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KR-20260065616-A - A lipophilic activity modifier in the form of dimethyl sulfone for use as a transition promoter of an active substance, a composition containing the same, and a method for preparing the same

KR20260065616AKR 20260065616 AKR20260065616 AKR 20260065616AKR-20260065616-A

Abstract

The object of the present invention is an active lipophilic modifier in the form of dimethylsulfone (MSM) for use as a transfer promoter for a high molecular weight active substance with Mw > 500 Da. Another object of the present invention is a cosmetic composition for transdermal administration comprising an active substance and a transfer promoter, wherein the active substance is encapsulated by a transfer promoter which is an active lipophilic modifier according to claim 1, and the active substance is a high molecular weight active substance with Mw > 500 Da. A further object of the present invention is a method for preparing a composition according to the present invention, said method being carried out by thermal emulsification or cold emulsification, wherein thermal emulsification comprises: (a) mixing dimethylsulfone with a diluent in a reaction vessel; (b) raising the mixture to 70 to 85°C; (c) stirring the mixture at 70 to 85°C, wherein the initiation of homogenization depends on the phase combination step; and (d) cooling the mixture to 20 to 40°C, preferably 30°C. (e) a step of adding a high molecular weight active material with Mw > 500 Da and homogenizing the mixture preferably for 1 to 3 minutes, wherein the cold emulsification comprises: (a) a step of mixing dimethyl sulfone with a diluent in a reaction vessel and dissolving it while maintaining a temperature of 20 to 25°C; (b) a step of raising the mixture to a temperature of 15 to 35°C, preferably ambient temperature or 25°C; (c) a step of stirring the mixture at a temperature of 15 to 80°C, preferably 25°C, wherein the initiation of homogenization depends on the phase combination step; (d) a step of adding a high molecular weight active material with Mw > 500 Da and homogenizing the mixture preferably for 1 to 3 minutes.

Inventors

  • 젠체우스카, 매그다레나
  • 다브로와, 카제탄
  • 스테파넥, 아가타
  • 트리자스코우스카, 폴리나
  • 시아치, 토마즈
  • 마주르키에위츠, 알리나
  • 마주르키에위츠-피사렉, 안나
  • 미키에위츠, 디아나

Assignees

  • 사이언스4뷰티 에스피.지.오.오.

Dates

Publication Date
20260508
Application Date
20240904
Priority Date
20230905

Claims (15)

  1. Active lipophilic modifier in the form of dimethylsulfone (MSM) for use as a transition promoter for high molecular weight active substances with Mw > 500 Da.
  2. In paragraph 1, An active lipophilic modifier, wherein the active substance is selected from the group including peptides.
  3. In paragraph 1 or 2, The above active substance is an active lipophilic modifier, which is a conopeptide having the amino acid sequence of SEQ ID NO. 2 or SEQ ID NO. 4.
  4. As a cosmetic composition for transdermal administration comprising an active substance and a transfer promoter, A cosmetic composition wherein the active substance is encapsulated by a transfer promoter which is an active lipophilic modifier as defined in any one of claims 1 to 3, and the active substance is a high molecular weight active substance with Mw > 500 Da.
  5. In paragraph 4, A cosmetic composition comprising at least one excipient acceptable for cosmetic use, advantageously selected from the group consisting of emulsifiers, homogenizers, softeners, thickeners, distilled water, preservatives, or combinations thereof.
  6. In paragraph 4 or 5, The above composition is a cosmetic composition that is an oil-in-water (o/w) or water-in-oil (w/o) emulsion.
  7. In any one of paragraphs 4 through 6, A cosmetic composition in which the weight ratio (%) of the active substance to the transfer promoter is 1:1 to 1:50.
  8. In any one of paragraphs 4 through 7, A cosmetic composition comprising at least one excipient permitted for cosmetic use.
  9. In any one of paragraphs 4 through 8, A cosmetic composition in which the above active substance is a conotoxin, preferably a μ-conotoxin.
  10. In Paragraph 9, A cosmetic composition in which the above μ-conotoxin is a conopeptide having the amino acid sequence of SEQ ID NO. 2.
  11. In Paragraph 9, A cosmetic composition in which the above μ-conotoxin is a conopeptide having the amino acid sequence of SEQ ID NO. 4 or a genetic modification thereof.
  12. In any one of paragraphs 4 through 11, A cosmetic composition comprising at least one additional active ingredient.
  13. A method for manufacturing a composition as defined in any one of paragraphs 4 through 12, The above method is carried out by hot emulsification or cold emulsification, and The above thermal emulsion is, a) A step of mixing dimethylsulfone and a diluent in a reaction vessel; b) a step of raising the above mixture to 70~85℃; c) a step of stirring the above mixture at 70 to 85°C, wherein the initiation of homogenization depends on the stage of the phase combination; d) a step of cooling the above mixture to 20~40℃, preferably 30℃; e) Adding a high molecular weight active substance with Mw > 500 Da and homogenizing the mixture, preferably for 1 to 3 minutes. Includes, The above cold emulsion is, a) a step of mixing the dimethyl sulfone with the diluent in a reaction vessel and dissolving it at 20 to 25°C; b) a step of raising the above mixture to a temperature of 15 to 35°C, preferably ambient temperature or 25°C; c) a step of mixing the above mixture at a temperature of 15 to 80°C, preferably 25°C, wherein the initiation of homogenization depends on the stage of the phase combination; d) adding a high molecular weight active substance with Mw > 500 Da and homogenizing the mixture, preferably for 1 to 3 minutes. A method that includes
  14. In Paragraph 13, A method in which, in at least one of steps a to e) of thermal emulsification, at least one additional active ingredient and/or at least one cosmetically acceptable excipient advantageously selected from the group consisting of emulsifiers, homogenizers, softeners, thickeners, distilled water, preservatives, or combinations thereof is added to the reaction vessel.
  15. In Paragraph 13, A method in which, in at least one of steps a to d) of cold emulsification, at least one additional active ingredient and/or at least one cosmetically acceptable excipient advantageously selected from the group consisting of emulsifiers, homogenizers, softeners, thickeners, distilled water, preservatives, or combinations thereof is added to the reaction vessel.

