (e.g. technical grades based on fats and oils) High pressure hydrogenation of aldehydes from red methyl esters or Roelen oxo synthesis and unsaturated fatty alcohols) and linear and and / or esters of branched fatty acids.

[0104] Examples of such ester oils are isopropyl myristate, isopropyl palmitate, Isopropyl stearate, isopropyl isostearate, isopropyl oleate, n-Butyl stearate, n-Hexyl laurate, n-Decyl oleate, stearin Isooctyl isononate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl isononanoate Silpalmitate, 2-hexyl laurate, 2-hexyldecyl stearate, 2-octyl Cetyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyl oleate Ethyl erucate, cetearyl octanoate, cetyl palmitate, stearin Cetyl oleate, cetyl behenate, cetyl acetate, myristyl myristate, Myristyl behenate, myristyl oleate, myristyl stearate, myristyl palmitate Listyl, Myristyl Lactate, Propylene Glycol Dicaprylate / Caprate, Heptane stearyl malate, diisostearyl malate, octyl hydroxystearate, etc. .

[0105] Other adjuvants Diethylhexyl 2,6-naphthalate, Di-n-butyl adipate, Di(2-ethyl Di(2-ethylhexyl)-adipate, di(2-ethylhexyl)-succinate and diisotride Silyl acetonitriles, as well as diol esters such as ethylene glycol dioleate. Cole, ethylene glycol diisotridecanoate, propylene glycol di(2-ethyl) Hexanoate), Propylene Glycol Diisostearate, Propylene Dipelargonate Glycol, Butanediol Diisostearate and Neopentyl Glycol Dicaprylate Cole. Aromatic carboxylic acids, saturated and / or unsaturated, especially C6-C2 with benzoic acid 4 Esters of fatty alcohols and / or Guerbet alcohols, 1 to 22 carbon atoms Straight-chain or branched alcohols having 2 to 10 carbon atoms and 2 to 6 C2-C with polyols having hydroxy groups 12 Esters of dicarboxylic acids.

[0106] Natural or synthetic triglycerides and derivatives, including glyceryl esters C6-C modified by reaction with other alcohols 18 Di- or tri-based fatty acids Glycerides (e.g., caprylic / capric triglyceride, wheat germ glyceride). Fatty acid esters of polyglycerin (polyglyceryl-n, e.g., polyglyceryl-4 caprylates) Plate, Polyglyceryl-2 Isostearate, etc.), or Castor Oil, Hydrogenated Vegetable Oil , sweet almond oil, wheat germ oil, sesame oil, hydrogenated cottonseed oil, coconut oil, avocado oil, Coconut oil, hydrogenated castor oil, shea butter, cocoa butter, soybean oil, mink oil, sunflower oil, safflower Na oil, macadamia nut oil, olive oil, hydrogenated tallow, apricot kernel oil, hazelnut oil, luli such as jisa oil.

[0107] Waxes, including esters of long chain acids and alcohols, and waxes with wax-like properties compounds that produce color, such as carnauba wax, beeswax (white or yellow), lanolin wax Candelilla wax, ozokerite, Japan wax, paraffin wax, Microcrystalline wax, ceresin, cetearyl ester wax, synthetic beeswax, etc. On top of that, hydrophilic waxes as cetearyl alcohol or partial glycerides.

[0108] Pearlescent Wax: Alkylene glycol esters, especially ethylene glycol distearate; fatty acid alkyl esters Canolamide, especially coco fatty acid diethanolamide; partial glycerides, especially stearin Acid monoglycerides; polyhydric, unsubstituted fatty alcohols having 6 to 22 carbon atoms or esters of hydroxy-substituted carboxylic acids, especially long-chain esters of tartaric acid; fatty substances , for example, fatty alcohols, fatty ketones, fatty acids, etc., having a total of at least 24 carbon atoms. Fatty aldehydes, fatty ethers and fatty carbonates, especially lauryl and distearate ethers; fatty acids, such as stearic acid, hydroxystearic acid or behenic acid, Fatty alcohols having 12 to 22 carbon atoms and ring-opening products of olefin epoxides having 2 to 15 carbon atoms and and polyols having 2 to 10 hydroxy groups, and mixtures thereof.

[0109] Hydrocarbon oils: Mineral oil (light or heavy), petrolatum (yellow or white), microcrystalline wax, paraffin Hydrogenated isoparaffins as olefinic and isoparaffinic compounds, polydecene and polybutene Paraffin molecules, hydrogenated polyisobutene, squalane, isohexadecane, isododecane and others from the plant and animal kingdoms.

[0110] Silicone or Siloxane (Organo-substituted Polysiloxane) Dimethylpolysiloxane, methylphenylpolysiloxane, cyclic silicone, and Additionally, amino, fatty acid, alcohol, which may be either liquid or resinous at room temperature , polyether, epoxy, fluorine, glycoside and / or alkyl modified silicone Compounds: Linear polysiloxane, dimethicone (Dow Corning 200 fluid, Rho Mirasil DM), Dimethiconol, Cyclic Silicone Fluid, Cyclopentasiloxane Siloxane Volatiles (Dow Corning 345 Fluid), Phenyl Trimethicone (D (Low Corning 556 fluid). Also suitable are 200 to 300 dimethylsilanes. Simethicone, a mixture of dimethicone and hydrogenated silicate with an average chain length of hydroxyl units. A detailed investigation of suitable volatile silicones is given by Todd et al. in Cosm. To il. 91, 27 (1976).

[0111] emulsifier Any conventionally available emulsifier can be used for the composition. The system may include, for example: carboxylic acids and their salts: sodium, potassium alkaline soaps of ammonium and ammonium, metallic soaps of calcium or magnesium, Organic basic soaps, such as lauric acid, palmitic acid, stearic acid, and oleic acid Alkyl phosphate or phosphate ester, acid phosphate, diethanolamine phosphate, etc. , potassium cetyl phosphate. Ethoxylated carboxylic acid or polyethylene glycol esters PEG-n-acylate. A linear fatty alcohol having 8 to 22 carbon atoms, Fatty acids with 2 to 22 carbon atoms and 8 to 15 in the alkyl group and alkylphenols having 2 to 30 moles of branched oxidized phenols Ethylene and / or 0 to 5 mol propylene oxide. Fatty alcohol polyglycol Cholesterol ethers, such as laureth-n, ceteareth-n, steareth-n, oleth-n Fatty acid polyglycol ethers, such as PEG-n stearate and PEG oleate -n, coconut oil fatty acid PEG-n, monoglycerides and polyol esters, polyols C12-C22 fatty acid mono- and di-addition products of 1 to 30 moles of ethylene oxide with and diesters. Fatty acid and polyglycerol esters, e.g., monostearate glycol Glycerol, Diisostearoyl Polyglyceryl-3-Diisostearate, Polyglyceryl Triglyceryl-3-diisostearate, Triglyceryl diisostearate, Polyglyceryl- 2-sesquiisostearate or polyglyceryl dimerate. Mixtures of compounds from the monostearate group are also suitable. Diethylene glycol tearates, fatty acids and polyethylene glycol esters, fats Acid and sucrose esters, e.g., sucroesters, glycerol and sucrose esters Sorbitol and sorbitan, 6 to 22 carbon atoms, e.g., sucroglycerides. Sorbitan mono- and diesters of saturated and unsaturated fatty acids with hydroxyl groups, and oxidized esters Styrene addition products. Polysorbate-n series, sorbitan esters, e.g., sesquioxane Isostearate, Sorbitan, PEG-(6)-Sorbitan Isostearate, PEG -(10)-Sorbitan laurate, PEG-17-sorbitan dioleate. Glyco Derivatives, C8-C22 alkyl mono- and oligo-glycosides and ethoxylated In analogues, glucose is preferred as the sugar component. O / W emulsifiers, e.g., methyl gluceth -20 Sesquistearate, Sorbitan Stearate / Sucrose Cocoate, Sesquis Methyl glucose tearate, cetearyl alcohol / cetearyl glucoside. With or without milk Acidifiers, such as methyl glucose dioleate / methyl glucose isostearate. sulfates and sulfonated derivatives, dialkyl sulfosuccinates, dioctyl succinate Alkyl lauryl sulfonate, linear sulfonated paraffin, sulfonated sulfonic acid Tetrapropylene, sodium lauryl sulfate, ammonium and ethanolamine lauryl sulfate Lauryl sulfate, lauryl ether sulfate, sodium laureth sulfate, sulfos Succinate, acetyl isothionate, alkanolamide sulfate, taurine, methyl taurine Polysiloxane / polyalkyl / polyether copolymers and Derivatives, Dimethicone, Copolyol, Silicone Polyethylene Oxide Copolymer, Silicone Corn glycol copolymer. Propoxylated or POE-n ether (meloxapolyether) poly(oxyethylene) m-block-poly(oxypropylene), poloxamer or poly(oxyethylene) m-block-poly(oxypropylene) n-block (oxyethylene). At least one quaternary ammonium group per molecule and carrying at least one carboxylate and / or sulfonate group Zwitterionic surfactants. Particularly suitable zwitterionic surfactants are betaines, e.g., N-alkyl-N, each having 8 to 18 carbon atoms in the alkyl or acyl group ,N-Dimethylammonium Glycinate, Cocoalkyldimethylammonium Glycinate acrylate, N-acylaminopropyl-N,N-dimethylammonium glycinate, cocoa Aminopropyldimethylammonium glycinate and 2-alkyl-3-carbo hydroxymethyl-3-hydroxyethylimidazoline, and also cocoacylaminoethyl Hydroxyethyl carboxymethyl glycinate, N-alkyl betaine, N-alkyl Alkyl imidazolines, alkyl peptides, lipoamino acids, and amino acids. Self-emulsifying bases, and K.F. DePolo, A short textbook of cosmetology, Chapter 8, Table e 8-7, p 250-251.

[0112] Non-ionic bases, such as PEG-6 beeswax (and) PEG-6 stearate ( and) Polyglyceryl-2-isostearate, Glyceryl stearate (and) P EG-100 Stearate, PEG-5 Glyceryl Stearate, Sorbitan Oleate (and) Polyglyceryl-3 Ricinoleate, Sorbitan Stearate, and Palm Fat Sucrose Stearate, Glyceryl Stearate and Laureth-23, Cetearyl Alcohol and and Ceteth-20, Cetearyl Alcohol and Polysorbate 60 and PEG-15 0 and Stearate-20, Cetearyl Alcohol and Cetearyl Polyglucoside, Cetearyl Alcohol and Ceteareth-20, Cetearyl Alcohol and PEG-4 0 Castor Oil, Cetearyl Alcohol and PEG-40 Castor Oil and Cetearyl Sulfate Sodium, Stearyl Alcohol and Steareth-7 and Steareth-10, Ceteareth Alcohol and Steareth-7 and Steareth-10, Glyceryl Stearate and PEG-75 stearate, propylene glycol ceteth-3 acetate, propylene glycol Cetearyl alcohol and ceteth-12 and and Oleth-12, PEG-6 Stearate and PEG-32 Stearate, Stearin PEG-6 Stearate and Ceteth-20 and Steareth-20, PEG-6 Stearate and and ceteth-20 and glyceryl stearate and steareth-20, glyceryl stearate Lyceryl and Ceteareth-20.

