IP Library › Granted Patent US 12678388

Granted Patent B2

US 12678388 · App. 18/551,350 · Granted Jul 14, 2026

Dermatological compositions and use thereof

Inventors: Yaron Rapaport (Lehavim, IL); Noa Harduf (Kibutz Gevim, IL); Hanna Rapaport (Lehavim, IL)

Assignee: BONE SCI. BIO LTD.

A61K8/64 A61K9/0014 A61K38/08 A61K38/10 A61K38/16 A61L27/26 A61L27/36 A61L27/3834 A61L27/52 A61L2300/252 A61L2400/06 A61L2430/04 A61L2430/34

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Quick Facts

Patent No.: US 12678388
App. No.: 18/551,350
Granted: Jul 14, 2026
Kind: B2

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Abstract

Dermatological compositions comprising amphiphilic peptides, derivatives or salts thereof are provided. The compositions are particularly useful as dermal fillers and for inducing soft tissue repair and regeneration.

Claims (260)

1 . A dermatological composition comprising at least one amphiphilic peptide comprising alternating hydrophobic/hydrophilic amino acid residues, or a derivative or a salt thereof, wherein the peptide comprises 1-20 pairs of hydrophobic-hydrophilic alternating amino acid residues, wherein the hydrophilic amino acid residue is selected from the group consisting of Glu, Asp, Tyr, Ser, Thr, Ser(PO 4 ), Thr(PO 4 ), and Tyr(PO 4 ), and the hydrophobic amino acid residue is selected from the group consisting of Phe, Leu, Ile, Val, Trp, and Ala, and wherein said peptide has no more than 10% positively charged amino acid residues, and a dermatologically acceptable carrier, wherein the dermatological composition is a soft tissue filler composition, and wherein the dermatological composition further comprises a plurality of cells obtained from adipose tissue.

2 . The dermatological composition of claim 1 , wherein the at least one amphiphilic peptide has 2 to 40 amino acids, or wherein the at least one amphiphilic peptide further comprises at least one terminal Pro residue.

3 . The dermatological composition of claim 1 , wherein the at least one amphiphilic peptide comprises an amino acid sequence according to Formula I:

X-(hydrophobic-hydrophilic) n -B (Formula I)

or a salt thereof,

wherein n designates an integer of 1 to 20, hydrophobic designates a hydrophobic amino acid residue selected from the group consisting of Phe, Leu, Ile, Val, Trp, and Ala, hydrophilic designates a hydrophilic amino acid residue selected from the group consisting of Glu, Asp, Tyr, Ser, Thr, Ser(PO 4 ), Thr(PO 4 ), and Tyr(PO 4 ), X designates Pro, Pro-hydrophilic or the peptide's amino terminus, and B designates Pro or the peptide's carboxy terminus; or wherein the at least one amphiphilic peptide comprises an amino acid sequence of any of the following formulae X-(Phe-Glu) n -B, X-(Phe-Asp) n -B, X-(Leu-Glu) n -B, and X-(Leu-Asp) n -B, or a salt thereof; or wherein the at least one amphiphilic peptide comprises at least one modification selected from a modification of the amino terminus X and a modification of the carboxy terminus B.

4 . The dermatological composition of claim 3 , wherein the modification comprises acetylation of the amino terminus, amidation of the carboxy terminus, or a combination thereof.

5 . The dermatological composition of claim 1 , wherein the at least one amphiphilic peptide comprises a sequence selected from the group consisting of:

(SEQ ID NO: 1)

Pro-(Asp-Phe) 5 -Asp-Pro,

(SEQ ID NO: 2)

Pro-Glu-(Phe-Glu) 5 ,

(SEQ ID NO: 3)

Glu-(Phe-Glu) 5 -Pro,

(SEQ ID NO: 4)

Pro-(Ser-Phe) 5 -Ser-Pro,

(SEQ ID NO: 5)

Pro-(SerPO 4 -Phe) 5 -SerPO 4 -Pro,

(SEQ ID NO: 6)

Pro-(TyrPO 4 -Phe) 5 -TyrPO 4 -Pro,

(SEQ ID NO: 7)

Pro-(Glu-Leu) 5 -Glu-Pro,

(SEQ ID NO: 8)

