Anti-carbonylation compositions and methods for protecting keratin materials from carbonylation stimulation using compositions comprising polylysine

Abstract

Provided herein are compositions comprising polylysine that reduce and / or inhibit protein carbonylation. Also provided herein are methods of protecting skin from carbonylation stimulation by using a composition comprising a polylysine, and non-therapeutic cosmetic methods of caring for keratin materials, particularly skin, by applying a composition comprising a polylysine that reduces and / or inhibits carbonylation of proteins.

Description

Technical Field

[0001] The present application relates to an anti-carbonylation composition comprising one or more polylysines, and also relates to a method for reducing and / or inhibiting protein carbonylation, in particular a method for protecting tissues (e.g., keratin materials, especially one or more keratin fibers, such as skin, etc.) from carbonylation stimulation using a composition comprising one or more polylysines. Background Art

[0002] The skin is the first barrier of the human body against external environmental stimuli. The important mechanism by which environmental pollutants, such as particulate matter, ultraviolet rays, and ozone, invade the skin is to attack the unsaturated lipids on the surface of the skin through oxidative damage, destroy the outermost protective layer of the skin, and produce active carbonyl substances, such as malondialdehyde, 4-hydroxynonenal, and acrolein. When the content of these types of substances exceeds the body's clearance capacity, carbonyl stimulation will occur, which induces carbonyl modification of biological macromolecules such as proteins, resulting in structural changes and loss of function.

[0003] During protein carbonylation, reactive aldehydes or ketones are introduced into proteins through oxidation. Protein carbonyls have been shown to be the major product of protein oxidation and can be formed by oxidative cleavage of proteins, direct oxidation of amino acid residues, or covalent reactions with aldehydes from lipid peroxidation.

[0004] It is generally believed that protein carbonylation refers to the process in which the amino or imino groups in the side chains of amino acid residues are attacked by oxygen free radicals and eventually converted into aldehyde groups and release NH3+. After the protein side chain amino acids are attacked by hydroxyl free radicals and oxidatively modified, the peptide bonds are broken, carbonyl groups are generated at the break, and the content of carbonyl groups is greatly increased.

[0005] Specifically, protein carbonylation occurs due to direct metal-catalyzed oxidation of amino acid side chains (primary protein carbonylation) or addition of reactive aldehydes to amino acid side chains (secondary protein carbonylation). Thus, it is well known that exogenous reactive aldehydes, such as acrolein, originate from cigarette smoke.

[0006] It has been previously reported that primary protein carbonylation plays a role in the reactive oxygen species (ROS) signaling mechanism. Reactive oxygen species (ROS) in the skin can alter proteins in the skin cell structure. If reactive oxygen species (ROS) are not fully controlled by the skin's antioxidant defense system, proteins in the skin will become carbonylated, leading to skin damage.

[0007] It is well documented that the production of carbonyl proteins is a hallmark of carbonylation stress, either as an extrinsic factor, such as that caused by UV radiation or externally applied oxidizing chemicals, or as an intrinsic factor, such as chemical attack by reactive carbonyls from lipid peroxidation degradation.

[0008] Carbonylated proteins in the skin are mainly found in the epidermis and dermis, and the content of carbonylated proteins in the epidermis is higher than that in the dermis. This is because the epidermis is constantly exposed to an oxidative environment and the unsaturated lipid environment secreted by the sebaceous glands, creating favorable conditions for the continuous generation of active aldehyde compounds.

[0009] In addition, carbonyl stress causes damage to the skin, such as accelerating skin aging or causing various pathological reactions in the skin. Protein carbonylation destroys the skin's water-holding capacity, affects the skin's light transmittance, and changes the skin's optical properties. Specifically, the presence of carbonylated proteins is associated with changes in the following skin properties: mechanical properties; water-holding capacity, including decreased water content and increased epidermal water loss; dull skin; and decreased skin transparency. At the same time, increased levels of carbonylated proteins can lead to inflammatory skin diseases such as psoriasis and dermatitis.

