Cyclodextrins preferentially substituted on their primary face by acid or amine functions

A method of cosmetic care comprising topically delivering on tissue zones to which said cosmetic care is sought, a cosmetically effective amount of at least one substituted cyclodextrin having the following chemical formula:

• CD(OH)w(P)x(X)y(M)z
• where:
• CD represents a structure based on a non-hydroxyalkylated cyclodextrin without its hydroxyl groups including α, β or γ-cyclodextrin,
• OH represents the free hydroxyl groups of the cyclodextrin,
• x and z independently represent a whole number in the range 0 to 17, or in the range 0 to 20, or in the range 0 to 23, when the cyclodextrins are respectively α, β or γ in type;
• y represents a whole number in the range 1 to 18, or in the range 1 to 21, or in the range 1 to 24 when the cyclodextrins are respectively α, β or γ in type,
• w represents a whole number such that the sum (w+x+y+z) is equal to 18, 21 or 24 when the cyclodextrins are respectively α, β or γ in type;
• X represents a substituent with formula —O—C(═O)—R or —N(R1R2) defined below, replacing the —OH portion of at least one primary alcohol function and optionally at least one secondary alcohol function;
• P represents a radical substituting a primary or secondary hydroxyl group, in particular a sulfate, phosphate, methyl, ose or oside substituent;
• when at least one X represents —NR1R2, —NR1R2 is a radical substituting at least one primary hydroxyl group and optionally at least one secondary hydroxyl group, attached to the cyclodextrin skeleton, in which R1 and R2 independently represent a linear or cyclic, saturated or unsaturated, hydroxylated or non-hydroxylated hydrocarbon radical containing 1 to 30 carbon atoms, preferably 1 to 22 carbon atoms, more preferably a fatty chain 2 to 22 carbon atoms;
• preferably when X represents NR1R2, 1% to 100% of the primary cyclodextrin hydroxyl groups are substituted by the amino group NR1R2;
• when at least one X represents —O—C(═O)—R, —O—C(═O)—R is a radical substituting at least one primary hydroxyl group, and optionally at least one secondary hydroxyl group, or the two, attached to the cyclodextrin skeleton, where R represents a linear or cyclic, saturated or unsaturated, hydroxylated or non-hydroxylated hydrocarbon radical containing 1 to 30 carbon atoms, preferably 1 to 22 carbon atoms, more preferably a fatty chain containing 2 to 22 carbon atoms;
• preferably, when X represents —O—COR, 1 to 100% of the primary hydroxyl groups of the cyclodextrins are substituted by the ester group —O—COR;
• (X)y can represent a mixture of groups —NR1R2 and —OCOR substituting at least one primary hydroxyl group and optionally at least one secondary hydroxyl group, or the two;
• M is a substituent for at least one primary or secondary alcohol function or the two of the cyclodextrin, M is a functional group G1 or a specific radical G2, either directly substituting a primary or secondary alcohol function of the cyclodextrin, or indirectly substituting said primary or secondary alcohol function via a spacer arm W, where:
• W is a spacer arm containing 1 to 20 carbon atoms, including the groups selected from the following functions and their derivatives:
• acid, sulfonic and phosphoric acid, alkanoyl, alkenyl, alkynyl, aldehyde, amine, amide, azide, acid anhydride, ketone, isocyanate, phenyl, hydroxyl, epoxy, ester, imide, amidine, halide, nitro, nitriles, peroxides, organometallic derivatives, sulfur-containing derivatives,
• G1 represents at least one of the following functions and its derivatives:
• an acid, a sulfonic, a phosphoric acid, an alkanoyl, an alkenyl, an alkynyl, an aldehyde, an amine, an amide, an azide, an acid anhydride, a ketone, an isocyanate, a phenyl, a hydroxyl, an epoxy, an ester, an imide, an amidine, a halide, a nitro, a nitrile, a peroxide, an organometallic compound, a sulfur-containing compound;
• and
• G2 represents at least one compound selected from the group consisting of a sugar, a polyol, an oligosaccharide, a polysaccharide, a lectin, an amino acid, a peptide, a protein, an antibody, a nucleotide, a nucleoside, an oligonucleotide, an oligonucleoside, a chromophore, a polymer, a sterol, a steroid, a hormone, a flavonoid, a terpene, caffeine, theophylline, nicotinic compound, a vitamin, a vitamin ester, a cholesterol, a phospholipid, a glycolipid, a sphingolipid, a ceramid, a triglyceride, a natural polyphenol, a synthetic polyphenol, an essential oil, a flavoring, a fragrance, a dye, and a cosmetically active substance.

