SKIN PROBIOTIC
The disclosure provides skin probiotics, fermented media extract and fermentation byproducts thereof for the treatment of skin disease and disorders as well as for the prevention/treatment of acne and MRSA.
1 . A topical probiotic composition for producing or maintaining skin microbiome balance, the composition comprising a therapeutically effective amount or inhibiting effective amount of one or more compounds having the structure of Formula I:
wherein
X is selected from —O—, —S—, and —NH—;
R, R 1 , and R 2 are independently selected from the group consisting of hydrogen, and optionally substituted (C 1 -C 12 )alkyl, optionally substituted hetero-(C 1 -C 12 )alkyl, optionally substituted (C 1 -C 12 )alkenyl, optionally substituted hetero-(C 1 -C 12 )alkenyl, optionally substituted (C 1 -C 12 )alkynyl, optionally substituted hetero-(C 1 -C 12 )alkynyl, optionally substituted (C 1 -C 12 )cycloalkyl, optionally substituted (C 1 -C 12 )cycloalkenyl, optionally substituted aryl, optionally substituted heterocycle, and optionally substituted mixed ring system, and —O—R 3 —O—Y;
R 3 is selected from the group consisting of an optionally substituted (C 1 -C 12 )alkyl, optionally substituted hetero-(C 1 -C 12 )alkyl, optionally substituted (C 1 -C 12 )alkenyl, optionally substituted hetero-(C 1 -C 12 )alkenyl, optionally substituted (C 1 -C 12 )alkynyl, and optionally substituted hetero-(C 1 -C 12 )alkynyl; and
Y is another compound of Formula I, or is selected from the group consisting of
and pharmaceutically acceptable salts thereof.
2 . The topical probiotic composition of claim 1 , wherein an optional substituent is independently selected from the group consisting of carboxyl, nitro, halogen, amino, hydroxyl, cyano, methoxy, polyalkylene glycol, and phenyl, further wherein the phenyl group may be optionally substituted with one or more substituents selected from the group consisting of carboxyl, nitro, halogen, amino, hydroxyl, cyano, methoxy, and polyalkylene glycol.
3 . A topical probiotic composition for producing or maintaining skin microbiome balance, the composition comprising a therapeutically effective amount or inhibiting effective amount of one or more compounds having the structure of Formula II:
wherein,
R 1 is selected from an optionally substituted (C 1 -C 6 )alkyl;
R 2 is selected from a hydroxyl, —O—CH 2 —R 3 , and —O—R 4 —O—X;
R 3 is selected from H, optionally substituted (C 1 -C 12 )alkyl, optionally substituted hetero-(C 1 -C 12 )alkyl, optionally substituted (C 1 -C 12 )alkenyl, optionally substituted hetero-(C 1 -C 12 )alkenyl, optionally substituted (C 1 -C 12 )alkynyl, optionally substituted hetero-(C 1 -C 12 )alkynyl, optionally substituted (C 1 -C 12 )cycloalkyl, optionally substituted (C 1 -C 12 )cycloalkenyl, optionally substituted aryl, optionally substituted heterocycle, and optionally substituted mixed ring system;
R 4 is selected from the group consisting of an optionally substituted (C 1 -C 12 )alkyl, optionally substituted hetero-(C 1 -C 12 )alkyl, optionally substituted (C 1 -C 12 )alkenyl, optionally substituted hetero-(C 1 -C 12 )alkenyl, optionally substituted (C 1 -C 12 )alkynyl, and optionally substituted hetero-(C 1 -C 12 )alkynyl;
X is either another compound of Formula II, or selected from the group consisting of
wherein, when R 2 is a hydroxyl then the pharmaceutical composition comprises at least two compounds comprising the structure of Formula II;
and pharmaceutically acceptable salts thereof.
4 . The topical probiotic composition of claim 3 , wherein the composition comprises one or more compounds comprising the structure of Formula II:
wherein,
R 1 is selected from an optionally substituted (C 1 -C 6 )alkyl;
R 2 is selected from a hydroxyl, —O—CH 2 —R 3 , and —O—R 4 —O—X;
R 3 is selected from H or an optionally substituted (C 1 -C 12 )alkyl;
R 4 is selected from an optionally substituted (C 1 -C 12 )alkyl or an optionally substituted hetero-(C 1 -C 12 )alkyl;
X is either another compound of Formula II, or selected from
and pharmaceutically acceptable salts thereof.
5 . The topical probiotic composition of claim 3 , wherein the composition comprises two or more compounds comprising the structure of Formula II:
wherein,
R 1 is selected from an optionally substituted (C 1 -C 6 )alkyl;
R 2 is a hydroxyl;
and pharmaceutically acceptable salts thereof.
6 . The topical probiotic composition of claim 3 , wherein the composition comprises one or more compounds comprising the structure of Formula II:
wherein,
R 1 is selected from an optionally substituted (C 1 -C 6 )alkyl;
R 2 is selected from —O—CH 2 —R 3 and —O—R 4 —O—X;
R 3 is selected from H or an optionally substituted (C 1 -C 12 )alkyl;
R 4 is selected from —(CH 2 )—, —(CH 2 ) 2 —, and —(CH 2 ) 2 —O—(CH 2 ) 2 —;
X is either another compound of Formula II, or selected from
and pharmaceutically acceptable salts thereof.