[0113] Anionic alkaline bases, such as PEG-2SE stearate, glycol stearate Lyceryl SE, propylene glycol stearate. Anionic acid-base, e.g., cetea Cetearyl Alcohol and Sodium Cetearyl Sulfate, Cetearyl Alcohol and Lauryl Sodium sulfate, trilaneth-4 phosphate and glycol stearate and stearyl alcohol PEG-2 Stearate, Glyceryl Stearate and Sodium Lauryl Sulfate. Acid-bases, such as cetearyl alcohol and cetrimonium bromide.

[0114] Adjuvants and additives Cosmetic sunscreen compositions, such as creams, gels, lotions, alcoholic and Aqueous / alcoholic solutions, emulsions, wax / fat compositions, stick preparations, powders The powder or ointment may additionally contain, as further adjuvants and additives, a mild surfactant. , superfatting agents, consistency regulators, thickeners, polymers, stabilizers, bioactive ingredients, swelling agents, further UV photoprotective factors, antioxidants, hydrotropic agents, preservatives, self-tanning agents, solubilizers, balms, It may contain colorants, bacterial inhibitors, etc.

[0115] Superfatting agent Suitable substances for use as superfatting agents include, for example, lanolin and lecithin, and Polyethoxylated or acetylated lanolin and lecithin derivatives, polyol fats fatty acid esters, monoglycerides and fatty acid alkanolamides, the latter of which also acts as a foam stabilizer. Acts as a stabilizer.

[0116] surfactants Suitable mild surfactants, i.e. surfactants that are particularly well tolerated by the skin, are preferred. Examples of anti-inflammatory agents include fatty alcohol polyglycol ether sulfate, monoglycol sulfate, Celite, mono and / or dialkyl sulfosuccinate, fatty acid isethionate, fat Fatty acid sarcosinate, fatty acid tauride, fatty acid glutamate, alpha-olefin Sulfonates, ether carboxylic acids, alkyl oligoglucosides, fatty acid glucamides, alkylamidobetaine and / or protein fatty acid condensation products, the latter of which is Preferably based on wheat protein.

[0117] Consistency Control Agents / Thickeners and Rheology Modifiers Silicon dioxide, magnesium silicate, aluminum silicate, polysaccharides or their derivatives Body, such as hyaluronic acid, xanthan gum, guar guar, agar, alginate, carrageenan Naan, gellan, pectin, or modified cellulose, e.g., hydroxycellulose, hydroxypropylcellulose, Hydroxypropyl methylcellulose, plus reticulated acrylic acid and polyacrylamide Polyacrylate or homopolymer, carbomer (CARBOPOL type 980, 98 1, 1382, ETD2001, ETD2020, ULTREZ10) or SALCA RE range, e.g., SALCARE SC80 (steareth-10 allyl ether / acrylamide Acrylate copolymer), Salcare SC81 (acrylate copolymer), Salcare SC9 1 and Salcare AST (sodium acrylate copolymer / PPG-1 trideceth-6 ), SEPIGEL 305 (Polyacrylamide / Laureth-7), SIMULGEL NS and SIMULGEL EG (hydroxyethyl acrylate / acryloyldimethyl acrylate) Sodium glutaurate copolymer), STABILEN30 (acrylate / isodeca Vinyl phosphate crosspolymer), PEMULEN TR-1 (Acrylate / C10-30 Acrylate alkyl crosspolymer), LUVIGEL EM (sodium acrylate crosspolymer) polymer), ACULYN28 (Acrylates / Beheneth-25 Methacrylate Copolymer ) etc.

[0118] polymer Anionic, zwitterionic, amphoteric and nonionic polymers include, for example, vinyl acetate. Vinyl / crotonic acid copolymer, Vinylpyrrolidone / vinyl acrylate copolymer, Vinyl acetate butyl maleate / isobornyl acrylate copolymer, methyl vinyl ether / Water-maleic acid copolymer and its ester, uncrosslinked polyacrylic acid and polyol Crosslinked polyacrylic acid, acrylamidopropyl-trimethylammonium chloride / Acrylates Copolymer, Octyl Acrylamide / Methyl Methacrylate-tert -Butylaminoethyl methacrylate / 2-hydroxypropyl methacrylate copolymer -, polyvinylpyrrolidone, vinylpyrrolidone / vinyl acetate copolymer, vinylpyrrolidone methacrylate / vinyl caprolactam terpolymer, and Additionally, optionally derivatized cellulose ethers and silicones are contemplated. Furthermore, in the specification of European Patent No. 1093796 (pages 3-8, paragraphs 17-68): The polymers as listed may be used.

[0119] Bioactive ingredients Bioactive ingredients include, for example, tocopherol, tocopherol acetate, tocopherol palmitate, cellulose, deoxyribonucleic acid, retinol, bisabolol, allantoin, phytanthol Ol, panthenol, AHA acid, amino acid, ceramide, pseudoceramide, essential oil, plant extract and multivitamin preparations.

[0120] antioxidants In addition to primary photoprotective agents, they are triggered when UV radiation penetrates the skin or hair. It is also possible to use secondary photoprotective substances of the antioxidant class which interrupt the photochemical chain. Typical examples of such antioxidants are amino acids (e.g., glycine, histidine, tyrosine, tryptophan) and its derivatives, imidazoles (e.g., urocanic acid) and its derivatives Derivatives, peptides, such as D,L-carnosine, D-carnosine, L-carnosine and and its derivatives (e.g., anserine), carotenoids, carotene, lycopene and its derivatives derivatives, chlorogenic acid and its derivatives, lipoic acid and its derivatives (e.g., dihydrolipoic acid acid), aurothioglucose, propylthiouracil and other thiols (e.g., thio Redoxin, glutathione, cysteine, cystine, cystamine, and their glycosylation N-acetyl, methyl, ethyl, propyl, amyl, butyl, lauryl, palmitoyl oleyl, linoleyl, cholesteryl and glyceryl esters) and Salt, Dilauryl Thiodipropionate, Distearyl Thiodipropionate, Thiodipropion Phosphonic acids and their derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides) amides and salts), and also sulfoximine compounds (e.g., buthionine sulfoximines, Homocysteine ​​sulfoximine, buthionine sulfone, penta-, hexa-, hepta- thionine sulfoximine), as well as (metal) chelating agents (e.g., hydroxy fatty acids acid, palmitic acid, phytic acid, lactoferrin), hydroxy acids (e.g., citric acid, milk acid, malic acid), humic acid, bile acids, bile extract, bilirubin, biliverdin, EDTA , EDDS, EGTA and its derivatives, unsaturated fatty acids and their derivatives (e.g., linoleic acid, oleic acid, linoleic acid, oleic acid), folic acid and its derivatives, ubiquinone and ubiquitin vitamin C and its derivatives (e.g., ascorbyl palmitate), , magnesium ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (e.g., vitamin E acetate), vitamin A and derivatives (e.g., vitamin A palm oil), mitate), as well as coniferyl benzoate, rutin acid and the like of benzoin resin. Derivatives of glycosyl rutin, ferulic acid, furfurylidene glucitol, carnosine, Butylhydroxytoluene, butylhydroxyanisole, nordihydroguaiaretic acid, Trihydroxybutyrophenone, uric acid and its derivatives, mannose and its derivatives, Superoxide dismutase, N-[3-(3,5-di-tert-butyl-4-hydroxybenzoate] (hydroxyphenyl)propionyl]sulfanilic acid (and its salts, e.g., disodium salts), selenium and its derivatives (e.g., selenium methionine), stilbene and its derivatives conductors (e.g., stilbene oxide, trans-stilbene oxide), as well as their described Suitable derivatives (salts, esters, ethers, sugars, nucleotides) of the active ingredients according to the present invention HALS (= Hindered Amine Ligands, nucleotides, peptides and lipids). "Stabilizer" compounds can also be described.

[0121] Hydrotropic agent To improve the flow behavior, hydrotropic agents, such as ethoxylated or non-ethoxylated olefins with a low number of carbon atoms, may be used. Ethoxylated mono-alcohols, diols or polyols or their ethers ( For example, ethanol, isopropanol, 1,2-dipropanediol, propylene glycol Coal, glycerin, ethylene glycol, ethylene glycol monoethyl ether, ethylene ethylene glycol monobutyl ether, propylene glycol monomethyl ether, Pyrene glycol monoethyl ether, propylene glycol monobutyl ether, diene Diethylene glycol monomethyl ether; Diethylene glycol monoethyl ether, Diethylene It is also possible to use ethylene glycol monobutyl ether and similar products. The polyols that come into consideration for this purpose preferably have from 2 to 15 carbon atoms and at least Polyols contain further functional groups, especially amino groups. and / or modified with nitrogen. Typical examples are: Glycerol, alkylene glycols such as ethylene glycol, diethylene glycol Glycol, Propylene Glycol, Butylene Glycol, Hexylene Glycol, and and polyethylene glycols having an average molecular weight of 100 to 1000 daltons. Coal; technical oligoglycerol mixtures with an intrinsic degree of condensation of 1.5 to 10, e.g. For example, technical diglycerol blends having a diglycerol content of 40% to 50% by weight. compounds; methylol compounds, for example, especially trimethylolethane, trimethylolpropane , trimethylolbutane, pentaerythritol and dipentaerythritol; lower alkyl Alkyl glucosides, especially those with 1 to 8 carbon atoms in the alkyl radical methyl and butyl glucosides; sugar alcohols having 5 to 12 carbon atoms; sugars, such as sorbitol or mannitol; sugars having 5 to 12 carbon atoms , e.g., glucose or sucrose; amino sugars, e.g., glucamine; dialcohol amino diethanolamine or 2-amino-1,3-propanediol.

[0122] Preservatives and Bacterial Inhibitors Suitable preservatives include, for example, methyl-, ethyl-, propyl-, and butyl-paraben. , benzalkonium chloride, 2-bromo-2-nitro-propane-1,3-diol, dehy Doroacetic acid, diazolidinyl urea, 2-dichlorobenzyl alcohol, DMDM ​​hydanto In, formaldehyde solution, methyldibromoglutaronitrile, phenoxyethanol , sodium hydroxymethylglycinate, imidazolidinyl urea, triclosan, and and further substance classes listed in the following references: KF DePolo-As hort textbook of cosmetology, Chapter 7, Table 7-2, 7-3, 7-4 and 7-5, p 210-219 .