Pro-(Asp-Leu) 5 -Asp-Pro,

(SEQ ID NO: 9)

Pro-(Ser-Leu) 5 -Ser-Pro,

(SEQ ID NO: 10)

Pro-(SerPO 4 -Leu) 5 -SerPO 4 -Pro,

(SEQ ID NO: 11)

Pro-(TyrPO 4 -Leu) 5 -TyrPO 4 -Pro,

(SEQ ID NO: 12)

Pro-(Glu-Phe-Ser-Phe) 4 -Glu-Pro,

(SEQ ID NO: 13)

Pro-(SerPO 4 -Phe-Ser-Phe) 4 -Ser-Pro,

(SEQ ID NO: 14)

Pro-(SerPO 4 -Phe-Glu-Phe) 4 -Glu-Pro,

(SEQ ID NO: 15)

Pro-(SerPO 4 -Phe-Asp-Phe) 4 -Asp-Pro,

(SEQ ID NO: 16)

Ala-Leu-Glu-(Phe-Glu) 3 -Pro-Ala-(Glu-Phe) 3 -Glu-Leu-

Pro-Ala-Leu-Glu-(Phe-Glu) 3 -Pro,

(SEQ ID NO: 17)

Pro-Glu-(Phe-Glu) 2 -Lys-(Glu-Phe) 2 -Glu-Pro,

(SEQ ID NO: 18)

Pro-Glu-(Phe-Glu) 5 -(Gly) 3 -Arg-Gly-Asp-Ser,

(SEQ ID NO: 19)

(Phe-Glu) 3 -Pro-(Gly) 3 -Arg-Gly-Asp-Ser,

(SEQ ID NO: 20)

Ac-Pro-Asp-(Phe-Asp) 5 -Pro-NH 2 ,

(SEQ ID NO: 21)

Pro-Asp-(Phe-Asp) 6 ,

(SEQ ID NO: 22)

(Phe-Asp) 6 ,

(SEQ ID NO: 23)

Pro-Glu-(Phe-Glu) 5 -Pro,

(SEQ ID NO: 24)

Pro-Asp-(Phe-Asp) 5 -Pro-NH 2 ,

(SEQ ID NO: 25)

(Phe-Glu) 5 ,

(SEQ ID NO: 26)

(Phe-Glu) 6 ,

(SEQ ID NO: 27)

(Phe-Glu) 7 ,

(SEQ ID NO: 28)

Pro-Asp-(Phe-Asp) 4 ,

(SEQ ID NO: 29)

Pro-Asp-(Phe-Asp) 6 ,

(SEQ ID NO: 30)

Pro-Asp-(Phe-Asp) 8 ,

(SEQ ID NO: 31)

(Phe-Asp) 5 ,

(SEQ ID NO: 32)

(Phe-Asp) 6 ,

(SEQ ID NO: 33)

(Phe-Asp) 7 ,

(SEQ ID NO: 34)

Pro-Asp-(Phe-Asp) 5 -Pro-Arg-Gly-Asp-Ser,

(SEQ ID NO: 35)

Pro-(Phe-Asp) 3 -Pro,

and

(SEQ ID NO: 36)

Pro-(Phe-Asp) 3 -Pro-(Gly) 3 -Arg-Gly-Asp-Ser,

or a salt thereof.

6 . The dermatological composition of claim 5 , wherein the at least one amphiphilic peptide comprises a sequence as set forth in SEQ ID NO: 1, or a salt thereof.

7 . The dermatological composition of claim 1 , formulated for intradermal or subcutaneous administration, or formulated for use in 3D bioprinting of an artificial tissue, and/or formulated in the form of a hydrogel.

8 . The dermatological composition of claim 1 , further comprising at least one of hyaluronic acid, collagen, gelatin, elastin, laminin, and fibronectin.

9 . The dermatological composition of claim 1 , wherein the plurality of cells obtained from adipose tissue comprise adipocytes and/or adipose-derived stem cells, or wherein the plurality of cells obtained from adipose tissue are autologous; or wherein the plurality of cells obtained from adipose tissue are obtained by lipoaspiration, or wherein the plurality of cells obtained from adipose tissue are allogeneic.

