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US-12622857-B2 - Skin lightening composition

US12622857B2US 12622857 B2US12622857 B2US 12622857B2US-12622857-B2

Abstract

The present invention relates to a cosmetic skin lightening composition comprising the combination of sclareolide, kojic acid and ascorbyl glucoside, wherein kojic acid is encapsulated within a targeted microcapsule or nanocapsule having a melanocortin 1 receptor (MC1R) agonist peptide bound to the surface. It was found that such combination of active substances provided synergistic kin-whitening effect. The present invention also relates to the cosmetic use of this composition for skin whitening, particularly, for the elimination or reduction of hyperpigmented marks of the skin, such as UV exposure related marks, post-scar marks, post-inflammation marks, melasma marks, lentigo marks or age-related marks.

Inventors

  • Sergi HERNÁNDEZ NAVARRO
  • Jordi SEGURA TEJEDOR

Assignees

  • Bella Aurora Labs, S.A.

Dates

Publication Date
20260512
Application Date
20200706
Priority Date
20190916

Claims (16)

  1. 1 . A skin-whitening composition comprising: (a) sclareolide; (b) kojic acid; and (c) ascorbyl glucoside; wherein kojic acid is encapsulated within a microcapsule or nanocapsule comprising a peptide of formula (I): R 2 -Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-(AA)-Gly-Lys-DPro-Val-R 1 (I) wherein: R 1 is the radical —NH—(CH 2 ) 3 —O—(CH 2 CH 2 O) n —(CH 2 ) 3 —NH 2 , wherein n is an integer from 1 to 10; R 2 is selected from (C 1-24 alkyl)-CO—, (C 2-24 alkenyl)-CO— and (C 6-10 aryl)-CO—; and AA is an amino acid containing an aromatic group; and cosmetically acceptable salts and solvates thereof, wherein the peptide is coupled to the outer surface of the microcapsule or nanocapsule, and wherein the content of kojic acid in the composition is comprised in the range 0.0001% (w/w)-0.01% (w/w).
  2. 2 . The composition according to claim 1 , characterized in that the content of kojic acid is comprised in the range 0.0001%-0.001% (w/w).
  3. 3 . The composition according to claim 1 , characterized in that n is 1 or 2.
  4. 4 . The composition according to claim 1 , characterized in that R 2 is selected from acetyl, propanoyl, pentadecanoyl, hexadecanoyl and heptadecanoyl.
  5. 5 . The composition according to claim 1 , characterized in that AA is selected from tryptophan, 3-(2-naphthyl)-D-alanine, 3-amino-3-(1-naphthyl)-propionic acid, 3-amino-3-(biphenyl)-propionic acid, phenylalanine, tyrosine, histidine, 5-hydroxytryptophan and L-3,4-dihydroxy-phenylalanine.
  6. 6 . The composition according to claim 1 , characterized in that the amount of sclareolide in the composition is comprised in the range 0.001%-5% (w/w).
  7. 7 . The composition according to claim 1 , characterized in that sclareolide is encapsulated in the form of liposomes.
  8. 8 . The composition according to claim 1 , characterized in that the amount of ascorbyl glucoside in the composition is comprised in the range 0.01%-10% (w/w).
  9. 9 . The composition according to claim 1 , characterized in that it also comprises saccharide isomerate.
  10. 10 . The composition according to claim 9 , characterized in that the amount of saccharide isomerate in the composition is comprised in the range 0.00001%-2% (w/w).
  11. 11 . The composition according to claim 1 , characterized in that it also comprises genistein and suforaphane.
  12. 12 . The composition according to claim 1 , characterized in that it also comprises Pancratium maritimum extract.
  13. 13 . The composition according to claim 1 , characterized in that it also comprises Lansium domesticum (Langstat) leaf extract.
  14. 14 . A method for skin whitening in a subject comprising the steps of topically applying an amount cosmetically effective of the composition of claim 1 to the subject.
  15. 15 . The method according to claim 14 for the elimination or reduction of hyperpigmented marks of the skin.