[0010] Therefore, there is a great need for anti-carbonylating agents that can inhibit or prevent protein carbonylation, as well as skin care compositions and methods comprising anti-carbonylating agents, to improve the appearance of the skin or improve at least one sign of skin aging (e.g., decreased water holding capacity, dull skin, yellowing of the skin, decreased skin transparency, elasticity, contrast, etc.) and reduce the occurrence of inflammatory skin diseases such as psoriasis and dermatitis.

[0011] The present application relates to cosmetic compositions comprising at least one polylysine. The present application also relates to a method for reducing or inhibiting protein carbonylation on keratin materials, especially the skin.

[0012] Detailed Description

[0013] Throughout the specification (including claims), unless otherwise specified, the term "comprising a" should be understood as being synonymous with "comprising at least one." In addition, the expression "at least one" used in this specification is equivalent to the expression "one or more."

[0014] "Topical application" means applying or spreading the composition onto the surface of a keratin material, such as at least one area of ​​the skin.

[0015] As used herein, "anti-carbonylation" refers to reducing and / or inhibiting protein carbonylation, particularly protecting tissues (eg, keratin materials, particularly one or more keratin fibers, such as skin, etc.) from carbonylation stimulation.

[0016] As used herein, "polylysine" refers to one or more lysine-based polymers.

[0017] It has been unexpectedly found that the anti-carbonylation composition (or agent) of the present invention comprises at least one polylysine (or consists of it), and an improved anti-carbonylation effect can be achieved. The present application relates to an anti-carbonylation composition (or agent) of the present invention as a cosmetic composition, which comprises at least one polylysine (or consists of it). The present application also relates to a method for reducing and / or inhibiting protein carbonylation on keratin materials (especially one or more keratin fibers, such as skin) by applying a composition comprising the anti-carbonylation composition (or agent) of the present invention (which comprises at least one polylysine (or consists of it).

[0018] In one embodiment, polylysine is preferably an L-lysine based polymer.

[0019] In another embodiment, the polylysine may be selected from linear α-polylysine, linear ε-polylysine, hyperbranched polylysine or dendritic polylysine.

[0020] In one embodiment, polylysine is preferably ε-polylysine and / or dendritic polylysine.

[0021] In other embodiments, the molecular weight of the polylysine is greater than 200, even greater than 300, or greater than 400, preferably greater than 500, or greater than 800. Specifically, the molecular weight of the polylysine is less than 200,000, even less than 150,000, or less than 100,000, preferably less than 50,000, or less than 20,000. For example, the molecular weight of the polylysine is 200 to 200,000, even 400 to 100,000, or 600 to 50,000, or 800 to 20,000, or 1,000 to 15,000, preferably 1,000 to 10,000. When the polylysine is α-polylysine, the preferred molecular weight of the α-polylysine is less than 30,000.

[0022] In other embodiments, the polylysine is present in the cosmetic composition in an amount of 0.0001% to 10% by weight, preferably 0.001% to 5% by weight, preferably 0.001% to 2% by weight relative to the total weight of the composition.

[0023] In other embodiments, the present composition further comprises a functional agent, which may be, for example, at least one active agent, such as one or more skin care agents, selected from moisturizers, such as protein hydrolysates, and polyols, such as glycerol, glycols, polyethylene glycols and sugar derivatives; natural extracts; vitamins, such as vitamin A (retinol), vitamin E (tocopherol), vitamin C (ascorbic acid), vitamin B5 (panthenol), vitamin B3 (niacinamide), derivatives of these vitamins (particularly esters) and mixtures thereof; urea; caffeine; salicylic acid and its derivatives; alpha-hydroxy acids, such as lactic acid and glycolic acid and their derivatives; retinoids, such as carotenoids and vitamin A derivatives; sunscreens; essential oils of mint, aloe vera or ginseng and mixtures thereof.