[0123] Bacterial inhibitors Typical examples of antibacterial agents are preservatives with specific action against gram-positive bacteria, e.g. 2,4,4'-trichloro-2'-hydroxydiphenyl ether, chlorhexidine ( 1,6-di(4-chlorophenyl-biguanide)hexane) or TCC(3,4,4' -trichlorocarbanilide). Many aromatic substances and ethereal oils have antimicrobial properties. Typical examples are the active ingredient eugenol in clove oil, mint oil and thyme oil. The natural deodorants of interest are phenol, menthol, and thymol in lime blossom oil. The terpene alcohol farnesol (3,7,11-trimethyl-2,6,1 Glycerol monolaurate is also a staphylococcus aureus (Schwarzwald-1999). It has been proven to be a fungicide.

[0124] coloring agent As coloring agents, for example, those described in the publication "Kosmetische Farbemittel" of the Farbstoffkommis sion der Deutschen Forschungsgemeinschaft, Verlag Chemie, Weinheim, 1984, pages Substances suitable and permitted for cosmetic purposes, as compiled in 81 to 106 can be used.

[0125] UV screening agent Suitable sunscreens include 1(+ / -)-1,7,7-trimethyl-3-[(4-methyl (phenyl)methylene]bicyclo-[2.2.1]heptan-2-one;p-Methylbenzene Lidene camphor, 1,7,7-trimethyl-3-(phenylmethylene)bicyclo[2. 2.1]Heptan-2-one; Benzylidene camphor, (2-hydroxy-4-methoxy (4-methylphenyl)methanone, 2,4-dihydroxybenzophenone, 2,2',4,4'-Tetrahydroxybenzophenone, 2-hydroxy-4-methoxy Benzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, 2, 2'-Dihydroxy-4,4'-dimethoxybenzophenone, 2,2'-dihydroxy- 4-Methoxybenzophenone, alpha-(2-oxoborn-3-ylidene)toluene -4-sulfonic acid and its salts, 1-[4-(1,1-dimethylethyl)phenyl]- 3-(4-Methoxyphenyl)propane-1,3-dione, Methyl N,N,N-trimethyl 4-[(4,7,7-trimethyl-3-oxobicyclo[2,2,1]-hepta-2 -ylidene)methyl]anilinium sulfate, 3,3,5-trimethylcyclohexyl 2-hydroxybenzoate, isopentyl p-methoxycinnamate, menthyl o-Aminobenzoate, 2-ethylhexyl 2-cyano, 3,3-diphenylacrylate ester, 2-ethylhexyl 4-(dimethylamino)benzoate, 2-ethylhexyl 4 -Methoxycinnamate, 2-ethylhexyl salicylate, benzoic acid, 4,4',4"- (1,3,5-triazine-2,4,6-triyltriimino)tris-, tris(2- Ethylhexyl) ester, 4-aminobenzoic acid, benzoic acid, 4-amino-, ethyl ester terephthalate, polymer with oxirane, 2-phenyl-1H-benzimidazole-5-sulfonyl Phosphonic acid, 2-propenamide, N-[[4-[(4,7,7-trimethyl-3-oxo-bis( chloro[2.2.1]hept-2-ylidene)methyl]phenyl]methyl]-, homopolymer -, Triethanolamine salicylate, 3,3'-(1,4-phenylenedimethylene)bis S[7,7-dimethyl-2-oxo-bicyclo[2.2.1]heptane-1-methanesulfonyl] phosphate], titanium dioxide, 2,2'-methylene-bis-[6-(2H-benzotriazolium (2-yl)-4-(1,1,3,3-tetramethylbutyl)-phenol], bis- Ethylhexyloxyphenol methoxyphenyl triazine, 1H-benzimidazo 4,6-disulfonic acid, 2,2'-(1,4-phenylene)bis-, disodium salt , benzoic acid, 4,4'-[[6-[[4-[[(1,1-dimethylethyl)amino]carboxamide [N-phenyl]amino]1,3,5-triazine-2,4-diyl]diimino]bi phenol, 2-(2H-benzotriazol-2-yl)-4-methyl-6-[2 -methyl-3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy] Disiloxanyl]propyl]-, dimethicone diethyl benzalmalonate, benzenesulfonate Acid, 3-(2H-benzotriazol-2-yl)-4-hydroxy-5-(1-methyl Propyl)-, monosodium salt, benzoic acid, 2-[4-(diethylamino)-2-hydro oxybenzoyl]-, hexyl ester, 1-dodecanaminium, N-[3-[[4- (Dimethylamino)benzoyl]amino]-propyl]N,N-dimethyl-, 4-methyl Salt with benzenesulfonic acid (1:1), 1-propaneaminium, N,N,N-trimethyl 3-[(1-oxo-3-phenyl-2-propenyl)amino]-, chloride, 1H -Benzimidazole-4,6-disulfonic acid, 2,2'-(1,4-phenylene)bis -, 1,3,5-triazine, 2,4,6-tris(4-methoxyphenyl)-, 1,3 ,5-triazine, 2,4,6-tris[4-[(2-ethylhexyl)oxy]phenyl 1-propanaminium, 3-[[3-[3-(2H-benzotriazole-2- yl)-5-(1,1-dimethylethyl)-4-hydroxyphenyl]-1-oxopropanol Pyr]amino]-N,N-diethyl-N-methyl-, methyl sulfate (salt), 2-propenoic acid , 3-(1H-imidazol-4-yl)-, benzoic acid, 2-hydroxy-, [4-(1 -methylethyl)phenyl]methyl ester, 1,2,3-propanetriol, 1-( 4-aminobenzoate), benzeneacetic acid, 3,4-dimethoxy-α-oxo-, 2-propanol Ropenoic acid, 2-cyano-3,3-diphenyl-, ethyl ester, anthranilic acid, p- Menth-3-yl ester, 2,2'-bis(1,4-phenylene)-1H-benzimi Dazole-4,6-disulfonic acid monosodium salt or phenyldibenzimidazole Disodium tetrasulfonate, 1,3,5-triazine-2,4,6-triamine and and N,N'-bis[4-[5-(1,1-dimethylpropyl)-2-benzoxazolyl ]phenyl]-N"-(2-ethylhexyl). Contains UV screening agent.

[0126] Agents that absorb ultraviolet light and / or provide photoprotection to the skin Absorbs UV rays and / or provides photoprotection to the skin and / or Suitable agents that provide sunless tanning are represented by Formula I:

[0127] [ka] or a salt thereof. (In the formula, Each R 1 are independently H, (C1-C6) alkyl, (C3-C7) carbocycle, or R a C( =O)- and two R 4 The groups taken together are -(C3-C8) alkyl groups, -(C2- C6) alkyl-Y-(C2-C6) alkyl group or -(C1-C6) alkyl-Y '-(C1-C6) alkyl group; or Each R 4 are independently H, (C1-C6) alkyl, (C3-C7) carbocycle, or R a C( =O)- and two R 1 The groups taken together are -(C3-C8) alkyl groups, -(C2- C6) alkyl-Y-(C2-C6) alkyl group or -(C1-C6) alkyl-Y '-(C1-C6) alkyl group; or The Two R's 4 The groups taken together form -(C3-C8) alkyl, -(C2-C6) alkyl -Y-(C2-C6) alkyl group or -(C1-C6) alkyl-Y'-(C1-C 6) Form an alkyl group and two R 1 The groups together form a -(C3-C8) alkyl group, (C2-C6) alkyl-Y-(C2-C6) alkyl group or -(C1-C6) alkyl Forming a alkyl-Y'-(C1-C6) alkyl group; The dashed bond labeled "a" does not exist, and the dashed bond labeled "b" does. are double bonds; or, all dashed bonds are single bonds; R 2 is H, (C1-C6) alkyl or aryl, where aryl is one or Multiple Zs 1 optionally substituted with a group; R 3 is H, (C1-C6) alkyl or aryl, where aryl is one or Multiple Zs 1 optionally substituted with a group; Y is O, S, NH, NR c , P, P(=O) or POH; Y' is Si(R b )2 or -Si(R b )2-O-Si(R b )2- and; Each R a are independently (C1-C6) alkyl, (C3-C7) carbocycle, or aryl. wherein aryl is one or more Z 1 optionally substituted with a group; Each R bare independently (C1-C6) alkyl, (C3-C7) carbocycle, or aryl. where aryl is one or more Z 1 optionally substituted with a group; Each R c is independently R g or oxo (=O), hydroxy, mercapto, (C (1-C6) alkoxy, (C1-C6) alkoxycarbonyl, (C1-C6) alkano Iloxy, NR d R e , carboxy, and aryl; or C1-C optionally substituted with multiple groups 18 a saturated or unsaturated carbon chain, where R c Any aryl in f and replaced as necessary with ; Each R d and R e is H, (C1-C6) alkyl, (C1-C6) alkanoyl, phenyl Nil, Benzyl, and R g are independently selected from; Each R f is (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) alkoxy oxycarbonyl, (C1-C6)alkanoyloxy, -C(=O)-phenyl, and -C(=O)CHC(=O)-phenyl, wherein any phenyl The group is independently selected from (C1-C6) alkyl, -SO3H, and (C1-C6) alkoxy. optionally substituted with one or more groups selected from the group consisting of: Each R g teeth,

[0128] [ka] and each Z1 is (C1-C6) alkyl, halogen, -CN, -OR n1 , -NR q1 R r1 , -NR n1 COR p1 , -NR n1 CO2R p1 , NO2, -C(O)R n1 , -C( O)OR n1 and -C(O)NR q1 R r1 , are independently selected from Z 1 Any of ( C1-C6) alkyl is one or more (e.g., 1, 2, 3, 4, 5, or 6) optionally substituted with halogen; Each R n1 are independently selected from H and (C1-C6) alkyl; R n1 Any of ( C1-C6) alkyl is one or more (e.g., 1, 2, 3, 4, 5, or 6) optionally substituted with halogen; Each R p1 are independently (C1-C6) alkyl; R q1 and R r1 are each independently selected from H and (C1-C6) alkyl; or R q1 and R r1 together with the nitrogen to which they are attached to form piperi azine, pyrrolidine, morpholine, azetidine, thiomorpholine, piperazine or 4- (forming methylpiperazine)

[0129] Specific groups and groups of compounds of formula I that can be incorporated into the topical compositions described herein Certain compounds of formula I, as well as methods for preparing such compounds, are disclosed in U.S. Pat. No. 9,403,777. 78 and U.S. Pat. No. 9,987,211, which are No. 6,029,139, which is incorporated herein by reference in its entirety.

