Polypeptides KXK and Their Use

• US 20110033507A1
• Filed: 02/16/2006
• Published: 02/10/2011
• Est. Priority Date: 02/16/2006
• Status: Active Grant

• Current Assignee: Sederma, Co.
• Original Assignee: Sederma, Co.
• Inventors: Mondon, Philippe, Lintner, Karl, Peschard, Olivier, Mas Chamberlin, Claire
• Granted Patent: US 8,404,648 B2
• Time in Patent Office: Days
• US Class Current: 424/401
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 8/64 Proteins; Peptides; Derivatives or degradation products thereof
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 17/16 Emollients or protectives, e.g. against radiation
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: A61Q 19/06 for countering cellulitis
• CPC Class Codes: A61Q 19/08 Anti-ageing preparations
• CPC Class Codes: C07K 5/0815 with the first amino acid being basic
• CPC Class Codes: C07K 5/1019 with the first amino acid being basic

Abstract

The invention concerns polypeptides of the general formula (I): A-(Xaa)_n-Lys-X-Lys-B wherein: i) A is —NH2, NH3+, or NH-D (D is an acyl group being biotin or an alkyl chain (C2-C22)), H) B is H, O⁻ OR¹ or NR²R³ and R¹, R² and R³ independently either: H or an alkyl chain (C1-C24), iii) (Xaa)_n is an amino acid chain including any amino acid natural or not, excluding arginine and lysine, iv) “n” is between 0-3, and v) X is either a chain of two any amino acids (Xaa1Xaa2), which may be the same or different, excluding arginine, lysine and excluding Xaa1Xaa2=Thr-Thr, Gly-His and Glu-His, or X is a spacer selected among beta-alanyl, 5-amino-valeroyl, 4-amino-cyclohexanoyl, 4-amino-butyroyl, 6-amino-caproyl and derivatives thereof. More particularly, the invention concerns polypeptides of formula (I) wherein “n” is 0 and with the formula: A-Lys-X-Lys-B; A, X and B being defined herein. Compositions containing at least one of said polypeptides and their use.

Claims

1. Polypeptide and derivatives thereof, peptide analogs and derivatives thereof, as well as pharmaceutically acceptable salts of these compounds, having the general formula (I):

A-(Xaa)n-Lys-X-Lys-B wherein;

i) A=—

NH2, NH3+, NH-D, D is an Acyl group being biotin or an alkyl chain from 2 to 22 carbons, linear, or branched or cyclic, substituted or unsubstituted, saturated or unsaturated, hydroxylated or non-hydroxylated, sulfurated or non-sulfurated,

ii) B═

H, O⁻

, OR1 or NR2R3 and R1, R2 and R3 independently either;

a hydrogen atom, or an alkyl chain of from 1 to 24 carbons, linear, branched or cyclic, substituted or unsubstituted, saturated or unsaturated, hydroxylated or non-hydroxylated, sulfurated or non-sulfurated,

iii) (Xaa)n is an amino acid chain and (Xaa) is any amino acid natural or non natural, excluding arginine and lysine,

iv) “

n”

is between 0 and 3,

v) X being

either a chain of two any amino acids (Xaa1Xaa2) which may be the same or different excluding arginine, lysine and excluding Xaa1Xaa2=Thr-Thr, Gly-His and Glu-His- (SEQ ID NO;

4)

or a spacer selected from the group consisting of beta-alanyl, 5-amino-valeroyl, 4-amino-cyclohexanoyl, 4-amino-butyroyl, 6-amino-caproyl and derivatives thereof, wherein the carbon chain may be substituted or unsubstituted, saturated or unsaturated, hydroxylated or non-hydroxylated, sulfurated or non-sulfurated, (SEQ ID NO;

5).

2. The compound according to claim 1, wherein “

n”

=0 and having the following structure;

A-Lys-X-Lys-B wherein;

i) A=—

NH2, NH3+, NH-D, D is an Acyl group being biotin or an alkyl chain from 2 to 22 carbons, linear, or branched or cyclic, substituted or unsubstituted, saturated or unsaturated, hydroxylated or non-hydroxylated, sulfurated or non-sulfurated,

ii) B═

H, O, OR1 or NR2R3 and R1, R2 and R3 independently either;

a hydrogen atom, or an alkyl chain of from 1 to 24 carbons, linear, branched or cyclic, substituted or unsubstituted, saturated or unsaturated, hydroxylated or non-hydroxylated, sulfurated or non-sulfurated,

iii) X being;

either a chain of two any amino acids (Xaa1Xaa2) which may be the same or different excluding arginine and lysine and excluding Xaa1Xaa2=Thr-Thr, Gly-His and Glu-His (SEQ ID NO;

6),

or a spacer selected from the group consisting of beta-alanyl, 5-amino-valeroyl, 4-amino-cyclohexanoyl, 4-amino-butyroyl, 6-amino-caproyl and derivatives thereof, wherein the carbon chain may be substituted or unsubstituted, saturated or unsaturated, hydroxylated or non-hydroxylated, sulfurated or non-sulfurated.