[0024] Another subject of the present application is to provide a method for preparing an anti-carbonylation composition, comprising the following steps:

[0025] - (1) optionally, providing a formulation base, and then cooling, for example, to room temperature,

[0026] - (2) dispersing the obtained polylysine in water, for example

[0027] and

[0028] - (3) mixing 1) the formulation base, and 2) one or more polylysine solutions at room temperature.

[0029] Another subject of the present application is to provide a non-therapeutic cosmetic method for combating degeneration of keratin materials, in particular of the skin, by applying the present composition.

[0030] Another subject of the present application is to provide a non-therapeutic cosmetic method for caring for keratin materials, in particular the skin, by applying the present anti-carbonylation composition.

[0031] A further subject matter of the present application relates to the use of the composition or the preparation of a care product for keratin materials, in particular the skin.

[0032] Another subject of the present application is to provide a cosmetic product comprising the present composition.

[0033] Other features and advantages of the present application will become more clearly apparent after reading the following description and examples.

[0034] In the present application, unless expressly stated otherwise, contents, parts and percentages are expressed on a weight basis.

[0035] Poly-L-lysine

[0036] Polylysine refers to several lysine-based homopolymers that may differ from each other in stereochemistry and attachment positions. Lysine, an essential amino acid for the human body, is the main structural unit of polylysine and is available in two chiral forms: L-lysine and D-lysine. Polymerization of specific chiral lysine monomers will produce L-polylysine and D-polylysine, respectively. The precursor amino acid lysine contains two amino groups, one at the α carbon and one at the ε carbon. Either position can be the position of polymerization, resulting in α-polylysine or ε-polylysine. Depending on the topological structure of the polymer chain, polylysine can be further divided into linear, hyperbranched, and dendritic polylysine. The molecular weight of polylysine can range from 100-1,000,000.

[0037] Polylysine in the present application refers to lysine-based polymers, such as linear ε-polylysine (ε-PL), linear α-polylysine (α-PL), hyperbranched polylysine and dendritic polylysine.

[0038] Typically, polylysine is present in the topical composition in a concentration ranging from 0.0001% to 10% by weight, preferably from 0.001% to 5% by weight, preferably from 0.001% to 2% by weight relative to the total weight of the composition.

[0039]

[0040] Applicants have surprisingly found that polylysine has better anti-carbonylation efficacy than monomeric lysine, optionally at concentrations such as 0.005% to 0.05%, and without wishing to be bound by theory, this may contribute to the "multivalent effect" of the polymer chains.

[0041] Surprisingly, without wishing to be bound by theory, the polylysine is preferably selected from ε-polylysine and / or dendritic polylysine.

[0042] Active Agent

[0043] According to one embodiment of the present application, the product of the present application may contain at least one functional agent, such as at least one active agent, for example, selected from desquamation agents or moisturizers; depigmentation agents or anti-depigmentation agents; anti-glycation agents; anti-NO agents; agents for stimulating the synthesis of dermal or epidermal macromolecules and / or preventing their degradation; agents for stimulating the proliferation of fibroblasts or keratinocytes and / or the differentiation of keratinocytes; muscle relaxants or skin relaxants (dermo-decontracting agents); free radical scavengers or anti-pollution agents; tightening agents; agents acting on capillary circulation; of course, especially the following active agents, and mixtures thereof.

[0044] Among all the active agents that can be used in the present application, mention may be made in particular of: α- or β-hydroxy acids, such as lactic acid, glycolic acid, citric acid, 5-octanoylsalicylic acid, α-hydroxydecanoic acid, α-hydroxylauric acid, tartaric acid, glucuronic acid, galacturonic acid, acrylic acid, α-hydroxybutyric acid, α-hydroxyisobutyric acid, malic acid, mandelic acid, phosphoric acid, pyruvic acid, lactobionic acid and salicylic acid.