10 . A method of treating a soft tissue defect, the method comprising the step of injecting or implanting to a subject in need thereof an effective amount of a dermatological composition comprising at least one amphiphilic peptide comprising alternating hydrophobic/hydrophilic amino acid residues, or a derivative or a salt thereof, wherein the peptide comprises 1-20 pairs of hydrophobic-hydrophilic alternating amino acid residues, wherein the hydrophilic amino acid residue is selected from the group consisting of Glu, Asp, Tyr, Ser, Thr, Ser(PO 4 ), Thr(PO 4 ), and Tyr(PO 4 ), and the hydrophobic amino acid residue is selected from the group consisting of Phe, Leu, Ile, Val, Trp, and Ala, and wherein said peptide has no more than 10% positively charged amino acid residues, and a dermatologically acceptable carrier, wherein the dermatological composition is a soft tissue filler composition.

11 . The method of claim 10 , wherein treating a soft tissue defect comprises face or body contouring; or wherein treating a soft tissue defect comprises breast augmentation following mastectomy.

12 . A pre-filled syringe comprising the dermatological composition of claim 1 .

13 . A method for treating an epidermal condition related to aging selected from the group consisting of elastosis, atrophy of the skin, fine lines, wrinkles, enlarged pores, hyperpigmentation, hypopigmentation, sagging skin, rough skin, and dry skin, or a method for treating a skin condition selected from the group consisting of cuts, wounds, burns, insect bites, jellyfish stings, a rash, skin allergic responses, and skin lesions, the method comprising the step of locally administering to a subject in need thereof an effective amount of a dermatological composition comprising at least one amphiphilic peptide comprising alternating hydrophobic/hydrophilic amino acid residues, or a derivative or a salt thereof, wherein the peptide comprises 1-20 pairs of hydrophobic-hydrophilic alternating amino acid residues, wherein the hydrophilic amino acid residue is selected from the group consisting of Glu, Asp, Tyr, Ser, Thr, Ser(PO 4 ), Thr(PO 4 ), and Tyr(PO 4 ), and the hydrophobic amino acid residue is selected from the group consisting of Phe, Leu, Ile, Val, Trp, and Ala, and wherein said peptide has no more than 10% positively charged amino acid residues, and a dermatologically acceptable carrier, wherein the dermatological composition is a cosmetic composition.

14 . The method of claim 13 , wherein the at least one amphiphilic peptide has 2 to 40 amino acids; or wherein the at least one amphiphilic peptide further comprises at least one terminal Pro residue; or wherein the at least one amphiphilic peptide comprises an amino acid sequence according to Formula I:

X-(hydrophobic-hydrophilic) n -B(Formula I)

or a salt thereof,

15 . The method of claim 13 , wherein the at least one amphiphilic peptide comprises a sequence selected from the group consisting of:

(SEQ ID NO: 1)

Pro-(Asp-Phe) 5 -Asp-Pro,

(SEQ ID NO: 2)

Pro-Glu-(Phe-Glu) 5 ,

(SEQ ID NO: 3)

Glu-(Phe-Glu) 5 -Pro,

(SEQ ID NO: 4)

Pro-(Ser-Phe) 5 -Ser-Pro,

(SEQ ID NO: 5)

Pro-(SerPO 4 -Phe) 5 -SerPO 4 -Pro,

(SEQ ID NO: 6)

Pro-(TyrPO 4 -Phe) 5 -TyrPO 4 -Pro,

(SEQ ID NO: 7)

Pro-(Glu-Leu) 5 -Glu-Pro,

(SEQ ID NO: 8)

Pro-(Asp-Leu) 5 -Asp-Pro,

(SEQ ID NO: 9)

Pro-(Ser-Leu) 5 -Ser-Pro,

(SEQ ID NO: 10)

Pro-(SerPO 4 -Leu) 5 -SerPO 4 -Pro,

(SEQ ID NO: 11)

Pro-(TyrPO 4 -Leu) 5 -TyrPO 4 -Pro,

(SEQ ID NO: 12)

Pro-(Glu-Phe-Ser-Phe) 4 -Glu-Pro,

(SEQ ID NO: 13)

Pro-(SerPO 4 -Phe-Ser-Phe) 4 -Ser-Pro,

(SEQ ID NO: 14)

Pro-(SerPO 4 -Phe-Glu-Phe) 4 -Glu-Pro,

(SEQ ID NO: 15)

