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EP-4486818-B1 - SURFACTANT AGENTS DERIVED FROM LINEAR POLYGLYCEROL

EP4486818B1EP 4486818 B1EP4486818 B1EP 4486818B1EP-4486818-B1

Inventors

  • DENORA, Nunzio
  • ANGELERI, Fabio
  • IACOBAZZI, Rosa Maria
  • ANNESE, Cosimo
  • PERRONE, Mara
  • LAQUINTANA, VALENTINO
  • FRANCO, MASSIMO
  • LOPEDOTA, Angela Assunta
  • CUTRIGNELLI, Annalisa
  • LOPALCO, Antonio
  • ARDUINO, Ilaria
  • RACANIELLO, Giuseppe Francesco
  • SIRAGUSA, Paolo

Dates

Publication Date
20260506
Application Date
20230303

Claims (10)

  1. A compound of formula (I) wherein: R 1 is a saturated or unsaturated, linear or branched, alkyl chain preferably C3-C29; X is a saturated or unsaturated, linear or branched, preferably C1-C10 alkyl chain; or a heteroatom preferably selected from O, S and N; or a saturated or unsaturated, linear or branched alkyl chain having one or more heteroatoms therein; said one or more heteroatoms preferably being O, S or N; Z is a saturated or unsaturated, linear or branched, preferably C1-C10 alkyl chain; or a heteroatom preferably selected from O, S and N; or a saturated or unsaturated, linear or branched alkyl chain having one or more heteroatoms therein; said one or more heteroatoms preferably being O, S or N; and R 2 is 2-hydroxymethyl 1,2 linPG, of formula: where n is an integer between 2 and 100.
  2. The compound of formula (I) according to claim 1, characterized in that R 1 is a C9-C23 alkyl chain derived from saturated and linear carboxylic acids selected from decanoic, undecanoic, dodecanoic (lauric), tridecanoic, tetradecanoic (myristic), pentadecanoic, hexadecanoic (palmitic), heptadecanoic, octadecanoic (stearic), nonadecanoic, icosanoic (arachidic), docosanoic (behenic), tetracosanoic (lignoceric) acid and the like; or derived from mono-unsaturated and linear carboxylic acids selected from deca-9-enoic (caproleic), (Z)-dodeca-9-enoic (lauroleic), (Z)-tetradeca-9-enoic (myristoleic), (Z)-hexadeca-9-enoic (palmitoleic), (Z)-octadeca-9-enoic (oleic), (E)-octadeca-9-enoic (elaidic), (E)-octadeca-11-enoic (vaccenic), (Z)-icosa-9-enoic (gadoleic), (Z)-docosa-13-enoic (erucic), (E)-docosa-13-enoic (brassidic), (Z)-tetracosa-15-enoic (nervonic) acid; or derived from polyunsaturated and linear or branched carboxylic acids.
  3. The compound of formula (I) according to claim 1, characterized in that n is an integer between 2 and 50, preferably between 2 and 25, more preferably between 2 and 15.
  4. The compound of formula (I) according to claim 1, characterized in that R 1 is a C11-C17 saturated linear alkyl group, preferably a derivative of lauric, or myristic, or palmitic, or stearic acid, or a C17 mono-unsaturated group, preferably a derivative of oleic acid; X is O or N; Z is CH 2 -, or -CH 2 -CH 2 -[N(CH 3 ) 2 ] + -CH 2 -; and n is between 2 and 15.
  5. A synthesis of the compound of general formula (I) according to claim 1 by controlled linear accretion, characterized in that the base monomer has general formula (II) where R is a protective group of the hydroxyl group capable of restoring the hydroxyl group at the end of the polymerization reaction through reaction of acid deprotection or catalytic hydrogenation.
  6. The synthesis according to claim 5 characterized in that said base monomer of general formula (II) is selected from TMSGE (trimethylsilyl glycidyl ether), EEGE (,ethoxyethyl glycidyl ether) t-BGE (terbutyl glycidyl ether), AGE (allyl glycidyl ether), IGG (isopropylidene glyceryl glycidyl ether), THFGE (tetrahydrofuranyl glycidyl ether), THPGE (tetrahydropyranyl glycidyl ether) and BGE (benzyl glycidyl ether).
  7. The synthesis according to claim 5, characterized in that an initial step of said synthesis is constituted by the conjugation, preceded by the opening of the epoxy ring of said monomer of general formula (II), of said monomer in open form with a fatty acid of formula (III) wherein R 1 is a saturated or unsaturated, linear or branched, preferably C3-C29 linear alkyl chain, and R 3 is a protecting group of the carboxylic acid capable of restoring the carboxylic group at the end of the addition/elimination reaction resulting in a base linPG chain, preferably is a saturated linear C1-C6 alkyl chain.
  8. The synthesis according to claim 5, characterized in that said base linPG chain undergoes AROP controlled linear accretion by addition of potassium tert-butoxylate and monomer (II), at 60-100 °C, for 24-72 h and in the absence of solvent, to provide the compound of general formula (I) according to claim 1, wherein R 2 is where n is an integer between 2 and 100.
  9. Use of the compound of general formula (I) according to claim 1, as surfactant.
  10. Use according to claim 9 in pharmaceutical, biomedical, cosmetic, and/or food applications.