[0130] Absorbs UV rays and / or provides photoprotection to the skin and / or Suitable agents that provide sunless tanning are represented by Formula II:

[0131] [ka] or a salt thereof. (In the formula, R 1 is H, (C1-C6) alkyl, (C3-C7) carbocycle or R a C(=O)- the law of nature; R 2 is H, (C1-C6) alkyl or aryl, where aryl is one or Multiple (e.g., 1, 2, 3, 4, or 5) Zs 1 optionally substituted with a group; R 4 is H, (C1~C 10 ) alkyl, (C3-C7) carbocycle or R a C(=O)- can be; R a is (C1-C6) alkyl, (C3-C7) carbocycle or aryl, Aryl can have one or more (e.g., 1, 2, 3, 4, or 5) Z 1 Based on the need has been replaced by; each Z 1 is (C1-C6) alkyl, halogen, -CN, -OR n1 , -NR q1 R r1 , -NR n1 COR p1 , -NR n1 CO2R p1 , NO2, -C(O)R n1 , -C( O)OR n1 and -C(O)NRq1 R r1 are independently selected from Z 1 Any (C 1-C6) alkyl is one or more (e.g., 1, 2, 3, 4, 5, or 6) alkyl groups. optionally substituted with methyl; Each R n1 are independently selected from H and (C1-C6) alkyl; R n1 Any of ( C1-C6) alkyl is one or more (e.g., 1, 2, 3, 4, 5, or 6) optionally substituted with halogen; Each R p1 are independently (C1-C6) alkyl; R q1 and R r1 are each independently selected from H and (C1-C6) alkyl; or R q1 and R r1 together with the nitrogen to which they are attached to form piperi azine, pyrrolidine, morpholine, azetidine, thiomorpholine, piperazine or 4- (forming methylpiperazine)

[0132] Certain groups of compounds of formula II that can be incorporated into the topical compositions described herein and Certain compounds of formula II, as well as methods for preparing such compounds, are disclosed in U.S. Pat. No. 9,987, ,211, which is incorporated herein by reference in its entirety. do.

[0133] Suitable agents that absorb ultraviolet radiation and / or provide photoprotection to the skin are represented by Formula III:

[0134] [ka] or a salt thereof. (In the formula, Each R1 are independently H, (C1-C6) alkyl, (C3-C7) carbocycle, or R a C( =O; or two R 1 The groups together form a -(C3-C8) alkyl group, a -(C (2-C6) alkyl-Y-(C2-C6) alkyl group or -(C1-C6) alkyl group forming a -Y'-(C1-C6) alkyl group; or The dashed bond labeled "a" does not exist, and the dashed bond labeled "b" does. are double bonds; or, all dashed bonds are single bonds; R 2 is H, (C1-C6) alkyl or aryl, where aryl is one or Multiple (e.g., 1, 2, 3, 4, or 5) Zs 1 optionally substituted with a group; R 3 is H, (C1-C6) alkyl or aryl, where aryl is one or Multiple (e.g., 1, 2, 3, 4, or 5) Zs 1 optionally substituted with a group; R 4 is hydroxy, carboxy, (C1-C6) alkoxycarbonyl, -OPO3H 2, -OR c , or -NR d R e and;R 5 is H; or R 4 and R 5 What is one Together they are oxo; Y is O, S, NH, P, P(=O) or POH; Y' is Si(R b )2 or -Si(R b )2-O-Si(R b )2- and; R a are independently (C1-C6) alkyl, (C3-C7) carbocycle, or aryl; aryl is selected from the group consisting of one or more (e.g., 1, 2, 3, 4, or 5) Z 1 Essential have been replaced as necessary; Each R b are independently (C1-C6) alkyl, (C3-C7) carbocycle, or aryl. wherein aryl is one or more (e.g., 1, 2, 3, 4, or 5) Z 1 Based on have been substituted as necessary; R c is R f or oxo (=O), hydroxy, mercapto, (C1-C6 ) alkoxy, (C1-C6) alkoxycarbonyl, (C1-C6) alkanoyloxy Shi, NR d R e one or more independently selected from , carboxy, and aryl C1-C optionally substituted with a group 20 Saturated or C2~C 20 Unsaturated carbon chain wherein aryl is one or more (e.g., 1, 2, 3, 4, or 5) Z 1 Based on have been substituted as necessary; R d is H, (C1-C6) alkyl, or (C1-C6) alkanoyl; R e is H or oxo (=O), hydroxy, mercapto, (C1-C6) Alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy , N.R. d R e one or more independently selected from , carboxy, and aryl; C1-C optionally substituted with groups 20 Saturated or C2~C 20 It is an unsaturated carbon chain aryl is selected from the group consisting of one or more (e.g., 1, 2, 3, 4, or 5) Z 1Essential have been replaced as necessary; Each R f teeth,

[0135] [ka] and each Z 1 is (C1-C6) alkyl, halogen, -CN, -OR n1 , -NR q1 R r1 , -NR n1 COR p1 , -NR n1 CO2R p1 , NO2, -C(O)R n1 , -C( O)OR n1 and -C(O)NR q1 R r1 , are independently selected from Z 1 Any of ( C1-C6) alkyl is one or more (e.g., 1, 2, 3, 4, 5, or 6) optionally substituted with halogen; Each R n1 are independently selected from H and (C1-C6) alkyl; R n1 Any of ( C1-C6) alkyl is one or more (e.g., 1, 2, 3, 4, 5, or 6) optionally substituted with halogen; Each R p1 are independently (C1-C6) alkyl; R q1 and R r1 are each independently selected from H and (C1-C6) alkyl; or R q1 and R r1 together with the nitrogen to which they are attached to form piperi azine, pyrrolidine, morpholine, azetidine, thiomorpholine, piperazine or 4- (forming methylpiperazine)

[0136] Certain groups of compounds of formula III and formula I that can be incorporated into the formulations described herein Certain compounds of formula II, as well as methods for preparing such compounds, are disclosed in U.S. Pat. No. 9,364, 406 and U.S. Pat. No. 9,987,211, is incorporated herein by reference in its entirety.

[0137] sunscreen Formulations disclosed herein include avobenzone, ecamsule, methyl anthranilate, benzoxan, oxybenzone, dioxybenzone, sulisobenzone, octinoxate, homoxan sunscreens such as octocrylene, octisalate, and octisalate Such compositions are suitable for use in the UVA and / or UVB and / or IR and / or organic UV filters active in the VIS region (absorbers), so-called hydrophilic or lipophilic These substances may contain active sun protection filters. These substances are in particular cinnamic acid derivatives, salicylic acid derivatives, Citric acid derivatives, camphor derivatives, triazine derivatives, β,β-diphenyl acrylate Derivatives, p-aminobenzoic acid derivatives, polymer filters and silicone filters These are described in WO 93 / 04665. Further examples of organic filters are described in EP 0 487 404 A1. Particularly suitable for combination are para-aminobenzoic acid and its derivatives. : PABA, Ethyl PABA, Ethyl Dihydroxypropyl PABA, Ethylhexyl Di Methyl PABA, such as that sold by ISP under the name "Escarol 507" Glyceryl PABA, PEG-25 PABA, e.g. "Uvinul P25" It is marketed by BASF under the name

[0138] Other UV filter ingredients that can be incorporated into the topical compositions of the present disclosure include: These include:

[0139] Salicylates: Marketed by Merck under the name "Eusolex HMS" Homosalate; ethylhexyl salicylate, e.g. "Neo Heliopan OS" Dipropylene glycol salicylate, marketed by Symrise under the name , for example, that sold by Scher under the name "Dipsal", salicylic acid T EA, for example, marketed by Symrise under the name "Neo Heliopan TS" Something that is being used.

[0140] β,β-Diphenylacrylate derivatives: Octocrylene, e.g., as marketed by Merck as " Eusolex® OCR" manufactured by BASF, inul N539" and octocrylene, e.g., "Uvinul N35" by BASF It is sold commercially under the name ".

[0141] Benzophenone derivatives: Benzophenone-1, for example, under the name "Uvinul 400" Benzophenone-2, for example, under the name "Uvinul D50" Benzophenone-3 or oxybenzone, e.g. "Uvin ul M40"; benzophenone-4, e.g., "Uvin ul MS40"; benzophenone-9, e.g., "Uvi benzophenone-, marketed by BASF under the name "DS-49" 5. Benzophenone-6, for example, "Helisorb 11" in Norquay More commercially available are benzophenone-8, e.g., American Cyanam The product sold under the name "Spectra-Sorb UV-24" by ID, Benzophenone-12 2-(4-diethylamino-2-hydroxybenzoyl)benzoic acid n-hexyl, or Eusolex® by Merck, Darmstadt ) 2-hydroxy-4-methoxybenzophenone, commercially available under the name 4360.

[0142] Benzylidene camphor derivatives: 3-benzylidene camphor, e.g., Chimex It is commercially available under the name "Mexoryl SD" from For example, it is marketed by Merck under the name "Eusolex 6300". benzylidene camphorsulfonic acid, e.g., "Mexory" by Chimex Camphor benzalkonium methosulfate, sold under the name "I SL" , for example, that sold under the name "Mexoryl SO" by Chimex, Terephthalylidene discamphorsulfonic acid, e.g., "Mexoryl" by Chimex SX" and polyacrylamide methyl benzylidene camphor. For example, the product sold by Chimex under the name "Mexoryl SW" .

[0143] Phenylbenzimidazole derivatives: phenylbenzimidazole sulfonic acids, e.g. The one sold by Merck under the name "Eusolex 232" is a phenyldiamine. Benzimidazole tetrasulfonate disodium, e.g., "Ne" by Symrise It is sold under the name "Heliopan AP".

[0144] Phenylbenzotriazole derivatives: drometrizole trisiloxane, e.g. Rho Marketed by dia Chimie under the name "Silatrizole".

[0145] Methylenebis(benzotriazolyl)tetramethylbutylphenol in solid form, e.g. For example, Fairmount Chemical may use the name "MIXXIM BB / 100" or in micronized form as an aqueous dispersion, e.g., by BASF It is sold commercially under the name "Tinosorb M."

[0146] Triazine derivatives: ethylhexyltriazone, e.g. "Uvinul" by BASF T150, diethylhexyl butamido triazone, e.g. For example, the one sold under the name "Uvasorb HEB" by Sigma 3V, 2,4,6-Tris(diisobutyl 4'-aminobenzalmalonate)-s-triazine or 2,4,6-tris(biphenyl)-1,3,5-triazine, T by BASF Commercially available as inosorb A2B, 2,2'-[6-(4-methoxyphenyl)- phenyl)-1,3,5-triazine-2,4-diyl]bis[5-(2-ethylhexyl )oxy]phenol, commercially available as Tinosorb S by BASF , N2,N4-bis[4-[5-(1,1-dimethylpropyl)-2-benzoxazolidinyl] phenyl]phenyl]-N-6-(2-ethylhexyl)-1,3,5-triazine-2,4, 6-Triamine, commercially available as Uvasorb K 2A by Sigma 3V Something that is needed.