[0045] It is also possible to use anti-acne agents, such as salicylic acid or benzoyl peroxide, octopirox, dextrorotatory and levorotatory sulfur-containing amino acids, their salts and their N-acetyl derivatives, such as N-acetylcysteine, or agents for preventing skin aging and / or improving its condition, such as the above-mentioned α- and β-hydroxy acids, retinoids, such as retinoic acid, retinol and its esters, such as retinyl propionate and retinyl acetate or retinyl palmitate, niacinamide, allantoin, aloe extract, azelaic acid, bisabolol, phytic acid, collagen or agents that stimulate collagen formation, vitamins, such as vitamin C or its derivatives. , such as ascorbyl glucoside, vitamin E or its derivatives, vitamin A or its derivatives, vitamin F or its derivatives, the above-mentioned right-handed and left-handed sulfur-containing amino acids and their derivatives, elastin, N-acetyl D-glucosamine, luteolin, or antioxidants such as green tea or its active parts, glycerol, laponite, caffeine, essential oils, colorants, free radical scavengers, moisturizers, depigmenting agents, agents for improving skin color such as dihydroxyacetone or tyrosine ester type artificial tanning agents, fat regulators, softeners, anti-wrinkle agents, keratolytic agents, fresheners, deodorants, anesthetics, nourishing agents and mixtures thereof. Bleaching agents such as kojic acid, ascorbyl phosphate, ascorbyl glucoside, ascorbic acid and mixtures thereof can also be used.

[0046] In the case of a mask, active agents that improve the skin condition may also be used, such as moisturizers or agents for improving the natural lipid barrier, such as ceramides, cholesterol sulfates and / or fatty acids and mixtures thereof. Enzymes active on the skin may also be used, such as proteases, lipases, cerebrosidases and / or melanases and mixtures thereof.

[0047] Other examples of active agents that may be suitable for use in the practice of the present application are pharmaceutical agents, peptides, proteins, detectable labels, contrast agents, analgesics, anesthetics, antibacterial agents, anti-yeast agents, anti-fungal agents, anti-viral agents, anti-dermatitis agents, antipruritics, antiemetics, vasoprotectants, anti-motion sickness agents, anti-irritants, anti-inflammatory agents, immunomodulators, anti-keratolytic agents, agents for treating dry skin, antiperspirants, anti-psoriatic agents, anti-dandruff agents, anti-aging agents, anti-asthma agents and bronchodilators, sunscreens, antihistamines, healing agents, corticosteroids, tanning agents, and mixtures thereof.

[0048] The content of the at least one active agent in the composition can be adjusted according to the intended use of the composition.

[0049] Auxiliary agents

[0050] In a known manner, the composition of the present application may also contain auxiliary agents commonly used in cosmetics and / or dermatology, such as preservatives, antioxidants, pH regulators (acidic or alkaline), fragrances, fillers, bactericides, odor absorbers, colorants (pigments and dyes), emulsifiers and lipid vesicles.

[0051] It goes without saying that a person skilled in the art will carefully choose this or these optional additional compounds and / or their amounts such that the benefits of the composition according to the present application are not or not substantially adversely affected by the intended addition.

[0052] Although the numerical ranges and parameters describing the broad scope of the application are approximate values, the numerical values ​​described in the specific examples are reported as accurately as possible. However, any numerical value inherently contains certain errors, which are necessarily caused by the standard deviation in their respective measurements. The following examples are intended to illustrate the application without limiting the scope thereof. Example

[0053] The amounts / concentrations of ingredients in the following compositions / formulations are expressed in parts by weight.

[0054] I. Evaluation of the present composition

[0055] 1. In vitro anti-carbonylation efficacy test

[0056] This assay provides an in vitro method for determining the effect of an anti-carbonylation agent / composition on the carbonylation degree of a protein. The anti-carbonylation agent / composition to be tested is prepared into a 1% solution with deionized water, bovine serum albumin (BSA) is prepared into a 10 mg / mL solution, and acrolein is prepared into a 10 mM solution. Then, in a 1.5 mL centrifuge tube, BSA (10 mg / mL), anti-carbonylation agent / composition (1%), acrolein (10 mM) and phosphate buffered saline (PBS) are added to the centrifuge tube according to the contents in Table 1. The sample containing only BSA and PBS is used as the baseline, and the sample containing BSA, acrolein and PBS is used as the blank. The final liquid volume in each centrifuge tube is 1.0 mL. Each group contains three replicate samples, and all samples are placed at 37°C overnight.