  16. 16 . The method according to claim 15 , wherein the hyperpigmented marks of the skin are selected from the group consisting of UV exposure related marks, post-scar marks, post-inflammation marks, melasma marks, lentigo marks and age-related marks.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS AND PRIORITY This patent application claims priority from PCT Application No. PCT/EP2020/068973 filed Jul. 6, 2020, which claims priority from European Patent Application No. 19382797.9 filed Sep. 16, 2019. Each of these patent applications are herein incorporated by reference in their entirety. TECHNICAL FIELD The present invention relates to a cosmetic composition useful for skin lightening, particularly, for removing dark spots and marks from the skin. STATE OF THE ART Melanin is a dark pigment which is responsible for skin colour and is synthesized in melanocytes, a type of cells found in the epidermis. Specifically, melanogenesis takes place within the melanosomes, which are vesicles inside the melanocytes. A key enzyme of melanogenesis is tyrosinase, a glycoprotein located in the membrane of the melanosomes, which catalyses two steps of the synthesis of melanin from L-tyrosine. Other two enzymes involved in melanogenesis are tyrosinase-related protein 1 (Tyrp1) and tyrosinase-related protein 2 (Tyrp2). Two types of melanin are produced: brownish black eumelanin and reddish yellow pheomelanin. Melanogenesis is a complex process which is regulated by a series of multistep signal transduction cascades and is influenced by a variety of extrinsic and intrinsic factors. Thus, for example, UV exposure induces activation of p53, which in turn induces increased expression of POMC (proopiomelanocortin), which is then cleaved into small peptides such as ACTH (adrenocorticotropic hormone), α-, β-, and γ-MSH (melanocyte-stimulating hormone). ACTH and α-MSH stimulate the melanocortin-1 receptor (MC1R) on melanocytes, resulting in increased production of melanin. Furthermore, UV radiation enhances the production of reactive oxygen species (ROS) in keratinocytes and melanocytes, and a high concentration ROS causes DNA damage, further activating p53, and thus triggering melanogenesis. The synthesis of melanin is also intrinsically regulated through microphthalmia-associated transcription factor (MITF) which regulates the key melanogenic enzymes tyrosinase, Tyrp1 and Tyrp2, and its activity is regulated by a number of signalling pathways, for example, cAMP, ERK/MAPK and NO/cGMP. As a result of this complex process, the synthesis of melanin may be activated by different stimuli, for example, solar radiation, inflammation, acne, stress, hormonal changes, pollution or inflammatory processes, among others. The pigmentation that occurs as a sequela of cutaneous inflammation is generally known as post-inflammatory hyperpigmentation (PI). The melanin generated in the melanocytes is transferred to neighbouring keratinocytes, thus the pigment becomes visible in the epidermis surface and becomes progressively darker due to photooxidation. While melanin plays a key role in protecting the skin from harmful ultraviolet (UV) radiation, abnormally high production and accumulation of melanin in the skin can lead to hyperpigmentation. Although it is usually harmless, hyperpigmentation of the skin, especially on the face, such as melasma, solar lentigines and freckles, is generally considered unsightly. Thus, the concern about skin appearance has boosted the research into skin whitening cosmetic products, which are able to reduce skin pigmentation. These products are generally used to eliminate different kinds of pigment spots on the skin, or to lighten a naturally dark skin colour or to prevent skin pigmentation. The mechanisms involved in skin pigmentation and the main skin-whitening agents available are disclosed, for example, in Gillbro et al., The melanogenesis and mechanisms of skin-lightening agents—existing and new approaches, Int. J. Cosm. Sci., 2011, 33, 210-221 or in Kumari et al., Melanogenesis inhibitors, Acta Derm. Venereol., 2018, 98, 924-931. The most common approach for the whitening and depigmentation of skin is to reduce the melanin production by means of tyrosinase inhibition. Among the known tyrosinase inhibitors useful for skin-lightening are, for example, hydroquinone and its derivatives arbutin and deoxyarbutin, which show inhibition of melanogenesis, though their use may cause melanocyte cytotoxicity. Kojic acid, which is a naturally occurring fungal metabolite obtained from several species of fungi, such as Aspergillus, Acetobacter and Penicillium, is successfully used for treating melasma, though it can cause several adverse effects, such as contact dermatitis, sensitization and erythema. Azelaic acid (nonanedioic acid) is another tyrosinase inhibitor also commonly used as depigmenting agent. Also, polyphenols such as resveratrol or isoflavones such as glabridin, have been reported to have skin-lightening effects through tyrosinase inhibition. Another approach used for skin-lightening is the inhibition of the transfer of mature melanosomes containing melanin to the keratinocytes. Some skin-lightening substances which are believed to act through this mechanism are proteas