[0147] Anthraniline derivatives: Menthyl anthranilate, e.g., " It is sold commercially under the name "Neo Heliopan MA."

[0148] Imidazole derivatives: Ethylhexyldimethoxybenzylidenedioxoimidazole Rhopionate.

[0149] Benzalmalonate derivatives: Polyorganosiloxanes containing functional benzalmalonate groups. siloxanes, such as polysilicone-15, e.g., Hoffmann LaRoch Marketed by e under the name "Parsol SLX."

[0150] 4,4-Diarylbutadiene derivatives: 1,1-dicarboxy(2,2'-dimethylpropane) propyl)-4,4-diphenylbutadiene.

[0151] Benzoxazole derivatives: 2,4-bis[5-(1-dimethylpropyl)benzoxazole] [Sazol-2-yl(4-phenyl)imino]-6-(2-ethylhexyl)imino-1 ,3,5-triazine, for example, Uvasorb K2A by Sigma 3V and mixtures containing same.

[0152] Suitable organic UV protection materials are preferably ethylhexyl salicylate, phenylbenzyl Imidazole sulfonic acid, benzophenone-3, benzophenone-4, benzophenone- 5. n-Hexyl 2-(4-diethylamino-2-hydroxybenzoyl)benzoate , 4-methylbenzylidene camphor, terephthalide discamphorsulfonic acid, phen Nildibenzimidazole tetrasulfonic acid disodium salt, methylene bis(benzotriazole) Zolyl) tetramethylbutylphenol, ethylhexyl triazone, diethylhexyl Butamidotriazon, Drometrizole Trisiloxane, Polysilicone-15, 1,1 -Dicarboxy(2,2'-dimethylpropyl)-4,4-diphenylbutadiene, 2, 4-bis[5-1(dimethylpropyl)benzoxazol-2-yl(4-phenyl) imino]-6-(2-ethylhexyl)imino-1,3,5-triazines and their It can be selected from a mixture.

[0153] The compositions of the present invention may contain further inorganic UV filters, so-called particulate UV filters. These combinations with particulate UV filters may be used as powders, dispersions or It can also be used as a paste. In one embodiment, the inorganic UV filter is titanium dioxide. , such as coated titanium dioxide (e.g., Eusolex® T-2000 , Eusolex(R) T-AQUA, Eusolex(R) T-AVO, zinc oxide (e.g., Sachtote), c) iron oxide or cerium oxide and / or zirconium oxide. It is also possible to combine it with titanium dioxide or zinc oxide of the grade, and the particle size of these pigments is 200n. m or more, for example, Hombitan® FG or Hombitan® Registered trademark FFPharma.

[0154] The compositions of the present invention are described, for example, in Cosmetics & Toiletries, 1990, 105, 53-64. The composition may also contain inorganic UV filters that have been post-treated by conventional methods, such as: The post-treatment component(s) may comprise one or more of an amino acid, beeswax, a fatty acid, a fatty acid alcohol, an anion, surfactants, lecithin, phospholipids, fatty acids containing sodium, potassium, zinc, iron or Aluminum salts, polyethylene, silicone, proteins (especially collagen or elastomers) tin), alkanolamines, silicon dioxide, aluminum oxide, further metal oxides, It may be a phosphate such as sodium hexametaphosphate, or glycerin.

[0155] In one embodiment, the particulate UV filters used in the compositions of the present invention are: Untreated titanium dioxide, e.g. the product Microtitanium Di from Tayca oxide MT 500 B; titanium dioxide P25 from Degussa; Micronized titanium dioxide post-treated with aluminum oxide and silicon dioxide post-treatment, e.g. Tayca Microtitanium Dioxide MT 100 SA"; or the product "Tioveil Fin" manufactured by Uniqema, Post-treatment with aluminum oxide and / or aluminum stearate / laurate Treated micronized titanium dioxide, e.g., Microtitanium from Tayca Dioxide MT 100 T, Eusolex T-2000 manufactured by Merck, Micronized titanium dioxide post-treated with iron oxide and / or iron stearate post-treatment, e.g. Tayca Microtitanium Dioxide MT 100 F”, Micronized diacid post-treated with silicon dioxide, aluminum oxide, and silicone post-treatment Titanium dioxide, for example the product "Microtitanium Dioxide" manufactured by Tayca MT 100 SAS" Micronized titanium dioxide post-treated with sodium hexametaphosphate, e.g. Tayca The product "Microtitanium Dioxide MT 150 W" manufactured by .

[0156] The treated micronized titanium dioxide used in the combination may also be: Octyltrimethoxysilane; for example, Evonik Goldschmidt G Tego Sun T 805, a product manufactured by mbH Silicon dioxide; for example, the product Parsol TX manufactured by DSM Aluminum oxide and stearic acid; for example, the product UV from Sachtleben -Titan M160, Aluminum and glycerin; for example, the product UV-Ti from Sachtleben tan, Aluminum and silicone oil; for example, the product UV from Sachtleben -Titan M262, sodium hexametaphosphate and polyvinylpyrrolidone, Polydimethylsiloxane, e.g., Cardre's product 70250 Cardre UF TiO2SI3" Polydimethylhydrogenosiloxane, e.g., Color Technique "Microtitanium Dioxide USP Grade Hydrophobic" manufactured by s, It may be post-treated with

[0157] In certain embodiments, the compositions of the present invention comprise untreated zinc oxide, e.g., BASF (S unsmart) and Nanox by Elementis. In another particular embodiment, the composition of the present invention comprises post-treated zinc oxide, such as Products: Toshibi's "Zinc Oxide CS-5" (Polymethyl Hydrogen ZnO post-treated with siloxane); Nanogard Zinc Oxide from Nanophase Technologies xide FN; "SPD-Z1" (silica dispersed in cyclodimethylsiloxane) manufactured by Shin-Etsu Chemical Co., Ltd. ZnO post-treated with ricone-grafted acrylic polymer); ISP's "Escalol Z100" (Ethylhexyl Methoxycinnamate / P Aluminum oxide post-treated Z dispersed in VP-hexadecene / methicone copolymer blend nO); and Fuji ZNO-SMS-10 (silicon dioxide and poly methylsilsesquioxane-post-treated ZnO).

[0158] In another particular embodiment, the composition of the present invention comprises an untreated cerium oxide fine pigment, e.g., R "Colloidal Cerium Oxide" manufactured by Hone Poulenc In another specific embodiment, the composition of the present invention may include those named Arnau The composition may also contain untreated and / or post-treated iron oxides under the name Nanogar manufactured by .

[0159] Examples include titanium dioxide and cerium oxide, with or without post-treatment. a mixture of various metal oxides such as Sunveil A, a product of Ikeda Bussan Co., Ltd. In addition, aluminum oxide, silicon dioxide and silicon dioxide can be used. Corn post-treated titanium dioxide, zinc oxide mixtures, e.g. products from Sachtleben UV-Titan M261 can also be used in combination with the UV protection agent according to the invention. can. How to use

[0160] In some embodiments, the present disclosure provides a method for treating a subject's skin against the effects of radical-induced damage. Radical-induced damage includes, for example, hydrolysis of elastin fibers in the skin. sun damage by breaking down collagen in the lower dermis layer of the skin. UVB, UVA, visible light), HEV (blue) light, infrared (IR), pollution, irritants, allergens These may include free radical damage from various environmental toxins that are destructive to the skin. After administering to the skin of a subject an effective amount of any of the topical compositions described herein, treatment As exemplary radical-induced damage that can be prevented, minimized, mitigated, or attenuated, These include, but are not limited to, severity of optical damage, lack of tactile smoothness, visual smoothness Lack of firmness, lack of softness, lack of brightness, lack of radiance, skin texture, skin wrinkles, facial small Wrinkles, crow's feet, skin discoloration, crayon skin texture, fine lines, rough skin, skin Looseness, loss of skin firmness and elasticity, age spots, hyperpigmentation, scars, skin surface Irregularities, rosacea, acne, psoriasis, slowed skin regeneration and renewal processes, sunburned appearance, yellowing These include eczema, redness, dryness, ichthyosis, and other damaged skin conditions.

[0161] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein for the duration of the tactile smoothness after administration of the formulation. The present invention relates to a method for improving bulk.

[0162] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein for a duration of time, The present invention relates to a method that exhibits improvements.

[0163] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein for the duration of the improvement in brightness after administration of the formulation. It concerns the method of presenting goodness.

[0164] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein for a duration of time, or improvement in radiance after administration of the formulation This relates to a method of exhibiting the above.

[0165] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein for the duration of the visually smooth The present invention relates to a method for improving bulk.

[0166] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or for a duration of a single value or subrange therein, improvement in firmness after administration of the preparation. This relates to a method of exhibiting the above.

[0167] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein for a duration of time, after administration of the formulation, The present invention relates to a method that exhibits improvements.

[0168] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein for a duration of time, after administration of the formulation, The present invention relates to a method for improving the appearance of aging.

[0169] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein for a duration of time, or a reduction in dryness after administration of the formulation This relates to a method of exhibiting the above.

[0170] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. to the skin of a subject, wherein the skin is treated with a comparative formulation. Compared with the increase in transepidermal water loss shown by administration of to about 14 weeks, about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value therein or for a partial range of duration after administration of the formulation, barrier damage (e.g., transepidermal water loss) The present invention relates to a method for treating retinoid-based steroid hormone-induced hyperlipidemia, which method exhibits a reduction in retinoid-based steroid hormone (as indicated by a reduction in the increase in retinoid loss). With the treatment of ulcerative colitis, some increase in transepidermal water loss (TEWL) can be expected, but in certain In certain embodiments, at a given time point of treatment (e.g., about 4 weeks, about 8 weeks, about 12 weeks, etc.), The increase in TEWL exhibited by skin treated with any of the formulations described herein was approximately 10 The increase in TEWL may be less than 0%, less than about 95%, less than about 90%, or less than about 88%. The increase can be measured by comparing it to a baseline measurement obtained at time zero before treatment began. Cut.

[0171] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein for the duration of crow's feet after administration of the formulation The present invention relates to a method for improving the appearance of scars.

[0172] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein for a duration of time, after administration of the product, The present invention relates to a method that exhibits improvements in the

[0173] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein for the duration of the tactile smoothness after administration of the formulation. Volume, softness, brightness, radiance, visual smoothness, firmness, skin texture, overall anti-photoaging The patient showed improvement in one or more of the following: dryness, crow's feet, or skin discoloration. experience improved tolerability when compared with comparably effective tretinoin formulations (e.g., (regarding one or more of itching, stinging, burning, redness, or swelling), Equally effective tretinoin formulations are available for application for about 1 to about 16 weeks, about 2 to about 14 weeks, and about 4 to about 18 weeks. weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or any single value or subrange therein After administration of the formulation, the patient experienced tactile smoothness, softness, brightness, brilliance, and visual Smoothness, firmness, skin texture, overall appearance of photoaging, dryness, crow's feet, or skin color and exhibit similar improvements in one or more of the abnormalities (i.e., the clinical (No statistically significant difference as defined in the clinical study) formulation.