3. The compound according to claim 1, wherein X is a chain of any two any amino acids (Xaa1Xaa2) in which Xaa1 is selected from the group consisting of threonine, alanine and phenylalanine.

4. The compound according to claim 1, wherein Xaa2 is an amino acid selected from the group consisting of phenylalanine, alanine and tyrosine.

5. The compound according to claim 1, wherein X is a spacer selected from the group consisting of beta-alanyl, 5-amino-valeroyl, 4-amino-cyclohexanoyl, 4-amino-butyroyl and 6-amino-caproyl.

6. The compound according to claim 1, wherein the N-acyl group is selected from the group consisting of acetyl, palmitoyl, elaidoyl, myristoyl, biotinyl, octanoyl, stearoyl, oleoyl or lipoyl.

7. The compound according to claim 1 wherein said compound is selected from the group consisting of:

Pal-Lys-Thr-Phe-Lys (SEQ ID NO;

7), Ela-Lys-Thr-Phe-Lys (SEQ ID NO;

8), Ela-Lys-Thr-Ala-Lys (SEQ ID NO;

9), Pal-Lys-Ava-Lys, Ela-Lys-Ala-Tyr-Lys (SEQ ID NO;

10), Ela-Lys-Phe-Tyr-Lys (SEQ ID NO;

11), Pal-Lys-β

Ala-Lys, Pal-Lys-Abu-Lys and Pal-Lys-Aca-Lys.

8. A cosmetic or dermopharmaceutical composition comprising

a) at least one compound according to claim 1 and

b) a dermatologically acceptable carrier.

9. The cosmetic or dermopharmaceutical composition according to claim 8 wherein said compound is present at a concentration between 0.00001% (w/w) and 15% (w/w), preferably at a concentration between 0.0001% (w/w) and 0.1% (w/w) by weight of the composition.

10. The cosmetic or dermopharmaceutical composition according to claim 8 further comprising one or more skin anti-aging agent, or anti-wrinkle agent, or anti-atrophy agent or an anti-oxidant/radical scavenger.

11. The cosmetic or dermopharmaceutical composition according to claim 8 further comprising at least one skin care active or additional ingredient.

12. The composition according to claim 8 wherein said compound is used in the form of solution, dispersion, emulsion, paste, or powder individually or as a premix in vehicles such as macro-, micro-, or nanocapsules, macro-, micro- or nanospheres, liposomes, oleosomes or chylomicrons, macro-, micro-, or nanoparticles or macro-, micro or nanosponges, or adsorbed on organic polymer powders, talcs, bentonites, or other inorganic supports.

13. The composition according to claim 8 wherein said composition is in the form of creams, lotions, ointments, milks, gels, emulsions, dispersions, solutions, suspensions, cleansers, foundations, anhydrous preparations (sticks, in particular lipsticks, body and bath oils), shower and bath gels, shampoos and scalp treatment lotions, cream or lotion for care of the skin or hair, sun-screen lotions, milks or creams, artificial suntan lotions, creams or creams, shaving creams or foams, aftershave lotions, make-up, mascaras or nail varnishes, lipsticks, skin “

essences,”

serums, adhesive or absorbent materials, transdermal patches, powders, emollient lotion, emollient milk, emollient cream, sprays, oils for the body and the bath, foundation tint bases, pomade, colloid, compact or solid suspension, pencil, sprayable formulation, brossable.

15. A method for increasing the expression of the extracellular matrix proteins, more preferably in order to exhibit collagen I synthesis, and/or collagen IV synthesis and/or fibronectin synthesis comprising administering the compound of formula I or a composition comprising the compound of formula I, of claim 1 to human skin cells.

16. A method of reducing at least one sign of aging comprising applying to skin in need of such treatment the composition of claim 8 to a portion of human skin showing signs of aging for a period of time at least sufficient to provide a reduction in at least one sign of aging, preferably wrinkles, of that portion of human skin.

17. A method of reducing stretch marks comprising applying to skin in need of such treatment the composition of claim 8 to a portion of human skin showing stretch marks for a period of time at least sufficient to provide a reduction in the visible signs of stretch marks of that portion of human skin.

18. A method of reducing dark circles under the eyes comprising applying to skin in need of such treatment the composition of claim 8 to a portion of human skin showing dark circles under the eyes at least once a day for a period of time at least sufficient to provide a reduction in the visible signs of dark circles under the eyes.

19. A pharmaceutical composition comprising one or more compounds of claim 1.

20. The pharmaceutical composition of claim 19 wherein said composition is a dermopharmaceutical or a cosmetic composition.

21. A method for treating or preventing the phenomena of cutaneous aging, more specifically wrinkles, and/or to improve the appearance of the skin, comprising administering the pharmaceutical composition of claim 19.

14. (canceled)