[0057] Table 1

[0058]

[0059]

[0060] 1.ε-PL comes from Chisso

[0061] 2. The dendritic PL is DENDIRCLEAR from Lucas Meyer.

[0062] The protein carbonyl determination kit of Nanjing Jiancheng Bioengineering Institute was used to detect the protein carbonyl content in the above samples. The detection method is as follows: take 0.1 mL of sample in a determination tube, then add 0.4 mL of reagent 3 in the kit, vortex mix for 1 min, and react at 37°C in the dark for 30 min. Add 0.5 mL of reagent 5 in the kit, vortex mix for 1 min, centrifuge at 4°C and 12000 r / min for 10 min, discard the supernatant, and leave the pellet. Add 1.0 mL of a mixed solution of anhydrous ethanol and ethyl acetate (1:1), vortex mix for 1 min, centrifuge at 4°C and 12000 r / min for 10 min, discard the supernatant, leave the precipitate, and repeat the above steps 4 times. Add 1.25 mL of reagent 6 in the kit, mix well, place at 37°C for 15 minutes, vortex mix to dissolve all the precipitate, and centrifuge at 12000 r / min for 15 minutes. Take the supernatant and place it in a quartz cuvette with a light diameter of 0.5 cm, adjust it to zero with reagent 6, and measure the absorbance of each tube at 370 nm (ultraviolet). The protein carbonyl content can be obtained according to the formula.

[0063]

[0064] Using Thermos' Micro BCA TM The protein assay kit is used to determine the protein content of the sample. First, prepare a diluted albumin (BSA) standard (working range = 20-750 μg / mL). Mix BCA reagent A with reagent B (reagent A: reagent B = 50: 1) to prepare a working solution. Take 25 μL of each protein standard and protein sample of different dilution concentrations and add them to the microplate. Add 200 μL of working solution to each well and shake on an oscillator for 30 seconds to mix. Seal the microplate and incubate at 37°C for 30 minutes. Cool the microplate to room temperature and measure the absorbance of the sample at a wavelength of 562 nm. The reading of each standard and sample minus the absorbance value of the blank sample is the corrected absorbance value. Read the protein concentration from the standard curve drawn based on a known amount of BSA. Referring to the standard curve, read the protein concentration of each sample within the linear range of the standard curve based on the corrected absorbance value of each protein sample. Calculate the protein content in the original sample based on the sample volume and dilution.

[0065] 2. Anti-carbonylation effect of polylysine

[0066] The carbonylation degree of the sample was divided by the BSA protein content to obtain the anti-carbonylation ability of each anti-carbonylation agent / composition. The results are shown in Tables 2 and 3 below.

[0067] Table 2

[0068]

[0069] Table 3

[0070]

[0071] As shown above, polylysine reduces and / or inhibits protein carbonylation.

[0072] II. Formulation Examples

[0073] The polylysine-containing composition of the present invention is prepared by thoroughly mixing the following ingredients.

[0074]

[0075]

[0076] III. Sensory Evaluation of Anti-Carbonylation Compositions

[0077] The sensory properties of compositions 1 to 4 after application to the skin were evaluated and are summarized in the following table:

[0078] Composition Sensory evaluation 1 Good spreadability, good residue softness, medium tack 2 Good spreadability, good residue softness, low tack 3 Good spreadability, good residue softness, low tack 4 Good spreadability, good residue softness, low tack

[0079] The cosmetic properties of compositions 1 to 4 were good, especially with regard to spreadability, softness and non-stickiness.