[0174] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein for the duration of the tactile smoothness after administration of the formulation. Volume, softness, brightness, radiance, visual smoothness, firmness, skin texture, overall anti-photoaging The patient showed improvement in one or more of the following: dryness, crow's feet, or skin discoloration. experience reduced barrier damage when compared to comparably effective tretinoin preparations (e.g., Equivalently effective tretinoin formulations are effective for approximately 1 week. to about 16 weeks, about 2 weeks to about 14 weeks, about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein, for a duration of time, after administration of the formulation, Lightness, softness, brightness, radiance, visual smoothness, firmness, skin texture, overall anti-photoaging Similar improvements in one or more of the following: appearance, dryness, crow's feet, or skin discoloration exhibiting a statistically significant difference (i.e., as defined in the clinical studies described in the Examples) It is a formulation that does not have any side effects.

[0175] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein for the duration of the newly formed The present invention relates to a method for producing collagen.

[0176] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. wherein the skin is treated with a medicament containing benzoyl peroxidase (BPO) for about 1 week. from about 16 weeks, from about 2 weeks to about 14 weeks, from about 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or a single value or subrange therein for a duration of time, after administration of the formulation, At a given time point of treatment (e.g., about 4 weeks, about 8 weeks, about 12 weeks, etc.), Acanthosis increased by approximately 1% compared to baseline (e.g., at time zero before treatment began). 0%, approximately 20%, approximately 30%, or approximately 40% to approximately 50%, approximately 60%, or approximately 70% , approximately 80%, approximately 90%, approximately 100%, approximately 150%, or approximately 200% In certain embodiments, at a given time point of treatment (e.g., about 4 weeks, about 8 weeks, about 1 Epidermal thickening at week 2, etc., is at least about 10%, at least about 20%, at least about It can be about 30%, at least about 40%, or at least about 50%.

[0177] In certain embodiments, the present disclosure is directed to an effective amount of any of the formulations described herein. a method of treating the skin of a subject by administering to the skin of an equally effective When compared with effective tretinoin preparations, the results were approximately 1 to 16 weeks, approximately 2 to 14 weeks, and approximately 4 weeks to about 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or any single value or subrange therein and the patient exhibits greater acanthosis after administration of the formulation for a duration of approximately Tretinoin preparations that are effective for this purpose are those that last from about 1 week to about 16 weeks, from about 2 weeks to about 14 weeks, and from about 4 weeks to about A duration of 12 weeks, about 4 weeks, about 8 weeks, about 12 weeks, or any single value or subrange therein. During the period, after administration of the formulation, tactile smoothness, softness, brightness, brilliance, visual smoothness , firmness, skin texture, overall appearance of photoaging, dryness, crow's feet, or dyschromic pustules and show similar improvements in one or more of these (i.e., in the clinical studies described in the Examples). As defined, there is no statistically significant difference between the two formulations.

[0178] In certain embodiments, the present disclosure provides a method for treating a subject who has undergone or will undergo a dermatological treatment. a treatment regimen comprising administering to the skin of an individual an effective amount of any of the formulations described herein. In certain embodiments, the methods described herein include administering to a subject a therapeutically effective amount of ... compound in accordance with a treatment regimen. In addition, dermatological treatments may be performed after and / or before administration of the topical composition. In certain embodiments, the topical compositions described herein may be used to treat, for example, promote healing. Promotes, soothes discomfort, inhibits reactive oxygen species (ROS), induces collagen formation, or Any combination of these can help improve the outcome of dermatological treatments.

[0179] An effective amount will depend on the particular condition or conditions being treated, the severity of the condition, the duration of treatment, the use The amount of HCl used will vary depending on the specific components of the formulation being used, as well as other factors. The formulations described herein are administered by frequent, regular applications, e.g., at least once a day. At least 3 days, at least 5 days, at least 7 days, at least 10 days, at least 14 days, at least 21 days, at least 30 days, at least 8 weeks, at least 12 weeks, etc. Suitable for administration by, for example, one, two, three or four or more applications daily for a sustained period of time. Thus, in certain embodiments, the methods described herein involve administering a formulation The method further includes periodically repeating the method.

[0180] In certain embodiments, the formulations described herein are used pre-treatment, such as before or after a dermatological treatment. Or suitable for administration after treatment. Preparation method

[0181] The present disclosure also relates to methods of preparing any of the formulations described herein. The agent and delivery system may be prepared under ambient conditions. The formulation is prepared under an inert atmosphere. In certain aspects of this embodiment, the inert atmosphere is Inert gases such as, but not limited to, nitrogen, argon, or combinations thereof. In certain embodiments, the formulations of the present disclosure are prepared under a dry, inert atmosphere, This includes, but is not limited to, dry nitrogen, dry argon, or a combination thereof. , comprising, consisting essentially of, or containing one or more dry inert gases In certain embodiments, any of the dry, inert atmospheres described herein may be used. By preparing the formulation under and / or stabilize the formulation against precipitation.

[0182] In certain embodiments, the method for preparing the formulations described herein comprises multiple steps. The process involves solubilizing various components and finally To stabilize the formulation and reduce and / or minimize and / or eliminate precipitation, Accurately divide and / or associate with the corresponding conditions (e.g., temperature, mixing intensity, and duration) It can be done.

[0183] For example, a first amount of isopentyl diol (or another suitable polyol described herein) ol) in a first amount of polysorbate 80 (or another suitable surfactant described herein), and a xanthine, such as caffeine, to form a first mixture. The first mixture is heated to a first temperature (e.g., from about 60°C to about 120°C, from about 70°C to about 180°C, about 110°C, or about 80°C to about 100°C) for a first duration (e.g., about 15 minutes to for about 90 minutes, about 30 minutes to about 60 minutes, or about 40 minutes to about 50 minutes), e.g., In a mixer, the xanthine (e.g., caffeine) dissolves and the initial mixture becomes clear. Mixing can be performed until no lumps remain. In certain embodiments, the first mixture is then added. The mixture is heated to a second temperature (e.g., from about 50°C to about 110°C, from about 60°C to about 100°C, or The mixture can be cooled to a temperature of about 70°C to about 90°C.

[0184] In certain embodiments, a first amount of DMI and / or a first amount of ethoxydiglycol The coals can be added one at a time to the first mixture to ultimately form the second mixture. After each ingredient is added, the mixture is stirred until the second mixture is uniform and lump-free. Duration (e.g., about 1 minute to about 30 minutes, about 5 minutes to about 25 minutes, or about 10 minutes to about 20 minutes) ), and then, in certain embodiments, the second mixture may be heated to a third temperature (e.g., For example, from about 30°C to about 90°C, from about 40°C to about 80°C, or from about 50°C to about 70°C. Allow to cool.

[0185] In certain embodiments, in a first separate container, a second amount of isopentyl diol ( or a separate suitable polyol as described herein) with tea plant (Camellia sinensis ( It can be combined with green tea polyphenols to form a third mixture. In one embodiment, a diol is used to produce a lactic acid bacteria, for example, a mixture of a diol and tea plant (Camellia sinensi s) (green tea) by forming complexes with polyphenols, The third mixture is a mixture of 100% ethanol and 100% ethanol. ... The mixture may be mixed for a third period of time until the mixture is lump-free. The third mixture is then cooled to a third temperature substantially similar to the third temperature of the cooled second mixture. degrees (e.g., from about 30°C to about 90°C, from about 40°C to about 80°C, or from about 50°C to about 70°C) In certain embodiments, heating the third mixture can result in: In certain embodiments, the tea plant (Camellia sinensis) (green Tea polyphenols were not added directly to the second mixture, but instead were first mixed in a separate container. First solubilized to more effectively release tea plant (Camellia sinensis) (green tea) polyphenols Solubilize in

[0186] In certain embodiments, the third mixture is added to the second mixture to form a fourth mixture. It is possible.

[0187] In certain embodiments, in a second separate container, retinol (polysorbate 20 and and combining the plurality of soluble proteins (which may be complexed and / or cosolubilized) from the fourth mixture in concentrated form. ingredients, e.g., a second amount of polysorbate 80, a second amount of DMI, and a second amount of ethoxydiglycol to form a fifth mixture. Although retinol is not a preservative, by incorporating it into multiple ingredients in the formulation, Therefore, it is believed that retinol will remain stable in the formulation and will not precipitate. , can be mixed until uniform, lump-free and clear.

[0188] In certain embodiments, the fifth mixture is added to the fourth mixture and heated to a fourth temperature (e.g., , about 30°C to about 70°C, about 40°C to about 60°C, or about 45°C to about 55°C) A mixture of the following can be formed:

[0189] In certain embodiments, bakuchiol and / or additional antioxidants (e.g., black tea) Extract and / or licorice root extract) are added one at a time to the sixth mixture, and finally After each component is added, the mixture is stirred until the final formulation is uniform and lump-free. for a period of time (e.g., from about 1 minute to about 15 minutes, from about 3 minutes to about 10 minutes, or about The final formulation may then be mixed for about 4 minutes to about 6 minutes. Temperature (e.g., from about 10°C to about 50°C, from about 20°C to about 40°C, or from about 25°C to about 3 It can be cooled to 0°C.

[0190] As can be seen from the above procedure, in certain embodiments, certain components of the formulation can be Either solubilized separately or added in two separate steps (e.g., in one specific step) and a second amount in a different step) to achieve a uniform, lump-free, stable formulation. In certain embodiments, the introduction of water, air, oxygen, or light into the process is minimized. The procedure is carried out under controlled conditions to minimize or eliminate various outcomes. (A few examples include retinol and Camellia sinensis (green tea) powder.) Maintains the stability of pharmaceuticals (e.g., phenol). [Example]

[0191] Illustrative Examples The following examples are included to aid in the understanding of the present invention and, of course, are not intended to be limiting unless otherwise specified. It should not be construed as specifically limiting the invention as described and claimed. It is within the skill of the art to substitute all equivalents now known or later developed. Such variations of the invention, as well as minor variations in formulation or experimental design, are expressly incorporated herein by reference. are considered to be within the scope of the present invention which is incorporated herein by reference.