Description

Summary of the Invention The present invention relates to novel derivatives of linear polyglycerol conjugated to fatty acids, their preparation process by linear controlled accretion of the polymer chain and their use as surfactant agents in various fields of the art, including cosmetics, pharmaceuticals and food. Technical background Surfactants are called those substances that, by their chemical nature, tend to position themselves at the level of the liquid-gas. liquid-liquid and/or liquid-solid interfaces, lowering the surface tension between a liquid and a gas or the interfacial tension between a liquid and a liquid or a solid, and thus facilitating the wettability of the surfaces of solids or the dispersion of two or more liquids of different natures, or of liquids and gases. In general, they are organic compounds constituted by a group, called the head, which is polar and a group, called the tail, which is non-polar. Compounds with such characteristics are also called "amphiphilic" or "amphipathic". Once they exceed a particular concentration level, called the critical micellar concentration, said compounds tend to organize themselves into spherical supra-molecular aggregates, the micelles, which stabilize the emulsions by hindering the re-aggregation of their different component phases. Depending on their chemical nature, various types of surfactants can be identified, generally divided into: non-ionic, anionic, cationic and amphoteric. On the other hand, the former have no charge on the polar head while the others are, respectively, negatively charged, positively charged or can express both charges depending on their environment. In recent years, a number of surfactants of polymeric nature have also been studied and developed: macromolecules that therefore contain both hydrophilic portions and repeated hydrophobic zones in their structure. Compounds normally referred to as PEG (polyethylene glycol), polyethers derived from the polymerization reaction of ethylene oxide, can be grouped into this class. PEGs differ according to their molecular weight, and thus the number of "monomers" that make them up, and are commercially available in a wide range that can range, with reference to their molecular weight (MW, expressed in g/mol) from 300 to 10,000,000 g/mol. Their uses are varied, but in the field of biological applications, the derivatives weighing less than 400 g/mol have the limitation of being recognized as potentially toxic because of the possibility of promoting enzyme-catalyzed oxidation reactions and causing hypersensitivity. Another group of polymeric surfactants that has been studied in recent years, structurally close to PEGs, are the polyglycerols (PGs): a heterogeneous chemical class of polymers that, compared to PEGs, has a greater variety of possible configurations and opportunities for functionalization. PGs derive from the polymerization of glycerol (1,2,3-propanthriol), the structures of their component chains can be linear, branched or cross-linked due to the presence of a large number of hydroxyl -OH groups, which also allow their possible functionalization with other molecules, such as for example fatty acid chains, to increase their lipophilic portion/affinity. US2012157366 describes a complex system acting as a mild skin cleanser that comprises: a low-molecular-weight linear acrylic copolymer, a glycerol polymer (glycerol monomer number from 8 to 14) functionalized with C10-C18 chain fatty acids, and another class of surfactants selected from a wide range of anionic or amphoteric compounds. EP2754684 describes the process of preparing hyper-ramified polyglycerols according to a synthetic poly-condensation route involving the use of calcium oxide catalysts and high temperatures and pressures. WO 2007/141248 A1 discloses difunctionalized methylated linear polyglyerols, wherein one of the end groups may be a carboxylic acid group. Thus, there is currently still a need for novel polymeric surfactant compounds, which are alternative to PEG-derived ones, that are versatile, can also be safely used in pharmaceutical, biomedical, cosmetic and/or food applications, and can be synthesized through an easily controllable and, possibly, environmentally friendly process. Objects of the invention An object of the present invention is to provide a novel group of polymeric surfactant molecules obtained by condensation of glycerol, which are biocompatible and usable in a wide range of applications. A further object of the present invention is to provide a synthetic process for obtaining said polymeric surfactants, which is based on controlled linear accretion of the chain from glycerol monomers. Another object of the present invention is the use of said polymeric surfactants in all areas of the art that require the presence of compounds characterized by surfactant properties and particularly in the pharmaceutical, biomedical, cosmetic and food fields. These and other objects are achieved by the s