7 . The topical probiotic composition of claim 3 , wherein the composition comprises one or more compounds comprising the structure of Formula II:
wherein,
R 1 is selected from —CH 2 —CH 3 , —(CH 2 ) 2 —CH 3 , —CH(OH)—CH 3 , and —(CH 2 ) 2 —COOH;
R 2 is selected from —O—CH 2 —R 3 and —O—R 4 —O—X,
R 3 is selected from H or an optionally substituted (C 1 -C 12 )alkyl;
R 4 is selected from —(CH 2 )—, —(CH 2 ) 2 —, and —(CH 2 ) 2 —O—(CH 2 ) 2 —; and
X is either another compound of Formula II, or selected from
and pharmaceutically acceptable salts thereof.
8 . The topical probiotic composition of claim 3 , wherein the composition comprises one or more compounds having a structure selected from:
9 - 10 . (canceled)
11 . The topical probiotic composition of claim 3 , wherein the composition comprises at least one compound selected from the group consisting of acetic acid, propionic acid, butyric acid, lactic acid, and succinic acid.
12 . The topical probiotic composition of claim 3 , wherein the composition comprises at least two compounds selected from the group consisting of acetic acid, propionic acid, butyric acid, lactic acid, and succinic acid.
13 . The topical probiotic composition of claim 3 , further comprising at least one probiotic commensal skin bacteria.
14 . The topical probiotic composition of claim 3 , further comprising a probiotic commensal skin bacteria fermentation extract.
15 . The topical probiotic composition of claim 14 , wherein the probiotic commensal skin bacteria is selected from the group consisting of a Propionibacterium species, a Paenibacillus species, a Staphylococcus species and any combination thereof.
16 . (canceled)
17 . The topical probiotic composition of claim 15 , wherein the Propionibacterium species is selected from the group consisting of P. acnes, P. granulosum, P. avidum , and any combination thereof.
18 . The topical probiotic composition of claim 15 , wherein the Staphylococcus species is S. epidermidis.
19 . (canceled)
20 . The topical probiotic composition of claim 3 , further comprising glycerol.
21 . A topical probiotic composition comprising a plurality of probiotic commensal skin bacteria selected from the group consisting of a Propionibacterium species, a Paenibacillus species, a Staphylococcus species and any combination thereof.
22 - 23 . (canceled)
24 . The topical probiotic composition of claim 21 , wherein the Propionibacterium species is selected from the group consisting of P. acnes, P. granulosum, P avidum , and any combination thereof.
25 . The topical probiotic composition of claim 21 , wherein the Staphylococcus species is S. epidermidis.
26 . The topical probiotic composition of claim 21 , wherein the composition lacks P. acnes.
27 . A topical probiotic composition comprising a probiotic commensal skin bacteria fermentation extract, the probiotic commensal skin bacterial fermentation extract obtained from bacteria selected from the group consisting of a Propionibacterium species, a Paenibacillus species, a Staphylococcus species, and any combination thereof.
28 . The topical probiotic composition of claim 27 , wherein the Propionibacterium species is selected from the group consisting of P. acnes, P. granulosum, P. avidum , and any combination thereof.
29 . The topical probiotic composition of claim 27 , wherein the Staphylococcus species is S. epidermidis.
30 - 32 . (canceled)
33 . The topical probiotic composition of claim 21 or 27 , wherein the composition further comprises at least one compound selected from acetic acid, propionic acid, butyric acid, lactic acid, and succinic acid.
34 . (canceled)
35 . The topical probiotic composition of claim 1 , 3 , 21 or 27 , wherein the composition is formulated as a lotion, shake lotion, cream, ointment, gel, foam, powder, solid, paste or tincture.
36 . A fermentation extract obtained by fermenting P acnes, S. epidermidis , and/or Paenibacillus sp. with glycerol under fermentation conditions.
37 . The fermentation extract of claim 36 for use in inhibiting infection or overgrowth of an organism selected from the group consisting of S. aureus , methicillin-resistant S. aureus (MRSA), Candida, P acnes and E. coli.
38 - 41 . (canceled)
42 . A bandage or dressing comprising at least one of the topical probiotic composition of claim 1 , a probiotic commensal skin bacteria fermentation extract, a probiotic commensal skin bacteria, glycerol, and any combination thereof.
43 - 46 . (canceled)
47 . A method of treating or preventing a skin infection comprising contacting the skin with the topical probiotic composition of claim 1 or 3 .
48 . The method of claim 47 , wherein the skin infection is caused by at least one organism selected from the group consisting of P acnes, S. aureus , methicillin-resistant S. aureus (MRSA), Candida and E. coli.
49 - 50 . (canceled)
51 . A method of treating a skin infection comprising contacting the skin with one or more probiotic commensal skin bacteria alone or in combination with glycerol and/or a short chain fatty acid.
52 - 55 . (canceled)
56 . The method of claim 51 , wherein the infection is an infection with an S. aureus or a MRSA infection.
57 - 62 . (canceled)
63 . A method of inhibiting the overgrowth of P. acnes comprising contacting the affected skin surface with a compound of claim 1 having the formula:
64 . A method of inhibiting or preventing the infection of S. aureus , methicillin-resistant S. aureus (MRSA), Candida species, or E. coli comprising contacting the affected skin surface with a compound of claim 3 having the formula:
65 - 70 . (canceled)