11 The method of claim 3, wherein the cyclodextrin derivative is further substituted by at least one substituent selected from the group consisting of 4-nitrophenylformate;

• ethyloxalic;
• chloroacetyl;
• succinic;
• oxalic;
• sulfonic;
• N-(2-aminoethyl)lactonamide.

A method of therapeutical treatment comprising delivering on tissue zones to which said therapeutical treatment is sought, a therapeutically effective amount of at least one cyclodextrin having the following chemical formula:

• CD(OH)w(P)x(X)y(M)z
• where:
• CD represents a structure based on a non-hydroxyalkylated cyclodextrin without its hydroxyl groups, including α, β or γ-cyclodextrin,
• OH represents the free hydroxyl groups of the cyclodextrin,
• x and z independently represent a whole number in the range 0 to 17, or in the range 0 to 20, or in the range 0 to 23, when the cyclodextrins are respectively α, β or γ in type;
• y represents a whole number in the range 1 to 18, or in the range 1 to 21, or in the range 1 to 24 when the cyclodextrins are respectively α, β or γ in type,
• w represents a whole number such that the sum (w+x+y+z) is equal to 18, 21 or 24 when the cyclodextrins are respectively α, β or γ in type;
• X represents a substituent with formula —O—C(═O)—R or —N(R1R2) defined below, replacing the —OH portion of at least one primary alcohol function and optionally at least one secondary alcohol function;
• P represents a radical substituting a primary or secondary hydroxyl group, in particular a sulfate, phosphate, methyl, ose or oside substituent;
• when at least one X represents —NR1R2, —NR1R2 is a radical substituting at least one primary hydroxyl group and optionally at least one secondary hydroxyl group, attached to the cyclodextrin skeleton, in which R1 and R2 independently represent a linear or cyclic, saturated or unsaturated, hydroxylated or non-hydroxylated hydrocarbon radical containing 1 to 30 carbon atoms, preferably 1 to 22 carbon atoms, more preferably a fatty chain 2 to 22 carbon atoms;
• preferably when X represents NR1R2, 1% to 100% of the primary cyclodextrin hydroxyl groups are substituted by the amino group NR1R2;
• when at least one X represents —O—C(═O)—R, —O—C(═O)—R is a radical substituting at least one primary hydroxyl group, and optionally at least one secondary hydroxyl group, or the two, attached to the cyclodextrin skeleton, where R represents a linear or cyclic, saturated or unsaturated, hydroxylated or non-hydroxylated hydrocarbon radical containing 1 to 30 carbon atoms, preferably 1 to 22 carbon atoms, more preferably a fatty chain containing 2 to 22 carbon atoms;
• preferably, when X represents —O—COR, 1 to 100% of the primary hydroxyl groups of the cyclodextrins are substituted by the ester group —O—COR;
• (X)y can represent a mixture of groups —NR1R2 and —OCOR substituting at least one primary hydroxyl group and optionally at least one secondary hydroxyl group, or the two;
• M is a substituent for at least one primary or secondary alcohol function or the two of the cyclodextrin, M is a functional group G1 or a specific radical G2, either directly substituting a primary or secondary alcohol function of the cyclodextrin, or indirectly substituting said primary or secondary alcohol function via a spacer arm W, where:
• W is a spacer arm containing 1 to 20 carbon atoms, including the groups selected from the following functions :
• acid, sulfonic and phosphoric acid, alkanoyl, alkenyl, alkynyl, aldehyde, amine, amide, azide, acid anhydride, ketone, isocyanate, phenyl, hydroxyl, epoxy, ester, imide, amidine, halide, nitro, nitriles, peroxides, organometallic derivatives, sulfur-containing derivatives,
• G1 represents at least one of the following functions and its derivatives:
• an acid, a sulfonic acid, a phosphoric acid, an alkanoyl, an alkenyl, an alkynyl, an aldehyde, an amine, an amide, an azide, an acid anhydride, a ketone, an isocyanate, a phenyl, a hydroxyl, an epoxy, an ester, an imide, an amidine, a halide, a nitro, a nitrile, a peroxide, an organometallic compound, a sulfur-containing compound;
• and
• G2 represents at least one compound selected from the group consisting of a sugar, a polyol, an oligosaccharide, a polysaccharide, a lectin, an amino acid, a peptide, a protein, an antibody, a nucleotide, a nucleoside, an oligonucleotide, an oligonucleoside, a chromophore, a polymer, a sterol, a steroid, a hormone, a flavonoid, a terpene, caffeine, theophylline, a nicotine compound, a vitamin, a vitamin ester, cholesterol, a phospholipid, a glycolipid, a sphingolipid, a ceramid, a triglyceride, a natural or synthetic polyphenol, an essential oil, a flavoring, a fragrance, a dye, and a cosmetically active substance.