Pro-(SerPO 4 -Phe-Asp-Phe) 4 -Asp-Pro,

(SEQ ID NO: 16)

Ala-Leu-Glu-(Phe-Glu) 3 -Pro-Ala-(Glu-Phe) 3 -Glu-Leu-

Pro-Ala-Leu-Glu-(Phe-Glu) 3 -Pro,

(SEQ ID NO: 17)

Pro-Glu-(Phe-Glu) 2 -Lys-(Glu-Phe) 2 -Glu-Pro,

(SEQ ID NO: 18)

Pro-Glu-(Phe-Glu) 5 -(Gly) 3 -Arg-Gly-Asp-Ser,

(SEQ ID NO: 19)

(Phe-Glu) 3 -Pro-(Gly) 3 -Arg-Gly-Asp-Ser,

(SEQ ID NO: 20)

Ac-Pro-Asp-(Phe-Asp) 5 -Pro-NH 2 ,

(SEQ ID NO: 21)

Pro-Asp-(Phe-Asp) 6 ,

(SEQ ID NO: 22)

(Phe-Asp) 6 ,

(SEQ ID NO: 23)

Pro-Glu-(Phe-Glu) 5 -Pro,

(SEQ ID NO: 24)

Pro-Asp-(Phe-Asp) 5 -Pro-NH 2 ,

(SEQ ID NO: 25)

(Phe-Glu) 5 ,

(SEQ ID NO: 26)

(Phe-Glu) 6 ,

(SEQ ID NO: 27)

(Phe-Glu) 7 ,

(SEQ ID NO: 28)

Pro-Asp-(Phe-Asp) 4 ,

(SEQ ID NO: 29)

Pro-Asp-(Phe-Asp) 6 ,

(SEQ ID NO: 30)

Pro-Asp-(Phe-Asp) 8 ,

(SEQ ID NO: 31)

(Phe-Asp) 5 ,

(SEQ ID NO: 32)

(Phe-Asp) 6 ,

(SEQ ID NO: 33)

(Phe-Asp) 7 ,

(SEQ ID NO: 34)

Pro-Asp-(Phe-Asp) 5 -Pro-Arg-Gly-Asp-Ser,

(SEQ ID NO: 35)

Pro-(Phe-Asp) 3 -Pro,

and

(SEQ ID NO: 36)

Pro-(Phe-Asp) 3 -Pro-(Gly) 3 -Arg-Gly-Asp-Ser,

or a salt thereof.

16 . The method of claim 15 , wherein the at least one amphiphilic peptide comprises a sequence as set forth in SEQ ID NO: 1, or a salt thereof.

17 . The method of claim 13 , wherein the dermatological composition is formulated for topical administration in the form of a hydrogel.

18 . The method of claim 10 , wherein the at least one amphiphilic peptide has 2 to 40 amino acids, or wherein the at least one amphiphilic peptide further comprises at least one terminal Pro residue.

19 . The method of claim 10 , wherein the at least one amphiphilic peptide comprises an amino acid sequence according to Formula I:

X-(hydrophobic-hydrophilic) n -B(Formula I)

or a salt thereof,

20 . The method of claim 19 , wherein the modification comprises acetylation of the amino terminus, amidation of the carboxy terminus, or a combination thereof.

21 . The method of claim 10 , wherein the at least one amphiphilic peptide comprises a sequence selected from the group consisting of:

(SEQ ID NO: 1)

Pro-(Asp-Phe) 5 -Asp-Pro,

(SEQ ID NO: 2)

Pro-Glu-(Phe-Glu) 5 ,

(SEQ ID NO: 3)

Glu-(Phe-Glu) 5 -Pro,

(SEQ ID NO: 4)

Pro-(Ser-Phe) 5 -Ser-Pro,

(SEQ ID NO: 5)

Pro-(SerPO 4 -Phe) 5 -SerPO 4 -Pro,

(SEQ ID NO: 6)

Pro-(TyrPO 4 -Phe) 5 -TyrPO 4 -Pro,

(SEQ ID NO: 7)

Pro-(Glu-Leu) 5 -Glu-Pro,

(SEQ ID NO: 8)

Pro-(Asp-Leu) 5 -Asp-Pro,

(SEQ ID NO: 9)