[0192] Skin care formulations include exemplary formulations of 0.25%, 0.5%, and 1.0% retinol. The agent was tested in a clinical study, where one cohort of users reported these Start using the disclosed formulation containing all-trans retinol at the lowest dose The first group received 1 month of anti-inflammatory drug treatment and then escalated to the next highest dose. It is a prescription retinoid that is considered the gold standard in anti-aging retinoid treatments. The same was done with tretinoin. Participants received increasing monthly doses (0.025%, 0.0 5%, and 0.1%) using the retinol formulations disclosed herein in the following examples. The group using tretinoin experienced excellent and surprising results, often in comparison to individuals in the group using tretinoin. It was just as good or even better and less irritating.

[0193] The data obtained demonstrate that the disclosed topical retinoid-containing formulations are effective in improving skin characteristics. This shows that...

[0194] The disclosed formulations may be used in the step-up program described above, or alone and / or may be used in conjunction with auxiliary products such as sunscreen, moisturizers and cleansers.

[0195] In an exemplary embodiment of the formulation disclosed herein, the components are: isopentyl diol, Dimethyl isosorbide, polysorbate 80, ethoxydiglycol, caffeine, tea Camellia sinensis (green tea) polyphenols, retinol, polysorbate 20 , Bakuchiol, Purified Water, Glycyrrhiza Glabra (Licorice) Root Extract, Camellia sinensis (black tea) leaf extract, glycerin.

[0196] In the disclosed formulation, ethoxydiglycol is added in a conventional manner and at 2.6% Used in accordance with European Union cosmetics regulations, which require that isopentyl diisopropyl ether be present in amounts less than 100mg / kg. ol, dimethyl isosorbide, and polysorbate 80 are effective in preventing retinol and retinol derivatives. It is a much weaker and milder solvent for conductors (retinoids) than for other conductors.

[0197] The formulations of the present disclosure provide skin care treatment with results comparable to prescription retinoids, The formulation can be used without restrictions, as it remains within Nol's cosmetic (non-drug) dosage.

[0198] Exemplary Compositions (all expressed in % w / w): [Example 1]

[0199] [Table 1]

[0200] [Example 2]

[0201] [Table 2]

[0202] [Example 3] 0.25% retinol

[0203] [Table 3]

[0204] [Example 4] 0.5% retinol

[0205] [Table 4]

[0206] [Example 5] 1.0% retinol

[0207] [Table 5] clinical research method

[0208] A single-site, double-blind, controlled study of patients aged 35-65 years, with Fitzpatrick skin Forty-five women with photoaging and moderate wrinkles (types I-IV) were enrolled. Subjects who used facial retinoids within 3 months and / or facial antiperspirants within 1 month Subjects who used sulfahydroxy acids were excluded. Subjects were randomized 2:1 to the following groups: I put it out.

[0209] Cell 1: 30 subjects were treated with a 0.25% retinal serum (e.g., the serum from Example 3 above). The composition was applied for 4 weeks. 0.25% retinal serum was applied twice a week for the first week, then twice a week for the second week. The eye area was used every other night, then every night for weeks 3 and 4. The test moisturizer (lipid-replenishing cream, T OPIX Pharmaceuticals, Inc., Amityville, NY) , placed on top of the retinal serum during nightly application and each morning.

[0210] Cell 2: 15 subjects applied 0.025% tretinoin cream for 4 weeks. 0.25% tretinoin cream twice a week for the first week, then every other night for the second week, then every other night for the third and fourth weeks. The test moisturizing cream (CeraVe moisturizing cream, L'Ore al, NY) at the time of application and every morning with tretinoin cream (Ortho Derma tologies, NJ).

[0211] The dermatologist-investigator and subjects assessed the following facial efficacy parameters: overall photoloss Severity of the wound, dryness, lack of smoothness to the touch, lack of smoothness to the visual sense, lack of softness, clarity Lack of brightness, lack of firmness, poor skin texture, fine lines on the face, crow's feet, Skin pigmentation and crepe cheek skin texture were assessed. All assessments were performed on a 5-point ordinal scale ( The symptoms were graded as follows: 0 = none, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe. The investigator and subjects assessed overall clinical improvement from baseline at week 12 on a 5-point scale. The scores were rated using a scale (1 = greatly improved, 2 = moderately improved, 3 = slightly improved, 4 = unchanged). (5 = none, 5 = worsening). The investigator and subject must provide the subject's baseline Line images (front, right, and left images) were referenced.

[0212] Tolerability was graded in terms of the following parameters: itching, stinging, burning, redness, swelling All ratings were recorded on a 5-point ordinal scale (0 = none, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe). (Severe)

[0213] Weekly diary sheets were used to reinforce adherence, and subjects were asked to record product application in the provided weekly diary. At week 2, a compliance text was sent and subjects were asked to record their actions and comments. Subjects were asked to contact the research center if they experienced any problems with the study product. Subjects were encouraged to remain consistent with treatment and to continue to maintain a daily diary.

[0214] At each outpatient visit, a VISIA CR43 camera system (Canfield Sci Clinical photographs of the central, right, and left face were taken using visible light by a CT scan performed by a CT scan specialist (Centific, NJ). Photographed by: Evaporimeter, Cyberderm, Broomall, PA used to assess the non-invasiveness of barrier function in the form of transepidermal water loss (TEWL) measurements from the left face. A clinical evaluation was performed.

[0215] Skin biopsies were obtained from six subjects in Cell 1 and four subjects in Cell 2. Skin biopsies were taken from the face in front of the right ear at baseline (Visit 1) and from the left ear at week 12 (Visit 4). Histological evaluation included epidermal plumpness, stratum corneum compaction, collagen Increased glycosaminoglycans (GAGs), decreased melanin, vascularity and epidermis These analyses included evaluation of the improvement of protrusions, as well as the reduction of solar elastosis. &E, elastic staining, and GAG staining (Garron Solomon, Triple poin Formalin was used to identify the markers in the MRI scan. This was performed on fixed specimens. statistics

[0216] In addition to descriptive statistics (means, standard deviations, and percentages), investigator non- Parametric ordinal data were analyzed using the Will test for pairwise comparisons within and between groups at different time points. Analysis was performed using the Coxon signed-rank test and the sign test. p values ​​were 0.05 or less. , the changes were considered significant. result

[0217] Forty-three of the 45 subjects successfully completed the study. Two of the 45 subjects completed the study in each study center. One patient discontinued from the study due to tolerability issues with retinoids. This was expected because the complex retinization protocol involved Immediately after discontinuing the retinoid, all facial irritation resolved. As a result of Chinaization, several adverse experiences (6 in Cell 1, 4 in Cell 2) occurred. These were expected to occur, but by changing the facial treatment regimen, All were resolved. No serious adverse events occurred during the study. Retinol Experience

[0218] All subjects were asked to rate their experience at the end of the 12-week study. The higher the level, the better the performance. The cream was statistically superior to the currently available cream used in the tretinoin group. Subjects in both groups reported improved self-confidence, beautiful skin, and empowerment (P = 0.038). reported improvements in the performance. Investigator-reported efficacy

[0219] The investigators conducted baseline (Visit 1), week 4 (Visit 2), week 8 (Visit 3), and and at week 12 (Visit 4), participants were scored on a 5-point ordinal scale (0 = none, 1 = minimal, 2 = mild, 3 = moderate). Facial skin appearance parameters were graded using a 4 = severe scale (4 = severe). According to the evaluated efficacy, there were no statistically significant differences between the two groups at any time point, and no significant differences were observed between the two groups. Equivalence between the serum and tretinoin was demonstrated.

[0220] The longitudinal evaluation within the groups was carried out after 4 weeks of use, and the tactile smoothness, softness, brightness, and The study showed a statistically significant improvement in skin radiance and radiance, but the significance was greater in the retinol group. In addition, the use of retinol had a statistically significant effect on visual smoothness. There was an improvement (P = 0.031) but no significant improvement was observed with tretinoin. This continued until the 8th week, and both groups reported tactile smoothness, visual smoothness, softness, brightness, brilliance, Statistical significance was demonstrated in firmness, skin texture, and overall appearance of photoaging. Retinol produced a highly statistically significant improvement in dry skin, but not in acetaminophen. After 12 weeks of use, statistical significance was not observed for retinol. The group continued to be higher, but both products showed comparable improvement. Investigator's overall efficacy

[0221] At week 12, the investigator graded the overall improvement in facial appearance using the following scale: Result: 1 = Much improved, 2 = Moderately improved, 3 = Slightly improved, 4 = No change, 5 = Worse There was no statistically significant difference between the overall improvement of retinol serum and tretinoin (P =0.778). Investigator-rated tolerability

[0222] The investigator will assess redness and swelling while also assessing itching, stinging, and burning. Tolerability was assessed by questioning the subjects. There were no statistically significant differences in any of the tolerability categories. Effectiveness by subject

[0223] Subjects were assessed at baseline, weeks 4, 8, and 12 on a 5-point ordinal scale (0 = none). and various photodamage parameters (1 = minimal, 2 = mild, 3 = moderate, 4 = severe) were used. Skin appearance was assessed over a period of 8 weeks. With the exception of better visual smoothness, there were no statistically significant differences between groups at any time point (P = 0. 045, Figure 3).

[0224] A longitudinal within-group analysis showed that both retinol serum and tretinoin users experienced improvements. showed that retinol serum users had a higher Statistical significance was observed. Specifically, for retinol at week 4, subject-rated visual acuity There were no significant differences in smoothness (P=0.003), softness (P=0.006), or crow's feet (P=0. 001), skin pigmentation abnormalities (P=0.004), and overall photoaged appearance (P=0.0 31), a statistically significant improvement was observed (Figure 4). The difference remained significant in the Nol serum group (P<0.001), but not in the tretinoin group. Both treatments showed statistical significance for most parameters at 12 weeks. did. Overall effectiveness by subject

[0225] After 12 weeks of use, subjects were asked to rate their overall clinical improvement from baseline using a 5-point scale. The scores were rated using a scale (1 = greatly improved, 2 = moderately improved, 3 = slightly improved, 4 = no change). , 5 = worsening). Subjects were assessed with reference to baseline images. There was no statistically significant difference between the two groups. No significant difference was observed (P=0.697). Both users reported, on average, a significant improvement in their skin. Tolerability by subject

[0226] Subjects were asked to rate tolerability in terms of itching, stinging, burning, redness, and swelling, with a low rating. Regarding itching at week 4, the retinol serum There was only one statistically significant difference between the retinol serum group and the tretinoin users. reported less itching (P = 0.010; Figure 5). Transepidermal water loss (TEWL)

[0227] TEWL (Evaporimeter, Cyberderm, Broomall, PA ) measurements were taken at baseline, week 8, and week 12. As expected, TEWL was significantly higher in the retinal The effect of both acetaminophen and tretinoin was increased, but not at 8 weeks (P = 0.337) or 12 weeks (P No statistically significant difference was observed between the two groups in the retinoid content (=0.604). Although the use of trehalose induced barrier damage consistent with the use of trehalose (P<0.001), longitudinal comparisons within groups showed that trehalose induced barrier damage consistent with the use of trehalose Retinol serum was shown to cause less barrier damage at 12 weeks than non-treatment. At week 2, tretinoin increased TEWL by 104% and retinol serum increased it by 88%. The increase in TEWL was 16% lower in the retinol group compared to the tretinoin group. It was. histology

[0228] Baseline histology was compared with histology at week 12. After 12 weeks of use, retinoids The tretinoin-treated subjects had significantly more newly formed collagen and showed greater acanthosis.