A micelle or nanoparticle based on substituted cyclodextrin, wherein the substituted cyclodextrin is non-hydroxyalkylated and has the following chemical formula:

• CD(OH)w(P)x(X)y(M)z
• where:
• CD represents a structure based on a non-hydroxyalkylated cyclodextrin without its hydroxyl groups, in particular α, β or γ-cyclodextrin,
• OH represents the free hydroxyl groups of the cyclodextrin,
• x and z independently represent a whole number in the range 0 to 17, or in the range 0 to 20, or in the range 0 to 23, when the cyclodextrins are respectively α, β or γ in type;
• y represents a whole number in the range 1 to 18, or in the range 1 to 21, or in the range 1 to 24 when the cyclodextrins are respectively α, β or γ in type,
• w represents a whole number such that the sum (w+x+y+z) is equal to 18, 21 or 24 when the cyclodextrins are respectively α, β or γ in type;
• X represents a substituent with formula —O—C(═O)—R or —N(R1R2) defined below, replacing the —OH portion of at least one primary alcohol function and optionally at least one secondary alcohol function;
• P represents a radical substituting a primary or secondary hydroxyl group, in particular a sulfate, phosphate, methyl, ose or oside substituent;
• when at least one X represents —NR1R2, —NR1R2 is a radical substituting at least one primary hydroxyl group and optionally at least one secondary hydroxyl group, attached to the cyclodextrin skeleton, in which R1 and R2 independently represent a linear or cyclic, saturated or unsaturated, hydroxylated or non-hydroxylated hydrocarbon radical containing 1 to 30 carbon atoms, preferably 1 to 22 carbon atoms, more preferably a fatty chain 2 to 22 carbon atoms;
• preferably when X represents NR1R2, 1% to 100% of the primary cyclodextrin hydroxyl groups are substituted by the amino group NR1R2;
• when at least one X represents —O—C(═O)—R, —O—C(═O)—R is a radical substituting at least one primary hydroxyl group, and optionally at least one secondary hydroxyl group, or the two, attached to the cyclodextrin skeleton, where R represents a linear or cyclic, saturated or unsaturated, hydroxylated or non-hydroxylated hydrocarbon radical containing 1 to 30 carbon atoms, preferably 1 to 22 carbon atoms, more preferably a fatty chain containing 2 to 22 carbon atoms,;
• preferably, when X represents —O—COR, 1% to 100% of the primary hydroxyl groups of the cyclodextrins are substituted by the ester group —O—COR;
• (X)y can represent a mixture of groups —NR1R2 or —OCOR substituting at least one primary hydroxyl group and optionally at least one secondary alcohol hydroxyl, or the two;
• M is a substituent of at least one primary or secondary alcohol function or the two of the cyclodextrin, M is a functional group G1 or a specific radical G2, either directly substituting a primary or secondary alcohol function of the cyclodextrin, or indirectly substituting said primary or secondary alcohol function via a spacer arm W, where:
• W is a spacer arm containing 1 to 20 carbon atoms, including the groups selected from the following functions and their derivatives:
• acid, sulfonic and phosphoric acid, alkanoyl, alkenyl, alkynyl, aldehyde, amine, amide, azide, acid anhydride, ketone, isocyanate, phenyl, hydroxyl, epoxy, ester, imide, amidine, halide, nitro, nitriles, peroxides, organometallic derivatives, sulfur-containing derivatives,
• G1 represents at least one of the following functions and its derivatives:
• acid, sulfonic and phosphoric acid, alkanoyl, alkenyl, alkynyl, aldehyde, amine, amide, azide, acid anhydride, ketone, isocyanate, phenyl, hydroxyl, epoxy, ester, imide, amidine, halide, nitro, nitriles, peroxides, organometallic derivatives, sulfur-containing derivatives;
• and
• G2 represents at least one of the following compounds or its derivatives selected from the group consisting of a sugar, a polyol, an oligosaccharide, a polysaccharide, a lectin, an amino acid, a peptide, a protein, an antibody, a nucleotide, a nucleoside, an oligonucleotide, an oligonucleoside, a chromophore, a polymer, a sterol, a steroid, a hormone, a flavonoid, a terpene, caffeine, theophylline and their derivatives, nicotine and its derivatives, a vitamin, a vitamin ester, cholesterol, a phospholipid, a glycolipid, a sphingolipid, a ceramid, a triglyceride, a natural or synthetic polyphenol, an essential oil, a flavoring, a fragrance, a dye, or a cosmetically, dermopharmaceutically, pharmaceutically, or alimentarily active substance.