Pro-(Ser-Leu) 5 -Ser-Pro,

(SEQ ID NO: 10)

Pro-(SerPO 4 -Leu) 5 -SerPO 4 -Pro,

(SEQ ID NO: 11)

Pro-(TyrPO 4 -Leu) 5 -TyrPO 4 -Pro,

(SEQ ID NO: 12)

Pro-(Glu-Phe-Ser-Phe) 4 -Glu-Pro,

(SEQ ID NO: 13)

Pro-(SerPO 4 -Phe-Ser-Phe) 4 -Ser-Pro,

(SEQ ID NO: 14)

Pro-(SerPO 4 -Phe-Glu-Phe) 4 -Glu-Pro,

(SEQ ID NO: 15)

Pro-(SerPO 4 -Phe-Asp-Phe) 4 -Asp-Pro,

(SEQ ID NO: 16)

Ala-Leu-Glu-(Phe-Glu) 3 -Pro-Ala-(Glu-Phe) 3 -Glu-Leu-

Pro-Ala-Leu-Glu-(Phe-Glu) 3 -Pro,

(SEQ ID NO: 17)

Pro-Glu-(Phe-Glu) 2 -Lys-(Glu-Phe) 2 -Glu-Pro,

(SEQ ID NO: 18)

Pro-Glu-(Phe-Glu) 5 -(Gly) 3 -Arg-Gly-Asp-Ser,

(SEQ ID NO: 19)

(Phe-Glu) 3 -Pro-(Gly) 3 -Arg-Gly-Asp-Ser,

(SEQ ID NO: 20)

Ac-Pro-Asp-(Phe-Asp) 5 -Pro-NH 2 ,

(SEQ ID NO: 21)

Pro-Asp-(Phe-Asp) 6 ,

(SEQ ID NO: 22)

(Phe-Asp) 6 ,

(SEQ ID NO: 23)

Pro-Glu-(Phe-Glu) 5 -Pro,

(SEQ ID NO: 24)

Pro-Asp-(Phe-Asp) 5 -Pro-NH 2 ,

(SEQ ID NO: 25)

(Phe-Glu) 5 ,

(SEQ ID NO: 26)

(Phe-Glu) 6 ,

(SEQ ID NO: 27)

(Phe-Glu) 7 ,

(SEQ ID NO: 28)

Pro-Asp-(Phe-Asp) 4 ,

(SEQ ID NO: 29)

Pro-Asp-(Phe-Asp) 6 ,

(SEQ ID NO: 30)

Pro-Asp-(Phe-Asp) 8 ,

(SEQ ID NO: 31)

(Phe-Asp) 5 ,

(SEQ ID NO: 32)

(Phe-Asp) 6 ,

(SEQ ID NO: 33)

(Phe-Asp) 7 ,

(SEQ ID NO: 34)

Pro-Asp-(Phe-Asp) 5 -Pro-Arg-Gly-Asp-Ser,

(SEQ ID NO: 35)

Pro-(Phe-Asp) 3 -Pro,

and

(SEQ ID NO: 36)

Pro-(Phe-Asp) 3 -Pro-(Gly) 3 -Arg-Gly-Asp-Ser,

or a salt thereof.

22 . The method of claim 21 , wherein the at least one amphiphilic peptide comprises a sequence as set forth in SEQ ID NO: 1, or a salt thereof.

23 . The method of claim 10 , wherein the dermatological composition is formulated for intradermal or subcutaneous administration, or wherein the dermatological composition is formulated for use in 3D bioprinting of an artificial tissue, and/or wherein the dermatological composition is in the form of a hydrogel.

24 . The method of claim 10 , wherein the dermatological composition further comprises at least one of hyaluronic acid, collagen, gelatin, elastin, laminin, and fibronectin.

25 . The method of claim 10 , wherein the dermatological composition further comprises a plurality of cells obtained from adipose tissue.

26 . The method of claim 25 , wherein the plurality of cells obtained from adipose tissue comprise adipocytes and/or adipose-derived stem cells, or wherein the plurality of cells obtained from adipose tissue are autologous; or wherein the plurality of cells obtained from adipose tissue are obtained by lipoaspiration, or wherein the plurality of cells obtained from adipose tissue are allogeneic.