[0229] 6A-6D show the results of the 100% to 100% increase in ... 6A-6D show that collagen deposition increased when compared to baseline. The results showed that the effect was approximately 2 to 3 times greater (initial and 12 weeks, same subjects, retinol group).

[0230] FIG. 6A shows a 100× magnification of the baseline sample, and FIG. 6C shows a 2× magnification of the baseline sample. Figure 6B shows a 100x magnification of the 12 week sample, and Figure 6D shows a 100x magnification of the 12 week sample. 200x magnification of 12 week sample. Consideration

[0231] After 12 weeks of use, both the retinol serum and tretinoin were found to be effective in treating many skin conditions, including: The results showed equivalence across the evaluation endpoints of interest, but on average, The retinol serum group had a higher saturation rate than the control group. At the first evaluation visit after 4 weeks, the skin appeared smoother and less dry. Retinol serum subjects had smoother-looking skin after four weeks of application. , softer skin, reduced appearance of fine lines and wrinkles around the eyes, even skin tone reported several areas of facial improvement, including improved sexual function and an overall reduction in photodamage The improvement in skin softness in the retinol group continued through week 8, while the improvement in skin softness in the tretinoin group was No improvement in skin softness was observed up to the 8th week.

[0232] Damage was measured by TEWL measurement in subjects who used retinol serum during the study period. This suggests that water loss through the barrier is 16% less. Newly formed collagen The presence of and increased acanthosis was also consistent with clinical and functional improvement by study completion. conclusion

[0233] Retinal serums containing bakuchiol are an effective alternative to prescription tretinoin and This results in rapid retinalization and improved appearance of photodamaged skin.

[0234] For ease of explanation, method embodiments of the present disclosure are depicted and described as a series of acts. However, acts according to this disclosure may be performed in various orders and / or simultaneously. and may occur together with other actions not shown and described herein. Furthermore, not all illustrated acts may be required to implement a methodology in accordance with the disclosed subject matter. In addition, those skilled in the art will appreciate that a methodology may be represented as a series of interactions via a state diagram or events. It will be understood and appreciated that these may alternatively be represented as states that are related to one another.

[0235] In the foregoing description, specific materials, dimensions, processes, etc. are used in order to provide a thorough understanding of the present invention. Numerous specific details are described, such as parameters, specific properties, structures, materials or Features may be combined in any suitable manner in one or more embodiments. The words "example" or "exemplary" are used herein to mean something that serves as an example, instance, or illustration. The term "example" or "exemplary" is used herein to mean that the Any aspect or design described is not intended to be preferred or advantageous over other aspects or designs. Rather, the word "example" or "exemplary" should not necessarily be construed as meaning The terms used are intended to present concepts in a concrete manner. The term "or" is used to refer to an inclusive "or" rather than an exclusive "or." is intended to mean "or"; that is, unless otherwise specified, Unless otherwise clear from the context, "X includes A or B" does not imply any inclusive ordering. is intended to mean either: X contains A; X contains B; or If X contains both A and B, then "X contains A or B" satisfies either of the previous examples. Additionally, the article "a" (one or more) used in this application and the appended claims ")" and "an" are used unless otherwise specified or intended to be singular. should generally be understood to mean "one or more" unless otherwise clear from the context. Throughout this specification, the terms "an embodiment," "a particular embodiment," or "one embodiment" may refer to References to "embodiments" or "modes" mean that a particular feature, structure, or characteristic described in connection with an embodiment It is intended to be included in at least one embodiment. The phrases "in one embodiment," "a particular embodiment," or "one embodiment" in The appearances do not necessarily all refer to the same embodiment.

[0236] References to numerical ranges throughout this specification should not be construed as limiting and should not be construed as limiting the scope of the recited ranges. Inclusive of each numerical value within a given range and / or narrower range, as well as the outer limits of that range. It should be understood then.

[0237] The term "about," when referring to a physical quantity, is understood to include measurement errors of up to 10%. For example, "approximately 100°C" should be understood to mean "100±10°C." be.

[0238] The present invention has been described with reference to specific exemplary embodiments thereof. The specification and drawings are to be regarded in an illustrative rather than a restrictive sense. Various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art. and are intended to fall within the scope of the appended claims.

Claims

1. Skin treatment active agents and isopentyldiol, dimethylisosorbide and non-ionic surfactants A topical formulation comprising an activated solvent system containing a carboxylic surfactant.

2. 10. The formulation of claim 1, further comprising an antioxidant.

3. 3. The method of claim 1, wherein the skin treatment active agent comprises retinol. formulation.

4. 4. The formulation of claim 1, further comprising bakuchiol.

5. The nonionic surfactant may be an ethoxylate, a fatty ethoxylate, a propoxylate, or a hydroxypropyl ethoxylate. esters, block copolymers, poloxamers, polyglyceryl esters, polyglyceryl lactate one or more of: acrylic acid, sorbitol anhydride, bipolar agents, phenolic nonionics 5. The formulation of claim 1, wherein

6. 6. Any of claims 1 to 5, wherein the nonionic surfactant comprises polysorbate 80. The formulation according to claim 1.

7. 7. The formulation of claim 1, further comprising polysorbate 20.

8. The antioxidants include green tea polyphenols, licorice extract, resveratrol, and silymarin. , curcuminoids, caffeine, astaxanthin, flavones, flavonoids, flavanones ol, tocopherol, ascorbate, coenzyme Q10, ergothioneine, glutamic acid, 2 or 3, which is one or more of tetrion, ectoine, bisabolol, and emblica.

8. The formulation according to any one of claims 1 to 7.

9. 10. The method of claim 2, wherein the antioxidant comprises tea plant (Camellia sinensis) polyphenols.

9. The formulation according to any one of claims 8 to 8.

10. 10. Any one of claims 2 to 9, wherein the antioxidant comprises a xanthine that is caffeine. The formulation described in

11. In (% w / w): about 10% to about 90% isopentyl diol; about 1% to about 40% polysorbate 80; about 0.01% to about 10% caffeine; about 5% to about 90% dimethyl isosorbide; up to about 80% ethoxydiglycol; About 0.1% to about 15% Camellia sinensis (green tea) polyphenols ； about 0.01% to about 30% retinol; up to about 30% polysorbate 20; up to about 20% bakuchiol; up to about 20% black tea extract; and Up to approximately 20% licorice root extract 11. The formulation of claim 1, comprising:

12. In (% w / w): about 45% to about 65% isopentyl diol; about 6% to about 10% polysorbate 80; about 0.5% to about 2.5% caffeine; about 20% to about 40% dimethyl isosorbide; about 1% to about 5% ethoxydiglycol; about 0.1% to about 5% Camellia sinensis (green tea) polyphenols; about 0.05% to about 1.5% retinol; about 0.05% to about 2% polysorbate 20; about 0.1% to about 3% bakuchiol; about 0.001% to about 5% black tea extract; and about 0.001% to about 5% licorice root extract 12. The formulation of any one of claims 1 to 11, comprising:

13. In (% w / w): 100% isopentyldiol from QS; about 8% to about 9% polysorbate 80; about 1% to about 1.5% caffeine; about 25% to about 35% dimethyl isosorbide; about 2% to about 3% ethoxydiglycol; about 1% to about 1.5% Camellia sinensis (green tea) polyphenols; about 0.2% to about 1.2% retinol; about 0.2% to about 1.2% polysorbate 20; about 0.5% to about 1.5% bakuchiol; about 0.001% to about 0.1% black tea extract; and about 0.001% to about 0.1% licorice root extract 13. The formulation of any one of claims 1 to 12, comprising:

14. Skin treatment active agents and isopentyldiol, dimethylisosorbide and non-ionic surfactants topically applying a therapeutically effective amount of a topical formulation comprising an activated solvent system containing a carboxylic surfactant to the affected area; 10. A method for the therapeutic treatment of a dermatological condition comprising:

15. 15. The method of claim 14, wherein the affected area is one or more of human skin, scalp, hair, and nails. method.

16. 16. The method of any one of claims 14 to 15, wherein the active agent comprises retinol. 。

17. 17. The method of claim 14, wherein the nonionic surfactant comprises polysorbate 80. The method according to any one of claims 1 to 5.

18. 18. The method of any one of claims 14 to 17, wherein the formulation further comprises an antioxidant. 。

19. 19. The formulation of any one of claims 14 to 18, wherein the formulation further comprises bakuchiol. method.

20. Antioxidant system and isopentyldiol, dimethylisosorbide and non-ionic surfactants forming a first mixture of an activating solvent system including a surfactant; Retinol was combined with isopentyldiol and dimethylisosorbide separately. forming a retinol mixture; and combining said first mixture with said retinol mixture; 1. A method for preparing a topical formulation comprising:

21. For a duration of at least 4 weeks, the skin treated with the formulation shows at least about 30% 20. The topical formulation of claim 1 or claim 20, wherein the topical formulation exhibits acanthosis nigricans. A topical formulation prepared by the method described in.

22. For a duration of at least 4 weeks, skin treated with the formulation shows a significant improvement compared to baseline.

14. The method of claim 1, wherein the subject exhibits at least two times more collagen deposition when treated with the method of claim 1.

21. A topical formulation according to claim 20 or prepared by the method of claim 20.

23. For a duration of at least 4 weeks, skin treated with the formulation shows a significant improvement compared to baseline.

14. The method of claim 1, wherein the method exhibits less than about a 100% increase in transepidermal water loss when 21. A topical formulation according to claim 20 or prepared by the method of claim 20.

24. For a duration of at least 4 weeks, the skin treated with the formulation shows at least about 30% 20. The method of any one of claims 14 to 19, wherein the skin is thickened with acanthosis nigricans.

25. For a duration of at least 4 weeks, skin treated with the formulation shows a significant improvement compared to baseline.

20. The method of claim 14, wherein the collagen deposition is at least twice as high when ... as when the collagen deposition is at least twice as high.

25. The method according to any one of claims 24 to 24.

26. For a duration of at least 4 weeks, skin treated with the formulation shows a significant improvement compared to baseline.

20. The method of claim 14, wherein the skin exhibits an increase in transepidermal water loss of less than about 100% when the skin is treated with the method of claim 14.

25. The method according to any one of claims 24 to 24.

Images