A micelle or nanoparticle based on a cyclodextrin derivative prepared from a non-hydroxyalkylated cyclodextrin derivative, wherein the cyclodextrin derivative comprises at least one primary or secondary hydroxyl function substituted by at least one M is a substituent of at least one primary or secondary alcohol function or the two of the cyclodextrin, M is a functional group G1 or a specific radical G2, either-directly substituting a primary or secondary alcohol function of the cyclodextrin, or indirectly substituting said primary or secondary alcohol function via a spacer arm W, where:

• W is a spacer arm containing 1 to 20 carbon atoms, including the groups selected from the following functions and their derivatives:
• an acid, a sulfonic and a phosphoric acid, an alkanoyl, an alkenyl, an alkynyl, an aldehyde, an amine, an amide, an azide, an acid anhydride, a ketone, an isocyanate, a phenyl, a hydroxyl, an epoxy, an ester, an imide, an amidine, a halide, a nitro, a nitrile, a peroxide, an organometallic compound, a sulfur-containing compound,
• G1 is selected from the group constituted by a nitro, a halide, an ester, an acid, a sulfonic, an amine, or a radical G2 selected from the group consisiting of a sugar, a polyol, an oligosaccharide, a polysaccharide, an amino acid, a peptide, a protein, a nucleotide, a nucleoside, an oligonucleotide, an oligonucleoside, a chromophore, a polymer, a sterol, a steroid, a hormone, a flavonoid, a terpene, caffeine, theophylline and their derivatives, nicotine and its derivatives, a vitamin, a vitamin ester, cholesterol, a phospholipid, a glycolipid, a sphingolipid, a ceramid, a triglyceride, a natural or synthetic polyphenol, an essential oil, a flavoring, a fragrance, a dye, and a cosmetically, dermopharmaceutically, pharmaceutically, or alimentarily acceptable excipient.