[0080] While the present invention has been described in conjunction with the preferred embodiments, it is not intended to limit the scope of the invention to the specific forms described, but on the contrary, it is intended to cover such alternatives, modifications and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims.

Claims

1. An anti-carbonylation composition comprising at least one polylysine.

2. The anti-carbonylation composition according to claim 1, wherein the polylysine is selected from at least one lysine-based polymer.

3. The anti-carbonylation composition according to any one of the preceding claims, wherein the at least one polylysine is an L-lysine based polymer.

4. The carbonylation-resistant composition according to any one of the preceding claims, wherein the at least one polylysine is selected from α-polylysine, ε-polylysine, hyperbranched polylysine and dendritic polylysine, preferably from ε-polylysine and / or dendritic polylysine.

5. The carbonylation-resistant composition according to any one of the preceding claims, wherein the molecular weight of the at least one polylysine is greater than 200, even greater than 300, or greater than 400, preferably greater than 500, or greater than 800; in particular, the molecular weight of the polylysine is less than 200,000, even less than 150,000, or less than 100,000, preferably less than 50,000, or less than 20,000, for example, the molecular weight of the polylysine is from 200 to 200,000, even from 400 to 100,000, or from 600 to 50,000, or from 800 to 20,000, or from 1,000 to 15,000, preferably from 1,000 to 10,000.

6. The anti-carbonylation composition according to any one of the preceding claims, wherein When the polylysine is α-polylysine, the molecular weight of the α-polylysine is lower than 30,000.

7. The anti-carbonylation composition according to any one of the preceding claims, wherein The at least one polylysine is present in the composition in an amount ranging from 0.0001% to 10% by weight, preferably from 0.001% to 5% by weight, preferably from 0.001% to 2% by weight relative to the total weight of the composition.

8. An anti-carbonylation composition according to any one of the preceding claims, wherein the composition further comprises at least one functional agent, such as at least one active agent, such as one or more skin care agents, preferably selected from moisturizers, such as protein hydrolyzates and polyols such as glycerol, glycols such as polyethylene glycol and sugar derivatives; natural extracts; vitamins, such as vitamin A (retinol), vitamin E (tocopherol), vitamin C (ascorbic acid), vitamin B5 (panthenol), vitamin B3 (niacinamide), derivatives (especially esters) of these vitamins and mixtures thereof; urea; caffeine; salicylic acid and its derivatives; alpha-hydroxy acids such as lactic acid and glycolic acid, and their derivatives; retinoids such as carotenoids and vitamin A derivatives; sunscreens; essential oils of mint, aloe vera or ginseng and mixtures thereof.

9. A cosmetic comprising the anti-carbonylation composition according to any one of the preceding claims 1 to 8.

10. A method for preparing the anti-carbonylation composition according to any one of the preceding claims 1 to 8 or the cosmetic according to claim 9, comprising the following steps: - (1) optionally, providing a formulation base, and then cooling, for example, to room temperature, - (2) dispersing one or more polylysines in, for example, water, and - (3) mixing 1) the formulation base, and 2) one or more polylysine solutions at room temperature.

11. Non-therapeutic cosmetic method for reducing and / or inhibiting protein carbonylation on keratin materials, in particular on the skin, by applying an anti-carbonylation composition according to any one of the preceding claims 1 to 8 or a cosmetic product according to claim 9.

12. Non-therapeutic cosmetic method for caring for keratin materials, in particular the skin, by applying an anti-carbonylation composition according to any one of the preceding claims 1 to 8 or a cosmetic product according to claim 9.

13. Use of a composition according to any one of the preceding claims 1 to 8 or a cosmetic according to claim 9 for preparing a product for caring for keratin materials, in particular the skin.

14. Use of a composition according to any one of the preceding claims 1 to 8 or a cosmetic according to claim 9 for the preparation of a product for reducing or inhibiting the carbonylation of proteins on keratin materials, in particular on the skin.

Images