Description

A lipophilic activity modifier in the form of dimethyl sulfone for use as a transition promoter of an active substance, a composition containing the same, and a method for preparing the same The object of the present invention is a lipophilic activity modifier in the form of dimethylsulfone (other name: methylsulfonylmethane, DMSO2, CAS number: 67-71-0) for use as a transfer promoter of an active substance, a composition containing the same, and a method for preparing the same. Conotoxins are small peptides derived from the venom of cone snails and have evolved to capture prey and defend against predators. They represent a class of bioactive molecules highly diverse in structure and function, and are highly selective for different ligand-gated and voltage-gated ion channel subtypes. For example, the μ-CnIIIC conopeptide from the cone snail * Conus consors * exhibits muscle relaxant effects through the specific blockade of skeletal muscle Nav (Nav1.4) channels. These properties can be utilized in cosmetics for daily wrinkle improvement therapy (References [ Green BR, Bulaj G., Norton RS (2014). Structure and function of μ-conotoxins, peptide-based sodium channel blockers with anglesis activity. Future Medicinal Chemistry 6(15); 1677-1698. doi:10.4155/FMC.14.107 ]; [ Markgraf R., Leipold E., et al. (2012). Mechanism and molecular basis of the sodium channel subtype specificity of μ-conopeptide CnIIIC. British Journal of Pharmacology 167; 576-586. doi:10.1111/j.1476-5381.2012.02004.x ]). Cosmetics applied through the skin constitute a major group of anti-aging agents. Transdermal administration of substances intended to exert systemic effects offers several significant advantages, including: avoiding first-pass effects (hepatic metabolism); eliminating the potential for degradation of therapeutic substances in the gastrointestinal tract; eliminating gastrointestinal side effects; eliminating interactions between therapeutic substances and food and other orally administered drugs; enabling therapeutic effects after absorption of lower doses; allowing the absorption rate of therapeutic substances to depend on their release rate (applied to transdermal therapeutic systems); and enabling a reduction in the frequency of administration of drugs with short biological half-lives, which is particularly important for the treatment of chronic diseases (applied to transdermal therapeutic systems) (Reference [ Cal K, Stefanowska J. Methods to increase the permeation of therapeutic substances through the skin. Farm Pol, 2010, 66(7): 514-520 ]). The epidermis, particularly the outer stratum corneum (SC), protects the skin from moisture loss and provides a sealing barrier to prevent other molecules, including active substances and irritants, from penetrating the skin. Studies have shown that the degree of hydrophilicity increases with higher molecular weight and the number of polar groups of active molecules. This relationship can be approximated by the logP partition coefficient (or clogP if these parameters are theoretically determined). Active molecules with logP < 0 are considered to exhibit hydrophilic properties that impede solubility in non-polar hydrophobic organic solvents. The epidermis exhibits hydrophobic properties that hinder the penetration of hydrophilic active molecules. It is estimated that only 1–2% of active substances applied to the skin penetrate to deeper layers to exhibit biological activity. This is due to the dense structure of the subcutaneous layer (SC), which resembles a brick wall and consists of hydrophobic regions composed of lipids and hydrophilic regions composed of water and hydrated keratinocytes. To date, many methods and techniques have been developed to improve the penetration of active substances through the epidermis. These include the encapsulation of active substances by specialized application systems (e.g., microperforations), lipophilic outer layers (e.g., microbubbles), or the use of low molecular weight organic compounds, so-called transfer promoters. The mechanism of action of transfer promoters is not precisely known, and some posit the formation of specific channels that temporarily facilitate the passage of active substances through the SC. However, in the case of promoters based on saturated fatty acids, this is posited to temporarily increase the permeability of SC lipids. In commercially available cosmetic formulations, the transfer promoters used are oils, e.g., cholesterol succinate, or commercially available mixtures, e.g., Roelmi’s Olifeel Skin or Innovi’s GPS-P and GPS-M. The principle of these promoters is to increase the fluidization, or relaxation, of the skin layers. This involves binding to lipid residues in the epidermis (a passive action rather than a bioactive one). Since similar substances dissolve in similar substances, lipid promoters bind to the fatty areas of the skin. This results in higher fluidity and greater passive diffusion. In contrast, these prom