A novel non-hydroxyalkylated cyclodextrin of formula:

• CD(OH)w(P)x(X)y(M)z
• wherein:
• CD represents a structure based on a non-hydroxyalkylated cyclodextrin without its hydroxyl groups including α, β or γ-cyclodextrin,
• OH represents the free hydroxyl groups of the cyclodextrin,
• x and z independently represent a whole number in the range 0 to 17, or in the range 0 to 20, or in the range 0 to 23, when the cyclodextrins are respectively α, β or γ in type;
• y represents a whole number in the range 1 to 18, or in the range 1 to 21, or in the range 1 to 24 when the cyclodextrins are respectively α, β or γ in type,
• w represents a whole number such that the sum (w+x+y+z) is equal to 18, 21 or 24 when the cyclodextrins are respectively α, βor γ in type;
• X represents a substituent with formula —O—C(═O)—R or —N(R1R2) defined below, replacing the —OH portion of at least one primary alcohol function and optionally at least one secondary alcohol function;
• P represents a radical substituting a primary or secondary hydroxyl group, in particular a sulfate, phosphate, methyl, ose or oside substituent;
• when at least one X represents —NR1R2, —NR1R2 is a radical substituting at least one primary hydroxyl group and optionally at least one secondary hydroxyl group, attached to the cyclodextrin skeleton, in which R1 and R2 independently represent a linear or cyclic, saturated or unsaturated, hydroxylated or non-hydroxylated hydrocarbon radical containing 1 to 30 carbon atoms;
• when at least one X represents —O—C(═O)—R, —O—C(═O)—R is a radical substituting at least one primary hydroxyl group, and optionally at least one secondary hydroxyl group, or the two, attached to the cyclodextrin skeleton, where R represents a linear or cyclic, saturated or unsaturated, hydroxylated or non-hydroxylated hydrocarbon radical containing 1 to 30 carbon atoms;
• preferably, and 1% to 100% of the primary hydroxyl groups of the cyclodextrins are substituted by the ester group —O—COR;
• (X)y can represent a mixture of groups —NR1R2 and —OCOR substituting at least one primary hydroxyl group and optionally at least one secondary alcohol hydroxyl, or the two;
• M is a substituent of at least one primary or secondary alcohol function or the two of the cyclodextrin, M is a functional group G1 or a specific radical G2, either directly substituting a primary or secondary alcohol function of the cyclodextrin, or indirectly substituting said primary or secondary alcohol function via a spacer arm W, where:
• W is a spacer arm containing 1 to 20 carbon atoms, including the groups selected from the following functions and their derivatives:
• acid, sulfonic and phosphoric acid, alkanoyl, alkenyl, alkynyl, aldehyde, amine, amide, azide, acid anhydride, ketone, isocyanate, phenyl, hydroxyl, epoxy, ester, imide, amidine, halide, nitro, a nitrile, a peroxide, an organometallic compound, a sulfur-containing compound,
• G1 is selected from the group consisting of an acid, a sulfonic acid, a phosphoric acid, an alkanoyl, an alkenyl, an alkynyl, an aldehyde, an amine, an amide, an azide, an acid anhydride, a ketone, an isocyanate, a phenyl, an hydroxyl, an epoxy, an ester, an imide, an amidine, a halide, a nitro, a nitrile, a peroxide, an organometallic compound, a sulfur-containing compound;
• and
• G2 is selected from the group consisting of a sugar, a polyol, an oligosaccharide, a polysaccharide, a lectin, an amino acid, a peptide, a protein, an antibody, a nucleotide, a nucleoside, an oligonucleotide, an oligonucleoside, a chromophore, a polymer, a sterol, a steroid, a hormone, a flavonoid, a terpene, caffeine, theophylline , a nicotinic compound, a vitamin, a vitamin ester, cholesterol, a phospholipid, a glycolipid, a sphingolipid, a ceramid, a triglyceride, a natural polyphenol, a synthetic polyphenol, an essential oil, a flavoring compound, a fragrance, a dye, and an active substance selected from the group consisting of a cosmetically active substance, a dermopharmaceutically active substance, a pharmaceutically active substance, and an alimentarily active substance.
• Wherein, further X is selected from the group consisting of:
• a) at least one X represents —N(R1R2) of a primary alcohol;
• b) at least one X represents —N(R1R2) combined with at least one —O—C(═O)—R;
• c) at least one X represents —O—C(═O)—R with at least one radical P and/or at least one radical M substituting at least one primary and/or secondary alcohol;
• and
• d) at least one X represents —O—C(═O)—R, the cyclodextrin then acting as a vector for an active ingredient with which said cyclodextrin is combined.